Sample records for diclofenac

  1. Diclofenac sodium overdose

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/002630.htm Diclofenac sodium overdose To use the sharing features on this page, please enable JavaScript. Diclofenac sodium is a prescription medicine used to relieve pain ...

  2. Diclofenac and Misoprostol

    MedlinePlus

    ... patients who have a high risk of developing stomach ulcers. Diclofenac is in a class of medications called ... you need to take an antacid during your treatment with diclofenac and misoprostol. You should not take ...

  3. Diclofenac Topical (osteoarthritis pain)

    MedlinePlus

    ... gel (Voltaren) is used to relieve pain from osteoarthritis (arthritis caused by a breakdown of the lining ... Diclofenac topical liquid (Pennsaid) is used to relieve osteoarthritis pain in the knees. Diclofenac is in a ...

  4. Bioequivalence of diclofenac sodium 2% and 1.5% topical solutions relative to oral diclofenac sodium in healthy volunteers.

    PubMed

    Holt, Robert J; Taiwo, Tolu; Kent, Jeffrey D

    2015-08-01

    Topical formulations of nonsteroidal anti-inflammatory drugs (NSAIDs) are generally considered to be safer alternatives to oral NSAIDs due to lower systemic absorption. We conducted randomized, crossover studies that compared the pharmacokinetics (PK), bioequivalence and safety of topical diclofenac sodium 2% twice daily (BID), diclofenac sodium 1.5% four times daily (QID) and oral diclofenac sodium in healthy subjects. The results of three bioequivalence studies are reviewed. Healthy adult subjects (n = 76) applied topical diclofenac sodium 2% solution (40.4 mg/2 mL) BID; or 1.5% solution (19.3 mg/40 drops) QID to each knee for 7.5 consecutive days separated by a washout period. Subjects (n = 22) in one study also received oral diclofenac sodium 75 mg BID for 7.5 days. Plasma diclofenac concentrations were determined from serial blood samples collected on Days 1 and 8 (steady state), and diclofenac PK parameters were estimated by noncompartmental methods. The studies demonstrated comparable bioequivalence between the 2% and 1.5% topical solutions as well as lower systemic exposure compared to oral dosing (approximately 93% less). Daily systemic exposure was comparable between the two formulations with only a 12% difference in the AUCss(0-24) (p = 0.140). Furthermore, both topical solutions demonstrated delayed elimination with a t(1/2) of 4- to 6-fold longer, as compared to oral diclofenac. The 2% solution provided more consistent dosing relative to the 1.5% solution when comparing AUCss(0-24) and Cmaxss across studies. Mild application site reactions were the most common treatment-emergent adverse event reported with topical diclofenac. The steady-state PK profile of topical diclofenac 2% solution administered BID is similar to that of the 1.5% solution administered QID. Systemic exposure to diclofenac is substantially lower after topical application as compared to oral administration. (Study 2 was registered with ClinicalTrials.gov; NCT01202799; https

  5. Diclofenac

    MedlinePlus

    ... powder for solution contains aspartame, a source of phenylalanine. ... Diclofenac may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: diarrhea constipation gas or ...

  6. Diclofenac and metabolite pharmacokinetics in children.

    PubMed

    van der Marel, Caroline D; Anderson, Brian J; Rømsing, Janne; Jacqz-Aigrain, Evelyne; Tibboel, Dick

    2004-06-01

    Data concerning metabolism of diclofenac in children are limited to intravenous and enteric coated oral formulations. There are no data examining diclofenac or its hydroxyl metabolite pharmacokinetics after rectal administration in children. Infants (n = 26) undergoing tonsillectomy were given diclofenac 2 mg.kg(-1) followed by 1 mg.kg(-1) 8 h as suppository formulation for postoperative analgesia. Serum was assayed for diclofenac, 4'-hydroxydiclofenac and 5'-hydroxydiclofenac concentrations during the procedure and 1, 2 and 4 h postoperatively. The formation clearances of diclofenac to hydroxyl metabolites were estimated using nonlinear mixed effects models. A single compartment, first order absorption and first order elimination model was used to describe diclofenac pharmacokinetics. Published data from 11 children given enteric-coated diclofenac tablets were used to assess relative bioavailability. Mean (sd) age and weight of the patients were 4.5 (1.5) years and 20.5 (4.1) kg. The formation clearance to 4'-hydroxydiclofenac (% CV) and to 5'-hydroxydiclofenac were 8.41 (8.1) and 3.41 (113) l.h(-1) respectively, standardized to a 70 kg person using allometric '1/4 power' models. Clearance by other routes contributed 33.0 (64) l.h(-1) 70 kg(-1). Elimination clearance of hydroxyl metabolites was fixed at 27.5 l.h(-1) 70 kg(-1). The volumes of distribution of parent diclofenac and its hydroxyl metabolite were 22.8 (19.0) and 45.3 (l.70) kg(-1). The suppository formulation had an absorption half-life of 0.613 (33.2) h with a lag time of 0.188 (24.9) h. Interoccasion variability of formation clearance to 4'-hydroxydiclofenac, diclofenac volume of distribution, absorption half-time and lag time for the suppository was 36%, 55%, 14% and 119%, respectively. The relative bioavailability of the suppository compared with an enteric-coated tablet was 1.26. The formation clearance of the active metabolite 4'-hydroxydiclofenac contributed 19% of total clearance (44.82 l.h(-1

  7. Ecotoxicogenomic assessment of diclofenac toxicity in soil.

    PubMed

    Chen, Guangquan; den Braver, Michiel W; van Gestel, Cornelis A M; van Straalen, Nico M; Roelofs, Dick

    2015-04-01

    Diclofenac is widely used as nonsteroidal anti-inflammatory drug leaving residues in the environment. To investigate effects on terrestrial ecosystems, we measured dissipation rate in soil and investigated ecotoxicological and transcriptome-wide responses in Folsomia candida. Exposure for 4 weeks to diclofenac reduced both survival and reproduction of F. candida in a dose-dependent manner. At concentrations ≥ 200 mg/kg soil diclofenac remained stable in the soil during a 21-day incubation period. Microarrays examined transcriptional changes at low and high diclofenac exposure concentrations. The results indicated that development and growth were severely hampered and immunity-related genes, mainly directed against bacteria and fungi, were significantly up-regulated. Furthermore, neural metabolic processes were significantly affected only at the high concentration. We conclude that diclofenac is toxic to non-target soil invertebrates, although its mode of action is different from the mammalian toxicity. The genetic markers proposed in this study may be promising early markers for diclofenac ecotoxicity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Veterinary diclofenac threatens Africa's endangered vulture species.

    PubMed

    Naidoo, V; Wolter, K; Cuthbert, R; Duncan, N

    2009-04-01

    Veterinary diclofenac has been responsible for the devastation of three species of Gyps vulture on the Indian subcontinent, and it is now regarded as one of the worst environmental contaminants in the recent past. While measures have been taken to control the manufacture of veterinary diclofenac in South Asia, the promotion of diclofenac on the African continent poses a risk to vultures in this region. In Southern Africa, the species of greatest conservation concern is the Cape Griffon Vulture (Gyps coprotheres), as only 2900 breeding pairs remain in the wild. The objective of this study was to test if this species is toxicologically sensitive to diclofenac. In a single dose-toxicity study, two adult Cape Griffon Vultures with severe injuries, that were considered to have a very poor prognostic outcome, were dosed intravenously with diclofenac at 0.8mg/kg. The changes in the clinical pathology were compared to the normal reference range established for 24 healthy Cape Griffon Vultures. Both birds died within 48h of dosing. The clinical signs, clinical pathology, gross pathology and histopathological finding were typical for diclofenac toxicity. It would appear that the sensitivity of the Cape Griffon is similar to that of their Asian counterparts and the African White-backed Vulture (Gyps africanus). Diclofenac is almost certainly toxic to all Gyps vultures species and strong efforts must be taken to ensure that veterinary diclofenac products are not licensed or introduced to the African continent.

  9. Efficacy and Safety of Oral Diclofenac Sustained release Versus Transdermal Diclofenac Patch in Chronic Musculoskeletal Pain: A Randomized, Open Label Trial.

    PubMed

    Shinde, Viraj Ashok; Kalikar, Mrunalini; Jagtap, Satyajeet; Dakhale, Ganesh N; Bankar, Mangesh; Bajait, Chaitali S; Motghare, Vijay M; Pashilkar, Ashlesha A; Raghute, Latesh B; Khamkar, Ajita D

    2017-01-01

    To compare the efficacy, safety, and tolerability of transdermal patches of diclofenac sodium with oral diclofenac sustained release (SR) in patients of chronic musculoskeletal MSK pain conditions. The eligible patients were given either transdermal diclofenac patch or tablet diclofenac SR. Pain was assessed at 2 and 4 weeks using a visual analog scale. Adverse events were recorded. Patients with 18-65 years old of either gender with score of ≥4 on a 11-item numeric rating scale-numeric version of visual analog scale for pain with diagnosis of primary osteoarthritis (OA) of the knee or hand of at least 3 months duration, with independent radiological confirmation of OA or having pain associated with other MSK conditions such as soft-tissue rheumatism, cervical and lumbar back pain, and fibromyalgia, of at least 3 months duration were included in this study. Transdermal diclofenac diethylamine patch and tablet diclofenac sodium sustained release (SR) do not significantly differ in the reduction of numerical rating scores at the end of 4 weeks (P = 0.8393). Transdermal diclofenac was equi-efficacious as tablet diclofenac sodium SR in reducing pain due to chronic MSK pain conditions.

  10. Efficacy and Safety of Oral Diclofenac Sustained release Versus Transdermal Diclofenac Patch in Chronic Musculoskeletal Pain: A Randomized, Open Label Trial

    PubMed Central

    Shinde, Viraj Ashok; Kalikar, Mrunalini; Jagtap, Satyajeet; Dakhale, Ganesh N.; Bankar, Mangesh; Bajait, Chaitali S.; Motghare, Vijay M.; Pashilkar, Ashlesha A.; Raghute, Latesh B.; Khamkar, Ajita D.

    2017-01-01

    Introduction: To compare the efficacy, safety, and tolerability of transdermal patches of diclofenac sodium with oral diclofenac sustained release (SR) in patients of chronic musculoskeletal MSK pain conditions. Materials and Methods: The eligible patients were given either transdermal diclofenac patch or tablet diclofenac SR. Pain was assessed at 2 and 4 weeks using a visual analog scale. Adverse events were recorded. Patients with 18–65 years old of either gender with score of ≥4 on a 11-item numeric rating scale-numeric version of visual analog scale for pain with diagnosis of primary osteoarthritis (OA) of the knee or hand of at least 3 months duration, with independent radiological confirmation of OA or having pain associated with other MSK conditions such as soft-tissue rheumatism, cervical and lumbar back pain, and fibromyalgia, of at least 3 months duration were included in this study. Results: Transdermal diclofenac diethylamine patch and tablet diclofenac sodium sustained release (SR) do not significantly differ in the reduction of numerical rating scores at the end of 4 weeks (P = 0.8393). Conclusion: Transdermal diclofenac was equi-efficacious as tablet diclofenac sodium SR in reducing pain due to chronic MSK pain conditions. PMID:29472748

  11. A comparison of preservative-free diclofenac and preserved diclofenac eye drops after cataract surgery in patients with diabetic retinopathy.

    PubMed

    Yasuda, Kanako; Miyazawa, Akiko; Shimura, Masahiko

    2012-06-01

    The aim of this study was to compare the anti-inflammatory efficacy of preservative-free and preserved 0.1% diclofenac eye drops for the management of postoperative inflammation after cataract surgery in patients with nonproliferative diabetic retinopathy and in normal controls. Forty-two diabetic patients and 50 normal control patients who underwent small-incision phacoemulsification cataract surgery bilaterally received topical preservative-free diclofenac in 1 eye and preserved diclofenac in the other eye. The corrected distance visual acuity (CDVA) as determined by a logarithm of the minimum angle of resolution (logMAR) chart, intraocular pressure (IOP), foveal thickness (FT) using optical coherence tomography (OCT), and the anterior chamber flare (ACF) score measured with a laser flare cell meter were monitored for 12 weeks after surgery. In the eyes with diabetic retinopathy, there were no significant differences in CDVA, IOP, FT, and ACF score between the right and left eyes at the initial exam. After cataract surgery, changes in CDVA, IOP, and FT were not influenced by the preservative in the diclofenac eye drops. In contrast, the ACF score in the eyes treated with preserved diclofenac showed slower recovery from postoperative inflammation than the eyes treated with preservative-free diclofenac. In the normal control eyes, similar but milder changes were observed in each of the clinical parameters. Because preservative suppressed the anti-inflammatory efficacy of topical diclofenac after cataract surgery, preservative-free diclofenac may have an improved safety profile during postoperative treatment, especially in patients with diabetic retinopathy.

  12. Diclofenac/misoprostol: novel findings and their clinical potential.

    PubMed

    Shield, M J

    1998-05-01

    The new class of antiinflammatory and analgesic drugs, the selective cyclooxygenase (COX-2) inhibitors, which promise to be devoid of the types of toxicity associated with nonsteroidal antiinflammatory drugs (NSAID), especially adverse gastrointestinal effects, are under clinical trial but are not yet available for use. All NSAID, including those most recently introduced, exhibit nonselectivity of action, producing therapeutic blood levels that inhibit constitutive COX-1 and deplete tissue protective prostaglandins. Among NSAID, the diclofenac/misoprostol combination (Arthrotec) is unique in possessing an active component, misoprostol, to help prevent NSAID induced gastrointestinal damage. Ulcer damage and associated serious complications probably represent only the tip of the iceberg in relation to clinically significant side effects associated with the use of NSAID. In this context, metaanalysis of 8 large multicenter studies reported here has shown that patients taking NSAID show a mean decrease in hemoglobin over 4 - 12 weeks' assessment, with some 10-20% of patients exhibiting clinically significant decreases (> or = 1 g/dl) early in treatment. Patients taking diclofenac/misoprostol showed significantly less of a decline in hemoglobin and up to 50% fewer clinically significant decreases than patients receiving diclofenac alone. The misoprostol component of diclofenac/misoprostol may also help to restore homeostasis in tissues other than the gut. Inhibition of the activity or release of various tissue damaging agents and inflammatory cytokines, e.g., thromboxane and interleukin 1, are described, as are in vivo animal studies that have revealed synergistic or potentiating analgesic and antiinflammatory activities between misoprostol and NSAID, particularly diclofenac. Clinical studies in postsurgical dental pain in more than 500 patients have now shown enhanced analgesia, with greater relief over a longer period, for the diclofenac/misoprostol combination

  13. Advances in NSAID development: evolution of diclofenac products using pharmaceutical technology.

    PubMed

    Altman, Roy; Bosch, Bill; Brune, Kay; Patrignani, Paola; Young, Clarence

    2015-05-01

    Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class with anti-inflammatory, analgesic, and antipyretic properties. Contrary to the action of many traditional NSAIDs, diclofenac inhibits cyclooxygenase (COX)-2 enzyme with greater potency than it does COX-1. Similar to other NSAIDs, diclofenac is associated with serious dose-dependent gastrointestinal, cardiovascular, and renal adverse effects. Since its introduction in 1973, a number of different diclofenac-containing drug products have been developed with the goal of improving efficacy, tolerability, and patient convenience. Delayed- and extended-release forms of diclofenac sodium were initially developed with the goal of improving the safety profile of diclofenac and providing convenient, once-daily dosing for the treatment of patients with chronic pain. New drug products consisting of diclofenac potassium salt were associated with faster absorption and rapid onset of pain relief. These include diclofenac potassium immediate-release tablets, diclofenac potassium liquid-filled soft gel capsules, and diclofenac potassium powder for oral solution. The advent of topical formulations of diclofenac enabled local treatment of pain and inflammation while minimizing systemic absorption of diclofenac. SoluMatrix diclofenac, consisting of submicron particles of diclofenac free acid and a proprietary combination of excipients, was developed to provide analgesic efficacy at reduced doses associated with lower systemic absorption. This review illustrates how pharmaceutical technology has been used to modify the pharmacokinetic properties of diclofenac, leading to the creation of novel drug products with improved clinical utility.

  14. Evaluation of diclofenac prodrugs for enhancing transdermal delivery.

    PubMed

    Lobo, Shabbir; Li, Henan; Farhan, Nashid; Yan, Guang

    2014-03-01

    Abstract Objective: The purpose of this study was to evaluate the approach of using diclofenac acid (DA) prodrugs for enhancing transdermal delivery. Methanol diclofenac ester (MD), ethylene glycol diclofenac ester (ED), glycerol diclofenac ester (GD) and 1,3-propylene glycol diclofenac ester (PD) were synthesized and evaluated for their physicochemical properties such as solubilities, octanol/water partition coefficients, stratum corneum/water partition coefficients, hydrolysis rates and bioconversion rates. In vitro fluxes across human epidermal membrane (HEM) in the Franz diffusion cell were determined on DA-, MD-, ED-, GD- and PD-saturated aqueous solutions. The formation of GD and ED led to the prodrugs with higher aqueous solubilities and lower partition coefficients than those of the parent drug. Prodrugs with improved aqueous solubility showed better fluxes across HEM in aqueous solution than that of the parent drug, with GD showing the highest aqueous solubility and also the highest flux. There is a linear relationship between the aqueous solubility and flux for DA, ED and PD, but GD and MD deviated from the linear line. Diclofenac prodrugs with improved hydrophilicity than the parent drug could be utilized for enhancing transdermal diclofenac delivery.

  15. Metabolism of aceclofenac in cattle to vulture-killing diclofenac.

    PubMed

    Galligan, T H; Taggart, M A; Cuthbert, R J; Svobodova, D; Chipangura, J; Alderson, D; Prakash, V M; Naidoo, V

    2016-10-01

    The nonsteroidal anti-inflammatory drug (NSAID) diclofenac is highly toxic to Gyps vultures, and its recent widespread use in South Asia caused catastrophic declines in at least 3 scavenging raptors. The manufacture of veterinary formulations of diclofenac has since been banned across the region with mixed success. However, at least 12 other NSAIDs are available for veterinary use in South Asia. Aceclofenac is one of these compounds, and it is known to metabolize into diclofenac in some mammal species. The metabolic pathway of aceclofenac in cattle, the primary food of vultures in South Asia, is unknown. We gave 6 cattle the recommended dose of aceclofenac (2 mg/kg), collected blood thereafter at intervals for up to 12 h, and used liquid chromatography with mass spectrometry in a pharmacokinetic analysis of aceclofenac and diclofenac in the plasma. Nearly all the aceclofenac administered to the cattle was very rapidly metabolized into diclofenac. At 2 h, half the aceclofenac had been converted into diclofenac, and at 12 h four-fifths of the aceclofenac had been converted into diclofenac. Therefore, administering aceclofenac to livestock poses the same risk to vultures as administering diclofenac to livestock. This, coupled with the risk that aceclofenac may replace diclofenac in the veterinary market, points to the need for an immediate ban on all aceclofenac formulations that can be used to treat livestock. Without such a ban, the recovery of vultures across South Asia will not be successful. © 2016 Society for Conservation Biology.

  16. Can Rectal Diclofenac Prevent Post Endoscopic Retrograde Cholangiopancreatography Pancreatitis?

    PubMed

    Lua, Guan Way; Muthukaruppan, Raman; Menon, Jayaram

    2015-10-01

    Non steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the incidence of post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). There were various trials using different routes and dosages of NSAIDs but meta-analysis revealed inconsistent results. The aims of this study were to determine the efficacy of rectal diclofenac in preventing PEP and to evaluate any adverse events. This was a randomized, open-label, two-arm, prospective clinical trial. Only patients at high risk of developing PEP were recruited. They received 100 mg rectal diclofenac or no intervention immediately after ERCP. The patients were reviewed 30 days after discharge to evaluate any adverse event. Among 144 recruited patients, 69 (47.9%) received diclofenac and 75 (52.1%) had no intervention. Eleven patients (7.6%) developed PEP, in which seven were from the diclofenac group and four were in the control group. Eight cases of PEP (5.5%) were mild and three cases (2.1%) were moderate. The differences in pancreatitis incidence and severity between both groups were not statistically significant. There were 11 adverse events reported. Clinically significant bleeding happened in four patients (2.8%): one from the diclofenac group and three from the control group. Other events included cholangitis: two patients (2.9%) from the diclofenac group and four (5.3%) from the control group. One patient from the diclofenac group (1.4%) had a perforation which was treated conservatively. In summary, prophylactic rectal diclofenac did not significantly decrease the incidence of PEP among patients at high risk for developing PEP. However, the administration of diclofenac was fairly safe with few clinical adverse events.

  17. Influence of Dosage Form on the Intravitreal Pharmacokinetics of Diclofenac

    PubMed Central

    Durairaj, Chandrasekar; Kim, Stephen J.; Edelhauser, Henry F.; Shah, Jaymin C.; Kompella, Uday B.

    2009-01-01

    Purpose To prepare a suspension form of diclofenac and compare the influence of the injected form (suspension versus solution) on the intravitreal pharmacokinetics of diclofenac in Dutch belted pigmented rabbits. Methods Diclofenac acid was prepared and characterized in a suspension formulation. Rabbit eyes were injected with either diclofenac sodium solution (0.3 mg) or diclofenac acid suspension (10 mg) prepared in 0.1 mL balanced salt solution. Rabbits were killed at regular time intervals, the eyes enucleated, and drug content quantified in the vitreous humor and retina-choroid tissue by high-performance liquid chromatography. Pharmacokinetic models were developed for both the dosage forms, and simulations were performed for different doses. Results Diclofenac acid with an approximate 5-μm particle size exhibited 3.5-fold lower solubility in vitreous humor, when compared with its sodium salt. The estimated settling velocity of the suspension in the vitreous humor was 3 cm/h. After diclofenac sodium salt solution injection, drug levels declined rapidly with no drug levels detectable after 24 hours in the vitreous humor and 4 hours in the RC. Throughout the assessed time course, drug levels were higher in the vitreous. However, sustained, high drug levels were observed in both the vitreous humor and the retina-choroid even on day 21 after diclofenac acid suspension injection, with retina-choroid drug levels being higher beginning at 0.25 hour. The elimination half-life of diclofenac suspension was 24 and 18 days in vitreous and retina-choroid, respectively, compared to 2.9 and 0.9 hours observed with diclofenac sodium. The pharmacokinetic models developed indicated a slow-release distribution or depot compartment for the diclofenac acid suspension in the posterior segment. Simulations indicated the inability of a 10-mg dose of diclofenac sodium solution to sustain drug levels in the vitreous beyond 11 days. Conclusions By choosing a less soluble form of a drug

  18. Release of salicylic acid, diclofenac acid and diclofenac acid salts from isotropic and anisotropic nonionic surfactant systems across rat skin.

    PubMed

    Gabboun, N H; Najib, N M; Ibrahim, H G; Assaf, S

    2001-01-05

    Release of salicylic acid, diclofenac acid, diclofenac diethylamine and diclofenac sodium, from lyotropic structured systems, namely; neat and middle liquid crystalline phases, across mid-dorsal hairless rat skin into aqueous buffer were studied. Release results were compared with those from the isotropic systems. The donor systems composed of the surfactant polyoxyethylene (20) isohexadecyl ether, HCl buffer of pH 1 or distilled water and the specific drug. High performance liquid chromatography (HPLC) methods were used to monitor the transfer of the drugs across the skin barrier. Results indicated that the rate-determining step in the transport process was the release of the drug from the specified donor system. Further, apparent zero order release was demonstrated with all systems. Except for diclofenac sodium, drug fluxes decreased as the donor medium changed from isotropic to anisotropic. The decrease in fluxes was probably due to the added constrains on the movement of drug molecules. By changing the anisotropic donor medium from neat to middle phase, drug flux decreased in case of salicylic acid and diclofenac sodium. In the mean time, flux increased in case of the diethylamine salt and appeared nearly similar in case of diclofenac acid. Rates of drug transfer across the skin from the anisotropic donors seemed to be largely controlled by the entropy contribution to the transport process. The type and extent of drug-liquid crystal interactions probably influenced the latter.

  19. Single dose oral diclofenac for acute postoperative pain in adults

    PubMed Central

    Derry, Philip; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), available as a potassium salt (immediate-release) or sodium salt (delayed-release). This review updates an earlier review published in The Cochrane Database of Systematic Reviews (Issue 2, 2004) on ‘Single dose oral diclofenac for postoperative pain’. Objectives To assess single dose oral diclofenac for the treatment of acute postoperative pain. Search methods Cochrane CENTRAL, MEDLINE, EMBASE, Biological Abstracts, the Oxford Pain Relief Database, and reference lists of articles were searched; last search December 2008. Selection criteria Randomised, double-blind, placebo-controlled clinical trials of single dose, oral diclofenac (sodium or potassium) for acute postoperative pain in adults. Data collection and analysis Two review authors independently assessed studies for inclusion and quality, and extracted data. The area under the pain relief versus time curve was used to derive the proportion of participants with at least 50% pain relief over 4 to 6 hours, using validated equations. Relative benefit (risk) and number needed to treat to benefit (NNT) were calculated. Information on adverse events, time to remedication, and participants needing additional analgesia was also collected. Main results Fifteen studies (eight additional studies) with 1512 participants more than doubled the information available at each dose. Overall 50% to 60% of participants experienced at least 50% pain relief over 4 to 6 hours at any dose with diclofenac, compared to 10 to 20% with placebo, giving NNTs of about 2.5 for doses of 25 mg to 100 mg (similar to earlier review); no dose response was demonstrated. At 50 mg and 100 mg, NNTs for diclofenac potassium (2.1 (1.8 to 2.4) and 1.9 (1.7 to 2.2)) were significantly lower (better) than for diclofenac sodium (6.7 (4.2 to 17) and 4.5 (3.2 to 7.7)). The median time to use of rescue medication was 2 hours for placebo, 4.3 hours for diclofenac 50 mg and 4.9 hours

  20. Effect of vehicles on diclofenac permeation across excised rat skin.

    PubMed

    Takahashi, K; Suzuki, T; Sakano, H; Mizuno, N

    1995-04-01

    The in vitro percutaneous permeation of diclofenac from various vehicles was examined using rat abdominal skin as a model membrane. The oleaginous vehicles used in this study consisted of three components: i.e. fatty acid, fatty acid ester and nonpolar oil. The solubilities of sodium diclofenac in formulated vehicles were above 0.2 M. The effect of each oleaginous component in the vehicle on the permeation of diclofenac across the skin was in the following order: oleic acid > isostearic acid, diisopropyl adipate = diethyl sebacate > Panasate 875 and squalane > liquid paraffin. To clarify the reason for the differences in permeation among the fatty acid esters, the release of diclofenac through either porous or lipoidal membranes from these vehicles in vitro and the solubility of sodium diclofenac in the vehicles were studied. However, no relationship was observed between the release rate or solubility and skin permeability. The skin permeation of diclofenac increased following pretreatment with diisopropyl adipate or diethyl sebacate, but not with middle chain triglyceride (Panasate 875). These results suggested that the main reason may be the enhancement effect of fatty acid esters. Emulsions and creams containing 3% sodium diclofenac were prepared using the above oleaginous vehicles. A large flux and short lag time were observed in these preparations compared with an aqueous suspension of sodium diclofenac. The incorporation of urea significantly enhanced the permeation of diclofenac from these preparations. These results suggest that the emulsion and cream prepared in this study are useful for development for practical purposes.

  1. Comparison of transdermal diclofenac patch with oral diclofenac as an analgesic modality following multiple premolar extractions in orthodontic patients: A cross over efficacy trial

    PubMed Central

    Bhaskar, Hemant; Kapoor, Pranav; Ragini

    2010-01-01

    Aims: This study was performed to compare the degree of post operative analgesia, patient compliance, and frequency of adverse events with the use of oral diclofenac tablets and transdermal diclofenac patch following multiple premolar extractions in patients undergoing orthodontic treatment. Materials and Methods: Twenty young pre-orthodontic patients requiring bilateral maxillary and mandibular first premolar extractions were selected for the study. The right maxillary and mandibular first premolars were extracted first and 50 mg oral diclofenac sodium tablets were prescribed to be taken thrice a day for three days. In the next appointment, the contralateral first premolars were extracted and a 100 mg transdermal diclofenac patch was applied once a day for three days. Pain relief and pain intensity with both the diclofenac formulations was recorded for each of the three postoperative days using 5-point Verbal Pain Intensity and Pain Relief Score Charts. Results and Conclusions: Statistical analyses revealed that there was a gradual increase in pain relief scores and a gradual decrease in pain intensity scores with the use of oral diclofenac tablets as well as with the transdermal patch. However, subjects reported that they were more comfortable using the transdermal patch particularly due to the once-a-day application and lesser frequency of systemic adverse effects. Results of this study indicate that the transdermal diclofenac patch provides as potent analgesia as the oral diclofenac tablets with the added advantage of better patient compliance and may be used for routine post extraction analgesia. PMID:22114407

  2. Effect of O-acylmenthol and salt formation on the skin permeation of diclofenac acid.

    PubMed

    Zhao, Ligang; Li, Yan; Fang, Liang; Ren, Changshun; Xu, Yongnan; He, Zhonggui

    2009-07-01

    To enhance the transdermal delivery of diclofenac acid (DA) by using O-acylmenthol as a penetration enhancer and complexing with amines, or by a combination of the two methods. The skin permeability of diclofenac was tested in vitro across rat skin with each of the evaluated permeants in a saturated isopropyl myristate (IPM) donor solution. A 4.5-fold increase in the flux of diclofenac was observed by ion-pair formation with diethylamine; however, the cations with hydroxyl groups had negative effects on the transdermal delivery of diclofenac. 2-isopropyl-5-methylcyclohexyl 2-hydroxypanoate and 2-isopropyl-5-methylcyclohexyl heptanoate produced significant increase in the permeation of diclofenac potassium (D-K); however, both of them were ineffective for the other diclofenac salts, including diclofenac diethylamine (D-DETA), diclofenac ethanolamine (D-EA), diclofenac diethanolamine (D-DEA), diclofenac triethanolamine, and diclofenac N-(hydroxylethyl) piperidine. 2-isopropyl-5-methylcyclohexyl tetradecanoate was effective on the penetration of D-K, D-DETA, D-EA, and D-DEA. Also, it is exciting to note that the combined use of diethylamine with 2-isopropyl-5-methylcyclohexyl tetradecanoate produced a 9.74-fold increase in accumulation amount of diclofenac compared with DA in IPM. The use of ion pair in combination with O-acylmenthol is necessary to further increase the diclofenac flux to provide better compliance for the patients undergoing clinical therapy.

  3. Diclofenac removal in urine using strong-base anion exchange polymer resins.

    PubMed

    Landry, Kelly A; Boyer, Treavor H

    2013-11-01

    One of the major sources of pharmaceuticals in the environment is wastewater effluent of which human urine contributes the majority of pharmaceuticals. Urine source separation has the potential to isolate pharmaceuticals at a higher concentration for efficient removal as well as produce a nutrient byproduct. This research investigated the efficacy of using strong-base anion exchange polymer resins to remove the widely detected and abundant pharmaceutical, diclofenac, from synthetic human urine under fresh and ureolyzed conditions. The majority of experiments were conducted using a strong-base, macroporous, polystyrene resin (Purolite A520E). Ion-exchange followed a two-step removal rate with rapid removal in 1 h and equilibrium removal in 24 h. Diclofenac removal was >90% at a resin dose of 8 mL/L in both fresh and ureolyzed urine. Sorption of diclofenac onto A520E resin was concurrent with desorption of an equivalent amount of chloride, which indicates the ion-exchange mechanism is occurring. The presence of competing ions such as phosphate and citrate did not significantly impact diclofenac removal. Comparisons of three polystyrene resins (A520E, Dowex 22, Dowex Marathon 11) as well as one polyacrylic resin (IRA958) were conducted to determine the major interactions between anion exchange resin and diclofenac. The results showed that polystyrene resins provide the highest level of diclofenac removal due to electrostatic interactions between quaternary ammonium functional groups of resin and carboxylic acid of diclofenac and non-electrostatic interactions between resin matrix and benzene rings of diclofenac. Diclofenac was effectively desorbed from A520E resin using a regeneration solution that contained 4.5% (m/m) NaCl in an equal-volume mixture of methanol and water. The greater regeneration efficiency of the NaCl/methanol-water mixture over the aqueous NaCl solution supports the importance of non-electrostatic interactions between resin matrix and benzene rings

  4. Novel Curcumin Diclofenac Conjugate Enhanced Curcumin Bioavailability and Efficacy in Streptococcal Cell Wall-induced Arthritis.

    PubMed

    Jain, S K; Gill, M S; Pawar, H S; Suresh, Sarasija

    2014-09-01

    Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; stability of curcumin-diclofenac conjugate in gastrointestinal fluids and in vitro efficacy have been evaluated. In vivo bioavailability of curcumin-diclofenac conjugate and curcumin in Sprague-Dawley rats, and antiarthritic activity of curcumin-diclofenac conjugate, curcumin and diclofenac in modified streptococcal cell wall-induced arthritis model in Balb/c mice to mimic rheumatoid arthritis in humans have also been studied. In all of the above studies, curcumin-diclofenac conjugate exhibited enhanced stability as compared to curcumin; its activity was twice that of diclofenac in inhibiting thermal protein denaturation taken as a measure of in vitro antiinflammatory activity; it enhanced the bioavailability of curcumin by more than five folds, and significantly (P<0.01) alleviated the symptoms of arthritis in streptococcal cell wall-induced arthritis model as compared to both diclofenac and curcumin.

  5. Spontaneous thigh hematoma associated with diclofenac.

    PubMed

    Salemis, Nikolaos S

    2009-01-01

    Spontaneous nongastrointestinal bleeding in patients treated with nonsteroidal anti-inflammatory drugs is an extremely rare occurrence. Herein, the case of a 60-year-old woman with severe bilateral hip osteoarthritis treated with diclofenac sodium, who presented with manifestations of a spontaneous hematoma of the right thigh, is described. There was no history of trauma or family history of bleeding disorder. Thorough investigation excluded a hemorrhagic disorder. The patient was treated conservatively with success and was advised to discontinue diclofenac.

  6. Action of diclofenac on kidney mitochondria and cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ng, Lin Eng; Vincent, Annette S.; Halliwell, Barry

    2006-09-22

    The mitochondrial membrane potential measured in isolated rat kidney mitochondria and in digitonin-permeabilized MDCK type II cells pre-energized with succinate, glutamate, and/or malate was reduced by micromolar diclofenac dose-dependently. However, ATP biosynthesis from glutamate/malate was significantly more compromised compared to that from succinate. Inhibition of the malate-aspartate shuttle by diclofenac with a resultant decrease in the ability of mitochondria to generate NAD(P)H was demonstrated. Diclofenac however had no effect on the activities of NADH dehydrogenase, glutamate dehydrogenase, and malate dehydrogenase. In conclusion, decreased NAD(P)H production due to an inhibition of the entry of malate and glutamate via the malate-aspartate shuttlemore » explained the more pronounced decreased rate of ATP biosynthesis from glutamate and malate by diclofenac. This drug, therefore affects the bioavailability of two major respiratory complex I substrates which would normally contribute substantially to supplying the reducing equivalents for mitochondrial electron transport for generation of ATP in the renal cell.« less

  7. Effect of different penetration enhancers on diclofenac permeation across horse skin.

    PubMed

    Ferrante, M; Andreeta, A; Landoni, M F

    2010-12-01

    Diclofenac is a hydrophilic non-steroidal anti-inflammatory drug widely used in humans and animals. Previous reports have shown that this compound has low percutaneous absorption in horses. The effect of five penetration enhancers (10% urea, 15% and 20% oleic acid and 5% and 10% d-limonene) on the percutaneous absorption of diclofenac diethylamine through horse skin was evaluated in vitro using Franz-type diffusion cells. All tested penetration enhancers induced a significant increase in diclofenac diethylamine permeation, with limonene showing the highest enhancing effect at the lowest concentration (5%) applied. The presence of the permeation enhancers did not affect lag-time. This is the first in vitro study of the effects of penetration enhancers on transdermal permeation of diclofenac diethylamine across horse skin. The results suggested that urea, limonene and 5% oleic acid were useful for enhancing the transdermal absorption of diclofenac diethylamine and may assist in the development of a transdermal formulation of diclofenac diethylamine for use in horses. Copyright © 2009. Published by Elsevier Ltd.

  8. Diclofenac Topical (actinic keratosis)

    MedlinePlus

    ... growths on the skin caused by too much sun exposure). Diclofenac is in a class of medications ... plan to avoid exposure to real and artificial sunlight (sun lamps) and to wear protective clothing and ...

  9. Chitosan nanoparticles as a modified diclofenac drug release system

    NASA Astrophysics Data System (ADS)

    Duarte Junior, Anivaldo Pereira; Tavares, Eraldo José Madureira; Alves, Taís Vanessa Gabbay; de Moura, Márcia Regina; da Costa, Carlos Emmerson Ferreira; Silva Júnior, José Otávio Carréra; Ribeiro Costa, Roseane Maria

    2017-08-01

    This study evaluated a modified nanostructured release system employing diclofenac as a drug model. Biodegradable chitosan nanoparticles were prepared with chitosan concentrations between 0.5 and 0.8% ( w/ v) by template polymerization method using methacrylic acid in aqueous solution. Chitosan-poly(methacrylic acid) (CS-PMAA) nanoparticles showed uniform size around 50-100 nm, homogeneous morphology, and spherical shape. Raw material and chitosan nanoparticles were characterized by thermal analysis, Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM), confirming the interaction between chitosan and methacrylic acid during nanoparticles preparation. Diclofenac sorption on the chitosan nanoparticles surface was achieved by incubation in water/ethanol (1:1) drug solution in concentrations of 0.5 and 0.8 mg/mL. The diclofenac amount sorbed per gram of CS-PMAA nanoparticles, when in a 0.5 mg/mL sodium diclofenac solution, was as follows: 12.93, 15, 20.87, and 29.63 mg/g for CS-PMAA nanoparticles 0.5, 0.6, 0.7, and 0.8% ( w/ v), respectively. When a 0.8 mg/mL sodium diclofenac solution was used, higher sorption efficiencies were obtained: For CS-PMAA nanoparticles with chitosan concentrations of 0.5, 0.6, 0.7, and 0.8% ( w/ v), the sorption efficiencies were 33.39, 49.58, 55.23, and 67.2 mg/g, respectively. Diclofenac sorption kinetics followed a second-order kinetics. Drug release from nanoparticles occurred in a period of up to 48 h and obeyed Korsmeyer-Peppas model, which was characterized mainly by Fickian diffusion transport. [Figure not available: see fulltext.

  10. Stability indicating HPLC method for simultaneous determination of mephenesin and diclofenac diethylamine.

    PubMed

    Mulgund, S V; Phoujdar, M S; Londhe, S V; Mallade, P S; Kulkarni, T S; Deshpande, A S; Jain, K S

    2009-01-01

    A simple, specific, accurate and stability-indicating reversed phase high performance liquid chromatographic method was developed for the simultaneous determination of mephenesin and diclofenac diethylamine, using a Spheri-5-RP-18 column and a mobile phase composed of methanol: water (70:30, v/v), pH 3.0 adjusted with o-phosphoric acid. The retention times of mephenesin and diclofenac diethylamine were found to be 3.9 min and 14.5 min, respectively. Linearity was established for mephenesin and diclofenac diethylamine in the range of 50-300 mug/ml and 10-60 mug/ml, respectively. The percentage recoveries of mephenesin and diclofenac diethylamine were found to be in the range of 99.06-100.60% and 98.95-99.98%, respectively. Both the drugs were subjected to acid, alkali and neutral hydrolysis, oxidation, dry heat, photolytic and UV degradation. The degradation studies indicated, mephenesin to be susceptible to neutral hydrolysis, while diclofenac diethylamine showed degradation in acid, H(2)O(2), photolytic and in presence of UV radiation. The degradation products of diclofenac diethylamine in acidic and photolytic conditions were well resolved from the pure drug with significant differences in their retention time values. This method can be successfully employed for simultaneous quantitative analysis of mephenesin and diclofenac diethylamine in bulk drugs and formulations.

  11. Conjunctival Goblet Cell Density Following Cataract Surgery With Diclofenac Versus Diclofenac and Rebamipide: A Randomized Trial.

    PubMed

    Kato, Kumiko; Miyake, Kensaku; Kondo, Nagako; Asano, Sayaka; Takeda, Junko; Takahashi, Akiko; Takashima, Yuko; Kondo, Mineo

    2017-09-01

    To determine the effects of topical diclofenac or betamethasone with concomitant application of topical rebamipide on the conjunctival goblet cell density in eyes after cataract surgery. Randomized clinical trial. Eighty patients who were scheduled for cataract surgery. Patients were randomized into 4 groups according to the postoperative topical drugs to be given; Group A, diclofenac alone; Group B, diclofenac and rebamipide; Group C, betamethasone alone; and Group D, betamethasone and rebamipide. Impression cytology was performed before and at 1 month after the surgery, and the mean density of goblet cells was determined. The mean (± SD) density of goblet cells before the surgery in Group A was 257.0 ± 188.7 cells/mm 2 , and it decreased significantly to 86.5 ± 76.7 cells/mm 2 at 1 month after the surgery (P = .002). In Group B, the goblet cell density was not statistically different between before (238.5 ± 116.6 cells/mm 2 ) and at 1 month after the surgery (211.3 ± 184.4 cells/mm 2 , P = .55). In Groups C and D, the mean density of goblet cells was decreased at 1 month after the surgery, but the decreases were not significant (P = .11 and P = .52, respectively). After cataract surgery with postoperative topical diclofenac, the conjunctival goblet cell density was significantly reduced, and this reduction was blocked by the concomitant use of topical rebamipide. These results suggest that the concomitant use of topical rebamipide with nonsteroidal anti-inflammatory drugs is beneficial, especially in cases with postoperative dry eyes. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. Adsorption and co-adsorption of diclofenac and Cu(II) on calcareous soils.

    PubMed

    Graouer-Bacart, Mareen; Sayen, Stéphanie; Guillon, Emmanuel

    2016-02-01

    Pharmaceuticals are emerging contaminants and their presence in different compartments of the environment has been detected in many countries. In this study, laboratory batch experiments were conducted to characterize the adsorption of diclofenac, a widely used non-steroidal anti-inflammatory drug, on six calcareous soils. The adsorption of diclofenac was relatively low, which may lead to a risk of groundwater contamination and plant uptake. A correlation between the soil-water distribution coefficient Kd and soil characteristics has been highlighted. Indeed, diclofenac adsorption as a function of soil organic matter content (% OM) and Rt=% CaCO3/% OM was successfully described through a simple empirical model, indicating the importance of considering the inhibiting effect of CaCO3 on OM retention properties for a better assessment of diclofenac fate in the specific case of calcareous soils. The simultaneous co-adsorption of diclofenac and copper - a ubiquitous pollutant in the environment - at the water/soil interface, was also investigated. It appeared quite unexpectedly that copper did not have a significant influence on diclofenac retention. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Montmorillonite-Alginate Composites as a Drug delivery System: Intercalation and In vitro Release of Diclofenac sodium

    PubMed Central

    Kevadiya, B. D.; Patel, H. A.; Joshi, G. V.; Abdi, S. H. R.; Bajaj, H. C.

    2010-01-01

    Diclofenac sodium and alginate was intercalated into montmorillonite to form uniform sized beads by gelation method. The structure and surface morphology of the synthesized composite beads were characterized by powdered X-ray diffraction, Fourier transform infrared spectroscopy, thermo gravimetric analysis and scanning electron microscopy. Diclofenac release kinetics of the composite in simulated intestinal fluid medium (pH 7.4) and effect of montmorillonite content on the in vitro release of diclofenac from diclofenac-montmorillonite-alginate composites bead was investigated by UV/Vis spectrophotometer. Diclofenac encapsulation efficiency in the montmorillonite-alginate composites bead increases with an increase in the montmorillonite content. The control release of diclofenac from diclofenac-montmorillonite-alginate composites beads was observed to be better as compared to diclofenac-alginate beads. PMID:21969745

  14. Physicochemical characterization and in vivo evaluation of thermosensitive diclofenac liquid suppository.

    PubMed

    Yong, Chul Soon; Choi, Young-Kwon; Kim, Yong-Il; Park, Byung-Joo; Quan, Qi-Zhe; Rhee, Jong-Dal; Kim, Chong-Kook; Choi, Han-Gon

    2003-02-01

    Liquid suppository systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and mucoadhesive to the rectal tissues without leakage after the dose. However, a liquid suppository containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a liquid suppository system using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers and sodium chloride were investigated. Furthermore, the pharmacokinetic study of diclofenac sodium delivered by the liquid suppository was performed. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. The liquid suppositories with less than 1.0% of sodium chloride, in which the drug was not precipitated, were inserted into the rectum without difficulty and leakage. Furthermore, liquid suppository gave significantly higher initial plasma concentrations and faster Tmax of diclofenac sodium than did solid suppository, indicating that drug from liquid suppository could be absorbed faster than that from solid one in rats. Our results suggested that a thermosensitive liquid suppository system with sodium chloride and poloxamers was a more physically stable, convenient and effective rectal dosage form for diclofenac sodium.

  15. Sol-gel processed porous silica carriers for the controlled release of diclofenac diethylamine.

    PubMed

    Czarnobaj, Katarzyna; Czarnobaj, Joanna

    2008-10-01

    Silica xerogels doped with diclofenac diethylamine were prepared by the sol-gel method from a hydrolysed tetraethoxysilane (TEOS) solution containing diclofenac diethylamine. Two different catalysts, drying conditions and levels of water content were used to alter the microstructure of the silica xerogels. The aim of this study was to determine the rate of Diclofenac release from the silica xerogels. This in vitro study showed that the sol-gel method is useful for entrapping Diclofenac in the pores of xerogels. It also showed that, in vitro, Diclofenac is released from the silica xerogel, through the pores, by diffusion. Base-catalysed gels proved to be much more effective than acid-catalyzed gels. (c) 2008 Wiley Periodicals, Inc.

  16. Rectal Diclofenac Versus Rectal Paracetamol: Comparison of Antipyretic Effectiveness in Children.

    PubMed

    Sharif, Mohammad Reza; Haji Rezaei, Mostafa; Aalinezhad, Marzieh; Sarami, Golbahareh; Rangraz, Masoud

    2016-01-01

    Fever is the most common complaint in pediatric medicine and its treatment is recommended in some situations. Paracetamol is the most common antipyretic drug, which has serious side effects such as toxicity along with its positive effects. Diclofenac is one of the strongest non-steroidal anti-inflammatory (NSAID) drugs, which has received little attention as an antipyretic drug. This study was designed to compare the antipyretic effectiveness of the rectal form of Paracetamol and Diclofenac. This double-blind controlled clinical trial was conducted on 80 children aged six months to six years old. One group was treated with rectal Paracetamol suppositories at 15 mg/kg dose and the other group received Diclofenac at 1 mg/kg by rectal administration (n = 40). Rectal temperature was measured before and one hour after the intervention. Temperature changes in the two groups were compared. The average rectal temperature in the Paracetamol group was 39.6 ± 1.13°C, and 39.82 ± 1.07°C in the Diclofenac group (P = 0.37). The average rectal temperature, one hour after the intervention, in the Paracetamol and the Diclofenac group was 38.39 ± 0.89°C and 38.95 ± 1.09°C, respectively (P = 0.02). Average temperature changes were 0.65 ± 0.17°C in the Paracetamol group and 1.73 ± 0.69°C in the Diclofenac group (P < 0.001). In the first one hour, Diclofenac suppository is able to control the fever more efficient than Paracetamol suppositories.

  17. Stability Indicating HPLC Method for Simultaneous Determination of Mephenesin and Diclofenac Diethylamine

    PubMed Central

    Mulgund, S. V.; Phoujdar, M. S.; Londhe, S. V.; Mallade, P. S.; Kulkarni, T. S.; Deshpande, A. S.; Jain, K. S.

    2009-01-01

    A simple, specific, accurate and stability-indicating reversed phase high performance liquid chromatographic method was developed for the simultaneous determination of mephenesin and diclofenac diethylamine, using a Spheri-5-RP-18 column and a mobile phase composed of methanol: water (70:30, v/v), pH 3.0 adjusted with o-phosphoric acid. The retention times of mephenesin and diclofenac diethylamine were found to be 3.9 min and 14.5 min, respectively. Linearity was established for mephenesin and diclofenac diethylamine in the range of 50-300 μg/ml and 10-60 μg/ml, respectively. The percentage recoveries of mephenesin and diclofenac diethylamine were found to be in the range of 99.06-100.60% and 98.95-99.98%, respectively. Both the drugs were subjected to acid, alkali and neutral hydrolysis, oxidation, dry heat, photolytic and UV degradation. The degradation studies indicated, mephenesin to be susceptible to neutral hydrolysis, while diclofenac diethylamine showed degradation in acid, H2O2, photolytic and in presence of UV radiation. The degradation products of diclofenac diethylamine in acidic and photolytic conditions were well resolved from the pure drug with significant differences in their retention time values. This method can be successfully employed for simultaneous quantitative analysis of mephenesin and diclofenac diethylamine in bulk drugs and formulations. PMID:20177453

  18. Pharmacokinetics of Diclofenac and Hydroxypropyl‐β‐Cyclodextrin (HPβCD) Following Administration of Injectable HPβCD‐Diclofenac in Subjects With Mild to Moderate Renal Insufficiency or Mild Hepatic Impairment

    PubMed Central

    Hamilton, Douglas A.; Ernst, Cynthia C.; Kramer, William G.; Madden, Donna; Lang, Eric; Liao, Edward; Lacouture, Peter G.; Ramaiya, Atulkumar

    2017-01-01

    Abstract Given their established analgesic properties, nonsteroidal anti‐inflammatory drugs (NSAIDs) represent an important postoperative pain management option. This study investigated: (1) the effects of mild or moderate renal insufficiency and mild hepatic impairment on the pharmacokinetics (PK) of diclofenac and hydroxypropyl‐β‐cyclodextrin (HPβCD) following administration of the injectable NSAID HPβCD‐diclofenac; and (2) the PK of HPβCD following administration of HPβCD‐diclofenac and intravenous itraconazole formulated with HPβCD in healthy adults. Diclofenac clearance (CL) and volume of distribution (Vz) tended to increase with decreasing renal function (moderate insufficiency versus mild insufficiency or healthy controls). Regression analysis demonstrated a significant relationship between Vz (but not CL or elimination half‐life, t½) and renal function. HPβCD CL was significantly decreased in subjects with renal insufficiency, with a corresponding increase in t½. There were no significant differences in diclofenac or HPβCD PK in subjects with mild hepatic impairment versus healthy subjects. Exposure to HPβCD in healthy subjects following HPβCD‐diclofenac administration was ∼12% of that with intravenous itraconazole, after adjusting for dosing schedule and predicted accumulation (<5% without adjustment). With respect to PK properties, these results suggest that HPβCD‐diclofenac might be administered to patients with mild or moderate renal insufficiency or mild hepatic impairment without dose adjustment (NCT00805090). PMID:29197175

  19. Enzyme-less electrochemical displacement heterogeneous immunosensor for diclofenac detection.

    PubMed

    Nguyen, T T K; Vu, T T; Anquetin, G; Tran, H V; Reisberg, S; Noël, V; Mattana, G; Nguyen, Q V; Dai Lam, Tran; Pham, M C; Piro, B

    2017-11-15

    We describe an electrochemical immunosensor based on functionalization of a working electrode by electrografting two functional diazonium salts. The first one is a molecular probe, diclofenac, coupled with an arylamine onto which a specific antibody is immobilized by affinity interactions; the second is a redox probe (a quinone) also coupled with an arylamine, able to transduce the hapten-antibody association into a change in electroactivity. The steric hindrance induced by the antibody leads to a current decrease upon binding of the antibody on the grafted molecular probe; conversely, when diclofenac is present in solution, a displacement equilibrium occurs between the target diffusing into the solution and the grafted probe. This leads to dissociation of the antibody from the electrode surface, event which is transduced into a current increase ("signal-on" detection). The detection limit is ca. 20 fM, corresponding to 6pgL -1 diclofenac, which is competitive compared to other label-free immunosensors. We demonstrate that the sensor is selective and is able to quantify diclofenac in tap water. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Sono-activated persulfate oxidation of diclofenac: Degradation, kinetics, pathway and contribution of the different radicals involved.

    PubMed

    Monteagudo, J M; El-Taliawy, H; Durán, A; Caro, G; Bester, K

    2018-06-20

    Degradation of a diclofenac aqueous solution was performed using persulfate anions activated by ultrasound. The objective of this study was to analyze different parameters affecting the diclofenac (DCF) removal reaction by the ultrasonic persulfate (US/PS) process and to evaluate the role played by various intermediate oxidative species such as hydroxyl- and sulfate radicals, superoxide radical anion or singlet oxygen in the removal process as well as to determine a possible reaction pathway. The effects of pH, initial persulfate anion concentration, ultrasonic amplitude and temperature on DCF degradation were examined. Sulfate and hydroxyl radicals were involved in the main reaction pathway of diclofenac. Diclofenac amide and three hydroxy-diclofenac isomers (3´-hydroxy diclofenac, 4´-hydroxy diclofenac and 5-hydroxy diclofenac) were identified as reaction intermediates. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Microbial Removal of the Pharmaceutical Compounds Ibuprofen and Diclofenac from Wastewater

    PubMed Central

    Inderfurth, Nadia; Schraa, Gosse; Kujawa-Roeleveld, Katarzyna; Rijnaarts, Huub

    2013-01-01

    Studies on the occurrence of pharmaceuticals show that the widely used pharmaceuticals ibuprofen and diclofenac are present in relevant concentrations in the environment. A pilot plant treating hospital wastewater with relevant concentrations of these pharmaceuticals was evaluated for its performance to reduce the concentration of the pharmaceuticals. Ibuprofen was completely removed, whereas diclofenac yielded a residual concentration, showing the necessity of posttreatment to remove diclofenac, for example, activated carbon. Successively, detailed laboratory experiments with activated sludge from the same wastewater treatment plant showed bioremediation potential in the treatment plant. The biological degradation pathway was studied and showed a mineralisation of ibuprofen and degradation of diclofenac. The present microbes were further studied in laboratory experiments, and DGGE analyses showed the enrichment and isolation of highly purified cultures that degraded either ibuprofen or diclofenac. This research illuminates the importance of the involved bacteria for the effectiveness of the removal of pharmaceuticals in a wastewater treatment plant. A complete removal of pharmaceuticals from wastewater will stimulate water reuse, addressing the worldwide increasing demand for clean and safe fresh water. PMID:24350260

  2. Topical versus systemic diclofenac in the treatment of temporo-mandibular joint dysfunction symptoms.

    PubMed

    Di Rienzo Businco, L; Di Rienzo Businco, A; D'Emilia, M; Lauriello, M; Coen Tirelli, G

    2004-10-01

    The most frequent symptom of craniomandibular dysfunction is pain in the preauricular area or in the temporo-mandibular joint, usually localized at the level of the masticatory musculature. Patients sometimes also complain of reflect otalgia, headaches and facial pain. Osteoarthrosis is a frequent degenerative debilitating chronic disorder that can affect the temporomandibular joint. It causes pain and articular rigidity, a reduction in mobility, and radiological alterations are visible in stratigraphy. The aim of this study was to compare the efficacy of a topically applied non-steroid anti-inflammatory drug that has recently become commercially available (diclofenac sodium in a patented carrier containing dimethyl sulfoxide, that favours transcutaneous absorption) which is commonly used to alleviate pain in knee or elbow joints, versus oral diclofenac, in the treatment of symptoms of temporomandibular joint dysfunction. Dysfunction of the temporomandibular joint was diagnosed in 36 adult patients. The patients were randomized in two age- and gender -matched groups. Group A (18 patients) received oral diclofenac sodium administered after a meal in 50-mg tablets twice a day for 14 days. Group B (18 patients) received 16 mg/ml topical diclofenac (diclofenac topical solution, 10 drops 4 times a day for 14 days). All patients completed a questionnaire at the start and end of therapy. Patients were asked to quantify on a graded visual analogue scale and to reply to questions about the pain and tenderness of the temporomandibular joint and the functional limitation of mouth opening. Patients were also requested to report side-effects of the treatment. All patients showed relief from pain after treatment: the difference between the two groups was not significant (p > 0.05). Post-treatment, 16 patients of group A had epigastralgic symptoms. Three patients treated with topical diclofenac showed a modest irritation of the temporomandibular joint region, and disappeared

  3. Fish embryo toxicity of carbamazepine, diclofenac and metoprolol.

    PubMed

    van den Brandhof, Evert-Jan; Montforts, Mark

    2010-11-01

    Frequently measured pharmaceuticals in environmental samples were tested in fish embryo toxicity (FET) tests with Danio rerio, based on the draft OECD test protocol. In this FET test 2-h-old zebrafish embryos were exposed for 72 h to carbamazepine, diclofenac and metoprolol to observe effects on embryo mortality, gastrulation, somite formation, tail movement and detachment, pigmentation, heartbeat, malformation of head, otoliths and heart, scoliosis, deformity of yolk, and hatching success at 24, 48 and 72 h. We found specific effects on growth retardation above 30.6 mg/l for carbamazepine, on hatching, yolk sac and tail deformation above 1.5mg/l for diclofenac, and on scoliosis and growth retardation above 12.6 mg/l for metoprolol. Scoring all effect parameters, the 72-h-EC(50) values were: for carbamazepine 86.5mg/l, for diclofenac 5.3mg/l and for metoprolol 31.0mg/l (mean measured concentrations). In conclusion, our results for carbamazepine and metoprolol are in agreement with other findings for aquatic toxicity, and also fish embryos responded in much the same way as rat embryos did. For diclofenac, the FET test performs comparably to Early Life Stage testing. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. Impact of Diclofenac Sodium on Tilmicosin-Induced Acute Cardiotoxicity in Rats (Tilmicosin and Diclofenac Cardiotoxicity).

    PubMed

    Oda, Samah S; Derbalah, Amira E

    2018-02-01

    To assess the influence of diclofenac sodium (DIC) treatment on tilmicosin (TIL) prompted cardiotoxicity, forty albino rats were randomly divided into four equal groups: control, TIL group (single subcutaneous injection of 75 mg/kg BW tilmicosin phosphate 30%), TIL + DIC group (single subcutaneous injection of tilmicosin phosphate 30% and then injection intramuscularly of 13.5 mg/kg BW/day for 6 days diclofenac sodium) and DIC group (intramuscular injection of 13.5 mg/kg BW/day diclofenac sodium for 6 days). Creatine kinase-MB, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, urea and creatinine significantly elevated in all treated groups, but markedly in TIL + DIC group serum. Lipid peroxidation significantly increased, and reduced glutathione significantly decreased in tissues of all groups. Several histopathological alterations were noticed in heart, liver, kidneys and lungs of all treated groups, particularly TIL + DIC group. Ultrastructurally, myocardium of TIL and TIL + DIC groups showed characteristic changes for myocardial apoptosis and degeneration. Significant differences were detected in area percentage of caspase-3 protein expression and bcl-2 immunoreactivity in cardiomyocytes, particularly in TIL + DIC group. This study is the first to indicate that one of the possible mechanisms of TIL cardiotoxicity is myocardial apoptosis. DIC amplifies TIL-induced cardiotoxicity besides its hepato-nephrotoxicity.

  5. No Benefit of Oral Diclofenac on Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

    PubMed

    Ishiwatari, Hirotoshi; Urata, Takahiro; Yasuda, Ichiro; Matsusaki, Shimpei; Hisai, Hiroyuki; Kawakami, Hiroshi; Ono, Michihiro; Iwashita, Takuji; Doi, Shinpei; Kawakubo, Kazumichi; Hayashi, Tsuyoshi; Sonoda, Tomoko; Sakamoto, Naoya; Kato, Junji

    2016-11-01

    Pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) is a serious complication. Rectal diclofenac (100 mg) has been shown to reduce the incidence of pancreatitis; however, this dosage form is unavailable in several countries. We aimed to investigate the preventive effect of oral diclofenac on pancreatitis after ERCP in a multicenter, randomized, prospective, placebo-controlled, double-blind trial. Patients undergoing a first ERCP in seven high-volume centers between July 2012 and August 2014 were considered eligible. Participants were administered oral diclofenac (50 mg) or placebo before and after ERCP. The primary endpoint was the incidence of pancreatitis. A subgroup analysis was performed for patients at high or low risk of pancreatitis. Secondary endpoints were pancreatic enzyme levels (amylase and lipase). We initially enrolled 430 patients (216 in the diclofenac and 214 in the placebo group), and 23 were excluded after randomization. The overall incidence of pancreatitis was 9.8 % (20/205) and 9.4 % (19/202) in the diclofenac and placebo groups, respectively (p = 0.90). The incidence of pancreatitis was 20.3 % (13/64) and 21.3 % (13/61) in patients at high risk of pancreatitis (p = 0.78) and 5.0 % (7/141) and 4.3 % (6/141) in patients at low risk of pancreatitis in the diclofenac and placebo groups (p = 0.94), respectively. There were no significant differences in serum amylase and lipase levels between the two groups before and 24 h after ERCP. Oral administration of diclofenac before and after ERCP showed no benefit in the prevention of pancreatitis. UMIN000008109.

  6. Transformation of diclofenac in hybrid biofilm-activated sludge processes.

    PubMed

    Jewell, Kevin S; Falås, Per; Wick, Arne; Joss, Adriano; Ternes, Thomas A

    2016-11-15

    The biotransformation of diclofenac during wastewater treatment was investigated. Attached growth biomass from a carrier-filled compartment of a hybrid-MBBR at the wastewater treatment plant (WWTP) in Bad Ragaz, Switzerland was used to test the biotransformation. Laboratory-scale incubation experiments were performed with diclofenac and carriers and high-resolution LC-QTof-MS was implemented to monitor the biotransformation. Up to 20 diclofenac transformation products (TPs) were detected. Tentative structures were proposed for 16 of the TPs after characterization by MS 2 fragmentation and/or inferring the structure from the transformation pathway and the molecular formula given by the high resolution ionic mass. The remaining four TPs were unambiguously identified via analytical reference standards. The postulated reactions forming the TPs were: hydroxylation, decarboxylation, oxidation, amide formation, ring-opening and reductive dechlorination. Incubation experiments of individual TPs, those which were available as reference standards, provided a deeper look into the transformation pathways. It was found that the transformation consists of four main pathways but no pathway accounted for a clear majority of the transformation. A 10-day monitoring campaign of the full-scale plant confirmed an 88% removal of diclofenac (from approximately 1.6 μg/L in WWTP influent) and the formation of TPs as found in the laboratory was observed. One of the TPs, N-(2,6-dichlorophenyl)-2-indolinone detected at concentrations of around 0.25 μg/L in WWTP effluent, accounting for 16% of the influent diclofenac concentration. The biotransformation of carriers was compared to a second WWTP not utilising carriers. It was found that in contact with activated sludge, similar hydroxylation and decarboxylation reactions occurred but at much slower rates, whereas some reactions, e.g. reductive dechlorination, were not detected at all. Finally, incubation experiments were performed with

  7. Pharmacological effects of Vitamin C & E on Diclofenac Sodium intoxicated Rats.

    PubMed

    El-Shafei, Reham A; Saleh, Rasha M

    2016-12-01

    The aim of this study was to evaluate the probable protective effect of vitamin C and vitamin E on diclofenac-induced acute nephrotoxicity using biochemical, molecular and histopathological examination in rats following administration of diclofenac sodium (50mg/kg, I.M). Ninety male Wister rats were allotted in six equal groups. Rats in the 1st group (control group) were injected with physiological saline, while rats in the 2nd group (C-group) were given vitamin C (100mg/kg orally via stomach tube) for 5 successive days. The 3rd group (E-group) was given vitamin E (250mg/kg orally in diet) for 5 successive days. Rats in the 4th group (D-group) were injected by diclofenac sodium (50mg/kg, I.M) for 5 successive days. The 5th group (DvC-group) was given diclofenac sodium (50mg/kg, I.M) and vitamin C (100mg/kg orally via stomach tube) for 5 successive days. Rats in the 6th group (DvE-group) were given diclofenac sodium (50mg/kg, I.M) and vitamin E (250mg/kg orally in diet) for 5 successive days. Blood samples were collected two days post treatment (1st week of experiment), 2nd and 4th week of the experiment for assessment of urea, creatinine, malondialdehyde, nitric oxide and superoxide dismutase activities. At the end of 4th week, rats were sacrificed and kidneys were excised for biochemical analyses, histopathological evaluation and determination of kidney interleukin-1β, interleukin-18, demsin and nepherin expressions in by reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that, diclofenac induced severe kidney damage as indicated by histopathological changes and increased serum oxidative stress parameters. Behavioral changes were monitored; a significant increase in uremia in intoxicated animals was also noted indicating that diclofenac sodium provoked kidney damage in rats. Application of vitamin C (DvC-group) and vitamin E (DvE-group) were found to improve the abovementioned abnormalities. The present data suggest that, vitamin C and

  8. Formation of ion-pairs in aqueous solutions of diclofenac salts.

    PubMed

    Fini, A; Fazio, G; Gonzalez-Rodriguez, M; Cavallari, C; Passerini, N; Rodriguez, L

    1999-10-05

    In this work we studied the ability of the diclofenac anion to form ion-pairs in aqueous solution in the presence of organic and inorganic cations: ion-pairs have a polarity and hydrophobicity more suitable to the partition than each ion considered separately and can be extracted by a lipid phase. The cations considered were those of the organic bases diethylamine, diethanolamine, pyrrolidine, N-(2-hydroxyethyl) pyrrolidine and N-(2-hydroxyethyl) piperidine; the inorganic cations studied were Li(+), Na(+), K(+), Rb(+), Cs(+). Related to each cation we determined the equilibrium constant (K(XD)) for the ion-pair formation with the diclofenac anion in aqueous solution and the water/n-octanol partition coefficient (P(XD)) for each type of ion-pair formed. Among the alkali metal cations, only Li(+) shows some interaction with the diclofenac anion, in agreement with its physiological behaviour of increasing clearance during the administration of diclofenac. The influence of the ionic radius and desolvation enthalpy of the alkali metal cations on the ion-pair formation and partition was briefly discussed. Organic cations promote the formation of ion-pairs with the diclofenac anion better than the inorganic ones, and improve the partition of the ion-pair according to their hydrophobicity. The values of the equilibrium parameters for the formation and partition of ion-pairs are not high enough to allow the direct detection of their presence in the aqueous solution. Their formation can be appreciated in the presence of a lipid phase that continuously extracts the ion-pair. Extraction constants (E(XD)=P(XD) times K(XD)) increase passing from inorga to organic cations. This study could help to clarify the mechanism of the percutaneous absorption of diclofenac in the form of a salt, a route where the formation of ion-pairs appears to play an important role.

  9. Low-dose rectal diclofenac for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a randomized controlled trial.

    PubMed

    Otsuka, Taiga; Kawazoe, Seiji; Nakashita, Shunya; Kamachi, Saori; Oeda, Satoshi; Sumida, Chinatsu; Akiyama, Takumi; Ario, Keisuke; Fujimoto, Masaru; Tabuchi, Masanobu; Noda, Takahiro

    2012-08-01

    Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). Rectal nonsteroidal anti-inflammatory drugs (specifically, 100 mg of diclofenac or indomethacin) have shown promising prophylactic activity in post-ERCP pancreatitis (PEP). However, the 100-mg dose is higher than that ordinarily used in Japan. We performed a prospective randomized controlled study to evaluate the efficacy of low-dose rectal diclofenac for the prevention of PEP. Patients who were scheduled to undergo ERCP were randomized to receive a saline infusion either with 50 mg of rectal diclofenac (diclofenac group) or without (control group) 30 min before ERCP. The dose of diclofenac was reduced to 25 mg in patients weighing <50 kg. The primary outcome measure was the occurrence of PEP. Enrollment was terminated early because the planned interim analysis found a statistically significant intergroup difference in the occurrence of PEP. A total of 104 patients were eligible for this study; 51 patients received rectal diclofenac. Twelve patients (11.5%) developed PEP: 3.9% (2/51) in the diclofenac group and 18.9% (10/53) in the control group (p = 0.017). After ERCP, the incidence of hyperamylasemia was not significantly different between the two groups. Post-ERCP pain was significantly more frequent in the control group than in the diclofenac group (37.7 vs. 7.8%, respectively; p < 0.001). There were no adverse events related to diclofenac. Low-dose rectal diclofenac can prevent PEP.

  10. Oral Versus Topical Diclofenac Sodium in the Treatment of Osteoarthritis.

    PubMed

    Tieppo Francio, Vinicius; Davani, Saeid; Towery, Chris; Brown, Tony L

    2017-06-01

    Osteoarthritis (OA) is one of the most common causes of joint pain in the United States and non-steroidal anti-inflammatories (NSAIDs), such as Diclofenac sodium, which is currently available in two main routes of administration; oral and topical distribution have been established as one of the standard treatments for OA. Generally, oral NSAIDs are well tolerated; however our narrative review suggests that the topical solution had a better tolerability property than oral Diclofenac sodium, especially due to side effects of gastrointestinal bleeding with the utilization of the oral format. In addition, the topical route may be considered a reasonable selection by clinicians for management of musculoskeletal pain in those patients with a history of potential risk and adverse side effects. Most studies reviewed comparing oral versus topical solution of Diclofenac sodium revealed comparable efficacy, with minimal side effects utilizing the topical route. The key point of this narrative review is to help clinicians that currently must decide between very inexpensive diclofenac oral presentations and expensive topical presentations especially in the elderly population and the pros and cons of such decision-making process.

  11. Removing the Threat of Diclofenac to Critically Endangered Asian Vultures

    PubMed Central

    Swan, Gerry; Naidoo, Vinasan; Cuthbert, Richard; Pain, Deborah J; Swarup, Devendra; Prakash, Vibhu; Taggart, Mark; Bekker, Lizette; Das, Devojit; Diekmann, Jörg; Diekmann, Maria; Killian, Elmarié; Meharg, Andy; Patra, Ramesh Chandra; Saini, Mohini; Wolter, Kerri

    2006-01-01

    Veterinary use of the nonsteroidal anti-inflammatory (NSAID) drug diclofenac in South Asia has resulted in the collapse of populations of three vulture species of the genusGyps to the most severe category of global extinction risk. Vultures are exposed to diclofenac when scavenging on livestock treated with the drug shortly before death. Diclofenac causes kidney damage, increased serum uric acid concentrations, visceral gout, and death. Concern about this issue led the Indian Government to announce its intention to ban the veterinary use of diclofenac by September 2005. Implementation of a ban is still in progress late in 2005, and to facilitate this we sought potential alternative NSAIDs by obtaining information from captive bird collections worldwide. We found that the NSAID meloxicam had been administered to 35 captiveGyps vultures with no apparent ill effects. We then undertook a phased programme of safety testing of meloxicam on the African white-backed vultureGyps africanus, which we had previously established to be as susceptible to diclofenac poisoning as the endangered AsianGyps vultures. We estimated the likely maximum level of exposure (MLE) of wild vultures and dosed birds by gavage (oral administration) with increasing quantities of the drug until the likely MLE was exceeded in a sample of 40G. africanus. Subsequently, sixG. africanus were fed tissues from cattle which had been treated with a higher than standard veterinary course of meloxicam prior to death. In the final phase, ten Asian vultures of two of the endangered species(Gyps bengalensis,Gyps indicus) were dosed with meloxicam by gavage; five of them at more than the likely MLE dosage. All meloxicam-treated birds survived all treatments, and none suffered any obvious clinical effects. Serum uric acid concentrations remained within the normal limits throughout, and were significantly lower than those from birds treated with diclofenac in other studies. We conclude that meloxicam is of low

  12. Formulation and pharmacokinetics of diclofenac lipid nanoemulsions for parenteral application.

    PubMed

    Ramreddy, Srividya; Kandadi, Prabhakar; Veerabrahma, Kishan

    2012-01-01

    The objective of the present study was to formulate and determine the pharmacokinetics of stable o/w parenteral lipid nanoemulsions (LNEs) of diclofenac acid used to treat arthritic conditions. The LNEs of diclofenac acid with a mean size ranging from 200 to 240 nm and a zeta potential of -29.4 ± 1.04 mV (negatively charged LNEs) and 62.1 ± 3.5 (positively charged LNEs) emulsions were prepared by hot homogenization and ultrasonication process. The influence of formulation variables, such as the change in proportion of cholesterol, was studied, and optimized formulations were developed. The optimized formulations were relatively stable during centrifugal stress, dilution stress, and storage. The drug content and entrapment efficiency were determined using high-performance liquid chromatography. The in vitro drug release was carried out in phosphate-buffered saline pH 7.4 and cumulative amount of drug released was estimated using a UV-visible spectro-photometer. During in vivo pharmacokinetic studies in male Wistar rats, diclofenac serum concentration from LNEs was higher than that of Voveran injection and was detectable up to 12 h. Diclofenac in LNEs showed improved pharmacokinetic profile with increase in area under the curve, elimination half-life and mean residence time in comparison to Voveran. Our aim was to prepare and determine the pharmacokinetics of injectable lipid nanoemulsions of diclofenac acid for treating arthritic conditions by reducing the frequency of dosing and pain at site of injection. The nanoemulsions of diclofenac acid were prepared by homogenization and ultrasonication process. The sizes and charges of oil globules were determined. The effect of cholesterol on stability of emulsion was studied, and an optimized preparation was developed. The optimized formulations were stable during centrifugation, dilution, and storage. The total amount of drug in emulsion and percentage amount of drug present in emulsion globules were determined using

  13. Rebamipide suppresses diclofenac-induced intestinal permeability via mitochondrial protection in mice.

    PubMed

    Diao, Lei; Mei, Qiao; Xu, Jian-Ming; Liu, Xiao-Chang; Hu, Jing; Jin, Juan; Yao, Qiang; Chen, Mo-Li

    2012-03-14

    To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice. Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A control group received the vehicle by gavage. Rebamipide (100 mg/kg, 200 mg/kg, 400 mg/kg) was administered intragastrically once a day for 3 d 4 h after diclofenac administration. Intestinal permeability was evaluated by Evans blue and the FITC-dextran method. The ultrastructure of the mucosal barrier was evaluated by transmission electron microscopy (TEM). Mitochondrial function including mitochondrial swelling, mitochondrial membrane potential, mitochondrial nicotinamide adenine dinucleotide-reduced (NADH) levels, succinate dehydrogenase (SDH) and ATPase activities were measured. Small intestinal mucosa was collected for assessment of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity. Compared with the control group, intestinal permeability was significantly increased in the diclofenac group, which was accompanied by broken tight junctions, and significant increases in MDA content and MPO activity. Rebamipide significantly reduced intestinal permeability, improved inter-cellular tight junctions, and was associated with decreases in intestinal MDA content and MPO activity. At the mitochondrial level, rebamipide increased SDH and ATPase activities, NADH level and decreased mitochondrial swelling. Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function.

  14. Diclofenac Does Not Reduce the Risk of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis in Low-Risk Units.

    PubMed

    Rainio, Mia; Lindström, Outi; Udd, Marianne; Louhimo, Johanna; Kylänpää, Leena

    2017-08-01

    Nonsteroidal anti-inflammatory drugs have an inhibitory role in pathogenesis of pancreatitis. Guidelines from the European Society of Gastrointestinal Endoscopy recommend routine rectal administration of 100 mg of diclofenac or indomethacin immediately before or after ERCP for all patients without contraindications. Our aim was to evaluate the effect of diclofenac in preventing post-ERCP pancreatitis (PEP) in a high-volume, low-PEP-risk ERCP unit. The rate and severity of PEP were compared in groups of 1000 historical controls prior to the routine use of diclofenac and in 1000 patients receiving 100 mg diclofenac before ERCP. PEP occurred in 56 (2.8%) of the 2000 patients, and the rate of the pancreatitis was 2.8% in control group and 2.8% in diclofenac group (p = 1.000). The PEP rate among the native papilla patients was 3.9% in control group and 3.6% in diclofenac group (p = 0.803). In subgroup analysis of patients with a high risk of PEP, diclofenac neither prevented PEP nor made its course milder. In an unselected patient population in a center with a low incidence of PEP, diclofenac seems to have no beneficial effect.

  15. Kounis syndrome resulting from anaphylaxis to diclofenac

    PubMed Central

    Tiwari, Akhilesh Kumar; Tomar, Gaurav Singh; Ganguly, Col. S; Kapoor, Mukul Chandra

    2013-01-01

    “Kounis syndrome” refers to acute coronary syndromes of varying degree (myocardial ischaemia to infarction) induced by mast cell activation as a result of allergic and anaphylactic reactions. ST-segment elevated myocardial infarction is a rare complication that can occur even in patients with normal coronary arteries due to anaphylactic reactions. We present a case that developed acute myocardial infarction following a diclofenac sodium-induced anaphylaxis. The patient did not have any previous coronary artery disease, but there was a temporal relationship with development of the anaphylactic reaction due to diclofenac sodium and the cardiac event. The patient was managed conservatively and the recovery was uneventful. PMID:23983288

  16. Developmental Toxicity of Diclofenac and Elucidation of Gene Regulation in zebrafish (Danio rerio)

    NASA Astrophysics Data System (ADS)

    Chen, Jia-Bin; Gao, Hong-Wen; Zhang, Ya-Lei; Zhang, Yong; Zhou, Xue-Fei; Li, Chun-Qi; Gao, Hai-Ping

    2014-05-01

    Environmental pollution by emerging contaminants, e.g. pharmaceuticals, has become a matter of widespread concern in recent years. We investigated the membrane transport of diclofenac and its toxic effects on gene expression and the development of zebrafish embryos. The association of diclofenac with the embryos conformed to the general partition model at low concentration, the partition coefficient being 0.0033 ml per embryo. At high concentration, the interaction fitted the Freundlich model. Most of the diclofenac remained in the extracellular aqueous solution with less than 5% interacting with the embryo, about half of which was adsorbed on the membranes while the rest entered the cytoplasm. Concentrations of diclofenac over 10.13 μM were lethal to all the embryos, while 3.78 μM diclofenac was teratogenic. The development abnormalities at 4 day post treatment (dpt) include shorter body length, smaller eye, pericardial and body edema, lack of liver, intestine and circulation, muscle degeneration, and abnormal pigmentation. The portion of the diclofenac transferred into the embryo altered the expression of certain genes, e.g. down-regulation of Wnt3a and Gata4 and up-regulation of Wnt8a. The alteration of expression of such genes or the regulation of downstream genes could cause defects in the cardiovascular and nervous systems.

  17. Diclofenac poisoning is widespread in declining vulture populations across the Indian subcontinent.

    PubMed

    Shultz, Susanne; Baral, Hem Sagar; Charman, Sheonaidh; Cunningham, Andrew A; Das, Devojit; Ghalsasi, G R; Goudar, Mallikarjun S; Green, Rhys E; Jones, Ainsley; Nighot, Prashant; Pain, Deborah J; Prakash, Vibhu

    2004-12-07

    Recent declines in the populations of three species of vultures in the Indian subcontinent are among the most rapid ever recorded in any bird species. Evidence from a previous study of one of these species, Gyps bengalensis, in the Punjab province of Pakistan, strongly implicates mortality caused by ingestion of residues of the veterinary non-steroidal anti-inflammatory drug diclofenac as the major cause of the decline. We show that a high proportion of Gyps bengalensis and G. indicus found dead or dying in a much larger area of India and Nepal also have residues of diclofenac and visceral gout, a post-mortem finding that is strongly associated with diclofenac contamination in both species. Hence, veterinary use of diclofenac is likely to have been the major cause of the rapid vulture population declines across the subcontinent.

  18. Transdermal delivery of diclofenac using water-in-oil microemulsion: formulation and mechanistic approach of drug skin permeation.

    PubMed

    Thakkar, Priyanka J; Madan, Parshotam; Lin, Senshang

    2014-05-01

    The objective of the present investigation was to enhance skin permeation of diclofenac using water-in-oil microemulsion and to elucidate its skin permeation mechanism. The w/o microemulsion formulations were selected based on constructed pseudoternary phase diagrams depending on water solubilization capacity and thermodynamic stability. These formulations were also subjected to physical characterization based on droplet size, viscosity, pH and conductivity. Permeation of diclofenac across rat skin using side-by-side permeation cells from selected w/o microemulsion formulations were evaluated and compared with control formulations. The selected w/o microemulsion formulations were thermodynamically stable, and incorporation of diclofenac sodium into microemulsion did not affect the phase behavior of system. All microemulsion formulations had very low viscosity (11-17 cps) and droplet size range of 30-160 nm. Microemulsion formulations exhibited statistically significant increase in diclofenac permeation compared to oily solution, aqueous solution and oil-Smix solution. Higher skin permeation of diclofenac was observed with low Smix concentration and smaller droplet size. Increase in diclofenac loading in aqueous phase decreased the partition of diclofenac. Diclofenac from the oil phase of microemulsion could directly partition into skin, while diclofenac from the aqueous droplets was carried through skin by carrier effect.

  19. Rebamipide suppresses diclofenac-induced intestinal permeability via mitochondrial protection in mice

    PubMed Central

    Diao, Lei; Mei, Qiao; Xu, Jian-Ming; Liu, Xiao-Chang; Hu, Jing; Jin, Juan; Yao, Qiang; Chen, Mo-Li

    2012-01-01

    AIM: To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice. METHODS: Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A control group received the vehicle by gavage. Rebamipide (100 mg/kg, 200 mg/kg, 400 mg/kg) was administered intragastrically once a day for 3 d 4 h after diclofenac administration. Intestinal permeability was evaluated by Evans blue and the FITC-dextran method. The ultrastructure of the mucosal barrier was evaluated by transmission electron microscopy (TEM). Mitochondrial function including mitochondrial swelling, mitochondrial membrane potential, mitochondrial nicotinamide adenine dinucleotide-reduced (NADH) levels, succinate dehydrogenase (SDH) and ATPase activities were measured. Small intestinal mucosa was collected for assessment of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity. RESULTS: Compared with the control group, intestinal permeability was significantly increased in the diclofenac group, which was accompanied by broken tight junctions, and significant increases in MDA content and MPO activity. Rebamipide significantly reduced intestinal permeability, improved inter-cellular tight junctions, and was associated with decreases in intestinal MDA content and MPO activity. At the mitochondrial level, rebamipide increased SDH and ATPase activities, NADH level and decreased mitochondrial swelling. CONCLUSION: Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function. PMID:22416180

  20. Metabolism of diclofenac in plants--hydroxylation is followed by glucose conjugation.

    PubMed

    Huber, Christian; Bartha, Bernadett; Schröder, Peter

    2012-12-01

    Pharmaceuticals from human or veterinary medication form a new class of micropollutants that poses a serious threat to our aquatic environment and its organisms. The intensively used nonsteroidal anti-inflammatory drug diclofenac is found in the environment worldwide due to its poor elimination during waste water treatment processes. In order to test phytoremediation as a tool for the removal of this drug from waste water, the uptake of the compound into plant tissues and its metabolic pathway was addressed using Hordeum vulgare (barley) and a hairy root cell culture of Armoracia rusticana (horse radish) as model species. Diclofenac is taken up by plants and undergoes rapid metabolization; already after 3h of exposure the drug and its metabolites could be detected in the plant tissues. Similar to its fate in mammalian cells the drug is activated in a phase I reaction resulting in the hydroxylated metabolite 4'OH-diclofenac which is conjugated subsequently in phase II to a glucopyranoside, a typical plant specific metabolite. After exposure to 10 and 100 μM diclofenac a concentration dependent formation of the hydroxylated metabolite was observed, while the formation of the phase II metabolite OH-diclofenac glucopyranoside was not positively affected by the higher concentration. To our knowledge this is the first time these two human painkiller metabolites are shown to occur in plant tissues. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. The Nonsteroidal Anti-inflammatory Drug Diclofenac Reduces Acid-Induced Heartburn Symptoms in Healthy Volunteers.

    PubMed

    Kondo, Takashi; Oshima, Tadayuki; Tomita, Toshihiko; Fukui, Hirokazu; Okada, Hiroki; Watari, Jiro; Miwa, Hiroto

    2015-07-01

    We investigated the effects of diclofenac, a nonsteroidal anti-inflammatory drug that inhibits prostaglandin production, on induction of esophageal sensation by acid perfusion in healthy men. We performed a prospective, double-blind, placebo-controlled, 2-period, cross-over study over 3 visits in 12 healthy men. Diclofenac was given 6 hours and 2 hours before an acid perfusion test. During the test, hydrochloric acid (0.15 mol/L) was perfused into the lower esophagus for 30 minutes; we evaluated upper gastrointestinal symptoms using a validated categoric rating scale. Then, we calculated and assessed the acid perfusion sensitivity score (APSS). Biopsy specimens were collected by endoscopy of the distal esophagus before and after acid perfusion; levels of prostaglandin E2 (PGE2) (pg/mg) were measured in the samples using an enzyme-linked immunosorbent assay. Compared with placebo, diclofenac significantly reduced the APSS for heartburn (82.2 ± 12.2 for placebo and 47.5 ± 8.9 for diclofenac; P < .01). Of the upper gastrointestinal symptoms, only the APSS for heartburn was reduced significantly by diclofenac. Compared with placebo, diclofenac reduced the overproduction of PGE2 by esophageal tissues after acid perfusion (23.3 ± 5.2 for placebo and 11.4 ± 3.5 for diclofenac; P < .05). APSS correlated with the development of heartburn and esophageal levels of PGE2 (r = 0.53; P < .05 for heartburn vs PGE2). Diclofenac attenuated acid-induced heartburn by inhibiting PGE2 overproduction in the esophagus. Esophageal PGE2 might be involved in producing heartburn symptoms. Clinical Trials Registry no: UMIN000014595. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  2. Pharmacokinetics of diclofenac and its interaction with enrofloxacin in sheep.

    PubMed

    Rahal, Anu; Kumar, Amit; Ahmad, A H; Malik, J K

    2008-06-01

    The pharmacokinetics of diclofenac was investigated in sheep given diclofenac alone (1mgkg(-1), i.v. or i.m.) and in combination with enrofloxacin (5mgkg(-1), i.v.). The plasma concentration-time data following i.v. administration of diclofenac was best described by a two compartment open pharmacokinetic model. The elimination half-life (t(1/2beta)), area under concentration-time-curve (AUC), volume of distribution (Vd(area)), mean residence time (MRT) and total body clearance (Cl(B)) were 1.03+/-0.18h, 12.17+/-1.98microg h ml(-1), 0.14+/-0.02Lkg(-1), 1.36+/-0.16h and 0.10+/-0.02Lkg(-1)h(-1), respectively. Following i.m. administration of diclofenac alone and in conjunction with enrofloxacin, the plasma concentration-time data best fitted to a one compartment open model. The t(1/2beta), AUC, Vd(area), MRT and Cl(B) were 1.33+/-0.10h, 7.32+/-1.01microg h mL(-1), 0.13+/-0.01Lkg(-1) and 0.07+/-0.01Lkg(-1)h(-1), respectively. Co-administration of enrofloxacin did not affect Vd(area) and MRT but absorption rate constant (K(a)), beta, t1/2Ka, t1/2beta, AUC, AUMC, Cl(B) and bioavailability (F) were significantly increased. This may be due to direct inhibition of cytochrome P(450) isozymes by enrofloxacin. A dose of 1.4mgkg(-1) of diclofenac administered every 6h may be appropriate for use in sheep.

  3. Synergistic effect of the interaction between curcumin and diclofenac on the formalin test in rats.

    PubMed

    De Paz-Campos, Marco A; Ortiz, Mario I; Chávez Piña, Aracely E; Zazueta-Beltrán, Liliana; Castañeda-Hernández, Gilberto

    2014-10-15

    The association of non-steroidal anti-inflammatory drugs with certain plant extracts can increase antinociceptive activity, permitting the use of lower doses and thus limiting side effects. Therefore, the aim objective of the current study was to examine the effects of curcumin on the nociception and pharmacokinetics of diclofenac in rats. Antinociception was assessed using the formalin test. Diluted formalin was injected subcutaneously into the dorsal surface of the right hind paw. Nociceptive behavior was quantified as the number of flinches of the injected paw during 60 min after injection, and a reduction in formalin-induced flinching was interpreted as an antinociceptive response. Rats were treated with oral diclofenac (1-31 mg/kg), curcumin (3.1-100 mg/kg) or the diclofenac-curcumin combination (2.4-38.4 mg/kg). To determine the possibility of a pharmacokinetic interaction, the oral bioavailability of diclofenac (10 mg/kg) was studied in presence and the absence of curcumin (31 mg/kg). Diclofenac, curcumin, or diclofenac-curcumin combination produced an antinociceptive effect on the formalin test. ED30 values were estimated for the individual drugs, and an isobologram was constructed. The derived theoretical ED30 for the antinociceptive effect (19.2 mg/kg) was significantly different from the observed experimental ED30 value (9.8 mg/kg); hence, the interaction between diclofenac and curcumin that mediates the antinociceptive effect was synergistic. Notwithstanding, the interaction does not appear to involve pharmacokinetic mechanisms, as oral curcumin failed to produce any significant alteration in oral diclofenac bioavailability. Data suggest that the diclofenac-curcumin combination can interact at the systemic level and may have therapeutic advantages for the clinical treatment of inflammatory pain. Copyright © 2014 Elsevier GmbH. All rights reserved.

  4. Evaluation of Skin Penetration of Diclofenac from a Novel Topical Non Aqueous Solution: A Comparative Bioavailability Study

    PubMed Central

    Nivsarkar, Manish; Patel, Ketan R.; Patel, Dixit D.

    2015-01-01

    Introduction Different topical formulations of diclofenac have varying skin penetration profile. Recent advances in science and technology has led to the development of many new formulations of drugs for topical drug delivery. One such technological development has led to the innovation of Dynapar QPS, a novel, non-aqueous, quick penetrating solution (QPS) of diclofenac diethylamine. Aim This study was aimed to measure the total exposure from the drug penetrating the skin in healthy human subjects and comparing the relative systemic bioavailability of Dynapar QPS® with diclofenac emulgel. Materials and Methods A 200 mg of diclofenac from either Dynapar QPS® (5 ml) or emulgel (20 g) was applied on back of subject as per the randomisation schedule. Blood samples were collected up to 16 hours post drug application. Plasma concentration of diclofenac was measured by pre-validated HPLC method. Pharmacokinetic (PK) parameters like Cmax, Tmax, t1/2, AUC0-t, AUC0-∞, and Kel, of diclofenac were determined for both the formulations. Results Mean Cmax after administration of Dynapar QPS® and diclofenac emulgel were 175.93 and 40.04 ng/ml, respectively. Tmax of diclofenac was almost half with QPS compared to emulgel (5.24 hrs versus 9.53 hrs respectively). The mean AUC0–t and AUC0-∞ after administration of Dynapar QPS® was higher as compared to diclofenac emulgel (AUC0–t: 1224.19 versus 289.78 ng.h/ml, respectively; AUC0-∞: 1718.21 versus 513.83 ng.h/ml, respectively). None of the subject experienced any adverse event during the study. Conclusion The results indicate an enhanced penetration and subsequent absorption of diclofenac from Dynapar QPS® as compared to diclofenac emulgel. Higher penetration is likely to translate into better pain relief in patients. PMID:26816910

  5. Evaluation of Skin Penetration of Diclofenac from a Novel Topical Non Aqueous Solution: A Comparative Bioavailability Study.

    PubMed

    Nivsarkar, Manish; Maroo, Sanjaykumar H; Patel, Ketan R; Patel, Dixit D

    2015-12-01

    Different topical formulations of diclofenac have varying skin penetration profile. Recent advances in science and technology has led to the development of many new formulations of drugs for topical drug delivery. One such technological development has led to the innovation of Dynapar QPS, a novel, non-aqueous, quick penetrating solution (QPS) of diclofenac diethylamine. This study was aimed to measure the total exposure from the drug penetrating the skin in healthy human subjects and comparing the relative systemic bioavailability of Dynapar QPS(®) with diclofenac emulgel. A 200 mg of diclofenac from either Dynapar QPS(®) (5 ml) or emulgel (20 g) was applied on back of subject as per the randomisation schedule. Blood samples were collected up to 16 hours post drug application. Plasma concentration of diclofenac was measured by pre-validated HPLC method. Pharmacokinetic (PK) parameters like Cmax, Tmax, t1/2, AUC0-t, AUC0-∞, and Kel, of diclofenac were determined for both the formulations. Mean Cmax after administration of Dynapar QPS(®) and diclofenac emulgel were 175.93 and 40.04 ng/ml, respectively. Tmax of diclofenac was almost half with QPS compared to emulgel (5.24 hrs versus 9.53 hrs respectively). The mean AUC0-t and AUC0-∞ after administration of Dynapar QPS(®) was higher as compared to diclofenac emulgel (AUC0-t: 1224.19 versus 289.78 ng.h/ml, respectively; AUC0-∞: 1718.21 versus 513.83 ng.h/ml, respectively). None of the subject experienced any adverse event during the study. The results indicate an enhanced penetration and subsequent absorption of diclofenac from Dynapar QPS(®) as compared to diclofenac emulgel. Higher penetration is likely to translate into better pain relief in patients.

  6. A new topical formulation enhances relative diclofenac bioavailability in healthy male subjects

    PubMed Central

    Brunner, Martin; Davies, David; Martin, Wolfgang; Leuratti, Chiara; Lackner, Edith; Müller, Markus

    2011-01-01

    AIMS To evaluate the relative plasma and tissue availability of diclofenac after repeated topical administration of a novel diclofenac acid-based delivery system under development (DCF100C). METHODS This was a single-centre, open-label, three-period, crossover clinical trial of five discrete diclofenac formulations. Test preparations comprised two concentrations (1.0% and 2.5%) of DCF100C, with and without menthol and eucalyptus oil (total daily doses of 5 mg and 12.5 mg). Voltaren® Emulgel® gel (1.0%) was the commercially available comparator (total daily dose of 40 mg). Topical application was performed onto the thigh of 20 male healthy subjects for 3 days. Applying a Youden square design, each drug was evaluated in 12 subjects, with each subject receiving three test preparations. Blood sampling and in vivo microdialysis in subcutaneous adipose and skeletal muscle tissues were performed for 10 h after additional final doses on the morning of day 4. RESULTS All four DCF100C formulations demonstrated a three- to fivefold, dose-dependent increase in systemic diclofenac availability compared with Voltaren® Emulgel® and were approximately 30–40 times more effective at facilitating diclofenac penetration through the skin, taking different dose levels into account. Tissue concentrations were low and highly variable. The 2.5% DCF100C formulation without sensory excipients reached the highest tissue concentrations. AUC(0,10 h) was 2.71 times greater than for Voltaren® Emulgel® (90% CI 99.27, 737.46%). Mild erythema at the application site was the most frequent adverse event associated with DCF100C. There were no local symptoms after treatment with the reference formulation. CONCLUSION DCF100C formulations were safe and facilitated greater diclofenac penetration through the skin compared with the commercial comparator. DCF100C represents a promising alternative to oral and topical diclofenac treatments that warrants further development. PMID:21241352

  7. Endoscopic evaluation of the gastro-duodenal tolerance of short-term analgesic treatment with 25 mg diclofenac-K liquid capsules.

    PubMed

    Hawkey, C; Burnett, I; Gold, M S; Garsed, K; Stevenson, D; Mannath, J; Norman, A; Shepherd, V; Subramanian, V; Johnston, R D; Brown, M

    2012-04-01

    Diclofenac-potassium (diclofenac--K) 25 mg liquid capsule is absorbed more quickly than the tablet formulation. It offers potential for rapid pain relief, but may alter gastro-duodenal tolerability. To evaluate the gastro-duodenal tolerance of diclofenac-K 25 mg liquid capsules vs. diclofenac-K 12.5 mg tablets, acetylsalicylic acid (ASA) 500 mg tablets and ibuprofen 200 mg liquid capsules. In an endoscopist-blinded, randomised, parallel-group study, volunteers received 15 doses of diclofenac-K 25 mg liquid capsules (n = 36), diclofenac-K 2 × 12.5 mg tablets (n = 36), ibuprofen 2 × 200 mg liquid capsules (n = 24) or ASA 2 × 500 mg tablets (n = 36) over 5 days. The primary outcome was the incidence of erosive gastro-duodenal lesions at Day 6. Secondary outcomes included modified Lanza score and change in gastric mucosal prostaglandin synthesis. The lowest incidence of erosive gastro-duodenal lesions was with diclofenac-K liquid capsules (53%), compared to 61% with diclofenac-K tablets (P = 0.52), 75% with ibuprofen (P = 0.08) and 94% with ASA (P = 0.001). Results were similar for the Lanza scores, although diclofenac-K liquid capsules were significantly superior to ibuprofen liquid capsules (P = 0.04). Diclofenac-K liquid capsules inhibited prostaglandin synthesis by 52% compared to 64% for diclofenac-K tablets (P = 0.10), 50% for ibuprofen (P = 0.85) and 79% for ASA (P = 0.002). With respect to safety, adverse events were most frequent in the ASA group, predominantly gastrointestinal events. Mucosal injury with diclofenac-K liquid 25 mg liquid capsules was similar to diclofenac-K 25 mg tablets, significantly lower than ASA 1 g tablets and showed some superiority over ibuprofen 400 mg liquid capsules (EudraCT Number 2009-011278-14). © 2012 Blackwell Publishing Ltd.

  8. Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal β-glucuronidase activity.

    PubMed

    Zhong, Ze-Yu; Sun, Bin-Bin; Shu, Nan; Xie, Qiu-Shi; Tang, Xian-Ge; Ling, Zhao-Li; Wang, Fan; Zhao, Kai-Jing; Xu, Ping; Zhang, Mian; Li, Ying; Chen, Yang; Liu, Li; Xia, Lun-Zhu; Liu, Xiao-Dong

    2016-07-01

    Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), which may cause serious intestinal adverse reactions (enteropathy). In this study we investigated whether co-administration of ciprofloxacin affected the pharmacokinetics of diclofenac and diclofenac-induced enteropathy in rats. The pharmacokinetics of diclofenac was assessed in rats after receiving diclofenac (10 mg/kg, ig, or 5 mg/kg, iv), with or without ciprofloxacin (20 mg/kg, ig) co-administered. After receiving 6 oral doses or 15 intravenous doses of diclofenac, the rats were sacrificed, and small intestine was removed to examine diclofenac-induced enteropathy. β-Glucuronidase activity in intestinal content, bovine liver and E coli was evaluated. Following oral or intravenous administration, the pharmacokinetic profile of diclofenac displayed typical enterohepatic circulation, and co-administration of ciprofloxacin abolished the enterohepatic circulation, resulted in significant reduction in the plasma content of diclofenac. In control rats, β-glucuronidase activity in small intestinal content was region-dependent: proximal intestinediclofenac, typical enteropathy was developed with severe enteropathy occurred in distal small intestine. Co-administration of ciprofloxacin significantly alleviated diclofenac-induced enteropathy. Co-administration of ciprofloxacin attenuated enterohepatic circulation of diclofenac and alleviated diclofenac-induced enteropathy in rats, partly via the inhibition of intestinal

  9. Apparent tolerance of turkey vultures (Cathartes aura) to the non-steroidal anti-inflammatory drug diclofenac

    USGS Publications Warehouse

    Rattner, B.A.; Whitehead, M.A.; Gasper, G.; Meteyer, C.U.; Link, W.A.; Taggart, M.A.; Meharg, A.A.; Pattee, O.H.; Pain, D.J.

    2008-01-01

    The nonsteroidal anti-inflammatory drug diclofenac is extremely toxic to Old World Gyps vultures (median lethal dose 0.1?0.2 mg/kg), evoking visceral gout, renal necrosis, and mortality within a few days of exposure. Unintentional secondary poisoning of vultures that fed upon carcasses of diclofenac-treated livestock decimated populations in the Indian subcontinent. Because of the widespread use of diclofenac and other cyclooxygenase-2 inhibiting drugs, a toxicological study was undertaken in turkey vultures (Cathartes aura) as an initial step in examining sensitivity of New World scavenging birds. Two trials were conducted entailing oral gavage of diclofenac at doses ranging from 0.08 to 25 mg/kg body weight. Birds were observed for 7 d, blood samples were collected for plasma chemistry (predose and 12, 24, and 48 h and 7 d postdose), and select individuals were necropsied. Diclofenac failed to evoke overt signs of toxicity, visceral gout, renal necrosis, or elevate plasma uric acid at concentrations greater than 100 times the estimated median lethal dose reported for Gyps vultures. For turkey vultures receiving 8 or 25 mg/kg, the plasma half-life of diclofenac was estimated to be 6 h, and it was apparently cleared after several days as no residues were detectable in liver or kidney at necropsy. Differential sensitivity among avian species is a hallmark of cyclooxygenase-2 inhibitors, and despite the tolerance of turkey vultures to diclofenac, additional studies in related scavenging species seem warranted.

  10. Metformin and phenformin block the peripheral antinociception induced by diclofenac and indomethacin on the formalin test.

    PubMed

    Ortiz, Mario I

    2012-01-02

    Recent evidence has shown that systemic administration of sulfonylureas and biguanides block the diclofenac-induced antinociception, but not the effect produced by indomethacin. However, there are no reports about the peripheral interaction between analgesics and the biguanides metformin and phenformin. Therefore, this work was undertaken to determine whether glibenclamide and glipizide and the biguanides metformin and phenformin have any effect on the peripheral antinociception induced by diclofenac and indomethacin. Diclofenac and indomethacin were administered locally in the formalin-injured rat paw, and the antinociceptive effect was evaluated using the 1% formalin test. To determine whether peripheral antinociception induced by diclofenac or indomethacin was mediated by either the ATP-sensitive K(+) channels or biguanides-induced mechanisms, the effect of pretreatment with the appropriates vehicles or glibenclamide, glipizide, metformin and phenformin on the antinociceptive effect induced by local peripheral diclofenac and indomethacin was assessed. Local peripheral injections of diclofenac (50-200 μg/paw) and indomethacin (200-800 μg/paw) produced a dose-dependent antinociception during the second phase of the test. Local pretreatment with glibenclamide, glipizide, metformin and phenformin blocked the diclofenac-induced antinociception. On the other hand, the pretreatment with glibenclamide and glipizide did not prevent the local antinociception produced by indomethacin. Nonetheless, metformin and phenformin reversed the local antinociception induced by indomethacin. Data suggest that diclofenac could activate the K(+) channels and biguanides-dependent mechanisms to produce its peripheral antinociceptive effects in the formalin test. Likewise, a biguanides-dependent mechanism could be activated by indomethacin consecutively to generate its peripheral antinociceptive effect. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal β-glucuronidase activity

    PubMed Central

    Zhong, Ze-yu; Sun, Bin-bin; Shu, Nan; Xie, Qiu-shi; Tang, Xian-ge; Ling, Zhao-li; Wang, Fan; Zhao, Kai-jing; Xu, Ping; Zhang, Mian; Li, Ying; Chen, Yang; Liu, Li; Xia, Lun-zhu; Liu, Xiao-dong

    2016-01-01

    Aim: Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), which may cause serious intestinal adverse reactions (enteropathy). In this study we investigated whether co-administration of ciprofloxacin affected the pharmacokinetics of diclofenac and diclofenac-induced enteropathy in rats. Methods: The pharmacokinetics of diclofenac was assessed in rats after receiving diclofenac (10 mg/kg, ig, or 5 mg/kg, iv), with or without ciprofloxacin (20 mg/kg, ig) co-administered. After receiving 6 oral doses or 15 intravenous doses of diclofenac, the rats were sacrificed, and small intestine was removed to examine diclofenac-induced enteropathy. β-Glucuronidase activity in intestinal content, bovine liver and E coli was evaluated. Results: Following oral or intravenous administration, the pharmacokinetic profile of diclofenac displayed typical enterohepatic circulation, and co-administration of ciprofloxacin abolished the enterohepatic circulation, resulted in significant reduction in the plasma content of diclofenac. In control rats, β-glucuronidase activity in small intestinal content was region-dependent: proximal intestinediclofenac, typical enteropathy was developed with severe enteropathy occurred in distal small intestine. Co-administration of ciprofloxacin significantly alleviated diclofenac-induced enteropathy. Conclusion: Co-administration of ciprofloxacin attenuated enterohepatic circulation of diclofenac and alleviated diclofenac-induced enteropathy in rats, partly via

  12. Simulation of the oxidative metabolism of diclofenac by electrochemistry/(liquid chromatography/)mass spectrometry.

    PubMed

    Faber, Helene; Melles, Daniel; Brauckmann, Christine; Wehe, Christoph Alexander; Wentker, Kristina; Karst, Uwe

    2012-04-01

    Diclofenac is a frequently prescribed drug for rheumatic diseases and muscle pain. In rare cases, it may be associated with a severe hepatotoxicity. In literature, it is discussed whether this toxicity is related to the oxidative phase I metabolism, resulting in electrophilic quinone imines, which can subsequently react with nucleophiles present in the liver in form of glutathione or proteins. In this work, electrochemistry coupled to mass spectrometry is used as a tool for the simulation of the oxidative pathway of diclofenac. Using this purely instrumental approach, diclofenac was oxidized in a thin layer cell equipped with a boron doped diamond working electrode. Sum formulae of generated oxidation products were calculated based on accurate mass measurements with deviations below 2 ppm. Quinone imines from diclofenac were detected using this approach. It could be shown for the first time that these quinone imines do not react with glutathione exclusively but also with larger molecules such as the model protein β-lactoglobulin A. A tryptic digest of the generated drug-protein adduct confirms that the protein is modified at the only free thiol-containing peptide. This simple and purely instrumental set-up offers the possibility of generating reactive metabolites of diclofenac and to assess their reactivity rapidly and easily.

  13. Comparative studies on osmosis based encapsulation of sodium diclofenac in porcine and outdated human erythrocyte ghosts.

    PubMed

    Bukara, Katarina; Drvenica, Ivana; Ilić, Vesna; Stančić, Ana; Mišić, Danijela; Vasić, Borislav; Gajić, Radoš; Vučetić, Dušan; Kiekens, Filip; Bugarski, Branko

    2016-12-20

    The objective of our study was to develop controlled drug delivery system based on erythrocyte ghosts for amphiphilic compound sodium diclofenac considering the differences between erythrocytes derived from two readily available materials - porcine slaughterhouse and outdated transfusion human blood. Starting erythrocytes, empty erythrocyte ghosts and diclofenac loaded ghosts were compared in terms of the encapsulation efficiency, drug releasing profiles, size distribution, surface charge, conductivity, surface roughness and morphology. The encapsulation of sodium diclofenac was performed by an osmosis based process - gradual hemolysis. During this process sodium diclofenac exerted mild and delayed antihemolytic effect and increased potassium efflux in porcine but not in outdated human erythrocytes. FTIR spectra revealed lack of any membrane lipid disorder and chemical reaction with sodium diclofenac in encapsulated ghosts. Outdated human erythrocyte ghosts with detected nanoscale damages and reduced ability to shrink had encapsulation efficiency of only 8%. On the other hand, porcine erythrocyte ghosts had encapsulation efficiency of 37% and relatively slow drug release rate. More preserved structure and functional properties of porcine erythrocytes related to their superior encapsulation and release performances, define them as more appropriate for the usage in sodium diclofenac encapsulation process. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Diclofenac residues as the cause of vulture population decline in Pakistan

    USGS Publications Warehouse

    Oaks, J.L.; Gilbert, M.; Virani, M.Z.; Watson, R.T.; Meteyer, C.U.; Rideout, B.A.; Shivaprasad, H.L.; Ahmed, S.; Chaudhry, M.J.I.; Arshad, M.; Mahmood, S.; Ali, A.; Khan, A.A.

    2004-01-01

    The Oriental white-backed vulture (OWBV; Gyps bengalensis) was once one of the most common raptors in the Indian subcontinent. A population decline of >95%, starting in the 1990s, was first noted at Keoladeo National Park, India. Since then, catastrophic declines, also involving Gyps indicus and Gyps tenuirostris, have continued to be reported across the subcontinent. Consequently these vultures are now listed as critically endangered by BirdLife International. In 2000, the Peregrine Fund initiated its Asian Vulture Crisis Project with the Ornithological Society of Pakistan, establishing study sites at 16 OWBV colonies in the Kasur, Khanewal and Muzaffargarha??Layyah Districts of Pakistan to measure mortality at over 2,400 active nest sites5. Between 2000 and 2003, high annual adult and subadult mortality (5a??86%) and resulting population declines (34a??95%) (ref. 5 and M.G., manuscript in preparation) were associated with renal failure and visceral gout. Here, we provide results that directly correlate residues of the anti-inflammatory drug diclofenac with renal failure. Diclofenac residues and renal disease were reproduced experimentally in OWBVs by direct oral exposure and through feeding vultures diclofenac-treated livestock. We propose that residues of veterinary diclofenac are responsible for the OWBV decline.

  15. The relative bioavailability of diclofenac with respect to time of administration.

    PubMed Central

    Mustofa, M; Suryawati, S; Dwiprahasto, I; Santoso, B

    1991-01-01

    The pharmacokinetics of diclofenac after a single oral dose (50 mg) were studied in 10 healthy adults on two occasions separated by 2 weeks, once in the morning (dose administered at 07.00 h) and once in the evening (dose at 19.00 h). Peak serum drug concentrations as well as the area under the drug concentration-time curve were significantly less during the night compared with the day (Cmax: 1886 +/- s.d 901 vs 2791 +/- 1565 ng ml-1 and AUC: 2807 +/- 1376 vs 3681 +/- 1986 ng ml-1 h). However, the time to reach peak concentration (tmax) and the half-life of diclofenac (t1/2) were not significantly different on the two occasions. We suggest that the extent of diclofenac absorption is slightly lower following administration in the evening compared with administration in the morning. PMID:1931476

  16. Contrasting effects of cord injury on intravenous and oral pharmacokinetics of diclofenac: a drug with intermediate hepatic extraction.

    PubMed

    Cruz-Antonio, L; Arauz, J; Franco-Bourland, R E; Guízar-Sahagún, G; Castañeda-Hernández, G

    2012-08-01

    Laboratory investigation in rats submitted to experimental spinal cord injury (SCI). To determine the effect of acute SCI on the pharmacokinetics of diclofenac, a marker drug of intermediate hepatic extraction, administered by the intravenous and the oral routes. Female Wistar rats were submitted to complete section of the spinal cord at the T8 level. SCI and sham-injured rats received 3.2 mg kg(-1) of diclofenac sodium either intravenously or orally, diclofenac concentration was measured in whole blood samples and pharmacokinetic parameters were estimated. Diclofenac was not selected as test drug because of its therapeutic properties, but because to its biopharmaceutical properties, that is, intermediate hepatic extraction. Diclofenac bioavailability after intravenous administration was increased in injured rats compared with controls due to a reduced clearance. In contrast, oral diclofenac bioavailability was diminished in SCI animals due to a reduction in drug absorption, which overrides the effect on clearance. Acute SCI induces significant pharmacokinetic changes for diclofenac, a marker drug with intermediate hepatic extraction. SCI-induced pharmacokinetic changes are not only determined by injury characteristics, but also by the route of administration and the biopharmaceutical properties of the studied drug.

  17. Days lost due to disability of diclofenac-induced adverse drug reactions.

    PubMed

    Thomas, Dixon; Mathew, Molly; Raghavan, C Vijaya; Mohanta, Guru P; Reddy, Y Padmanabha

    2012-01-01

    Disability Adjusted Life Years (DALY) is a widely used measure to quantify the burden of diseases or illness. DALYs for a disease is calculated as the sum of the Years of Life Lost (YLL) due to premature mortality in the population and the equivalent healthy Years Lost due to Disability (YLD). The only difference from the YLD and Days Lost due to Disability (DLD) calculation is that instead of considering the duration of Adverse Drug Reaction (ADR) in years, it is calculated in days. DLD was measured for diclofenac tablets to prepare the ADR profile. The study was done on the patients (18-65 years old) attending the community pharmacy at Kasaragod district, South India, with prescription of diclofenac tablets. Patients reported ADRs on their next visit to the pharmacy or they had called to the provided phone number and reported it. Disability Weight (DW) was calculated in an analogue scale from 0-1. Zero represent complete health and 1 represent death or equivalent condition. DW was multiplied with occurrence and duration of ADRs in days. About 943 patients received diclofenac tablets in 1000 prescriptions were successfully followed up for possible, probable and definite ADRs. A total of 561 reactions reported in 2010 for diclofenac tablet in the study population. There were 34 different types of ADRs under 12 physiological systems/organs. Most common reactions were on gastrointestinal (GI) system (48%), followed by skin (14%), Central Nervous System (10%), renal (7%), and cardiovascular (7%). Abdominal pain, cramps or flatulence was the highest occurring GI ADR (107), followed by 43 rashes, 42 nausea/vomiting, 37 indigestion, 34 peptic ulcers, 31 edema etc. DLD for peptic ulcer was considerably high (0.078) per 1000 of the study population on diclofenac. The most damaging ADR were peptic ulcer with or without perforation, followed by rash 0.036 DLD and edema 0.027 DLD. There was considerable DLD by acute renal failure (0.012) Steven-Johnson syndrome (0.013) even

  18. Efficacy and safety of topical diclofenac/menthol gel for ankle sprain: A randomized, double-blind, placebo- and active-controlled trial

    PubMed Central

    Collaku, Agron; Reed, Kenneth

    2017-01-01

    Purpose This study was performed to evaluate topical 1% diclofenac/3% menthol gel in treating ankle sprain. Design In this randomized, double-blind, placebo-controlled trial, adolescents and adults with acute ankle sprain (N = 385) applied 4 g of gel containing 1% diclofenac/3% menthol (n = 117), 1% diclofenac (n = 112), 3% menthol (n = 77), or placebo (n = 75) four times daily. The primary outcome was the area under the curve of pain intensity (PI) on movement [0 (no pain) to 10 (extreme pain)] from 24 to 72 hours post-application (AUC1–3 days). Secondary outcomes included pain relief (PR); PI; time to onset of PR, meaningful PR, cooling, and complete recovery; PI difference; sum of PI difference; total PR; reduction in ankle swelling; and the patient’s global assessment of response to treatment. Results There were no statistically significant differences in AUC1–3 between 1% diclofenac/3% menthol and placebo, diclofenac, or menthol gels and no meaningful advantages of 1% diclofenac/3% menthol for any secondary outcome. There was a higher incidence of skin and application-site events with 1% diclofenac/3% menthol than with placebo or 1% diclofenac. Conclusion No significant improvement was observed with topical 1% diclofenac/3% menthol gel compared with placebo, 1% diclofenac, or 3% menthol gel in treating pain from ankle sprain. ClinicalTrials.Gov Identifier: NCT02100670 PMID:28345425

  19. Photocatalytic degradation of diclofenac using TiO2-SnO2 mixed oxide catalysts.

    PubMed

    Mugunthan, E; Saidutta, M B; Jagadeeshbabu, P E

    2017-12-26

    The complex nature of diclofenac limits its biological degradation, posing a serious threat to aquatic organisms. Our present work aims to eliminate diclofenac from wastewater through photocatalytic degradation using TiO 2 -SnO 2 mixed-oxide catalysts under various operating conditions such as catalyst loading, initial diclofenac concentration and initial pH. Different molar ratios of Ti-Sn (1:1, 5:1, 10:1, 20:1 and 30:1) were prepared by the hydrothermal method and were characterized. The results indicated that addition of Sn in small quantity enhances the catalytic activity of TiO 2 . Energy Band gap of the TiO 2 -SnO 2 catalysts was found to increase with an increase in Tin content. TiO 2 -SnO 2 catalyst with a molar ratio of 20:1 was found to be the most effective when compared to other catalysts. The results suggested that initial drug concentration of 20 mg/L, catalyst loading of 0.8 g/L and pH 5 were the optimum operating conditions for complete degradation of diclofenac. Also, the TiO 2 -SnO 2 catalyst was effective in complete mineralization of diclofenac with a maximum total organic carbon removal of 90% achieved under ultraviolet irradiation. The repeatability and stability results showed that the TiO 2 -SnO 2 catalyst exhibited an excellent repeatability and better stability over the repeated reaction cycles. The photocatalytic degradation of diclofenac resulted in several photoproducts, which were identified through LC-MS.

  20. [Technological and pharmacotherapeutic properties of selected drugs with modified release of diclofenac sodium].

    PubMed

    Kołodziejczyk, Michał Krzysztof; Kołodziejska, Justyna; Zgoda, Marian Mikołaj

    2012-01-01

    Diclofenac and its sodium salt is one of the best-known and popular therapeutic agents from the group of NSAIDs used in medicine in many various pharmaceutical forms. Therapeutic products containing diclofenac sodium salt in doses of 100 mg and 75 mg with a qualitatively and quantitatively diversified share of excipients and a variable dosage form of the drug (solid capsules, tablets with modified release) were subjected to technological and pharmaceutical analysis. The effect of solid formulation components of polymer character making the core and the coating of the pharmaceutical form of therapeutic products on the disintegration time and pharmaceutical availability in pharmacopoeial receptor fluids was estimated. Market therapeutic products with diclofenac sodium in doses of 75 mg and 100 mg, technological analysis of the drug dosage form was conducted, disintegration time of solid oral dosage forms of the drug with diclofenac sodium salt was examined and research on pharmaceutical availability of diclofenac sodium salt from tested therapeutic products was conducted using the acid phase and the buffer phase according to the FP standards for delayed release enteral dosage forms. The experimental data was supplemented with the statistical analysis. There are three formulations in the form of solid capsules and one formulation in the form of a coated tablet. All therapeutic products bear features of a dosage form of modified release of diclofenac sodium salt, frequently of a delayed release formula in the duodenum or the small intestine with regard to the limitation of typical undesirable effects after taking NSAIDs. Considerable diversity between solid capsules and the tablet with modified release during disintegration or hydration and swelling has been observed. In the environment of a receptor fluid--purified water (pH = 7) the capsule Dicloberl retard disintegrates at the fastest rate in 5,49 minutes, and then in the order: DicloDuo 75 mg--8,13 minutes and

  1. Efficacy of topical diclofenac diethylamine gel in osteoarthritis of the knee.

    PubMed

    Niethard, Fritz U; Gold, Morris S; Solomon, Gail S; Liu, Jiun-Min; Unkauf, Markus; Albrecht, Helmut H; Elkik, Francois

    2005-12-01

    To assess the efficacy and safety of topical diclofenac diethylamine gel, 1.16%, 4 g applied qid for 3 weeks to relieve the symptoms of osteoarthritis (OA) of the knee. Patients with OA of the knee washed out their OA medications for at least 5 drug half-lives. Patients with adequately high baseline pain scores were randomized to apply either double-blind active or placebo gel for 3 weeks. Acetaminophen (up to 2 g/day) was supplied as rescue medication. In a diary, patients recorded compliance to dosing and use of rescue medication and assessed daily pain on movement, spontaneous pain, and pain relief. At weekly site visits, patients completed the Western Ontario and McMaster (WOMAC) Osteoarthritis Index Questionnaire, which includes assessment of pain, stiffness, and physical function, and assessed pain intensity "right now." At the final visit, a global assessment of treatment efficacy was completed. Of 238 randomized patients, 237 were included in the intent to treat efficacy analysis. Treatments differed significantly for daily pain on movement at Day 5, and continued on most days through end of study. Peak differences were achieved in the second week. On the primary outcome, average pain on movement over Days 1-14, diclofenac gel was significantly superior to placebo gel. Scores for all 3 WOMAC indices for diclofenac gel treatment were significantly superior to placebo at Weeks 2 and 3. A significant difference was achieved on pain intensity "right now" at all 3 weeks. At the end of the study, patients rated diclofenac gel as significantly more effective in treating the pain of OA of the knee (p = 0.03) compared to placebo. There were no safety issues concerning adverse events or laboratory values. Diclofenac gel was effective and safe for relief of symptoms of OA of the knee over 3 weeks of dosing.

  2. Crocheted ETFE-reactor for on-line post-column photoderivatization of diclofenac in high-performance liquid chromatography.

    PubMed

    Kuhlmann, O; Krauss, G J

    1997-12-01

    A sensitive and selective bioanalytical method for diclofenac using reversed-phase HPLC and fluorescence detection is described. Diclofenac was detected as its fluorescent derivative after on-line post-column photoderivatization. Irradiation with UV light of diclofenac in aqueous solutions leads to the sequential loss of both chlorine substituents and ring closure. The major product, carbazole-1-acetic acid, was detected by a fluorescence detector using an excitation wavelength of 286 nm and an emission wavelength of 360 nm. The self-made reactor was a crocheted ethylene and tetrafluoroethylene (ETFE, named TEFZEL) capillary, 20 m in length, wound directly around a 253.7 nm UV lamp. The capillary was crocheted in order to overcome peak widening. Chromatographic separation was achieved by using a Regis SPS 100 RP-8 column (5 microm; 150 mm x 4.6 mm i.d.) and a LiChrospher 100 RP-18 (5 microm) guard column from E. Merck. The detection limit was 1 ng ml(-1) at an injection volume of 20 microl. Daily relative standard deviations (RSD) were 5.5%, (73 ng diclofenac/ml, n = 9), and 5.1% (405 ng diclofenac/ml, n = 6), respectively. Chromatograms of human aqueous humor and human serum containing diclofenac, and figures showing the time dependent increase/decrease of the photoderivatization product, are shown.

  3. Ketoprofen is more effective than diclofenac after oral surgery when used as a preemptive analgesic: a pilot study.

    PubMed

    Velásquez, Grace Carolaine Esquivel; Santa Cruz, Luis A German; Espinoza, Mario Alberto Isiordia

    2014-01-01

    To evaluate the preemptive analgesia of ketoprofen in comparison with diclofenac after mandibular third molar surgery. This study was a double-blind, randomized clinical trial. Forty patients were randomized into two treatment groups (each with 20 patients) by using a series of random numbers: group A received ketoprofen 100 mg and group B received diclofenac 75 mg, all intramuscularly. Surgery was done 30 minutes after analgesic treatments. The durations of analgesia, pain intensity, analgesic consumption, and side effects were evaluated. The statistical analysis was done using the chi-square, Student t, Mann-Whitney U, and Log-Rank tests. The duration of analgesia was longer in the ketoprofen group when compared with the diclofenac group. The number of patients taking the first rescue analgesic at 6 hours was lower in the ketoprofen group in comparison with the diclofenac group. Patients who received ketoprofen had lower pain intensity compared with patients who received diclofenac. Intramuscular ketoprofen 100 mg is more effective than intramuscular diclofenac 75 mg after mandibular third molar extraction when used as a preemptive analgesic.

  4. Catalytic dechlorination of diclofenac by biogenic palladium in a microbial electrolysis cell

    PubMed Central

    Gusseme, Bart De; Soetaert, Maarten; Hennebel, Tom; Vanhaecke, Lynn; Boon, Nico; Verstraete, Willy

    2012-01-01

    Summary Diclofenac is one of the most commonly detected pharmaceuticals in wastewater treatment plant (WWTP) effluents and the receiving water bodies. In this study, biogenic Pd nanoparticles (‘bio‐Pd’) were successfully applied in a microbial electrolysis cell (MEC) for the catalytic reduction of diclofenac. Hydrogen gas was produced in the cathodic compartment, and consumed as a hydrogen donor by the bio‐Pd on the graphite electrodes. In this way, complete dechlorination of 1 mg diclofenac l−1 was achieved during batch recirculation experiments, whereas no significant removal was observed in the absence of the biocatalyst. The complete dechlorination of diclofenac was demonstrated by the concomitant production of 2‐anilinophenylacetate (APA). Through the addition of −0.8 V to the circuit, continuous and complete removal of diclofenac was achieved in synthetic medium at a minimal HRT of 2 h. Continuous treatment of hospital WWTP effluent containing 1.28 µg diclofenac l−1 resulted in a lower removal efficiency of 57%, which can probably be attributed to the affinity of other environmental constituents for the bio‐Pd catalyst. Nevertheless, reductive catalysis coupled to sustainable hydrogen production in a MEC offers potential to lower the release of micropollutants from point‐sources such as hospital WWTPs. PMID:22221490

  5. An isobolographic analysis of the antinociceptive effect of xylopic acid in combination with morphine or diclofenac

    PubMed Central

    Woode, Eric; Ameyaw, Elvis Ofori; Abotsi, Wonder Kofi Mensah; Boakye-Gyasi, Eric

    2015-01-01

    Background: A common practice of managing pain globally is the combination of analgesics and this is aimed at facilitating patient compliance, simplifying prescription, and improving efficacy without increasing adverse effects. Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders and xylopic acid (XA) present in the fruit extract have been shown to possess analgesic properties in animals. There is the likelihood of concomitant use of XA and the commonly used analgesics in traditional settings. This study, therefore, evaluated the pharmacologic interaction between XA/morphine and xylopic/diclofenac combinations. Methods: The formalin test and acetic acid writhing test were used to study the antinociceptive activity of XA, morphine, and diclofenac. The isobolographic analysis was used to study the antinociceptive interactions between XA co-administered with morphine or diclofenac. Results: Results obtained revealed that XA (10–100 mg/kg), morphine (1–10 mg/kg), and diclofenac (1–10 mg/kg) produced dose-related antinociception with different potencies in the formalin and acetic acid writhing tests. Isobolographic analysis of XA/morphine and XA/diclofenac combinations revealed potentiation of their antinociceptive effects. The degree of potentiation calculated as interaction index showed synergism for both combinations in all the nociceptive tests. Conclusion: In conclusion, the present study demonstrated synergism for the co-administration of XA with morphine or diclofenac. PMID:26692735

  6. Physicochemical characterization of diclofenac sodium-loaded poloxamer gel as a rectal delivery system with fast absorption.

    PubMed

    Yong, Chul Soon; Sah, Hongkee; Jahng, Yurngdong; Chang, Hyeun Wook; Son, Jong-Keun; Lee, Seung Ho; Jeong, Tae Cheon; Rhee, Jong-Dal; Baek, Suk Hwan; Kim, Chong-Kook; Choi, Han-Gon

    2003-05-01

    Rectal poloxamer gel systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and were mucoadhesive to the rectal tissues without leakage after the dose. However, a poloxamer gel containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a poloxamer gel using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength, and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers, and sodium chloride were investigated. Furthermore, the pharmacokinetic study of diclofenac sodium delivered by the poloxamer gel was performed. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. The poloxamer gels with less than 1.0% sodium chloride, in which the drug was not precipitated, were inserted into the rectum without difficulty and leakage, and were retained in the rectum of rats for at least 6 hr. Furthermore, poloxamer gel gave significantly higher initial plasma concentrations and faster Tmax of diclofenac sodium than did solid suppository, indicating that drug from poloxamer gel could be absorbed faster than that from the solid one in rats. Our results suggested that a rectal poloxamer gel system with sodium chloride and poloxamers was a more physically stable, convenient, and effective rectal dosage form for diclofenac sodium.

  7. Vinpocetine reduces diclofenac-induced acute kidney injury through inhibition of oxidative stress, apoptosis, cytokine production, and NF-κB activation in mice.

    PubMed

    Fattori, Victor; Borghi, Sergio M; Guazelli, Carla F S; Giroldo, Andressa C; Crespigio, Jefferson; Bussmann, Allan J C; Coelho-Silva, Letícia; Ludwig, Natasha G; Mazzuco, Tânia L; Casagrande, Rubia; Verri, Waldiceu A

    2017-06-01

    Acute kidney injury (AKI) represents a complex clinical condition associated with significant morbidity and mortality. Approximately, 19-33% AKI episodes in hospitalized patients are related to drug-induced nephrotoxicity. Although, considered safe, non-steroidal anti-inflammatory drugs such as diclofenac have received special attention in the past years due to the potential risk of renal damage. Vinpocetine is a nootropic drug known to have anti-inflammatory properties. In this study, we investigated the effect and mechanisms of vinpocetine in a model of diclofenac-induced AKI. We observed that diclofenac increased proteinuria and blood urea, creatinine, and oxidative stress levels 24h after its administration. In renal tissue, diclofenac also increased oxidative stress and induced morphological changes consistent with renal damage. Moreover, diclofenac induced kidney cells apoptosis, up-regulated proinflammatory cytokines, and induced the activation of NF-κB in renal tissue. On the other hand, vinpocetine reduced diclofenac-induced blood urea and creatinine. In the kidneys, vinpocetine inhibited diclofenac-induced oxidative stress, morphological changes, apoptosis, cytokine production, and NF-κB activation. To our knowledge, this is the first study demonstrating that diclofenac-induced AKI increases NF-κB activation, and that vinpocetine reduces the nephrotoxic effects of diclofenac. Therefore, vinpocetine is a promising molecule for the treatment of diclofenac-induced AKI. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Anaphylaxis to diclofenac: nine cases reported to the Allergy Vigilance Network in France.

    PubMed

    Picaud, J; Beaudouin, E; Renaudin, J M; Pirson, F; Metz-Favre, C; Dron-Gonzalvez, M; Moneret-Vautrin, D A

    2014-10-01

    Nine cases of diclofenac hypersensitivity recorded by the Allergy Vigilance Network in France from 2002 to 2012 were studied. Data from history, symptoms, skin tests, basophil activation tests, and oral challenge (OC) were recorded. Grade 3 severe anaphylactic reactions occurred in seven cases of nine. IgE-dependent anaphylaxis was confirmed in six cases: positive intradermal tests (n = 4), a syndromic reaction during skin tests (n = 1), and one case with grade 1 reaction and negative skin tests had an anaphylactic shock to the OC. A nonimmune reaction was suspected in one case. An IgE-dependent mechanism may be the predominant cause of adverse reactions to diclofenac. Allergy skin tests must be carried out sequentially at the recommended concentrations. BATs may be helpful because they can support the diagnosis of anaphylaxis. Given the risks of a direct challenge to diclofenac, OC to aspirin should be performed first to exclude a nonimmunologic hypersensitivity to NSAIDs. Tests for specific IgEs to most frequently used NSAIDs such as diclofenac and ibuprofen are urgently needed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Optimization of naltrexone diclofenac codrugs for sustained drug delivery across microneedle-treated skin.

    PubMed

    Ghosh, Priyanka; Lee, DoMin; Kim, Kyung Bo; Stinchcomb, Audra L

    2014-01-01

    The purpose of this work was to optimize the structure of codrugs for extended delivery across microneedle treated skin. Naltrexone, the model compound was linked with diclofenac, a nonspecific cyclooxygenase inhibitor to enhance the pore lifetime following microneedle treatment and develop a 7 day transdermal system for naltrexone. Four different codrugs of naltrexone and diclofenac were compared in terms of stability and solubility. Transdermal flux, permeability and skin concentration of both parent drugs and codrugs were quantified to form a structure permeability relationship. The results indicated that all codrugs bioconverted in the skin. The degree of conversion was dependent on the structure, phenol linked codrugs were less stable compared to the secondary alcohol linked structures. The flux of naltrexone across microneedle treated skin and the skin concentration of diclofenac were higher for the phenol linked codrugs. The polyethylene glycol link enhanced solubility of the codrugs, which translated into flux enhancement. The current studies indicated that formulation stability of codrugs and the flux of naltrexone can be enhanced via structure design optimization. The polyethylene glycol linked naltrexone diclofenac codrug is better suited for a 7 day drug delivery system both in terms of stability and drug delivery.

  10. Effect of rubbing on the in vitro skin permeation of diclofenac-diethylamine 1.16% gel.

    PubMed

    Hasler-Nguyen, Nathalie; Fotopoulos, Grigorios

    2012-06-21

    Rubbing a topical NSAID (non steroidal anti-inflammatory drug) on the skin may increase local drug permeation, affecting its distribution to the site of pain and inflammation. The present study evaluates this hypothesis, by assessing in vitro the effect on skin permeation of applying diclofenac-dieythylamine 1.16% gel with or without rubbing. A single dose of 5 mg/cm2 diclofenac-diethylamine 1.16% gel was applied on excised human skin mounted in Franz-type diffusion cells without or with rubbing for 45 s. Drug penetration into the skin layers was determined after 1 h using the tape stripping technique. In vitro cutaneous permeation into the receptor fluid of the diffusion chamber was measured up to 24 h. Skin electrical resistance was also recorded. Application of diclofenac-diethylamine 1.16% gel with rubbing resulted to a 5-fold higher flux of diclofenac through the skin than when applied without rubbing at 8 h (P = 0.04). Skin rubbing for 45 s decreased by 2-fold skin electrical resistance when compared to the standard application. Application of diclofenac-diethylamine 1.16% gel with rubbing tended to result in higher accumulation in the stripped skin vs. the superficial skin layers when applied without rubbing (P = 0.2). These results suggest that rubbing may alter the superficial skin layer resulting in a transient faster initial diffusion of topically applied diclofenac through the stratum corneum into the deeper skin layer of the dermis to the tissue target.

  11. Effect of rubbing on the in vitro skin permeation of diclofenac-diethylamine 1.16% gel

    PubMed Central

    2012-01-01

    Background Rubbing a topical NSAID (non steroidal anti-inflammatory drug) on the skin may increase local drug permeation, affecting its distribution to the site of pain and inflammation. The present study evaluates this hypothesis, by assessing in vitro the effect on skin permeation of applying diclofenac-dieythylamine 1.16% gel with or without rubbing. Methods A single dose of 5 mg/cm2 diclofenac-diethylamine 1.16% gel was applied on excised human skin mounted in Franz-type diffusion cells without or with rubbing for 45 s. Drug penetration into the skin layers was determined after 1 h using the tape stripping technique. In vitro cutaneous permeation into the receptor fluid of the diffusion chamber was measured up to 24 h. Skin electrical resistance was also recorded. Results Application of diclofenac-diethylamine 1.16% gel with rubbing resulted to a 5-fold higher flux of diclofenac through the skin than when applied without rubbing at 8 h (P = 0.04). Skin rubbing for 45 s decreased by 2-fold skin electrical resistance when compared to the standard application. Application of diclofenac-diethylamine 1.16% gel with rubbing tended to result in higher accumulation in the stripped skin vs. the superficial skin layers when applied without rubbing (P = 0.2). Conclusion These results suggest that rubbing may alter the superficial skin layer resulting in a transient faster initial diffusion of topically applied diclofenac through the stratum corneum into the deeper skin layer of the dermis to the tissue target. PMID:22720797

  12. Muscle Injury After Intramuscular Administration of Diclofenac: A Case Report Supported by Magnetic Resonance Imaging.

    PubMed

    Probst, Mareike; Kühn, Jens-Peter; Modeß, Christiane; Scheuch, Eberhard; Seidlitz, Anne; Hosten, Norbert; Siegmund, Werner; Weitschies, Werner

    2017-12-01

    Intramuscular injection of diclofenac is still frequently practiced, although there is ample evidence that the risk of local tissue intolerability is highly underestimated. The aim of this study was to evaluate local toxicity in a patient using magnetic resonance imaging. A patient who gave written informed consent received a medically indicated intramuscular administration of diclofenac 75 mg/2 mL. Simultaneously with magnetic resonance imaging of the depot, a clinical-chemical evaluation and quantification of diclofenac in plasma was performed. A manifold enhancement of the T2-weighted magnetic resonance signal was observed in a muscle area of approximately 60 mL volume, with maximum signal intensity 30 min after injection, the time of maximum diclofenac plasma exposure. Plasma creatine kinase activity was elevated approximately sixfold within 8 h and normalized within 1 week, whereas the magnetic resonance enhancement disappeared within 5 weeks. Interestingly, the patient did not complain about any clinical symptoms at the injection site. Asymptomatic tissue injury after intramuscular injection of diclofenac, caused by intramuscular dosing, can be reliably evaluated by magnetic resonance imaging and should be applied early during the development of parenteral dosage forms. Clinical Trials Registration Number: BB130/16 (Ethics Committee of the University Medicine Greifswald).

  13. Pentadecapeptide BPC 157 and its effects on a NSAID toxicity model: diclofenac-induced gastrointestinal, liver, and encephalopathy lesions.

    PubMed

    Ilic, Spomenko; Drmic, Domagoj; Franjic, Sandra; Kolenc, Danijela; Coric, Marijana; Brcic, Luka; Klicek, Robert; Radic, Bozo; Sever, Marko; Djuzel, Viktor; Filipovic, Marinko; Djakovic, Zeljko; Stambolija, Vasilije; Blagaic, Alenka Boban; Zoricic, Ivan; Gjurasin, Miroslav; Stupnisek, Mirjana; Romic, Zeljko; Zarkovic, Kamelija; Dzidic, Senka; Seiwerth, Sven; Sikiric, Predrag

    2011-03-14

    We attempted to fully antagonize the extensive toxicity caused by NSAIDs (using diclofenac as a prototype). Herein, we used the stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419), an anti-ulcer peptide shown to be efficient in inflammatory bowel disease clinical trials (PL 14736) and various wound treatments with no toxicity reported. This peptide was given to antagonize combined gastrointestinal, liver, and brain toxicity induced by diclofenac (12.5mg/kg intraperitoneally, once daily for 3 days) in rats. Already considered a drug that can reverse the toxic side effects of NSAIDs, BPC 157 (10 μg/kg, 10 ng/kg) was strongly effective throughout the entire experiment when given (i) intraperitoneally immediately after diclofenac or (ii) per-orally in drinking water (0.16 μg/mL, 0.16 ng/mL). Without BPC 157 treatment, at 3h following the last diclofenac challenge, we encountered a complex deleterious circuit of diclofenac toxicity characterized by severe gastric, intestinal and liver lesions, increased bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) serum values, increased liver weight, prolonged sedation/unconsciousness (after any diclofenac challenge) and finally hepatic encephalopathy (brain edema particularly located in the cerebral cortex and cerebellum, more in white than in gray matter, damaged red neurons, particularly in the cerebral cortex and cerebellar nuclei, Purkinje cells and less commonly in the hippocampal neurons). The very extensive antagonization of diclofenac toxicity achieved with BPC 157 (μg-/ng-regimen, intraperitoneally, per-orally) may encourage its further use as a therapy to counteract diclofenac- and other NSAID-induced toxicity. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Efficacy of gabapentin versus diclofenac in the treatment of chest pain and paresthesia in patients with sternotomy.

    PubMed

    Biyik, Ismail; Gülcüler, Metin; Karabiga, Murat; Ergene, Oktay; Tayyar, Nezih

    2009-10-01

    Chronic post-sternotomy chest pain and paresthesia (PCPP) are frequently seen and reduce the quality of life. We aimed to demonstrate the efficacy and safety of gabapentin compared with diclofenac in the treatment of PCPP and to elucidate the similarities of PCPP to neuropathic pain syndromes. The prospective, randomized, open-label, blinded end-point design of study was used. One hundred and ten patients having PCPP lasting three months or more were randomized to receive 800 mg/daily gabapentin (n=55) and 75 mg/daily diclofenac (n=55) for thirty days. All patients have undergone cardiac surgery and median sternotomy. The perception of pain or paresthesia was evaluated as 0--Normal (no pain or paresthesia), 1--Mild, 2--Moderate, 3--Severe at baseline and after thirty days of treatment. Recurrences were questioned after three months. Statistical analyses were performed using independent samples t, Chi-square, continuity correction, Fisher's exact, Mann Whitney U and Kruskal Wallis tests. In gabapentin group, mean pain and paresthesia scores regressed from 2.12+/- 0.76 to 0.54+/- 0.83 (p<0.001) and from 1.72+/- 0.74 to 0.49+/- 0.62 (p<0.001), respectively. Mean pain and paresthesia scores regressed in diclofenac group from 1.93+/- 0.8 to 1.0+/- 1.13 (p<0.001) and from 1.76+/- 0.74 to 1.24+/- 0.96 (p=0.002), respectively. Although, both gabapentin and diclofenac were found to be effective without obvious side effects in the treatment of PCPP (p<0.001), gabapentin was found to be superior to diclofenac (p=0.001 and p<0.001, respectively). Adverse effects were seen in 7% of patients on gabapentin and 4% of patients on diclofenac. Results also showed that symptomatic relief with gabapentin lasts longer than diclofenac (p<0.001). Both gabapentin and diclofenac are effective in the treatment of chronic PCPP, without obvious side effects. However, gabapentin is found to be superior to diclofenac and its effects sustain longer. The results show that there may be some

  15. Effects of water extract of Hibiscus sabdariffa, Linn (Malvaceae) 'Roselle' on excretion of a diclofenac formulation.

    PubMed

    Fakeye, T O; Adegoke, A O; Omoyeni, O C; Famakinde, A A

    2007-01-01

    The effect of beverages prepared from the dried calyx of the flowers of Hibiscus sabdariffa on the excretion of diclofenac was investigated using a controlled study in healthy human volunteers. A high pressure liquid chromatographic method was used to analyse the 8 h urine samples collected after the administration of diclofenac with 300 mL (equivalent to 8.18 mg anthocyanins) of the beverage administered daily for 3 days. An unpaired two-tailed t-test was used to analyse for significant difference observed in the amount of diclofenac excreted before and after administration of the beverage. There was a reduction in the amount of diclofenac excreted and the wide variability observed in the control with the water beverage of Hibiscus sabdariffa (p < 0.05). There is an increasing need to counsel patients against the use of plant beverages with drugs.

  16. Degradation of diclofenac sodium using combined processes based on hydrodynamic cavitation and heterogeneous photocatalysis.

    PubMed

    Bagal, Manisha V; Gogate, Parag R

    2014-05-01

    Diclofenac sodium, a widely detected pharmaceutical drug in wastewater samples, has been selected as a model pollutant for degradation using novel combined approach of hydrodynamic cavitation and heterogeneous photocatalysis. A slit venturi has been used as cavitating device in the hydrodynamic cavitation reactor. The effect of various operating parameters such as inlet fluid pressure (2-4 bar) and initial pH of the solution (4-7.5) on the extent of degradation have been studied. The maximum extent of degradation of diclofenac sodium was obtained at inlet fluid pressure of 3 bar and initial pH as 4 using hydrodynamic cavitation alone. The loadings of TiO2 and H2O2 have been optimised to maximise the extent of degradation of diclofenac sodium. Kinetic study revealed that the degradation of diclofenac sodium fitted first order kinetics over the selected range of operating protocols. It has been observed that combination of hydrodynamic cavitation with UV, UV/TiO2 and UV/TiO2/H2O2 results in enhanced extents of degradation as compared to the individual schemes. The maximum extent of degradation as 95% with 76% reduction in TOC has been observed using hydrodynamic cavitation in conjunction with UV/TiO2/H2O2 under the optimised operating conditions. The diclofenac sodium degradation byproducts have been identified using LC/MS analysis. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. A new approach to the compartmental analysis in pharmacokinetics: fractional time evolution of diclofenac.

    PubMed

    Popović, Jovan K; Atanacković, Milica T; Pilipović, Ana S; Rapaić, Milan R; Pilipović, Stevan; Atanacković, Teodor M

    2010-04-01

    This study presents a new two compartmental model and its application to the evaluation of diclofenac pharmacokinetics in a small number of healthy adults, during a bioequivalence trial. In the model the integer order derivatives are replaced by derivatives of real order often called fractional order derivatives. Physically that means that a history (memory) of a biological process, realized as a transfer from one compartment to another one with the mass balance conservation, is taken into account. This kind of investigations in pharmacokinetics is founded by Dokoumetzidis and Macheras through the one compartmental models while our contribution is the analysis of multi-dimensional compartmental models with the applications of the two compartmental model in evaluation of diclofenac pharmacokinetics. Two experiments were preformed with 12 healthy volunteers with two slow release 100 mg diclofenac tablet formulations. The agreement of the values predicted by the proposed model with the values obtained through experiments is shown to be good. Thus, pharmacokinetics of slow release diclofenac can be described well by a specific two compartmental model with fractional derivatives of the same order. Parameters in the model are determined by the least-squares method and the Particle Swarm Optimization (PSO) numerical procedure is used. The results show that the fractional order two compartmental model for diclofenac is superior in comparison to the classical two compartmental model. Actually this is true in general case since the classical one is a special case of the fractional one.

  18. Diclofenac in hyaluronic acid gel: an alternative treatment for actinic cheilitis

    PubMed Central

    LIMA, Giana da Silveira; da SILVA, Gabriela Ferrari; GOMES, Ana Paula Neutzling; de ARAÚJO, Lenita Maria Aver; SALUM, Fernanda Gonçalves

    2010-01-01

    Objective Actinic cheilitis (AC) is a precancerous lesion of the lip vermillion caused by prolonged exposure to ultraviolet light. The aim of this study was to evaluate the effect of 3% diclofenac in 2.5% hyaluronic acid gel in the treatment of AC. Methods Thirty-four patients with chronic AC were treated twice a day with topical diclofenac during a period of 30 to 180 days. The individuals were followed up every 15 days by means of clinical examination and digital photographic documentation. Results Of the 27 patients that completed the study, 12 (44%) showed complete remission of the whitish plaques and exfoliative areas, and 15 (56%) had partial remission of the clinical picture of cheilitis. The latter group was submitted to excision of the leukoplakic areas which diagnosis varied from mild to moderate epithelial dysplasia. Conclusion The results suggest a promising role for diclofenac in hyaluronic acid gel in the treatment of AC. This treatment has the advantages of not being invasive and showing few side effects. PMID:21085813

  19. Diclofenac patch for topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study

    PubMed Central

    Predel, H; Koll, R; Pabst, H; Dieter, R; Gallacchi, G; Giannetti, B; Bulitta, M; Heidecker, J; Mueller, E

    2004-01-01

    Objectives: To investigate the clinical efficacy and safety of a newly developed diclofenac patch in the topical treatment of blunt impact injuries. Methods: This was a randomised, placebo controlled, double blind, multicentre study in 120 patients with traumatic blunt soft tissue injury. Within 3 h of the injury participants of sport competitions and training camps were enrolled and treated twice daily with the diclofenac or a placebo patch over a period of 7 days. Patients were randomised (1:1) to two parallel groups. Tenderness produced by pressure was measured twice daily during the first 3 days after enrolment as well as at day 7. Tenderness was defined as the amount of pressure (measured by a calibrated caliper at the centre of the injury) that first produced a pain reaction as reported by the patient. Results: The primary efficacy variable was the area under the curve for tenderness over the first 3 days. The diclofenac patch was significantly more effective than placebo (p<0.0001). The treatment effect was 64.7 kp h/cm2 (95% confidence interval 48.7 to 80.9) between diclofenac and placebo patches. These results were supported by all secondary efficacy variables. The diclofenac patch produced rapid pain relief as reflected by the time to reach resolution of pain at the injured site which was significantly shorter compared to placebo (p<0.0001). The diclofenac patch was well tolerated. The most frequently observed adverse events were local cutaneous adverse reactions (pruritus, rash) of minor severity occurring with the same frequency as in the placebo group. Conclusions: A newly developed diclofenac patch is effective and safe for the treatment of blunt impact injuries. PMID:15155436

  20. Efficacy of Arnica montana D4 for healing of wounds after Hallux valgus surgery compared to diclofenac.

    PubMed

    Karow, Jens-Hagen; Abt, Hans-Peter; Fröhling, Markus; Ackermann, Hanns

    2008-01-01

    This study was undertaken to answer the question: "Is Arnica D4 as efficacious as diclofenac in relation to symptoms and wound healing after foot surgery?" In this randomized double-blinded, parallel-group study (GCP-standard), the efficacy of Arnica D4 10 pillules (taken orally, 3 times per day) and diclofenac sodium, 50 mg (taken orally, 3 times per day) were investigated for equivalence in 88 patients 4 days after hallux valgus surgery. Outcome parameters were (1) postoperative irritation, (2) patient mobility, (3) rated pain, and (4) use of analgesics. The hierarchic equivalence test based on one-sided Wilcoxon-Mann-Whitney-U confidence intervals (CIs) was used. Equivalence was perceived, when the lower margin of the 95% CI was > 0.36 corresponding to a range of equivalence of 1/2 standard deviation. Arnica D4 and diclofenac were equivalent for wound irritation (lower margin of the 95% CI on day 4: 0.4729 for rubor; 0.3674 for swelling; 0.4106 for calor) and patient mobility (0.4726). A descriptive analysis showed the superiority of Arnica D4 with respect to patient mobility (p = 0.045). With respect to pain, Arnica D4 was inferior to diclofenac (lower margin of the 95% CI 0.026). No significant differences were found regarding the use of additional analgesics during the 4 postoperative days (Dipidolor, Janssen-Cilag, Neuss, Germany; p = 0.54; Tramal, Grünenthal, Aachen, Germany; p = 0.1; and Novalgin, AVENTIS-Pharma, Bad Soden, Germany; p = 0.1). Arnica D4 was significantly better tolerated than diclofenac (p = 0.049). Nine (9) patients (20.45%) of the diclofenac group and 2 (4.5%) of the Arnica D4 group reported intolerance. There was no disturbance in wound healing in any of the patients. Arnica D4 is 60% cheaper than diclofenac. After foot operations, Arnica D4 can be used instead of diclofenac to reduce wound irritation.

  1. A Review of Chronic Musculoskeletal Pain: Central and Peripheral Effects of Diclofenac.

    PubMed

    Atzeni, Fabiola; Masala, Ignazio Francesco; Sarzi-Puttini, Piercarlo

    2018-06-05

    Diclofenac is widely used to manage chronic inflammatory and degenerative joint diseases such as osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, and extra-articular rheumatism. Its various mechanisms of action make it particularly effective in treating nociceptive pain, but it is also an alternative for treating spinal and chronic central pain. Osteoarthritis and rheumatoid arthritis are the most frequently encountered arthritic conditions in adults. The management of nociceptive pain requires a sequential hierarchical approach, with the initial NSAID treatment being characterized by the replacement of one drug with another, or complete discontinuation usually because of insufficient pain control. OA- and RA-related pain is complex and multifactorial, and due to physiological interactions between the signaling of the central and peripheral nervous systems. The mechanisms of action of diclofenac make it particularly effective in treating both nociceptive pain and chronic central pain. This review underlines the mechanisms of diclofenac involved in chronic and acute joint pain, the most relevant adverse events.

  2. Comparison of skin permeability for three diclofenac topical formulations: an in vitro study.

    PubMed

    Folzer, E; Gonzalez, D; Singh, R; Derendorf, H

    2014-01-01

    Diclofenac is a hydrophilic non-steroidal anti-inflammatory drug (NSAID) widely used in humans and animals. There are limited published studies evaluating diclofenac's skin permeation following topical administration. The aim of our study was to evaluate and compare the in vitro permeation of three different diclofenac-containing formulations (patch, gel, solution) over 24 hours. These formulations were applied (n = 6 per formulation) to pig skin sandwiched between the two chambers in a static Franz diffusion cell and aliquots from the receptor medium were sampled at pre-defined time points. An HPLC method with UV detection was developed and validated with the aim of characterizing the transepidermal penetration in the in vitro system. Using this assay to determine the permeation parameters, results at 24 hours showed that the Flector patch released the highest drug amount (54.6%), whereas a lower drug amount was delivered with the Voltaren Emulgel (38.2%) and the solution (34.4%). The commercial gel showed the highest flux (39.9 +/- 0.9 microg/cm2/h) and the shortest lag-time (1.97 +/- 0.02 h). Based on these in vitro results using pig skin, the transdermal patch resulted in a long-lasting controlled release of diclofenac, while the gel had the shortest lag-time.

  3. Role of diclofenac sodium and paracetamol on colonic anastomosis: An experimental rodent model.

    PubMed

    Gulcicek, Osman Bilgin; Solmaz, Ali; Yigitbas, Hakan; Ercetin, Candas; Yavuz, Erkan; Ozdogan, Kamil; Biricik, Aytac; Akkalp, Asli Kahraman; Uzun, Hafize; Kutnu, Muge; Celebi, Fatih; Celik, Atilla

    2018-05-01

    Despite many advances in surgery and technology, colonic anastomosis remains a challenge after colonic resection. The purpose of this study is to compare the safety of using diclofenac sodium and paracetamol for analgesia in colonic anastomosis on rats. Wistar-Hannover rats were randomly allocated to four groups: Group 1, sham-operated group; Group 2, control group; Group 3, diclofenac sodium group; Group 4, paracetamol group. After laparotomy, the left colon was transected and a single-layer anastomosis was made with 5/0 vicryl in Groups 2, 3, and 4. Only laparotomy was performed in Group 1. After anastomosis, we administered saline to Group 2, diclofenac sodium to Group 3, and paracetamol to Group 4 for 7 days. Then, all animals were decapitated. The anastomotic region was resected, and bursting pressure was measured. Then, the specimen was sent to the laboratory for histological examination and hydroxyproline analysis. Bursting pressure and hydroxyproline level were significantly higher in the paracetamol group (p<0.05). When we looked at the fibrosis levels of these groups, it was also higher in paracetamol group. Bursting pressure, hydroxyproline levels, and fibrosis levels indicate that the perioperative use of paracetamol for analgesia when undergoing colonic anastomosis is safer than diclofenac sodium. Copyright © 2017. Published by Elsevier Taiwan.

  4. Diclofenac and 2‐anilinophenylacetate degradation by combined activity of biogenic manganese oxides and silver

    PubMed Central

    Meerburg, Francis; Hennebel, Tom; Vanhaecke, Lynn; Verstraete, Willy; Boon, Nico

    2012-01-01

    Summary The occurrence of a range of recalcitrant organic micropollutants in our aquatic environment has led to the development of various tertiary wastewater treatment methods. In this study, biogenic manganese oxides (Bio‐MnOx), biogenic silver nanoparticles (Bio‐Ag0) and ionic silver were used for the oxidative removal of the frequently encountered drug diclofenac and its dechlorinated form, 2‐anilinophenylacetate (APA). Diclofenac was rapidly degraded during ongoing manganese oxidation by Pseudomonas putida MnB6. Furthermore, whereas preoxidized Bio‐MnOx, Bio‐Ag0 and Ag+ separately did not show any removal capacity for diclofenac, an enhanced removal occurred when Bio‐MnOx and silver species were combined. Similar results were obtained for APA. Finally, a slow removal of diclofenac but more rapid APA degradation was observed when silver was added to manganese‐free P. putida biomass. Combining these results, three mechanisms of diclofenac and APA removal could be distinguished: (i) a co‐metabolic removal during active Mn2+ oxidation by P. putida; (ii) a synergistic interaction between preoxidized Bio‐MnOx and silver species; and (iii) a (bio)chemical process by biomass enriched with silver catalysts. This paper demonstrates the use of P. putida for water treatment purposes and is the first report of the application of silver combined with biogenic manganese for the removal of organic water contaminants. PMID:22221449

  5. The Distinction of Hot Herbal Compress, Hot Compress, and Topical Diclofenac as Myofascial Pain Syndrome Treatment.

    PubMed

    Boonruab, Jurairat; Nimpitakpong, Netraya; Damjuti, Watchara

    2018-01-01

    This randomized controlled trial aimed to investigate the distinctness after treatment among hot herbal compress, hot compress, and topical diclofenac. The registrants were equally divided into groups and received the different treatments including hot herbal compress, hot compress, and topical diclofenac group, which served as the control group. After treatment courses, Visual Analog Scale and 36-Item Short Form Health survey were, respectively, used to establish the level of pain intensity and quality of life. In addition, cervical range of motion and pressure pain threshold were also examined to identify the motional effects. All treatments showed significantly decreased level of pain intensity and increased cervical range of motion, while the intervention groups exhibited extraordinary capability compared with the topical diclofenac group in pressure pain threshold and quality of life. In summary, hot herbal compress holds promise to be an efficacious treatment parallel to hot compress and topical diclofenac.

  6. The Effectiveness of the Rectal Administration of Low-dose Diclofenac for the Prevention of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis.

    PubMed

    Okuno, Mitsuru; Shiroko, Junko; Taguchi, Daisuke; Yamaguchi, Kimihiro; Takada, Jun; Imai, Susumu; Sato, Hiroyuki; Thanabashi, Shinobu

    2018-03-30

    Objective A 50-100-mg rectal dose of nonsteroidal anti-inflammatory drugs (NSAIDs; diclofenac or indomethacin) has been shown to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, this is higher than the recommended 25-mg dose that is commonly administered to Japanese patients. The objective of this study was to evaluate the safety and efficacy of 25-mg rectal dose of diclofenac in preventing PEP. Methods Between January 2016 and March 2017, a total of 147 patients underwent ERCP with or without the rectal administration of diclofenac (25 mg) 20 min before the procedure. A retrospective analysis was conducted to evaluate the efficacy and safety of this dose in preventing PEP. Results Thirteen patients (8.8%) developed PEP: 3 patients (4.1%) in the diclofenac group and 10 (13.7%) in the control group (p=0.0460). After ERCP, there were no cases of gastrointestinal hemorrhage, ulceration, acute renal failure, or death. A multivariate logistic regression analysis revealed that the non-administration of rectal diclofenac was a risk factor for PEP (odds ratio=3.530; 95% confidence interval=1.017-16.35; p=0.0468). Conclusions A 25-mg rectal dose of diclofenac might prevent PEP.

  7. Stir bar sorptive extraction of diclofenac from liquid formulations: a proof of concept study.

    PubMed

    Kole, Prashant Laxman; Millership, Jeff; McElnay, James C

    2011-03-25

    A new stir bar sorptive extraction (SBSE) technique coupled with HPLC-UV method for quantification of diclofenac in pharmaceutical formulations has been developed and validated as a proof of concept study. Commercially available polydimethylsiloxane stir bars (Twister™) were used for method development and SBSE extraction (pH, phase ratio, stirring speed, temperature, ionic strength and time) and liquid desorption (solvents, desorption method, stirring time etc) procedures were optimised. The method was validated as per ICH guidelines and was successfully applied for the estimation of diclofenac from three liquid formulations viz. Voltarol(®) Optha single dose eye drops, Voltarol(®) Ophtha multidose eye drops and Voltarol(®) ampoules. The developed method was found to be linear (r=0.9999) over 100-2000ng/ml concentration range with acceptable accuracy and precision (tested over three QC concentrations). The SBSE extraction recovery of the diclofenac was found to be 70% and the LOD and LOQ of the validated method were found to be 16.06 and 48.68ng/ml, respectively. Furthermore, a forced degradation study of a diclofenac formulation leading to the formation of structurally similar cyclic impurity (indolinone) was carried out. The developed extraction method showed comparable results to that of the reference method, i.e. method was capable of selectively extracting the indolinone and diclofenac from the liquid matrix. Data on inter and intra stir bar accuracy and precision further confirmed robustness of the method, supporting the multiple re-use of the stir bars. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Using photodynamic therapy to estimate effectiveness of innovative combined diclofenac and tazaroten therapy of disseminated actinic keratosis.

    PubMed

    Osiecka, Beata J; Jurczyszyn, Kamil; Nockowski, Piotr; Lipinski, Artur; Sieja, Agnieszka; Ziółkowski, Piotr

    2015-01-01

    Early diagnosis and therapy of precancerous lesions and malignant tumors belong to the most challenging tasks in modern medicine. Photodynamic diagnosis can help diagnose both precancerous lesions and early carcinoma. Actinic keratosis (AK) is the most common precancerous lesion of the skin. The available data show a high effectiveness of diclofenac in treating multifocal AK. We report a case of a 52-year-old woman who complained of multiple disseminated AK lesions predominantly on the lower limbs and trunk with a significant exacerbation within the last 6 months. Due to the spreading of disease and a high number of AK foci, as well as technical problems with visiting the hospital (PDT Laboratory), photodynamic therapy was not applied. The patient was treated for 2 months with a combination of local administration of 3% diclofenac and 0.1% tazaroten and 3% diclofenac only as a half side (left-right) comparison. The effects of therapy were later clinically evaluated and verified by means of photodynamic diagnosis (PDD) directly after therapy and at a follow-up examination 3 months later. The evaluation of treatment was blinded. Treatment with diclofenac only on the right side of the body resulted in clearing of 55% of all treated lesions, which increased to 60% three months after finishing therapy. On the left side of the body, where combined therapy (diclofenac 2 times daily on uneven dates and diclofenac once a day + tazaroten once a day on even dates) was used, 77.5% pathologic lesions disappeared, but this did not increase at follow up. The treatment of multifocal, disseminated AK is a difficult task and also burdensome for the patient due to side effects like scarring or burning and itching which occur during most therapies. Combined therapy with diclofenac and tazaroten supported by PDD may improve the effects of routine treatment of AK.

  9. Photo-fenton degradation of diclofenac: identification of main intermediates and degradation pathway.

    PubMed

    Pérez-Estrada, Leónidas A; Malato, Sixto; Gernjak, Wolfgang; Agüera, Ana; Thurman, E Michael; Ferrer, Imma; Fernández-Alba, Amadeo R

    2005-11-01

    In recent years, the presence of pharmaceuticals in the aquatic environment has been of growing interest. These new contaminants are important because many of them are not degraded under the typical biological treatments applied in the wastewater treatment plants and represent a continuous input into the environment. Thus, compounds such as diclofenac are present in surface waters in all Europe and a crucial need for more enhanced technologies that can reduce its presence in the environment has become evident. In this sense, advanced oxidation processes (AOPs) represent a good choice for the treatment of hazardous nonbiodegradable pollutants. This work deals with the solar photodegradation of diclofenac, an antiinflammatory drug, in aqueous solutions by photo-Fenton reaction. A pilot-scale facility using a compound parabolic collector (CPC) reactor was used for this study. Results obtained show rapid and complete oxidation of diclofenac after 60 min, and total mineralization (disappearance of dissolved organic carbon, DOC) after 100 min of exposure to sunlight. Although diclofenac precipitates during the process at low pH, its degradation takes place in the homogeneous phase governed by a precipitation-redissolution-degradation process. Establishment of the reaction pathway was made possible by a thorough analysis of the reaction mixture identifying the main intermediate products generated. Gas chromatography-mass spectrometry (GC/ MS) and liquid chromatography coupled with time-of-flight mass spectrometry (LC/TOF-MS) were used to identify 18 intermediates, in two tentative degradation routes. The main one was based on the initial hydroxylation of the phenylacetic acid moiety in the C-4 position and subsequent formation of a quinone imine derivative that was the starting point for further multistep degradation involving hydroxylation, decarboxylation, and oxidation reactions. An alternative route was based on the transient preservation of the biphenyl amino moiety

  10. A RP-HPLC method for quantification of diclofenac sodium released from biological macromolecules.

    PubMed

    Bhattacharya, Shiv Sankar; Banerjee, Subham; Ghosh, Ashoke Kumar; Chattopadhyay, Pronobesh; Verma, Anurag; Ghosh, Amitava

    2013-07-01

    Interpenetrating network (IPN) microbeads of sodium carboxymethyl locust bean gum (SCMLBG) and sodium carboxymethyl cellulose (SCMC) containing diclofenac sodium (DS), a nonsteroidal anti-inflammatory drug, were prepared by single water-in-water (w/w) emulsion gelation process using AlCl3 as cross-linking agent in a complete aqueous environment. Pharmacokinetic study of these IPN microbeads was then carried out by a simple and feasible high-performance liquid chromatographic method with UV detection which was developed and validated for the quantification of diclofenac sodium in rabbit plasma. The chromatographic separation was carried out in a Hypersil BDS, C18 column (250 mm × 4.6 mm; 5 m). The mobile phase was a mixture of acetonitrile and methanol (70:30, v/v) at a flow rate of 1.0 ml/min. The UV detection was set at 276 nm. The extraction recovery of diclofenac sodium in plasma of three quality control (QC) samples was ranged from 81.52% to 95.29%. The calibration curve was linear in the concentration range of 20-1000 ng/ml with the correlation coefficient (r(2)) above 0.9951. The method was specific and sensitive with the limit of quantification of 20 ng/ml. In stability tests, diclofenac sodium in rabbit plasma was stable during storage and assay procedure. Copyright © 2013. Published by Elsevier B.V.

  11. Diclofenac pretreatment modulates exercise-induced inflammation in skeletal muscle of rats through the TLR4/NF-κB pathway.

    PubMed

    Barcelos, Rômulo Pillon; Bresciani, Guilherme; Cuevas, Maria José; Martínez-Flórez, Susana; Soares, Félix Alexandre Antunes; González-Gallego, Javier

    2017-07-01

    Nonsteroidal anti-inflammatory drugs, such as diclofenac, are widely used to treat inflammation and pain in several conditions, including sports injuries. This study analyzes the influence of diclofenac on the toll-like receptor-nuclear factor kappa B (TLR-NF-κB) pathway in skeletal muscle of rats submitted to acute eccentric exercise. Twenty male Wistar rats were divided into 4 groups: control-saline, control-diclofenac, exercise-saline, and exercise-diclofenac. Diclofenac or saline were administered for 7 days prior to an acute eccentric exercise bout. The inflammatory status was evaluated through mRNA levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), IL-1β, and tumor necrosis factor alpha (TNF-α), and protein content of COX-2, IL-6, and TNF-α in vastus lateralis muscle. Data obtained showed that a single bout of eccentric exercise significantly increased COX-2 gene expression. Similarly, mRNA expression and protein content of other inflammation-related genes also increased after the acute exercise. However, these effects were attenuated in the exercise + diclofenac group. TLR4, myeloid differentiation primary response gene 88 (MyD88), and p65 were also upregulated after the acute eccentric bout and the effect was blunted by the anti-inflammatory drug. These findings suggest that pretreatment with diclofenac may represent an effective tool to ameliorate the pro-inflammatory status induced by acute exercise in rat skeletal muscle possibly through an attenuation of the TLR4-NF-κB signaling pathway.

  12. Phase IIB Randomized Study of Topical Difluoromethylornithine and Topical Diclofenac on Sun-Damaged Skin of the Forearm.

    PubMed

    Jeter, Joanne M; Curiel-Lewandrowski, Clara; Stratton, Steven P; Myrdal, Paul B; Warneke, James A; Einspahr, Janine G; Bartels, Hubert G; Yozwiak, Michael; Bermudez, Yira; Hu, Chengcheng; Bartels, Peter; Alberts, David S

    2016-02-01

    Prevention of nonmelanoma skin cancers remains a health priority due to high costs associated with this disease. Diclofenac and difluoromethylornithine (DFMO) have demonstrated chemopreventive efficacy for cutaneous squamous cell carcinomas. We designed a randomized study of the combination of DFMO and diclofenac in the treatment of sun-damaged skin. Individuals with visible cutaneous sun damage were eligible. Subjects were randomized to one of the three groups: topical DFMO applied twice daily, topical diclofenac applied daily, or DFMO plus diclofenac. The treatment was limited to an area on the left forearm, and the duration of use was 90 days. We hypothesized that combination therapy would have increased efficacy compared with single-agent therapy. The primary outcome was change in karyometric average nuclear abnormality (ANA) in the treated skin. Individuals assessing the biomarkers were blinded regarding the treatment for each subject. A total of 156 subjects were randomized; 144 had baseline and end-of-study biopsies, and 136 subjects completed the study. The ANA unexpectedly increased for all groups, with higher values correlating with clinical cutaneous inflammation. Nearly all of the adverse events were local cutaneous effects. One subject had cutaneous toxicity that required treatment discontinuation. Significantly more adverse events were seen in the groups taking diclofenac. Overall, the study indicated that the addition of topical DFMO to topical diclofenac did not enhance its activity. Both agents caused inflammation on a cellular and clinical level, which may have confounded the measurement of chemopreventive effects. More significant effects may be observed in subjects with greater baseline cutaneous damage. ©2015 American Association for Cancer Research.

  13. Diclofenac toxicity in Gyps vulture is associated with decreased uric acid excretion and not renal portal vasoconstriction.

    PubMed

    Naidoo, V; Swan, G E

    2009-04-01

    Diclofenac (DF), a non-steroidal anti-inflammatory drug (NSAID), is largely regarded as one of the most devastating environmental toxicant in recent times, after accidental exposure via their food-chain lead to massive mortalities in three vulture species on the Asian subcontinent. Although the use of diclofenac was recently banned on the Indian subcontinent, following the favourable safety profile of meloxicam, its mechanism of toxicity remains unknown. In an attempt to establish this mechanism, we test three hypotheses using models established from either the domestic chicken (Gallus domesticus) or the African White-backed vulture (Gyps africanus). We demonstrate that both DF and meloxicam are toxic to renal tubular epithelial (RTE) cells following 12 h of exposure, due to an increase in production of reactive oxygen species (ROS), which could be temporarily ameliorated by pre-incubation with uric acid (UA). When cultures were incubated with either drug for only 2 h, meloxicam showed no toxicity in contrast to diclofenac. In both cases no increase in ROS production was evident. In addition, diclofenac decreased the transport of uric acid, by interfering with the p-amino-hippuric acid (PAH) channel. We conclude that vulture susceptibility to diclofenac results from a combination of an increased ROS, interference with UA transport and the duration of exposure.

  14. Bioavailability and biochemical effects of diclofenac sodium 0.1% ophthalmic solution in the domestic chicken (Gallus gallus domesticus).

    PubMed

    Griggs, Angela N; Yaw, Taylor J; Haynes, Joseph S; Ben-Shlomo, Gil; Tofflemire, Kyle L; Allbaugh, Rachel A

    2017-03-01

    To determine if topical ophthalmic diclofenac sodium 0.1% solution alters renal parameters in the domestic chicken, and to determine if the drug is detectable in plasma after topical ophthalmic administration. Thirty healthy domestic chickens. Over 7 days, six birds were treated unilaterally with one drop of artificial tear solution (group 1), 12 birds were treated unilaterally (group 2) and 12 bilaterally (group 3) with diclofenac sodium 0.1% ophthalmic solution. Treatments were provided every 12 h in all groups. Pre- and post-treatment plasma samples from all birds were evaluated for changes in albumin, total protein, and uric acid. Post-treatment samples of all birds, collected 15 min post-administration, were analyzed by high-performance liquid chromatography with mass spectrometry for diclofenac sodium detection. A randomly selected renal sample from each group was submitted for histopathologic review. Changes in pre- and post-treatment plasma albumin were significant (P < 0.05) in groups 2 and 3, but not for group 1. Pre- and post-treatment changes in total protein and uric acid were not significant for any group. Diclofenac sodium was not detectable (limit of detection = 0.10 ng/mL) in plasma samples from birds in group 1. Post-treatment concentration of diclofenac in group 3 was statistically greater than group 2 (P = 0.0008). Histopathologic changes did not identify diclofenac-induced acute renal tubular necrosis. Ophthalmic diclofenac sodium 0.1% administered topically every 12 h in one or both eyes for 7 days is detectable in systemic circulation in the domestic chicken, but does not cause overt significant changes in plasma uric acid or total protein. © 2016 American College of Veterinary Ophthalmologists.

  15. Ultrastructural effects of pharmaceuticals (carbamazepine, clofibric acid, metoprolol, diclofenac) in rainbow trout (Oncorhynchus mykiss) and common carp (Cyprinus carpio).

    PubMed

    Triebskorn, R; Casper, H; Scheil, V; Schwaiger, J

    2007-02-01

    In order to assess potential effects of human pharmaceuticals in aquatic wildlife, laboratory experiments were conducted with carbamazepine, clofibric acid, metoprolol, and diclofenac using fish as test organisms. For each substance, at least one environmentally relevant concentration was tested. In liver, kidney, and gills of trout and carp exposed to carbamazepine, clofibric acid, and metoprolol, ultrastructural effects were qualitatively described and semi-quantitatively assessed. The obtained assessment values were compared with previously published data for diclofenac-induced effects in rainbow trout tissues. Quantitative analyses of protein accumulated in kidneys of diclofenac-exposed trout corroborated previously published data which indicated that diclofenac induced a severe glomerulonephritis resulting in a hyaline droplet degeneration of proximal kidney tubules. The investigations provided information on the general health status of the pharmaceutical-exposed fish, and allowed a differential diagnosis of harmful effects caused by these human pharmaceuticals in non-target species. For the different cytological effects observed, lowest observed effect concentration (LOECs) for at least three of the test substances (diclofenac, carbamazepine, metoprolol) were in the range of environmentally relevant concentrations (1 microg/L).

  16. Comparison of the effects of chronic intra-articular administration of tenoxicam, diclofenac, and methylprednisolone in healthy rats.

    PubMed

    Orak, Mehmet Müfit; Ak, Dursun; Midi, Ahmet; Laçin, Berna; Purisa, Sevim; Bulut, Güven

    2015-01-01

    Lyophilized drug manufacturing and intra-articular (IA) applications have increased to address gastrointestinal side effects resulting from chronic treatment with non-steroidal anti-inflammatory drugs (NSAIDs) for degenerative joint disease. Accordingly, we histologically examined joint and stomach tissues from rats to determine and compare the effects of long-term treatment with an IA corticosteroid (methylprednisolone acetate), lyophilized NSAID (tenoxicam), and non-lyophilized NSAID (diclofenac) following application to the knee joint. One hundred Wistar albino rats were divided into 4 groups of 25 rats: control, methylprednisolone, tenoxicam, and diclofenac. Ten IA injections were administered at 1-week intervals. Rats were sacrificed at 48 h and 1, 2, 4, and 8 weeks after the tenth injection. Histomorphologically, knee joint samples were examined for osteoarthritic changes and stomach tissue samples for gastric changes. Unlike methylprednisolone, diclofenac and tenoxicam caused increased fibrosis and fibroblast production; furthermore, chronic methylprednisolone use had no negative effects on the synovium or cartilage. Chronic tenoxicam and diclofenac use affects joints more negatively than chronic steroid treatment.

  17. Immunogenomics reveal molecular circuits of diclofenac induced liver injury in mice

    PubMed Central

    Lee, Eun-Hee; Oh, Jung-Hwa; Selvaraj, Saravanakumar; Park, Se-Myo; Choi, Mi-Sun; Spanel, Reinhard

    2016-01-01

    Diclofenac is a non-steroidal anti-inflammatory drug and its use can be associated with severe adverse reactions, notably myocardial infarction, stroke and drug-induced liver injury (DILI). In pursue of immune-mediated DILI mechanisms an immunogenomic study was carried out. Diclofenac treatment of mice at 30 mg/kg for 3 days caused significant serum ALT and AST elevations, hepatomegaly and degenerative changes including hepatic glycogen depletion, hydropic swelling, cholesterolosis and eosinophilic hepatocytes with one animal presenting subsegmental infarction due to portal vein thrombosis. Furthermore, portal/periportal induction of the rate limiting enzyme in ammonia detoxification, i.e. carbamoyl phosphate synthetase 1 was observed. The performed microarray studies informed on > 600 differential expressed genes of which 35, 37 and 50 coded for inflammation, 51, 44 and 61 for immune and 116, 129 and 169 for stress response, respectively after single and repeated dosing for 3 and 14 days. Bioinformatic analysis defined molecular circuits of hepatic inflammation with the growth hormone (Ghr)− and leptin receptor, the protein-tyrosine-phosphatase, selectin and the suppressor-of-cytokine-signaling (Socs) to function as key nodes in gene regulatory networks. Western blotting confirmed induction of fibronectin and M-CSF to hallmark tissue repair and differentiation of monocytes and macrophages. Transcript expression of the macrophage receptor with collagenous structure increased > 7-fold and immunohistochemistry of CD68 evidenced activation of tissue-resident macrophages. Importantly, diclofenac treatment prompted strong expression of phosphorylated Stat3 amongst individual animals and the associated 8- and 4-fold Soc3 and Il-6 induction reinforced Ghr degradation as evidenced by immunoblotting. Moreover, immunohistochemistry confirmed regulation of master regulatory proteins of diclofenac treated mice to suggest complex pro-and anti-inflammatory reactions in immune

  18. HPLC detection of plasma concentrations of diclofenac in human volunteers administered with povidone-ethylcellulose-based experimental transdermal matrix-type patches.

    PubMed

    Mukherjee, B; Mahapatra, S; Das, S; Roy, G; Dey, S

    2006-06-01

    By developing a high-performance liquid chromatography (HPLC) method, we estimated the blood concentrations of diclofenac in human volunteers administered with the transdermal patches prepared with povidone-ethylcellulose and oral diclofenac tablets. Drug-excipient interaction studies were done using the FTIR technique. The external morphology of the prepared patch before and after application to human skin was analyzed with scanning electron microscopy. FTIR studies revealed that there was no predominant interaction between the drug and polymers. In vivo studies revealed that the average concentrations of drug in plasma were 376, 1562, 2953, 2902, 2864, and 2948 ng/ml after 2, 4, 8, 24, 30, and 48 h from patches each containing 50 mg of diclofenac diethylamine, respectively, and the mean concentrations of drug in plasma after the oral administration of marketed tablet containing 50 mg diclofenac sodium were 383.7, 2569, 3693.5, 162.5, and 55.3 ng/ml at 2, 4, 8, 24, and 30 h after oral administration. Values of Cmax were 3693.5 after oral administration and 2953.8 ng/ml in the case of transdermal application. From this study, we have achieved the sustained blood level of diclofenac from the experimental patches along with an analytical method based on HPLC to determine the diclofenac blood level. Copyright 2006 Prous Science.

  19. Effects of ibuprofen, diclofenac and paracetamol on hatch and motor behavior in developing zebrafish (Danio rerio).

    PubMed

    Xia, Liang; Zheng, Liang; Zhou, Jun Liang

    2017-09-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) which are widely used as pain relief medicines are causing increasing environmental concern due to their incomplete removal in wastewater treatment plant and potential toxicity on endocrine, kidney and reproduction in teleost fish. This study focused on the effects of widely used ibuprofen, diclofenac and paracetamol on the hatch and motor ability of early-stage zebrafish, by exposing embryos to the target chemicals at 5, 50 and 500 μg/L starting from 6 h postfertilization (hpf). A significant reduction in hatch rate at 55 hpf was caused by both ibuprofen (-63%) and diclofenac (-58%) at 500 μg/L. Exposure to high concentration of ibuprofen significantly decreased the spontaneous movement by 25%, and reduced the free swimming distance, duration and speed under dark condition by 41%, 29% and 30%, respectively. High concentration of diclofenac also caused 23% decrease in spontaneous movement, and reduced the swimming distance as well as active duration by 17% and 13% under light stimulation. In comparison, the exposure to paracetamol did not cause any notable effect. Among neuron related genes tested, the expression of neurog1 was down-regulated from ibuprofen and diclofenac exposure by 19% and 26%, while the expression of neurod1 was up-regulated only by ibuprofen (31%). These findings indicated that ibuprofen and diclofenac significantly affected embryo locomotivity and were potentially neurotoxic, thus posing threats to zebrafish development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Physicochemical characterization and in vivo evaluation of poloxamer-based solid suppository containing diclofenac sodium in rats.

    PubMed

    Yong, Chul Soon; Oh, Yu-Kyoung; Kim, Yong-Il; Kim, Jong Oh; Yoo, Bong-Kyu; Rhee, Jong-Dal; Lee, Kang Choon; Kim, Dae-Duk; Park, Young-Joon; Kim, Chong-Kook; Choi, Han-Gon

    2005-09-14

    To develop a poloxamer-based solid suppository with poloxamer mixtures, the melting point of various formulations composed of poloxamer 124 (P 124) and poloxamer 188 (P 188) were investigated. The dissolution and pharmacokinetic study of diclofenac sodium delivered by the poloxamer-based suppository were performed. Furthermore, the identification test in the rectum and morphology test of rectal tissues were carried out after its rectal administration in rats. The poloxamer mixtures composed of P 124 and P 188 were homogeneous phases. Very small amounts of P 188 affected the melting point of poloxamer mixtures. In particular, the poloxamer mixture [P 124/P 188 (97/3%)] with the melting point of about 32 degrees C was a solid form at room temperature and instantly melted at physiological temperature. Very small amounts of P 188 hardly affected the dissolution rates of diclofenac sodium from the suppository. Dissolution mechanism analysis showed the dissolution of diclofenac sodium was proportional to the time. The poloxamer-based suppository gave significantly higher initial plasma concentrations and faster T(max) of diclofenac sodium than did conventional PEG-based suppository, indicating that the drug from poloxamer-based suppository could be absorbed faster than that from PEG-based one in rats. It retained in the rectum for at least 4 h and could not irritate or damage the rectal tissues of rats. Thus, the poloxamer-based solid suppository with P 124 and P 188 was a mucoadhesive, safe and effective rectal dosage form for diclofenac sodium.

  1. Comparison of rectal indomethacin, diclofenac, and naproxen for the prevention of post endoscopic retrograde cholangiopancreatography pancreatitis.

    PubMed

    Mohammad Alizadeh, Amir H; Abbasinazari, Mohammad; Hatami, Behzad; Abdi, Saeed; Ahmadpour, Forozan; Dabir, Shideh; Nematollahi, Aida; Fatehi, Samira; Pourhoseingholi, Mohammad A

    2017-03-01

    NSAIDs are commonly utilized for the prevention of post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). However, not much is known about the most effective drug in preventing this complication. This study aims to clarify which drug (indomethacin, diclofenac, or naproxen) is most effective for the prevention of post endoscopic retrograde cholangiopancreatography (ERCP). In a double-blind, randomized study, patients received a single rectal dose of one of the three drugs 30 min before undergoing ERCP: diclofenac (100 mg), indomethacin (100 mg), or naproxen (500 mg). The primary outcome measured was the development of pancreatitis. The levels of serum amylase, lipase, lipoxin A4, and resolvin E1 were measured before ERCP, and at 24 h after the procedure. Three hundred and seventy-two patients completed the study. The overall incidence of PEP was 8.6%, which occurred in five of the 124 (4%) patients who received diclofenac, seven of the 122 (5.8%) patients who received indomethacin, and 20 of the 126 (15.9%) patients who received naproxen. There were no significant differences in amylase and lipase levels among the three groups (P=0.183 and 0.597, respectively). Unlike patients in the naproxen group, patients in the diclofenac and indomethacin groups showed a significant increase in lipoxin A4 and resolvin E1 (P=0.001 and 0.02, respectively). Diclofenac and indomethacin patient groups had a lower incidence of PEP than the naproxen group.

  2. In vitro permeation of diclofenac salts from lyotropic liquid crystalline systems.

    PubMed

    Yariv, Doron; Efrat, Rivka; Libster, Dima; Aserin, Abraham; Garti, Nissim

    2010-07-01

    In this paper we examined feasible correlations between the structure of different lyotropic mesophases and transdermal administration of three diclofenac derivatives with varying degrees of kosmotropic or chaotropic properties, solubilized within the mesophases. It was found that the most chaotropic derivative of diclofenac diethyl amine (DEA-DFC) interacted with the polar heads of glycerol monooleate (GMO), thus expanding the water-lipid interface of the lamellar and cubic mesophases. This effect was detected by an increase in the lattice parameter of both mesophases, enhanced elastic properties, and increased solid-like response of the systems in the presence of DEA. Potassium diclofenac (K-DFC), a less chaotropic salt, had less pronounced effect on the structural features of the mesophases. Kosmotropic Na+ salt (Na-DFC) had only minor influence on both lamellar and cubic structures. The locus of solubilization of the molecules with the host mesophases was correlated with their delivery. It was suggested that transdermal delivery of kosmotropic Na-DFC was accelerated by the aqueous phase and less constrained by the interaction with monoglyceride. On the other hand, the chaotropic cations (K+ and DEA+), presumably entrapped in the water-lipid interface, interacted with monoglyceride headgroups, which is likely to be the key cause for their sustained administration. 2010 Elsevier B.V. All rights reserved.

  3. Statistical optimisation of diclofenac sustained release pellets coated with polymethacrylic films.

    PubMed

    Kramar, A; Turk, S; Vrecer, F

    2003-04-30

    The objective of the present study was to evaluate three formulation parameters for the application of polymethacrylic films from aqueous dispersions in order to obtain multiparticulate sustained release of diclofenac sodium. Film coating of pellet cores was performed in a laboratory fluid bed apparatus. The chosen independent variables, i.e. the concentration of plasticizer (triethyl citrate), methacrylate polymers ratio (Eudragit RS:Eudragit RL) and the quantity of coating dispersion were optimised with a three-factor, three-level Box-Behnken design. The chosen dependent variables were cumulative percentage values of diclofenac dissolved in 3, 4 and 6 h. Based on the experimental design, different diclofenac release profiles were obtained. Response surface plots were used to relate the dependent and the independent variables. The optimisation procedure generated an optimum of 40% release in 3 h. The levels of plasticizer concentration, quantity of coating dispersion and polymer to polymer ratio (Eudragit RS:Eudragit RL) were 25% w/w, 400 g and 3/1, respectively. The optimised formulation prepared according to computer-determined levels provided a release profile, which was close to the predicted values. We also studied thermal and surface characteristics of the polymethacrylic films to understand the influence of plasticizer concentration on the drug release from the pellets.

  4. Highly sensitive determination of diclofenac based on resin beads and a novel polyclonal antibody by using flow injection chemiluminescence competitive immunoassay

    NASA Astrophysics Data System (ADS)

    Shi, Jing; Xu, Mingxia; Tang, Qinghui; Zhao, Kang; Deng, Anping; Li, Jianguo

    2018-02-01

    A novel flow injection chemiluminescence immunoassay for simple, sensitive and low-cost detection of diclofenac was established based on specific binding of antigen and antibody. Carboxylic resin beads used as solid phase carrier materials provided good biocompatibility and large surface-to-volume ratio for modifying more coating antigen. There was a competitive process between the diclofenac in solution and the immobilized coating antigen to react with the limited binding sites of the polyclonal antibody to form the immunocomplex. The second antibody labelled with horseradish peroxidase was introduced into the immunosensor and trapped by captured polyclonal antibody against diclofenac, which could effectively amplify chemiluminescence signals of luminol-PIP-H2O2. Under optimal conditions, the diclofenac could be detected quantitatively. The chemiluminescence intensity decreased linearly with the logarithm of the diclofenac concentration in the range of 0.1-100 ng mL- 1 with a detection limit of 0.05 ng mL- 1 at a signal-to-noise ratio of 3. The immunosensor exhibited high sensitivity, specificity and acceptable stability. This easy-operated and cost-effective analytical method could be valuable for the diclofenac determination in real water samples.

  5. Optimization of diclofenac sodium profile from halloysite nanotubules.

    PubMed

    Krejčová, Kateřina; Deasy, Patrick B; Rabišková, Miloslava

    2013-04-01

    Halloysite, aluminosilicate clay with the particle shape of multilayered hollow nanotubes, used in various non-medical applications, e.g. in ceramic industry, was discovered for pharmaceutical purposes in recent years. Several drugs of hydrophilic and lipophilic nature have been successfully encapsulated into halloysite tubules in order to modify their dissolution profile. The main goal of this experiment was to optimize the dissolution profile of diclofenac sodium - a drug with problematic solubility - from halloysite tubules using various polymers. Loading of the drug together with povidone or Eudragit® RS did not lead to drug burst effect reduction and its slower dissolution. In the case of povidone, drug improved wettability and solubilization rather than viscosity increasing expectations were observed. Eudragit® RS formed a solid dispersion with diclofenac sodium and thus the solvent/drug solution penetration through the polymer and not the drug solubility was the dissolution rate limiting factor. Reduction of the burst effect and further prolongation of drug release was achieved by coating the drug-loaded halloysite with chitosan. This formulation exhibited a diffusion-controlled prolonged release following Higuchi kinetic model.

  6. Formation of the accumulative human metabolite and human-specific glutathione conjugate of diclofenac in TK-NOG chimeric mice with humanized livers.

    PubMed

    Kamimura, Hidetaka; Ito, Satoshi; Nozawa, Kohei; Nakamura, Shota; Chijiwa, Hiroyuki; Nagatsuka, Shin-ichiro; Kuronuma, Miyuki; Ohnishi, Yasuyuki; Suemizu, Hiroshi; Ninomiya, Shin-ichi

    2015-03-01

    3'-Hydroxy-4'-methoxydiclofenac (VI) is a human-specific metabolite known to accumulate in the plasma of patients after repeated administration of diclofenac sodium. Diclofenac also produces glutathione-conjugated metabolites, some of which are human-specific. In the present study, we investigated whether these metabolites could be generated in humanized chimeric mice produced from TK-NOG mice. After a single oral administration of diclofenac to humanized mice, the unchanged drug in plasma peaked at 0.25 hour and then declined with a half-life (t1/2) of 2.4 hours. 4'-Hydroxydiclofenac (II) and 3'-hydroxydiclofenac also peaked at 0.25 hour and were undetectable within 24 hours. However, VI peaked at 8 hours and declined with a t1/2 of 13 hours. When diclofenac was given once per day, peak and trough levels of VI reached plateau within 3 days. Studies with administration of II suggested VI was generated via II as an intermediate. Among six reported glutathione-conjugated metabolites of diclofenac, M1 (5-hydroxy-4-(glutathion-S-yl)diclofenac) to M6 (2'-(glutathion-S-yl)monoclofenac), we found three dichlorinated conjugates [M1, M2 (4'-hydroxy-3'-(glutathion-S-yl)diclofenac), and M3 (5-hydroxy-6-(glutathion-S-yl)diclofenac)], and a single monochlorinated conjugate [M4 (2'-hydroxy-3'-(glutathion-S-yl)monoclofenac) or M5 (4'-hydroxy-2'-(glutathion-S-yl)monoclofenac)], in the bile of humanized chimeric mice. M4 and M5 are positional isomers and have been previously reported as human-specific in vitro metabolites likely generated via arene oxide and quinone imine-type intermediates, respectively. The biliary monochlorinated metabolite exhibited the same mass spectrum as those of M4 and M5, and we discuss whether this conjugate corresponded to M4 or M5. Overall, humanized TK-NOG chimeric mice were considered to be a functional tool for the study of drug metabolism of diclofenac in humans. Copyright © 2015 by The American Society for Pharmacology and Experimental

  7. Celecoxib or diclofenac hepatic status in the presence or absence of rebamipide.

    PubMed

    Murrell, D E; Rahmasari, Y; Denham, J W; Panus, P C; Harirforoosh, S

    2015-09-01

    Utilization of nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, can produce gastrointestinal ulceration. Thus, cyclooxygenase-2-selective inhibitors, such as celecoxib, and protective agents (e.g. rebamipide) have been employed to alleviate harmful NSAID effects. This study sought to explore the influence of rebamipide on the hepatic outcomes following administration of two commonly prescribed NSAIDs. Rats were given either vehicle or rebamipide (30 mg/kg) orally twice daily for two days, then on the third day respective groups were dosed with either vehicle, celecoxib (40 mg/kg), or diclofenac (10 mg/kg) in addition to a respective dose of vehicle or rebamipide. Livers were collected on day 4 following euthanasia. Hepatic tissue was examined via histopathology and assayed for oxidative stress and specific NSAID concentration. The liver sections were found to be free from structural changes. Oxidative stress biomarkers, reduced glutathione and malondialdehyde, were discovered to be unaltered among the groups tested. The hepatic NSAID concentrations were not significantly affected by the presence of rebamipide. The concomitant administration of rebamipide does not influence the hepatic condition of rats administered either celecoxib or diclofenac at the dosages and over the time course examined.

  8. Square Wave Voltammetric Determination of Diclofenac in Pharmaceutical Preparations and Human Serum

    PubMed Central

    Ciltas, Ulvihan; Yilmaz, Bilal; Kaban, Selcuk; Akcay, Bilge Kaan; Nazik, Gulsah

    2015-01-01

    In this study, a simple and reliable square wave voltammetric (SWV) method was developed and validated for determination of diclofenac in pharmaceutical preparations and human serum. The proposed method was based on electrooxidation of diclofenac at platinum electrode in 0.1 M TBAClO4/acetonitrile solution. The well-defined two oxidation peaks were observed at 0.87 and 1.27 V, respectively. Calibration curves that were obtained by using current values measured for second peak were linear over the concentration range of 1.5-17.5 μg mL-1 and 2-20 μg mL-1 in supporting electrolyte and serum, respectively. Precision and accuracy were also checked in all media. Intra- and inter-day precision values for diclofenac were less than 3.64, and accuracy (relative error) was better than 2.49%. Developed method in this study is accurate, precise and can be easily applied to Diclomec, Dicloflam and Voltaren tablets as pharmaceutical preparation. Also, the proposed technique was successfully applied to spiked human serum samples. No electroactive interferences from the endogenous substances were found in human serum. PMID:26330859

  9. Square Wave Voltammetric Determination of Diclofenac in Pharmaceutical Preparations and Human Serum.

    PubMed

    Ciltas, Ulvihan; Yilmaz, Bilal; Kaban, Selcuk; Akcay, Bilge Kaan; Nazik, Gulsah

    2015-01-01

    In this study, a simple and reliable square wave voltammetric (SWV) method was developed and validated for determination of diclofenac in pharmaceutical preparations and human serum. The proposed method was based on electrooxidation of diclofenac at platinum electrode in 0.1 M TBAClO4/acetonitrile solution. The well-defined two oxidation peaks were observed at 0.87 and 1.27 V, respectively. Calibration curves that were obtained by using current values measured for second peak were linear over the concentration range of 1.5-17.5 μg mL(-1) and 2-20 μg mL(-1) in supporting electrolyte and serum, respectively. Precision and accuracy were also checked in all media. Intra- and inter-day precision values for diclofenac were less than 3.64, and accuracy (relative error) was better than 2.49%. Developed method in this study is accurate, precise and can be easily applied to Diclomec, Dicloflam and Voltaren tablets as pharmaceutical preparation. Also, the proposed technique was successfully applied to spiked human serum samples. No electroactive interferences from the endogenous substances were found in human serum.

  10. Removal of diclofenac and sulfamethoxazole from synthetic municipal waste water in microcosm downflow constructed wetlands: Start-up results.

    PubMed

    Nowrotek, Monika; Sochacki, Adam; Felis, Ewa; Miksch, Korneliusz

    2016-01-01

    The objectives of this study were to investigate the start-up removal of pharmaceutical compounds diclofenac and sulfamethoxazole in microcosm downflow constructed wetlands and their effect on the performance of the studied constructed wetlands, and also to assess the effect of plants on the removal of these compounds. The experimental system that was used in this 86-day experiment consisted of 24 columns filled up to 70 cm with predominantly sandy material. Four types of columns were used (six replicates) depending on the presence of plants (Phalaris arundinacea L. var. picta L.) and the presence of pharmaceutical compounds in the influent. The influent was synthetic municipal waste water to which a mixture of 5 mg/L of diclofenac and 5 mg/L of sulfamethoxazole was added. The observed removal of diclofenac was moderate (approx. 50%) and the removal of sulfamethoxazole was relatively low (24-30%). It was found that the removal of diclofenac and sulfamethoxazole was not affected by the vegetation. The presence of diclofenac and sulfamethoxazole in the influent had significant effect on the effluent concentration of N-NO3 and the water loss in the columns, which in both cases were lower than in the control columns. The scope for further research was discussed.

  11. Investigating the sonophoresis effect on the permeation of diclofenac sodium using 3D skin equivalent.

    PubMed

    Aldwaikat, Mai; Alarjah, Mohammed

    2015-01-01

    Ultrasound temporally increases skin permeability by altering stratum corneum SC function (sonophoresis). The objective of this study was to evaluate the effect of variable ultrasound conditions on the permeation of diclofenac sodium DS with range of physicochemical properties through EpiDerm™. Permeation studies were carried out in vitro using Franz diffusion cell. HPLC method was used for the determination of the concentration of diclofenac sodium in receiving compartment. Parameters like ultrasound frequency, application time, amplitude, and mode of sonication and distance of ultrasound horn from skin were investigated, and the conditions where the maximum enhancement rate obtained were determined. Application of ultrasound enhanced permeation of diclofenac sodium across EpiDerm™ by fivefolds. The most effective enhancing parameters were power sonication of 20kHz frequency, 20% amplitude at continuous mode for 5min. Copyright © 2014. Published by Elsevier B.V.

  12. Evaluation of the effect of physical variables on in vitro release of diclofenac pellets using Box-Behnken design

    PubMed Central

    Enayatifard, Reza; Mahjoob, Aiding; Ebrahimi, Pouneh; Ebrahimnejad, Pedram

    2015-01-01

    Objective(s): A Box-Behnken design was used for evaluation of Eudragit coated diclofenac pellets. The purpose of this work was to optimize diclofenac pellets to improve the physicochemical properties using experimental design. Materials and Methods: Diclofenac was loaded onto the non-pareil beads using conventional coating pan. Film coating of pellets was done at the same pan. The effect of plasticizer level, curing temperature and curing time was determined on the release of diclofenac from pellets coated with polymethacrylates. Results: Increasing the plasticizer in the coating formula led to decrease in drug release and increasing the curing temperature and time resulted in higher drug release. The optimization process generated an optimum of 35% drug release at 3 hr. The level of plasticizer concentration, curing temperature and time were 20% w/w, 55 °C and 24 hr, respectively. Conclusion: This study showed that by controllinig the physical variables optimum drug release were obtained. PMID:26351563

  13. Relieving perineal pain after perineorrhaphy by diclofenac rectal suppositories: a randomized double-blinded placebo controlled trial.

    PubMed

    Achariyapota, Vuthinun; Titapant, Vitaya

    2008-06-01

    Perineal pain after episiotomy is a common problem following vaginal birth. The pain affects either physical or mental function negatively. There are many methods in perineal pain relief such as local ice pack and a bath, ultrasound, oral anesthesia, and intravenous anesthesia. Analgesic rectal suppository is one of various methods in pain relief especially in drowsy patients, or when oral preparation causes gastric discomfort, nausea or vomiting. To assess the effectiveness of diclofenac rectal suppositories for relief perineal pain after perineorrhaphy. A randomized double-blinded placebo controlled trial. Seventy-two term, singleton, pregnant women who gave vaginal birth with second to third degree episiotomy tears were randomized with envelop concealment to either diclofenac or placebo rectal suppositories group. Each group received two tablets of 50 mg diclofenac or two tablets of look-alike placebo rectal suppositories. Visual analogue scale was used for scaling pain score before administration of the medications, and at 30 minutes, 1, 2, 12, and 24 hours after administration. No differences were found in the median pain scores before administration of medications and at 30 min, 1 hour and 2 hour after administration (p > 0.05), while the median pain scores were significantly reduced in the diclofenac group at 12 and 24 hours after administration compared to the control group (4.5 vs. 0.0; p < 0.001 and 2.0 vs. 0.0; p = 0.02 for 12 hours and 24 hours, consecutively). The present study suggested that diclofenac suppository was effective on reducing perineal pain after episiotomy, especially at 12 and 24 hours after administration.

  14. Evaluation of systemic absorption and renal effects of topical ophthalmic flurbiprofen and diclofenac in healthy cats.

    PubMed

    Lanuza, Rick; Rankin, Amy J; KuKanich, Butch; Meekins, Jessica M

    2016-07-01

    To investigate systemic absorption and renal effects of topically applied ophthalmic flurbiprofen and diclofenac in healthy cats. Twelve domestic shorthair cats. Cats were randomly assigned to two treatment groups (n = 6) and administered one drop (approximately 40 μL) of either flurbiprofen 0.03% or diclofenac 0.1% in both eyes four times daily (6 am, 12 pm, 6 pm, and 12 am) for 14 days. Blood samples were collected on days 0, 4, 8, 14, 16, and 17 and analyzed by liquid chromatography and mass spectrometry for flurbiprofen and diclofenac plasma concentrations. A complete blood count (CBC), serum chemistry, and urinalysis were analyzed at the beginning of the study (Day 0) and at the end of topical drug administration (Day 15). Both drugs demonstrated systemic absorption. Flurbiprofen was detected (mean ± SD) at day 4 (237 ± 65 ng/mL), day 8 (396 ± 91 ng/mL), day 14 (423 ± 56 ng/mL), day 16 (350 ± 66 ng/mL), and day 17 (270 ± 62 ng/mL), and diclofenac was detected (mean ± SD) at day 4 (130 ± 44 ng/mL), day 8 (131 ± 25 ng/mL), day 14 (150 ± 36 ng/mL), and sporadically on day 16 [corrected]. Flurbiprofen plasma concentration decreased slowly over 48 h after the last dose. No clinically significant abnormalities were noted in the serum blood urea nitrogen, creatinine, or urine specific gravity at the end of topical drug administration compared to the beginning of the study. Flurbiprofen and diclofenac were systemically absorbed after topical administration four times daily to both eyes of healthy cats. Flurbiprofen reached higher plasma concentrations compared to diclofenac. © 2015 American College of Veterinary Ophthalmologists.

  15. Nanostructured lipid carriers to enhance transdermal delivery and efficacy of diclofenac.

    PubMed

    Nguyen, Chien Ngoc; Nguyen, Thi Thuy Trang; Nguyen, Hanh Thuy; Tran, Tuan Hiep

    2017-10-01

    Lipid carrier-mediated transdermal drug delivery offers several advantages because it is non-irritating and non-toxic, provides effective control of drug release, and forms an adhesive film that hydrates the outer skin layers. However, to penetrate the deeper skin layers, these formulations need to overcome several barriers in the stratum corneum. This study evaluates factors influencing particle size and drug-loading capacity, which play a key role in drug permeation and efficacy. Diclofenac sodium was chosen as the model drug. The fabrication of diclofenac sodium-loaded lipid nanoparticles was optimized by modulating several parameters, including the lipids and surfactants employed, the drug/lipid ratio, and the pH of the aqueous phase. The physical properties and loading efficiencies of the nanoparticles were characterized. The optimized formulation was then dispersed into a polymer solution to form a gel, which demonstrated a sustained ex vivo permeation of diclofenac sodium over 24 h through excised rat skin and a higher drug penetrating capacity than that of a commercially available gel. In vivo anti-inflammatory activity was assessed in a rat carrageenan-induced paw edema model; the anti-edema effects of the prepared gel and commercially available gel over 24 h were comparable. The present findings indicate the effects of particle size and drug loading on the ability of nanostructured lipid carrier preparations to provide transdermal drug delivery.

  16. Comparison of ketorolac 0.45% versus diclofenac 0.1% for macular thickness and volume after uncomplicated cataract surgery.

    PubMed

    Lee, Tae Hee; Choi, Won; Ji, Yong Sok; Yoon, Kyung Chul

    2016-05-01

    To compare the effects of ketorolac 0.45% and diclofenac 0.1% on macular thickness and volume after uncomplicated cataract surgery. A total of 76 eyes of 76 patients who underwent uncomplicated cataract surgery were included. Patients were treated with either diclofenac 0.1% (38 eyes) or ketorolac 0.45% (38 eyes) after surgery. The macular thickness and volume were obtained with optical coherence tomography (OCT). Central subfield thickness (CST, OCT 1 mm zone), total foveal thickness (TFT, OCT 3 mm zone), total macular thickness (TMT, OCT 6 mm zone), average macular thickness (AMT) and total macular volume (TMV) were compared between the two study groups. No significant differences between groups were found in macular thickness or volume 1 month after cataract surgery. Two months after surgery, the ketorolac group had significantly lower CST, TFT, TMT and AMT than the diclofenac group (p < 0.05 for all). Additionally, 1 and 2 months after surgery, changes from preoperative values in CST (both p = 0.04), AMT (p = 0.02 and p < 0.01, respectively) and TMV (both p = 0.04) were significantly less in the ketorolac group than in the diclofenac group. Following uncomplicated cataract surgery, topical ketorolac 0.45% was more effective than diclofenac 0.1% in preventing increases in macular thickness and volume. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  17. Simulation of interindividual differences in inactivation of reactive para-benzoquinone imine metabolites of diclofenac by glutathione S-transferases in human liver cytosol.

    PubMed

    den Braver, Michiel W; Zhang, Yongjie; Venkataraman, Harini; Vermeulen, Nico P E; Commandeur, Jan N M

    2016-07-25

    Diclofenac is a widely prescribed NSAID that causes severe idiosyncratic drug induced liver injury (IDILI) in a small part of the patient population. Formation of protein-reactive metabolites is considered to play a role in the development of diclofenac-induced IDILI. Therefore, a high hepatic activity of enzymes involved in bioactivation of diclofenac is expected to increase the risk for liver injury. However, the extent of covalent protein binding may also be determined by activity of protective enzymes, such as glutathione S-transferases (GSTs). This is supported by an association study in which a correlation was found between NSAID-induced IDILI and the combined null genotypes of GSTM1 and GSTT1. In the present study, the activity of 10 different recombinant human GSTs in inactivation of protein-reactive quinoneimine (QI) metabolites of diclofenac was tested. Both at low and high GSH concentrations, high activities of GSTA1-1, A2-2, A3-3, M1-1, M3-3 and P1-1 in the inactivation of these QIs were found. By using the expression levels of GSTs in livers of 22 donors, a 6-fold variation in GST-dependent inactivation of reactive diclofenac metabolites was predicted. Moreover, it was shown in vitro that GSTs can strongly increase the efficiency of GSH to protect against the alkylation of the model thiol N-acetylcysteine by reactive diclofenac metabolites. The results of this study demonstrate that variability of GST expression may significantly contribute to the inter-individual differences in susceptibility to diclofenac-induced liver injury. In addition, expression levels of GSTs in in vitro models for hepatotoxicity may be important factors determining sensitivity to diclofenac cytotoxicity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Removal of diclofenac from a non-sterile aqueous system using Trametes versicolor with an emphasis on adsorption and biodegradation mechanisms.

    PubMed

    Stenholm, Åke; Hedeland, Mikael; Arvidsson, Torbjörn; Pettersson, Curt E

    2018-03-04

    This paper describes the search for procedures through which the xenobiotic pollutant diclofenac can be removed from non-sterile aquatic systems. Specifically, adsorption to solid supports (carriers) in combination with biodegradation by non-immobilized and immobilized white rot fungus Trametes versicolor were investigated. Batch experiments using polyurethane foam (PUF)-carriers resulted in 99.9% diclofenac removal after 4 h, with monolayer adsorption of diclofenac to carrier and glass surfaces accounting for most of the diclofenac decrease. Enzymatic reactions contributed less, accounting for approximately < 0.5% of this decrease. In bioreactor experiments using PUF-carriers, an initial 100% removal was achieved with biodegradation contributing approximately 7%. In batch experiments that utilized polyethylene-carriers with negligible immobilization of Trametes versicolor, a 98% total diclofenac removal was achieved after one week, with a biodegradation contribution of approximately 14%. Five novel enzyme-catalyzed biodegradation products were tentatively identified in the batch-wise and bioreactor experiments using full scan ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry. Both reduction and oxidation products were found, with the contents estimated to be at µg L -1 concentration levels.

  19. Diclofenac salts. III. Alkaline and earth alkaline salts.

    PubMed

    Fini, Adamo; Fazio, Giuseppe; Rosetti, Francesca; Angeles Holgado, M; Iruín, Ana; Alvarez-Fuentes, Josefa

    2005-11-01

    Diclofenac salts containing the alkaline and two earth alkaline cations have been prepared and characterized by scanning electron microscopy (SEM) and EDAX spectroscopy; and by thermal and thermogravimetric analysis (TGA): all of them crystallize as hydrate when precipitated from water. The salts dehydrate at room temperature and more easily on heating, but recovery the hydration, when placed in a humid environment. X-ray diffraction spectra suggest that on dehydration new peaks appear on diffractograms and the lattice of the salts partially looses crystallinity. This phenomenon is readily visible in the case of the calcium and magnesium salts, whose thermograms display a crystallization exotherm, before melting or decomposing at temperatures near or above 200 degrees C; these last salts appear to form solvates, when prepared from methanol. The thermogram of each salt shows a complex endotherm of dehydration about 100 degrees C; the calcium salt displays two endotherms, well separated at about 120 and 160 degrees C, which disappear after prolonged heating. Decomposition exotherms, before or soon after the melting, appear below 300 degrees C. The ammonium salt is thermally unstable and, when heated to start dehydration, dissociates and leaves acidic diclofenac.

  20. Diclofenac sodium, 0.1% (Voltaren Ophtha), versus sodium chloride, 5%, in the treatment of filamentary keratitis.

    PubMed

    Avisar, R; Robinson, A; Appel, I; Yassur, Y; Weinberger, D

    2000-03-01

    To compare the efficacy and short-term safety of diclofenac sodium, 0.1% (Voltaren Ophtha; Ciba-Vision) and of sodium chloride, 5% ophthalmic solution, in the treatment of filamentary keratitis (FK) in patients with dry-eye syndrome due to secondary Sjögren's syndrome. Thirty-two patients (64 eyes) with dry-eye syndrome due to secondary Sjögren' syndrome were enrolled in a randomized study (patients and authors were aware of which medication was being used). All patients had FK. Sixteen patients were treated with sodium chloride, 5% drops, and 16 patients received diclofenac sodium, 0.1% eyedrops. Treatment regimen included instillation of 1 drop, 4 times a day for 28 days, for both groups. Clinical assessment was performed once a week during the study period. Data on the efficacy and safety of the different therapeutic regimens were collected and compared. Both medications achieved disappearance of filaments at the end of the study. Treatment with diclofenac sodium, 0.1%, revealed a significantly more rapid improvement of the clinical symptoms as compared with sodium chloride, 5%. No significant adverse effects were observed in both groups. Diclofenac sodium, 0.1%, may be an effective and safe topical therapy in patients with FK caused by secondary Sjögren's disease.

  1. A Double-Blind Placebo-Controlled Comparison of a Novel Formulation of Intravenous Diclofenac and Ketorolac for Postoperative Third Molar Extraction Pain

    PubMed Central

    Christensen, Kyle; Daniels, Stephen; Bandy, Donald; Ernst, Cynthia C.; Hamilton, Douglas A.; Mermelstein, Fred H.; Wang, Jianyuan; Carr, Daniel B.

    2011-01-01

    Dyloject is a novel formulation of diclofenac intended for intravenous (IV) administration. This formulation employs the solubilizing agent hydroxypropyl-β-cyclodextrin to permit bolus IV administration. The efficacy and safety of 5 dose levels of IV diclofenac were compared with IV ketorolac and placebo following third molar extraction. This was a single-dose, randomized, double-blind, placebo- and comparator-controlled, parallel-group study. A total of 353 subjects with moderate to severe pain received placebo; ketorolac 30 mg; or IV diclofenac 3.75, 9.4, 18.75, 37.5, or 75 mg (N  =  51 for all groups, except N  =  47 for ketorolac). The primary endpoint was total pain relief over 6 hours (TOTPAR6) as measured by the visual analog scale (VAS). Secondary endpoints included multiple measures of pain intensity and relief; patient global evaluation; and times to pain relief and rescue medication. Dropouts and adverse effects (AEs) were also monitored. IV diclofenac was superior to placebo as measured by TOTPAR6 (P < .0001 for all doses except 3.75 mg, for which P  =  .0341). IV diclofenac 3.75 mg was statistically superior to placebo for TOTPAR2 and TOTPAR4. IV diclofenac at both 37.5 and 75 mg was superior to placebo (P < .05) at the earliest (5 minute) assessments of pain intensity and pain relief, but ketorolac was not. The proportion of patients reporting 30% or greater pain relief at 5 minutes was significantly greater after IV diclofenac 37.5 and 75 mg than after ketorolac 30 mg or placebo. Secondary endpoints confirmed the primary findings. Treatment-related AEs were generally mild to moderate and were typical for nonsteroidal anti-inflammatory drugs (NSAIDs). The more rapid onset of action of IV diclofenac compared with the reference injectable NSAID ketorolac suggests additional clinical benefit. If confirmed in larger series, these findings may improve the safety and efficacy of postoperative NSAID analgesia. PMID:21679043

  2. Rectal analgesia for the relief of perineal pain after childbirth: a randomised controlled trial of diclofenac suppositories.

    PubMed

    Dodd, Jodie M; Hedayati, Hedyeh; Pearce, Elizabeth; Hotham, Neil; Crowther, Caroline A

    2004-10-01

    To evaluate rectal diclofenac in the relief of perineal pain after trauma during childbirth. A randomised, double-blind trial. Delivery Suite, Women's and Children's Hospital, South Australia. Women with a second-degree (or greater) perineal tear or episiotomy. Women were randomly allocated to either diclofenac or placebo suppositories (Anusol), using a computer-generated randomisation schedule with stratification for parity and mode of birth. Treatment packs contained two x 100 mg diclofenac or two placebo suppositories, the first being inserted when suturing was complete, and the second 12-24 hours after birth. Women were asked to complete questionnaires at 24 and 48 hours after birth relating to their degree of perineal pain using the validated Short Form McGill Pain Questionnaire. Pain scores at 24 and 48 hours after birth. A total of 133 women were recruited, with 67 randomised to diclofenac suppositories and 66 to placebo. Women in the diclofenac group were significantly less likely to experience pain at 24 hours while walking (RR 0.8; 95% CI 0.6 to 1.0), sitting (RR 0.8; 95% CI 0.6 to 1.0), passing urine (RR 0.6; 95% CI 0.4 to 1.0) and on opening their bowels (RR 0.6; 95% CI 0.2 to 0.9) compared with those women who received placebo. These differences were not sustained 48 hours after birth. The use of rectal non-steroidal anti-inflammatory drug suppositories is a simple, effective and safe method of reducing the pain experienced by women following perineal trauma within the first 24 hours after childbirth.

  3. Topical ketoprofen TDS patch versus diclofenac gel: efficacy and tolerability in benign sport related soft‐tissue injuries

    PubMed Central

    Esparza, Francisco; Cobián, César; Jiménez, José Fernando; García‐Cota, Juan José; Sánchez, Carlos; SETRADE, Antonio Maestro and the working group for the acute pain study of

    2007-01-01

    Objective To compare the ketoprofen TDS patch with diclofenac gel in the treatment of traumatic acute pain in benign sport‐related soft‐tissue injuries. Design 7–14 treatment days, prospective, randomised, open study. Patients Outpatients aged 18–70 years diagnosed for painful benign sport‐related soft‐tissue injury (sprains, strains and contusions within the prior 48 h), randomised to either ketoprofen patch 100 mg once daily (n = 114) or diclofenac gel 2–4 g three times daily (n = 109). Intervention 7–14 days of topical non‐steroidal anti‐inflammatory drugs treatment to assess the pain intensity changes (daily activities and spontaneous at rest) in a daily diary (100‐mm Visual Analogue Scale (VAS)). Main outcome measurement Pain intensity (VAS). Results The ketoprofen patch was not inferior to diclofenac gel in reducing the baseline pain during daily activities (difference of –1.17 mm in favour of ketoprofen patch, 95% CI (–5.86 to 3.52), reducing to the baseline VAS 79%. Ketoprofen patch presented also a higher cure rate (64%) than diclofenac gel (46%) at day 7 (p = 0.004). Patient opinions about the treatment comfort (pharmaceutical shape, application and dosage) were also statistically higher for the ketoprofen patch (>80% of the patients rated as good or excellent the patch removal and skin adherence). Conclusion Ketoprofen patches are effective and safe pain relievers for the treatment of sports injury pain with advantages compared with diclofenac gel. PMID:17138642

  4. Diclofenac rectal suppository: an effective modality for perineal pain.

    PubMed

    Naz, Shabnam; Memon, Naila Yousuf; Sattar, Asma; Baloch, Rafia

    2016-08-01

    To determine the frequency of perineal pain after childbirth after a single dose of diclofenac rectal suppository. This cross-sectional study was conducted at Shaikh Zayed Women Hospital, Larkana, Pakistan, from April to September 2014, and comprised patients who were admitted to the labour room for normal vaginal delivery. A single dose of rectal diclofenac suppository of 100mg was given to the patients delivered vaginally or by second-stage emergency Caesarean section. Post-partum pain was noted after 12 and 24 hours of the administration of analgesia. SPSS 16 was used for data analysis. Of the 169 subjects, 63(37.28%) were aged 20 years or less, 85(50.3%) between 21 and 30 years, and 21(12.43%) between 31 and 40 years. Frequency of perineal pain was predominantly mild in 95(56%) patients, moderate in 60(35.5%) and severe in 14(8.28%). The use of non-steroidal anti-inflammatory rectal suppositories was found to be a simple and highly effective modality of reducing the perineal pain.

  5. Aminopropyl groups of the functionalized Mobil Crystalline Material 41 as a carrier for controlled diclofenac sodium and piroxicam delivery.

    PubMed

    Khodaverdi, Elham; Ahmadi, Mina; Kamali, Hossein; Hadizadeh, Farzin

    2017-01-01

    Synthetic Mobil Crystalline Material 41 (MCM-41) as a mesoporous material and functionalized MCM-41 using aminopropyl groups were studied in order to investigate their ability to encapsulate and to control the release of diclofenac sodium and piroxicam. MCM-41 was synthesized through sol-gel procedure and functionalized with aminopropyl groups. The physicochemical properties of MCM-41 were studied through particle size analysis, infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and carbon-hydrogen-nitrogen analysis. Diclofenac sodium and piroxicam were loaded into the MCM-41 matrix using the filtration and solvent evaporation methods. The drug-loading capacity was determined by ultraviolet, Fourier transform infrared, X-ray diffraction, and Brunauer-Emmett-Teller analysis. According to the results for pure drug release, >57% was released in the 1 st h, but when these drugs were loaded into pure Mobil Crystalline Material 41 (MCM-41) and functionalized MCM-41, the release into the simulated gastrointestinal medium was less, continuous, and slower. The release of piroxicam from functionalized MCM-41 was slower than that from MCM-41 in the simulated intestinal medium because of the formation of electrostatic bonds between piroxicam and the aminopropyl groups of the functionalized MCM-41. However, in the case of diclofenac sodium, there was no significant difference between pure MCM-41 and functionalized MCM-41. The difference between piroxicam and diclofenac sodium was due to the high solubility of diclofenac sodium in the intestinal medium (pH 6.8), which caused more rapid release from the matrixes than for piroxicam. Our findings indicate that, after functionalization of MCM-41, it could offer a good means of delivering controlled diclofenac sodium and piroxicam.

  6. Parenteral diclofenac infusion significantly decreases brain-tissue oxygen tension in patients with poor-grade aneurysmal subarachnoid hemorrhage

    PubMed Central

    2013-01-01

    Introduction Diclofenac, a nonsteroidal antiinflammatory drug, is commonly used as antipyretic therapy in intensive care. The purpose of this study was to investigate the effects of parenteral diclofenac infusion on brain homeostasis, including brain-tissue oxygen tension (PbtO2) and brain metabolism after aneurysmal subarachnoid hemorrhage (aSAH). Methods We conducted a prospective, observational study with retrospective analysis of 21 consecutive aSAH patients with multimodal neuromonitoring. Cerebral perfusion pressure (CPP), mean arterial pressure (MAP), intracranial pressure (ICP), body temperature, and PbtO2 were analyzed after parenteral diclofenac infusion administered over a 34-minute period (20 to 45 IQR). Data are given as mean ± standard error of mean and median with interquartile range (IQR), as appropriate. Time-series data were analyzed by using a general linear model extended by generalized estimation equations (GEEs). Results One-hundred twenty-three interventions were analyzed. Body temperature decreased from 38.3°C ± 0.05°C by 0.8°C ± 0.06°C (P < 0.001). A 10% decrease in MAP and CPP (P < 0.001) necessitated an increase of vasopressors in 26% (n = 32), colloids in 33% (n = 41), and crystalloids in 5% (n = 7) of interventions. PbtO2 decreased by 13% from a baseline value of 28.1 ± 2.2 mm Hg, resulting in brain-tissue hypoxia (PbtO2 <20 mm Hg) in 38% (n = 8) of patients and 35% (n = 43) of interventions. PbtO2 <30 mm Hg before intervention was associated with brain-tissue hypoxia after parenteral diclofenac infusion (likelihood ratio, 40; AUC, 93%; 95% confidence interval (CI), 87% to 99%; P < 0.001). Cerebral metabolism showed no significant changes after parenteral diclofenac infusion. Conclusions Parenteral diclofenac infusion after aSAH effectively reduces body temperature, but may lead to CPP decrease and brain-tissue hypoxia, which were both associated with poor outcome after aSAH. PMID:23663770

  7. Acetylated cashew gum-based nanoparticles for transdermal delivery of diclofenac diethyl amine.

    PubMed

    Dias, Sávia Francisca Lopes; Nogueira, Silvania Siqueira; de França Dourado, Flaviane; Guimarães, Maria Adelaide; de Oliveira Pitombeira, Nádia Aline; Gobbo, Graciely Gomides; Primo, Fernando Lucas; de Paula, Regina Célia Monteiro; Feitosa, Judith Pessoa Andrade; Tedesco, Antonio Claudio; Nunes, Lívio Cesar Cunha; Leite, José Roberto Souza Almeida; da Silva, Durcilene Alves

    2016-06-05

    Nanoprecipitation and dialysis methods were employed to obtain nanoparticles (NPs) of acetylated cashew gum (ACG). NPs synthesized by dialysis showed greater average size compared to those synthesized by nanoprecipitation, but they presented improved stability and yield. NPs were loaded with diclofenac diethylamine and the efficiency of the drug incorporation was over 60% for both methods, for an ACG:NP a weight ratio of 10:1. The cytotoxicity assay demonstrated that the NPs had no significant effect on the cell viability, verifying their biocompatibility. The release profile for the diclofenac diethylamine associated with the ACG-NPs showed a more controlled release compared to the free drug and a Fickian diffusion mechanism was observed. Transdermal permeation reached 90% penetration of the drug. Copyright © 2016. Published by Elsevier Ltd.

  8. Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats.

    PubMed

    Lojo, Nermin; Rasic, Zarko; Zenko Sever, Anita; Kolenc, Danijela; Vukusic, Darko; Drmic, Domagoj; Zoricic, Ivan; Sever, Marko; Seiwerth, Sven; Sikiric, Predrag

    2016-01-01

    Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and

  9. Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats

    PubMed Central

    Lojo, Nermin; Rasic, Zarko; Zenko Sever, Anita; Kolenc, Danijela; Vukusic, Darko; Drmic, Domagoj; Zoricic, Ivan; Sever, Marko; Seiwerth, Sven; Sikiric, Predrag

    2016-01-01

    Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and

  10. Critical role of free cytosolic calcium, but not uncoupling, in mitochondrial permeability transition and cell death induced by diclofenac oxidative metabolites in immortalized human hepatocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lim, M.S.; Lim, Priscilla L.K.; Gupta, Rashi

    2006-12-15

    Diclofenac is a widely used nonsteroidal anti-inflammatory drug that has been associated with rare but serious hepatotoxicity. Experimental evidence indicates that diclofenac targets mitochondria and induces the permeability transition (mPT) which leads to apoptotic cell death in hepatocytes. While the downstream effector mechanisms have been well characterized, the more proximal pathways leading to the mPT are not known. The purpose of this study was to explore the role of free cytosolic calcium (Ca{sup 2+} {sub c}) in diclofenac-induced cell injury in immortalized human hepatocytes. We show that exposure to diclofenac caused time- and concentration-dependent cell injury, which was prevented bymore » the specific mPT inhibitor cyclosporin A (CsA, 5 {mu}M). At 8 h, diclofenac caused increases in [Ca{sup 2+}]{sub c} (Fluo-4 fluorescence), which was unaffected by CsA. Combined exposure to diclofenac/BAPTA (Ca{sup 2+} chelator) inhibited cell injury, indicating that Ca{sup 2+} plays a critical role in precipitating mPT. Diclofenac decreased the mitochondrial membrane potential, {delta}{psi}{sub m} (JC-1 fluorescence), even in the presence of CsA or BAPTA, indicating that mitochondrial depolarization was not a consequence of the mPT or elevated [Ca{sup 2+}]{sub c}. The CYP2C9 inhibitor sulphaphenazole (10 {mu}M) protected from diclofenac-induced cell injury and prevented increases in [Ca{sup 2+}]{sub c}, while it had no effect on the dissipation of the {delta}{psi}{sub m}. Finally, diclofenac exposure greatly increased the mitochondria-selective superoxide levels secondary to the increases in [Ca{sup 2+}]{sub c}. In conclusion, these data demonstrate that diclofenac has direct depolarizing effects on mitochondria which does not lead to cell injury, while CYP2C9-mediated bioactivation causes increases in [Ca{sup 2+}]{sub c}, triggering the mPT and precipitating cell death.« less

  11. Gravimetric method for the determination of diclofenac in pharmaceutical preparations.

    PubMed

    Tubino, Matthieu; De Souza, Rafael L

    2005-01-01

    A gravimetric method for the determination of diclofenac in pharmaceutical preparations was developed. Diclofenac is precipitated from aqueous solution with copper(II) acetate in pH 5.3 (acetic acid/acetate buffer). Sample aliquots had approximately the same quantity of the drug content in tablets (50 mg) or in ampules (75 mg). The observed standard deviation was about +/- 2 mg; therefore, the relative standard deviation (RSD) was approximately 4% for tablet and 3% for ampule preparations. The results were compared with those obtained with the liquid chromatography method recommended in the United States Pharmacopoeia using the statistical Student's t-test. Complete agreement was observed. It is possible to obtain more precise results using higher aliquots, for example 200 mg, in which case the RSD falls to 1%. This gravimetric method, contrary to what is expected for this kind of procedure, is relatively fast and simple to perform. The main advantage is the absolute character of the gravimetric analysis.

  12. Comparison of analgesic effect of preoperative topical diclofenac and ketorolac on postoperative pain after photorefractive keratectomy.

    PubMed

    Hong, Jin Pyo; Nam, Sang Min; Im, Chan Young; Yoon, Sangchul; Kim, Tae-Im; Kim, Eung Kweon; Seo, Kyoung Yul

    2014-10-01

    To investigate changes in the pain-suppressing potency of 2 preoperatively applied topical nonsteroidal antiinflammatory drugs (NSAIDs) after photorefractive keratectomy (PRK) using a time-serial pain-scoring system. Saeyan Eye Center, Seoul, South Korea. Comparative case series. Ninety-four patients were randomly assigned to 2 groups: ketorolac group (ketorolac 0.5% in 1 eye and ofloxacin 0.3% in the other eye) and diclofenac group (diclofenac 0.1% in 1 eye and ofloxacin 0.3% in the other eye). One drop of each ophthalmic drug was applied 3 times to each eye 30 minutes before PRK. No other NSAID or steroid was prescribed until 4 days after PRK. The patients were asked to score the postoperative pain in each eye with a visual analog scale at 6, 18, 24, 36, 48, 72, and 96 hours. The natural peak of pain was located between 24 and 36 hours. Initially, the degree of pain reduction was constant for both NSAIDs; it dropped after 24 hours and 36 hours in the ketorolac group and the diclofenac group, respectively. The postoperative time-serial pattern of the pain score changed in the diclofenac group but not in the ketorolac group compared with the pattern in the ofloxacin-treated eye. The visual outcome was not affected by either NSAID, and significant complications were not noticed for a mean of 7 months. The duration and pattern of the action may vary according to types of NSAIDs. Preemptive topical diclofenac 0.1% was a safe and effective method for post-PRK pain control. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  13. Comparison of the effect of naproxen, etodolac and diclofenac on postoperative sequels following third molar surgery: A randomised, double-blind, crossover study

    PubMed Central

    Akbulut, Nihat; Atakan, Cemal; Çölok, Gülümser

    2014-01-01

    Objectives: To compare the three non-steroidal anti-inflammatory agents (NSAIDs) diclofenac potassium, etodolac and naproxen sodium in relation to pain, swelling and trismus following impacted third molar surgery. Study Design: The study was a randomized and a double-blinded study which included 42 healthy young individuals with impacted third molars and bone retention. Patients were randomly assigned to 3 groups (n: 14) to which diclofenac potassium, naproxen sodium and etodolac were administered orally an hour before the operation. Impacted third molars were surgically extracted with local anaesthesia. Visual analog scales (VAS) were used to assess the pain in the 6th, 12th hours and on the 1st, 2nd, 3rd, 5th, and 7th days postoperatively. Swelling was evaluated using ultrasound (US) and mouth opening (trismus) was measured with a composing stick pre and post operatively on the 2nd and 7th days respectively. Results: Regarding pain alleviation, diclofenac potassium was better than naproxen sodium and naproxen sodium was better than etodolac but these differences were not statistically significant. US measurements showed that the swelling on postoperative 2nd day was significantly lowest with diclofenac potassium as compared to others (p= 0.027) while naproxen sodium and etodolac acted similarly (p=0.747). No difference was noted regarding trismus in any of the groups. Conclusions: NSAIDs (diclofenac, naproxen and etodolac) are somehow similarly effective for controlling pain and trismus following extraction of mandibular third molars but diclofenac potassium surpasses others in reduction of swelling. Key words:Diclofenac potassium, naproxen sodium, etodolac, impacted third molar surgery, pain, swelling, trismus. PMID:24316711

  14. Routes of uptake of diclofenac, fluoxetine, and triclosan into sediment-dwelling worms.

    PubMed

    Karlsson, Maja V; Marshall, Stuart; Gouin, Todd; Boxall, Alistair B A

    2016-04-01

    The present study investigated the route and degree of uptake of 2 ionizable pharmaceuticals (diclofenac and fluoxetine) and 1 ionizable compound used in personal care products (triclosan) into the sediment-dwelling worm Lumbriculus variegatus. Studies were done on complete worms ("feeding") and worms where the head was absent ("nonfeeding") using (14) C-labeled ingredients. Biota sediment accumulation factors (BSAF), based on uptake of (14) C, for feeding worms increased in the order fluoxetine (0.3) < diclofenac (0.5) < triclosan (9), which is correlated with a corresponding increase in log octanol-water partition coefficient. Biota sediment accumulation factor estimates are representative of maximum values because the degree of biotransformation in the worms was not quantified. Although no significant differences were seen between the uptake of diclofenac and that of fluoxetine in feeding and nonfeeding worms, uptake of the more hydrophobic antimicrobial, triclosan, into the feeding worms was significantly greater than that in the nonfeeding worms, with the 48-h BSAF for feeding worms being 36% higher than that for the nonfeeding worms. The results imply that dietary uptake contributes to the uptake of triclosan, which may be a result of the high hydrophobicity of the compound. Models that estimate exposure of ionizable substances may need to consider uptake from both the water column and food, particularly when assessing risks from dynamic exposures to organic contaminants. © 2015 SETAC.

  15. Aminopropyl groups of the functionalized Mobil Crystalline Material 41 as a carrier for controlled diclofenac sodium and piroxicam delivery

    PubMed Central

    Khodaverdi, Elham; Ahmadi, Mina; Kamali, Hossein; Hadizadeh, Farzin

    2017-01-01

    Objective: Synthetic Mobil Crystalline Material 41 (MCM-41) as a mesoporous material and functionalized MCM-41 using aminopropyl groups were studied in order to investigate their ability to encapsulate and to control the release of diclofenac sodium and piroxicam. Materials and Methods: MCM-41 was synthesized through sol–gel procedure and functionalized with aminopropyl groups. The physicochemical properties of MCM-41 were studied through particle size analysis, infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and carbon–hydrogen–nitrogen analysis. Diclofenac sodium and piroxicam were loaded into the MCM-41 matrix using the filtration and solvent evaporation methods. The drug-loading capacity was determined by ultraviolet, Fourier transform infrared, X-ray diffraction, and Brunauer–Emmett–Teller analysis. Results: According to the results for pure drug release, >57% was released in the 1st h, but when these drugs were loaded into pure Mobil Crystalline Material 41 (MCM-41) and functionalized MCM-41, the release into the simulated gastrointestinal medium was less, continuous, and slower. The release of piroxicam from functionalized MCM-41 was slower than that from MCM-41 in the simulated intestinal medium because of the formation of electrostatic bonds between piroxicam and the aminopropyl groups of the functionalized MCM-41. However, in the case of diclofenac sodium, there was no significant difference between pure MCM-41 and functionalized MCM-41. The difference between piroxicam and diclofenac sodium was due to the high solubility of diclofenac sodium in the intestinal medium (pH 6.8), which caused more rapid release from the matrixes than for piroxicam. Conclusion: Our findings indicate that, after functionalization of MCM-41, it could offer a good means of delivering controlled diclofenac sodium and piroxicam. PMID:29692976

  16. Once-daily, controlled-release tramadol and sustained-release diclofenac relieve chronic pain due to osteoarthritis: A randomized controlled trial

    PubMed Central

    Beaulieu, André D; Peloso, Paul M; Haraoui, Boulos; Bensen, William; Thomson, Glen; Wade, John; Quigley, Patricia; Eisenhoffer, John; Harsanyi, Zoltan; Darke, Andrew C

    2008-01-01

    OBJECTIVE: The present study was a randomized, parallel, double-blind comparison between controlled-release (CR) tramadol and sustained-release (SR) diclofenac in patients with chronic pain due to osteoarthritis of the hips and/or knees. METHODS: Patients with at least moderate pain intensity, and having received analgesics over the past three months, underwent a two-to seven-day washout of current analgesics before initiation of 200 mg CR tramadol or 75 mg SR diclofenac. During the eight-week study, patients returned to the clinic biweekly. CR tramadol doses were titrated to a maximum of 200 mg, 300 mg or 400 mg per day. SR diclofenac doses were titrated to 75 mg or 100 mg once daily, or 75 mg twice a day based on pain relief and the presence of side effects. For rescue analgesic, patients took acetaminophen as needed, up to 650 mg three times a day. RESULTS: Forty-five patients on CR tramadol and 52 patients on SR diclofenac were evaluable. Significant improvements from prestudy treatment were shown for visual analogue scale pain (P=0.0001), stiffness (P<0.0005) and physical function (P=0.0001) scores for both treatments. There were no significant differences between the two treatments in the Western Ontario and McMaster Universities subscales, overall pain, pain and sleep, or the clinical effectiveness evaluation. Overall incidence of adverse events was similar in both groups, with more opioid-related adverse events with CR tramadol, and two serious adverse events occurring with the use of SR diclofenac. CONCLUSIONS: CR tramadol is as effective as SR diclofenac in the treatment of pain due to knee or hip osteoarthritis, with the potential for fewer of the serious side effects that characterize nonsteroidal anti-inflammatory drug administration. PMID:18443672

  17. Ex vivo study of transdermal permeation of four diclofenac salts from different vehicles.

    PubMed

    Minghetti, Paola; Cilurzo, Francesco; Casiraghi, Antonella; Montanari, Luisa; Fini, Adamo

    2007-04-01

    The ex vivo permeation of diclofenac was studied using four different salts (sodium, potassium, diethylamine, and epolamine) dissolved in four different solvents (water, propylene glycol (PG), Transcutol, and oleic acid (OA)) as donor phases through a human skin membrane. The four salts show different solubility values and different behavior in the four solvents, which are also permeation enhancers and this fact further is connected to the permeation results. The same order of magnitude of fluxes through the membrane as those previously reported for acidic diclofenac released from buffer solutions of pH >7 were found, taking into account differences originated by different membranes and other parameters tested in the experiments. Saturation concentration for the four salts in different solvents, necessary to calculate permeation coefficients, was critically evaluated; a short discussion made it possible to explain that corrections in the solubility values must be considered, related to the complex behavior in solution of these salts. Statistical processing of the experimental data suggests that differences between the four salts in promoting absorption of the drug is unproven; while differences are evident between the solvents, water is the most effective enhancing vehicle. Aqueous formulations containing diclofenac salt with an organic base appear to be the best combination to promote permeation in topical applications. (c) 2007 Wiley-Liss, Inc.

  18. Measured and predicted environmental concentrations of carbamazepine, diclofenac, and metoprolol in small and medium rivers in northern Germany.

    PubMed

    Meyer, Wibke; Reich, Margrit; Beier, Silvio; Behrendt, Joachim; Gulyas, Holger; Otterpohl, Ralf

    2016-08-01

    This study evaluated the impact of secondary municipal effluent discharge on carbamazepine, diclofenac, and metoprolol concentrations in small and medium rivers in northern Germany and compared the measured environmental concentrations (MECs) to the predicted environmental concentrations (PECs) calculated with four well-established models. During a 1-year sampling period, secondary effluent grab samples were collected at four wastewater treatment plants (WWTPs) together with grab samples from the receiving waters upstream and downstream from the wastewater discharge points. The carbamazepine, diclofenac, and metoprolol concentrations were analyzed with high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS-MS) after solid phase extraction. In the secondary effluents, 84-790 ng/L carbamazepine, 395-2100 ng/L diclofenac, and 745-5000 ng/L metoprolol were detected. The carbamazepine, diclofenac, and metoprolol concentrations analyzed in the rivers downstream from the secondary effluent discharge sites ranged from <5 to 68, 370, and 520 ng/L, respectively. Most of the downstream pharmaceutical concentrations were markedly higher than the corresponding upstream concentrations. The impact of wastewater discharge on the MECs in rivers downstream from the WWTPs was clearly demonstrated, but the correlations of the MECs with dilution factors were poor. The smallest rivers exhibited the largest maximum MECs and the widest ranges of MECs downstream from the wastewater discharge point. Three of the four tested models were conservative, as they showed higher PECs than the MECs in the rivers downstream from the WWTPs. However, the most detailed model underestimated the diclofenac concentrations.

  19. Effects of ketoprofen and diclofenac potassium on blood coagulation tests after removal of third molars.

    PubMed

    Naclério-Homem, Maria da Graça; Deboni, Maria Christina Zindel; Rapoport, Abrăo; Chin, Veronica Kei Len

    2009-04-01

    Nonsteroidal anti-inflammatory drugs inhibit platelet aggregation and increase bleeding time; however, they are required to control pain and swelling following dental surgery. The objective of this study was to evaluate possible changes on blood coagulation tests by using ketoprofen and diclofenac potassium after removal of mandibular third molars. Fifty-one subjects between 16 and 30 years old, with no history of gastrointestinal disorders or allergy to anti-inflammatory components, were randomly assigned to 2 groups: 27 patients received 50 mg of ketoprofen, and 24 patients received 25 mg of diclofenac potassium. Subjects started the oral medication 2 hours before surgery and continued taking it every 8 hours for 5 days. Blood samples were collected preoperatively and on the final day of the drug regime to evaluate prothrombin time, activated partial thromboplastin time, clot retraction, and platelet count. Student t test for matched pairs did not show a significant difference between pre- and posttreatment variables for both anti-inflammatory drugs. These results suggest that the safety of ketoprofen and diclofenac potassium is comparable to their anticoagulation effect.

  20. The anti-inflammatory effect of diclofenac is considerably augmented by topical capsaicinoids-containing patch in carrageenan-induced paw oedema of rat.

    PubMed

    Ercan, Nilufer; Uludag, Mecit Orhan; Agis, Erol Rauf; Demirel-Yilmaz, Emine

    2013-12-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most used drugs in musculoskeletal disorders, but their systemic adverse effects limit their therapeutic benefit in local inflammation. On the other hand, topical preparations of capsaicinoids are widely used for musculoskeletal disorders as a complementary therapy. In this study, the effects of both topical capsaicinoids-containing patch and local subcutaneous capsaicin application on the anti-inflammatory action of NSAID were examined. Carrageenan-induced paw oedema of rats was used as the inflammation model. The volume and weight of the paw oedema and plasma extravasation in the paw were determined after carrageenan injection. The systemic application of diclofenac (3 mg/kg), which is an NSAID, significantly decreased the volume and weight of the paw oedema. Topical capsaicinoids-containing patch application or local capsaicin injection (2, 10, 20 μg/paw) alone did not cause any effect on oedema volume and weight. However, the combination of diclofenac with topical capsaicinoids-containing patch significantly increased the effectiveness of diclofenac on inflammation. Evans blue content of the paws that represents plasma extravasation was decreased by capsaicinoids-containing patch with and without diclofenac and diclofenac combination with the lowest dose of capsaicin injection. The results of this study indicate that topical application of capsaicinoids-containing patch enhances the anti-inflammatory effect of diclofenac and its beneficial effect may not purely relate to its capsaicin content. In the treatment of local inflammatory disorders, the combination of NSAID with topical capsaicinoids-containing patch could increase the anti-inflammatory efficiency of drug without systemic side effects.

  1. Disparate effects of non-steroidal anti-inflammatory drugs on apoptosis in guinea-pig gastric mucous cells: inhibition of basal apoptosis by diclofenac

    PubMed Central

    Ashton, Miranda; Hanson, Peter J

    2002-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) induce apoptosis in gastrointestinal cancer cell lines. Similar actions on normal gastric epithelial cells could contribute to NSAID gastropathy. The present work therefore compared the actions of diclofenac, ibuprofen, indomethacin, and the cyclo-oxygenase-2 selective inhibitor, NS-398, on a primary culture of guinea-pig gastric mucous epithelial cells. Cell number was assessed by staining with crystal violet. Apoptotic activity was determined by condensation and fragmentation of nuclei and by assay of caspase-3-like activity. Necrosis was evaluated from release of cellular enzymes. Ibuprofen (250 μM for 24 h) promoted cell loss, and apoptosis, under both basal conditions and when apoptosis was increased by 25 μM N-Hexanoyl-D-sphingosine (C6-ceramide). Diclofenac (250 μM for 24 h) reduced the proportion of apoptotic nuclei from 5.2 to 2.1%, and caused inhibition of caspase-3-like activity, without causing necrosis under basal conditions. No such reduction in apoptotic activity was evident in the presence of 25 μM C6-ceramide. The inhibitory effect of diclofenac on basal caspase-3-like activity was also exhibited by the structurally similar mefenamic and flufenamic acids (1–250 μM), but not by niflumic acid. Inhibition of superoxide production by the cells increased caspase-3-like activity, but the inhibitory action of diclofenac on caspase activity remained. Diclofenac did not affect superoxide production. Diclofenac inhibited caspase-3-like activity in cell homogenates and also inhibited human recombinant caspase-3. In conclusion, NSAIDs vary in their effect on apoptotic activity in a primary culture of guinea-pig gastric mucous epithelial cells, and the inhibitory effect of diclofenac on basal apoptosis could involve an action on caspase activity. PMID:11815376

  2. Efficacy and Safety Profile of Diclofenac/Cyclodextrin and Progesterone/Cyclodextrin Formulations: A Review of the Literature Data.

    PubMed

    Scavone, Cristina; Bonagura, Angela Colomba; Fiorentino, Sonia; Cimmaruta, Daniela; Cenami, Rosina; Torella, Marco; Fossati, Tiziano; Rossi, Francesco

    2016-06-01

    According to health technology assessment, patients deserve the best medicine. The development of drugs associated with solubility enhancers, such as cyclodextrins, represents a measure taken in order to improve the management of patients. Different drugs, such as estradiol, testosterone, dexamethasone, opioids, non-steroidal anti-inflammatories (NSAIDs; i.e. diclofenac), and progesterone are associated with cyclodextrins. Products containing the association of diclofenac/cyclodextrins are available for subcutaneous, intramuscular, and intravenous administration in doses that range from 25 to 75 mg. Medicinal products containing the association of progesterone/cyclodextrins are indicated for intramuscular and subcutaneous injection at a dose equal to 25 mg. The effects of cyclodextrins have been discussed in the solubility profile and permeability through biological membranes of drug molecules. A literature search was performed in order to give an overview of the pharmacokinetic characteristics, and efficacy and safety profiles of diclofenac/hydroxypropyl-β-cyclodextrin (HPβCD) and progesterone/HPβCD associations. The results of more than 20 clinical studies were reviewed. It was suggested that the new diclofenac/HPβCD formulation gives a rapid and effective response to acute pain and, furthermore, has pharmacokinetic and efficacy/safety profiles comparable to other medicinal products not containing cyclodextrins. One of the principal aspects of these new diclofenac formulations is that in lowering the dose (lower than 50 mg) the drugs could be more tolerable, especially in patients with comorbid conditions. Moreover, results of studies investigating the characteristics of progesterone and cyclodextrins showed that the new formulation (progesterone/HPβCD 25 mg solution) has the same bioavailability as other products containing progesterone. It is more rapidly absorbed and allows the achievement of peak plasma concentrations in a shorter time. Finally, the

  3. Bax-mediated mitochondrial outer membrane permeabilization (MOMP), distinct from the mitochondrial permeability transition, is a key mechanism in diclofenac-induced hepatocyte injury: Multiple protective roles of cyclosporin A

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Siu, W.P.; Pun, Pamela Boon Li; Latchoumycandane, Calivarathan

    2008-03-15

    Diclofenac, a widely used nonsteroidal anti-inflammatory drug, has been associated with rare but severe cases of clinical hepatotoxicity. Diclofenac causes concentration-dependent cell death in human hepatocytes (after 24-48 h) by mitochondrial permeabilization via poorly defined mechanisms. To explore whether the cyclophilin D (CyD)-dependent mitochondrial permeability transition (mPT) and/or the mitochondrial outer membrane permeabilization (MOMP) was primarily involved in mediating cell death, we exposed immortalized human hepatocytes (HC-04) to apoptogenic concentrations of diclofenac (> 500 {mu}M) in the presence or absence of inhibitors of upstream mediators. The CyD inhibitor, cyclosporin A (CsA, 2 {mu}M) fully inhibited diclofenac-induced cell injury, suggesting thatmore » mPT was involved. However, CyD gene silencing using siRNA left the cells susceptible to diclofenac toxicity, and CsA still protected the CyD-negative cells from lethal injury. Diclofenac induced early (9 h) activation of Bax and Bak and caused mitochondrial translocation of Bax, indicating that MOMP was involved in cell death. Inhibition of Bax protein expression by using siRNA significantly protected HC-04 from diclofenac-induced cell injury. Diclofenac also induced early Bid activation (tBid formation, 6 h), which is an upstream mechanism that initiates Bax activation and mitochondrial translocation. Bid activation was sensitive to the Ca{sup 2+} chelator, BAPTA. In conclusion, we found that Bax/Bak-mediated MOMP is a key mechanism of diclofenac-induced lethal cell injury in human hepatocytes, and that CsA can prevent MOMP through inhibition of Bax activation. These data support our concept that the Ca{sup 2+}-Bid-Bax-MOMP axis is a critical pathway in diclofenac (metabolite)-induced hepatocyte injury.« less

  4. Occurrence and fate of carbamazepine, clofibric acid, diclofenac, ibuprofen, ketoprofen, and naproxen in surface waters.

    PubMed

    Tixier, Céline; Singer, Heinz P; Oellers, Sjef; Müller, Stephan R

    2003-03-15

    Although various single-concentration measurements of pharmaceuticals are available in the literature, detailed information on the variation over time of the concentration and the load in wastewater effluents and rivers and on the fate of these compounds in the aquatic environment are lacking. We measured the concentrations of six pharmaceuticals, carbamazepine, clofibric acid, diclofenac, ibuprofen, ketoprofen, and naproxen, in the effluents of three wastewater treatment plants (WWTPs), in two rivers and in the water column of Lake Greifensee (Switzerland) over a time period of three months. In WWTP effluents, the concentrations reached 0.95 microg/L for carbamazepine, 0.06 microg/L for clofibric acid, 0.99 microg/L for diclofenac, 1.3 microg/L for ibuprofen, 0.18 microg/L for ketoprofen, and 2.6 microg/L for naproxen. The relative importance in terms of loads was carbamazepine, followed by diclofenac, naproxen, ibuprofen, clofibric acid, and ketoprofen. An overall removal rate of all these pharmaceuticals was estimated in surface waters, under real-world conditions (in a lake), using field measurements and modeling. Carbamazepine and clofibric acid were fairly persistent. Phototransformation was identified as the main elimination process of diclofenac in the lake water during the study period. With a relatively high sorption coefficient to particles, ibuprofen might be eliminated by sedimentation. For ketoprofen and naproxen, biodegradation and phototransformation might be elimination processes. For the first time, quantitative data regarding removal rates were determined in surface waters under real-world conditions. All these findings are important data for a risk assessment of these compounds in surface waters.

  5. Diclofenac-induced biochemical and histopathological changes in white leghorn birds (Gallus domesticus).

    PubMed

    Jain, Teenu; Koley, K M; Vadlamudi, V P; Ghosh, R C; Roy, S; Tiwari, Sandhya; Sahu, Upasana

    2009-10-01

    To evaluate diclofenac-induced biochemical and histopathological changes in White Leghorn birds. Six-week-old birds were equally divided into three groups of six birds each. Group I served as control and received vehicle orally. The birds of Group II and III were orally administered with a single low (2 mg/kg) and high dose (20 mg/kg) of diclofenac sodium, respectively, and were observed for 7 days. The acute toxicity was assessed by observing the clinical signs and symptoms, mortality, alterations in blood biochemistry, and necropsy findings. The birds of Group II showed only mild symptoms of diarrhea. In Group III, 50% of birds died in between 24 and 36 h post-treatment showing the symptoms of segregatory behavior, lethargy, terminal anorexia, and severe bloody diarrhea. The birds of Group II and the surviving birds of Group III showed a significantly (P<0.05) increased plasma uric acid, creatinine and plasma glutamic pyruvic transaminase (PGPT), and decreased total protein and albumin at 12 and 24 h post-treatment which returned to the normal levels at 36 h post-treatment. The dead birds of the high-dose group also showed similar pattern of biochemical changes at 12 and 24 h post-treatment and revealed extensive visceral gout with characteristic histopathological lesions in liver, kidney, heart, spleen, and intestine on post-mortem. The results indicate that diclofenac sodium has hepatotoxic, nephrotoxic, and visceral gout inducing potentials in White Leghorn birds, especially at higher dose.

  6. Assessment of diclofenac LC50 reference values in juvenile and embryonic stages of the zebrafish (Danio rerio).

    PubMed

    Praskova, E; Voslarova, E; Siroka, Z; Plhalova, L; Macova, S; Marsalek, P; Pistekova, V; Svobodova, Z

    2011-01-01

    The aim of the study was to compare the acute toxicity of diclofenac to juvenile and embryonic stages of the zebrafish (Danio rerio). Acute toxicity tests were performed on the aquarium fish Danio rerio, which is one of the model organisms most commonly used in toxicity testing. The tests were performed using a semi-static method according to OECD guideline No. 203 (Fish, acute toxicity test). Embryo toxicity tests were performed in zebrafish embryos (Danio rerio) in compliance with OECD No. 212 methodology (Fish, short-term toxicity test on embryo and sac-fry stages). The results were subjected to a probit analysis using the EKO-TOX 5.2 programme to determine 96hLC50 and 144hLC50 (median lethal concentration, 50% mortality after a 96 h or 144 h interval, respectively) values of diclofenac. The statistical significance of the difference between LC50 values in juvenile and embryonic stages of Danio rerio was tested using the Mann-Whitney non-parametric test implemented in the Unistat 5.1 programme. The LC50 mean value of diclofenac was 166.6 +/- 9.8 mg/L in juvenile Danio rerio, and 6.11 +/- 2.48 mg/L in embryonic stages of Danio rerio. The study demonstrated a statistically higher sensitivity to diclofenac (P < 0.05) in embryonic stages compared to the juvenile fish.

  7. Evaluation of removal efficiency of residual diclofenac in aqueous solution by nanocomposite tungsten-carbon using design of experiment.

    PubMed

    Salmani, M H; Mokhtari, M; Raeisi, Z; Ehrampoush, M H; Sadeghian, H A

    2017-09-01

    Wastewater containing pharmaceutical residual components must be treated before being discharged to the environment. This study was conducted to investigate the efficiency of tungsten-carbon nanocomposite in diclofenac removal using design of experiment (DOE). The 27 batch adsorption experiments were done by choosing three effective parameters (pH, adsorbent dose, and initial concentration) at three levels. The nanocomposite was prepared by tungsten oxide and activated carbon powder in a ratio of 1 to 4 mass. The remaining concentration of diclofenac was measured by a spectrometer with adding reagents of 2, 2'-bipyridine, and ferric chloride. Analysis of variance (ANOVA) was applied to determine the main and interaction effects. The equilibrium time for removal process was determined as 30 min. It was observed that the pH had the lowest influence on the removal efficiency of diclofenac. Nanocomposite gave a high removal at low concentration of 5.0 mg/L. The maximum removal for an initial concentration of 5.0 mg/L was 88.0% at contact time of 30 min. The results of ANOVA showed that adsorbent mass was among the most effective variables. Using DOE as an efficient method revealed that tungsten-carbon nanocomposite has high efficiency in the removal of residual diclofenac from the aqueous solution.

  8. Downregulation of PI3-K/Akt/PTEN pathway and activation of mitochondrial intrinsic apoptosis by Diclofenac and Curcumin in colon cancer.

    PubMed

    Rana, Chandan; Piplani, Honit; Vaish, Vivek; Nehru, Bimla; Sanyal, S N

    2015-04-01

    Phosphatidylinositol 3-kinase (PI3-K)/PTEN/Akt signaling is over activated in various tumors including colon cancer. Activation of this pathway regulates multiple biological processes such as apoptosis, metabolism, cell proliferation, and cell growth that underlie the biology of a cancer cell. In the present study, the chemopreventive effects have been observed of Diclofenac, a preferential COX-2 inhibitory non-steroidal anti-inflammatory drugs, and Curcumin, a natural anti-inflammatory agent, in the early stage of colorectal carcinogenesis induced by 1,2-dimethylhydrazine dihydrochloride in rats. The tumor-promoting role of PI3-K/Akt/PTEN signal transduction pathway and its association with anti-apoptotic family of proteins are also observed. Both Diclofenac and Curcumin downregulated the PI3-K and Akt expression while promoting the apoptotic mechanism. Diclofenac and Curcumin administration significantly increased the expression of pro-apoptotic Bcl-2 family members (Bad and Bax) while decreasing the anti-apoptotic Bcl-2 protein. An up-regulation of cysteine protease family apoptosis executioner, such as caspase-3 and -9, is seen. Diclofenac and Curcumin inhibited the Bcl-2 protein by directly interacting at the active site by multiple hydrogen bonding, as also evident by negative glide score of Bcl-2. These drugs stimulated apoptosis by increasing reactive oxygen species (ROS) generation and simultaneously decreasing the mitochondrial membrane potential (ΔΨ M). Diclofenac and Curcumin showed anti-neoplastic effects by downregulating PI3-K/Akt/PTEN pathway, inducing apoptosis, increasing ROS generation, and decreasing ΔΨ M. The anti-neoplastic and apoptotic effects were found enhanced when both Diclofenac and Curcumin were administered together, rather than individually.

  9. The pathogenesis of diclofenac induced immunoallergic hepatitis in a canine model of liver injury

    PubMed Central

    Selvaraj, Saravanakumar; Oh, Jung-Hwa; Spanel, Reinhard; Länger, Florian; Han, Hyoung-Yun; Lee, Eun-Hee; Yoon, Seokjoo; Borlak, Jürgen

    2017-01-01

    Hypersensitivity to non-steroidal anti-inflammatory drugs is a common adverse drug reaction and may result in serious inflammatory reactions of the liver. To investigate mechanism of immunoallergic hepatitis beagle dogs were given 1 or 3 mg/kg/day (HD) oral diclofenac for 28 days. HD diclofenac treatment caused liver function test abnormalities, reduced haematocrit and haemoglobin but induced reticulocyte, WBC, platelet, neutrophil and eosinophil counts. Histopathology evidenced hepatic steatosis and glycogen depletion, apoptosis, acute lobular hepatitis, granulomas and mastocytosis. Whole genome scans revealed 663 significantly regulated genes of which 82, 47 and 25 code for stress, immune response and inflammation. Immunopathology confirmed strong induction of IgM, the complement factors C3&B, SAA, SERPING1 and others of the classical and alternate pathway. Alike, marked expression of CD205 and CD74 in Kupffer cells and lymphocytes facilitate antigen presentation and B-cell differentiation. The highly induced HIF1A and KLF6 protein expression in mast cells and macrophages sustain inflammation. Furthermore, immunogenomics discovered 24, 17, 6 and 11 significantly regulated marker genes to hallmark M1/M2 polarized macrophages, lymphocytic and granulocytic infiltrates; note, the latter was confirmed by CAE staining. Other highly regulated genes included alpha-2-macroglobulin, CRP, hepcidin, IL1R1, S100A8 and CCL20. Diclofenac treatment caused unprecedented induction of myeloperoxidase in macrophages and oxidative stress as shown by SOD1/SOD2 immunohistochemistry. Lastly, bioinformatics defined molecular circuits of inflammation and consisted of 161 regulated genes. Altogether, the mechanism of diclofenac induced liver hypersensitivity reactions involved oxidative stress, macrophage polarization, mastocytosis, complement activation and an erroneous programming of the innate and adaptive immune system. PMID:29296203

  10. Diclofenac Salts. V. Examples of Polymorphism among Diclofenac Salts with Alkyl-hydroxy Amines Studied by DSC and HSM

    PubMed Central

    Fini, Adamo; Cavallari, Cristina; Ospitali, Francesca

    2010-01-01

    Nine diclofenac salts prepared with alkyl-hydroxy amines were analyzed for their properties to form polymorphs by DSC and HSM techniques. Thermograms of the forms prepared from water or acetone are different in most cases, suggesting frequent examples of polymorphism among these salts. Polymorph transition can be better highlighted when analysis is carried out by thermo-microscopy, which in most cases made it possible to observe the processes of melting of the metastable form and re-crystallization of the stable one. Solubility values were qualitatively related to the crystal structure of the salts and the molecular structure of the cation. PMID:27721347

  11. Rate of Decline of the Oriental White-Backed Vulture Population in India Estimated from a Survey of Diclofenac Residues in Carcasses of Ungulates

    PubMed Central

    Green, Rhys E.; Taggart, Mark A.; Senacha, Kalu Ram; Raghavan, Bindu; Pain, Deborah J.; Jhala, Yadvendradev; Cuthbert, Richard

    2007-01-01

    The non-steroidal anti-inflammatory drug diclofenac is a major cause of the rapid declines in the Indian subcontinent of three species of vultures endemic to South Asia. The drug causes kidney failure and death in vultures. Exposure probably arises through vultures feeding on carcasses of domesticated ungulates treated with the drug. However, before the study reported here, it had not been established from field surveys of ungulate carcasses that a sufficient proportion was contaminated to cause the observed declines. We surveyed diclofenac concentrations in samples of liver from carcasses of domesticated ungulates in India in 2004–2005. We estimated the concentration of diclofenac in tissues available to vultures, relative to that in liver, and the proportion of vultures killed after feeding on a carcass with a known level of contamination. We assessed the impact of this mortality on vulture population trend with a population model. We expected levels of diclofenac found in ungulate carcasses in 2004–2005 to cause oriental white-backed vulture population declines of 80–99% per year, depending upon the assumptions used in the model. This compares with an observed rate of decline, from road transect counts, of 48% per year in 2000–2003. The precision of the estimate based upon carcass surveys is low and the two types of estimate were not significantly different. Our analyses indicate that the level of diclofenac contamination found in carcasses of domesticated ungulates in 2004–2005 was sufficient to account for the observed rapid decline of the oriental white-backed vulture in India. The methods we describe could be used again to assess changes in the effect on vulture population trend of diclofenac and similar drugs. In this way, the effectiveness of the recent ban in India on the manufacture and importation of diclofenac for veterinary use could be monitored. PMID:17668064

  12. W/O/W multiple emulsions with diclofenac sodium.

    PubMed

    Lindenstruth, Kai; Müller, Bernd W

    2004-11-01

    The disperse oil droplets of W/O/W multiple emulsions contain small water droplets, in which drugs could be incorporated, but the structure of these emulsions is also the reason for possible instability. Due to the middle oil phase which acts as a 'semipermeable' membrane the passage of water across the oil phase can take place. However, the emulsions have been produced in a two-step-production process so not only the leakage of encapsulated drug molecules out of the inner water phase during storage but also a production-induced reduction of the encapsulation rate should be considered. The aim of this study was to ascertain how far the production-induced reduction of the encapsulation rate relates to the size of inner water droplets and to evaluate the relevance of multiple emulsions as drug carrier for diclofenac sodium. Therefore multiple emulsions were produced according to a central composite design. During the second production step it was observed that the parameters pressure and temperature have an influence on the size of the oil droplets in the W/O/W multiple emulsions. Further experiments with different W/O emulsions resulted in W/O/W multiple emulsions with different encapsulation rates of diclofenac sodium, due to the different sizes of the inner water droplets, which were obtained in the first production step.

  13. The effects of topical diclofenac, topical flurbiprofen, and humidity on corneal sensitivity in normal dogs.

    PubMed

    Dorbandt, Daniel M; Labelle, Amber L; Mitchell, Mark A; Hamor, Ralph E

    2017-03-01

    To determine the immediate and chronic effects of topical 0.1% diclofenac and 0.03% flurbiprofen on corneal sensitivity in normal canine eyes. Eighteen normal, nonbrachycephalic dogs. A prospective, randomized, masked, crossover study was performed. To determine the immediate effects associated with treatment, the study drug was instilled into the eye every 5 min for five doses, and corneal sensitivity of treated and untreated eyes was obtained prior to treatment and every 15 min post-treatment for 60 min. To determine the chronic effects, the study drug was instilled every 12 h for 30 days, and corneal sensitivity of treated and untreated eyes was obtained prior to treatment on days 0 and 30. A washout period of at least 30 days occurred between drug crossover. Ambient temperature and humidity were measured throughout the study. After multiple instillations, there was no difference in corneal sensitivity between eyes over time for diclofenac (P = 0.67) or flurbiprofen (P = 0.54), with a median sensitivity of 25 mm (1.8 g/mm 2 ). After chronic dosing, there was no difference in corneal sensitivity between eyes over time for diclofenac (P = 0.82) or flurbiprofen (P = 0.56), with a median sensitivity of 35 mm (1.0 g/mm 2 ). Decreasing ambient humidity was associated with an increase in sensitivity measurements (P = 0.0001). Neither diclofenac nor flurbiprofen had an effect on corneal sensitivity after multiple-drops or twice-daily dosing for 30 days. Ambient humidity may have an effect on corneal sensitivity measurements, with a longer filament length eliciting a blink response at lower humidity. © 2016 American College of Veterinary Ophthalmologists.

  14. Comparison of the physicochemical properties of the N-(2-hydroxyethyl) pyrrolidine, diethylamine and sodium salt forms of diclofenac.

    PubMed

    O'Connor, K M; Corrigan, O I

    2001-07-17

    Non steroidal anti-inflammatory agents (NSAIDs) such as diclofenac have very low aqueous solubilities and consequently salt formation may be used to enhance solubility and dissolution rate. In this study, we examined the physicochemical properties of three diclofenac salts, diclofenac sodium (DNa), diclofenac N-(2-hydroxyethyl)pyrrolidine (DHEP) and diclofenac diethylamine (DDEA), and their different solid state forms to determine the influence of salt form on solubility, dissolution rate and membrane transport. The equilibrium solubility of DDEA at 25 degrees C was determined as 33 mM, lower than the solubilities of DHEP (273 mM) and DNa (66 mM) previously reported (Ledwidge and Corrigan, 1998). In addition to the dihydrate form of DHEP previously characterised, monohydrate forms of DHEP and DDEA were identified. Intrinsic dissolution rate studies were used to determine the solubility ratios of the hydrated and anhydrous forms. The monohydrate form of DHEP was found to be 1.8 times less soluble than the anhydrate, whereas DDEA anhydrate was approximately 1.7 times as soluble as the monohydrate form. On investigation of the pH-solubility profile (25 degrees C) of DDEA, appreciable supersaturation (76 mM) relative to the theoretical profile, was detected at the pH(max). This contrasts with values of >800 and 67 mM for DHEP and DNa, respectively. The transport of salt solutions through a porous membrane (Visking) was investigated. A linear relationship between concentration (mM) and rate of transport (mmol/h) was established for DNa and DHEP solutions. The mass transfer coefficient determined for DHEP was lower than that for the other two salts. Nevertheless, the maximum transport rate obtained for DHEP is almost six times higher than that obtained for DDEA.

  15. Topical bioavailability of diclofenac from locally-acting, dermatological formulations.

    PubMed

    Cordery, S F; Pensado, A; Chiu, W S; Shehab, M Z; Bunge, A L; Delgado-Charro, M B; Guy, R H

    2017-08-30

    Assessment of the bioavailability of topically applied drugs designed to act within or beneath the skin is a challenging objective. A number of different, but potentially complementary, techniques are under evaluation. The objective of this work was to evaluate in vitro skin penetration and stratum corneum tape-stripping in vivo as tools with which to measure topical diclofenac bioavailability from three approved and commercialized products (two gels and one solution). Drug uptake into, and its subsequent clearance from, the stratum corneum of human volunteers was used to estimate the input rate of diclofenac into the viable skin layers. This flux was compared to that measured across excised porcine skin in conventional diffusion cells. Both techniques clearly demonstrated (a) the superiority in terms of drug delivery from the solution, and (b) that the two gels performed similarly. There was qualitative and, importantly, quantitative agreement between the in vitro and in vivo measurements of drug flux into and beyond the viable skin. Evidence is therefore presented to support an in vivo - in vitro correlation between methods to assess topical drug bioavailability. The potential value of the stratum corneum tape-stripping technique to quantify drug delivery into (epi)dermal and subcutaneous tissue beneath the barrier is demonstrated. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Enhanced percutaneous permeability of diclofenac using a new U-type dilutable microemulsion.

    PubMed

    Shevachman, Marina; Garti, Nissim; Shani, Arnon; Sintov, Amnon C

    2008-04-01

    Enhanced systemic absorption in vivo and percutaneous penetration in vitro was demonstrated after transdermal administration of diclofenac sodium formulated in U-type microemulsion. Diclofenac sodium was solubilized in a typical four-component system consisting of an oil, polyoxyethylene-10EO-oleyl alcohol (Brij 96V) as the surfactant, and 1-hexanol along water dilution line W46 (40 wt % surfactant and 60 wt % oil phase before water titration). Viscosity and small angle X-ray scattering measurements have evidenced bicontinuous structures within water fractions of 0.25 and 0.5 along the dilution line. Self-diffusion NMR studies showed that drug molecules accumulated in the interfacial film and, to some extent, dissolved in the oil. Relative to a commercial macro-emulsion cream (Voltaren Emulgel), microemulsions containing paraffin oil or isopropyl myristate increased the in vivo transdermal penetration rate of diclofenac by two order of magnitude, whereas the rat plasma levels were increased by one order of magnitude. The in vitro data obtained from excised rat skin were comparable to the in vivo results, but suffered from discrepancies from the ideal in vivo-in vitro correlation, which might be explained by optimal in vitro conditions of perfusion and hydration. It has also been found that when jojoba oil is formulated as the oil phase in the microemulsion, the penetration rate of the drug decreases significantly. Based on the three-dimensional structure of jojoba oil, the wax is presumed to prevent the drug from being freely diffused into the skin while migrating from the interfacial film into the continuous oil phase.

  17. Topical nonsteroidal anti-inflammatory drugs for the treatment of pain due to soft tissue injury: diclofenac epolamine topical patch

    PubMed Central

    Lionberger, David R; Brennan, Michael J

    2010-01-01

    The objective of this article is to review published clinical data on diclofenac epolamine topical patch 1.3% (DETP) in the treatment of acute soft tissue injuries, such as strains, sprains, and contusions. Review of published literature on topical nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac, and DETP in patients with acute soft tissue injuries was included. Relevant literature was identified on MEDLINE using the search terms topical NSAIDs, diclofenac, diclofenac epolamine, acute pain, sports injury, soft tissue injury, strain, sprain, and contusion, and from citations in retrieved articles covering the years 1978–2008. Review of published, randomized clinical trials and meta-analyses shows that topical NSAIDs are significantly more effective than placebo in relieving acute pain; the pooled average relative benefit was 1.7 (95% confidence interval, 1.5–1.9). In a limited number of comparisons, topical and oral NSAIDs provided comparable pain relief, but the use of topical agents produced lower plasma drug concentrations and fewer systemic adverse events (AEs). The physical–chemical properties of diclofenac epolamine make it well suited for topical use. In patients with acute soft tissue injuries treated with DETP, clinical data report an analgesic benefit within hours of the first application, and significant pain relief relative to placebo within 3 days. Moreover, DETP displayed tolerability comparable with placebo; the most common AEs were pruritus and other application site reactions. Review of published literature suggests that DETP is generally safe and well tolerated, clinically efficacious, and a rational treatment option for patients experiencing acute pain associated with strains, sprains, and contusions, and other localized painful conditions. PMID:21197326

  18. Pathology and proposed pathophysiology of diclofenac poisoning in free-living and experimentally exposed oriental white-backed vultures (Gyps bengalensis)

    USGS Publications Warehouse

    Meteyer, C.U.; Rideout, B.A.; Gilbert, M.; Shivaprasad, H.L.; Oaks, J.L.

    2005-01-01

    Oriental white-backed vultures (Gyps bengalensis; OWBVs) died of renal failure when they ingested diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), in tissues of domestic livestock. Acute necrosis of proximal convoluted tubules in these vultures was severe. Glomeruli, distal convoluted tubules, and collecting tubules were relatively spared in the vultures that had early lesions. In most vultures, however, lesions became extensive with large urate aggregates obscuring renal architecture. Inflammation was minimal. Extensive urate precipitation on the surface and within organ parenchyma (visceral gout) was consistently found in vultures with renal failure. Very little is known about the physiologic effect of NSAIDs in birds. Research in mammals has shown that diclofenac inhibits formation of prostaglandins. We propose that the mechanism by which diclofenac induces renal failure in the OWBV is through the inhibition of the modulating effect of prostaglandin on angiotensin II-mediated adrenergic stimulation. Renal portal valves open in response to adrenergic stimulation, redirecting portal blood to the caudal vena cava and bypassing the kidney. If diclofenac removes a modulating effect of prostaglandins on the renal portal valves, indiscriminant activation of these valves would redirect the primary nutrient blood supply away from the renal cortex. Resulting ischemic necrosis of the cortical proximal convoluted tubules would be consistent with our histologic findings in these OWBVs.

  19. Diclofenac Loaded Lipid Nanovesicles Prepared by Double Solvent Displacement for Skin Drug Delivery.

    PubMed

    Sala, M; Locher, F; Bonvallet, M; Agusti, G; Elaissari, A; Fessi, H

    2017-09-01

    Herein, we detail a promising strategy of nanovesicle preparation based on control of phospholipid self-assembly: the Double Solvent Displacement. A systematic study was conducted and diclofenac as drug model encapsulated. In vitro skin studies were carried out to identify better formulation for dermal/transdermal delivery. This method consists in two solvent displacements. The first one, made in a free water environment, has allowed triggering a phospholipid pre-organization. The second one, based on the diffusion into an aqueous phase has led to liposome formation. Homogeneous liposomes were obtained with a size close to 100 nm and a negative zeta potential around -40 mV. After incorporation of acid diclofenac, we obtained nanoliposomes with a size between 101 ± 45 and 133 ± 66 nm, a zeta potential between 34 ± 2 and 49 ± 3 mV, and the encapsulation efficiency (EE%) was between 58 ± 3 and 87 ± 5%. In vitro permeation studies showed that formulation with higher EE% dispayed the higher transdermal passage (18,4% of the applied dose) especially targeting dermis and beyond. Our results suggest that our diclofenac loaded lipid vesicles have significant potential as transdermal skin drug delivery system. Here, we produced cost effective lipid nanovesicles in a merely manner according to a process easily transposable to industrial scale. Graphical Abstract ᅟ.

  20. Simultaneous determination of diclofenac and oxybuprocaine in human aqueous humor with HPLC and electrochemical detection.

    PubMed

    Kuhlmann, O; Stoldt, G; Struck, H G; Krauss, G J

    1998-09-01

    A sensitive and selective bioanalytical method for simultaneous determination of diclofenac and oxybuprocaine in human aqueous humor using reversed-phase HPLC and electrochemical detection is described. Chromatographic separation was achieved by using a Regis SPS 100 RP-8 column (5 microns; 150 x 4.6 mm I.D.). This support is coated with a hydrophilic polyoxyethylenepolymer. It allows protein-containing samples to be injected directly onto the column. The electrochemical detector permit a detection limit of 500 pg diclofenac per ml (daily relative standard deviation 6.3%) and 50 ng oxybuprocaine per ml (daily R.S.D. 2.6%), respectively. Results of administered and measured drug-concentrations in time dependent decrease are presented.

  1. Diclofenac sodium (DS) loaded bioerodible polymer based constructs

    NASA Astrophysics Data System (ADS)

    Piras, M.; Chiellini, F.; Nikkola, L.; Ashammakhi, N.; Chiellini, E.

    2008-02-01

    Pain is a prevalent problem that can raise morbidity of patients. Pain killer releasing biodegradable materials have been developed by using different techniques and biomaterials. The objective of the current study is to evaluate the use of a new bioerodible polymer for release of diclofenac sodium (DS). 1-butanol hemiester poly(maleic anhydride-alt-2-methoxyethyl vinyl ether) (PAM14) was prepared in the university of Pisa and selected as polymer of choice for the study. Polymer solutions of 5-10% (in ethanol or in acetic acid) were prepared, half of them containing 2% DS. The solutions were then electrospun to produce nanomats that were subsequently characterized using SEM. Fiber diameter was 160 nm 1 μm. Increasing polymer concentration increased the size of the fibers but reduced the number of beads (with or without DS). In the specimens obtained from acetic acid solution, the addition of DS resulted in a reduction in fiber diameter and an increase in the inter-bead distance. Corresponding ethanol solutions gave more homogeneous specimens than did acetic acid, having a lower number of beads. With the addition of DS a reduction in fiber diameter was observed for the acetic acid specimens. However, in ethanol, adding DS resulted in increased fiber diameter. Accordingly, it can be concluded that it is feasible to develop electrospun diclofenac releasing bioerodible nanostructures that have potential use in pain management. Their further evaluation is however, needed both in vitro and in vivo.

  2. Diclofenac Potassium in Acute Postoperative Pain and Dysmenorrhoea: Results from Comprehensive Clinical Trial Reports

    PubMed Central

    2018-01-01

    We compared the efficacy of diclofenac potassium in unpublished clinical study reports (CSRs) and published reports to examine publication bias, industry bias, and comprehensiveness. Novartis provided CSRs of randomised double-blind trials of diclofenac potassium involving postoperative patients following third molar extraction (3 trials, n=519), gynaecological surgery (3 trials, n=679), and dysmenorrhoea (2 trials, n=711) conducted in 1988–1990. Searches identified published reports of 6 trials. Information from 599/1909 patients was not published; trials with 846/1909 patients were published in a defunct journal. Greater methodological information in CSRs contributed to lesser risk of bias than published trials. Numbers needed to treat (NNT) from CSRs for all six postoperative trials for at least 50% of maximum pain relief over 6 h were 2.2 (95% confidence interval, 1.9–2.6) and 2.1 (1.8–2.4) for 50 and 100 mg diclofenac potassium, respectively. A Cochrane review of published trial data reported NNTs of 2.1 and 1.9, and one comprehensive analysis reported NNTs of 2.2 and 2.1, respectively. All analyses had similar results for patients remedicating within 8 h. No data from dysmenorrhoea CSRs appeared in a Cochrane review. CSRs provide useful information and increase confidence. Stable efficacy estimates with standard study designs reduce the need for updating reviews. PMID:29623148

  3. Diclofenac enables unprecedented week-long microneedle-enhanced delivery of a skin impermeable medication in humans

    PubMed Central

    Brogden, Nicole K.; Banks, Stan L.; Crofford, Leslie J.; Stinchcomb, Audra L.

    2013-01-01

    Microneedles applied to the skin create micropores, allowing transdermal drug delivery of skin-impermeable compounds. The first human study with this technique demonstrated delivery of naltrexone (an opioid antagonist) for two to three days. Rapid micropore closure, however, blunts the delivery window. Application of diclofenac (an anti-inflammatory) allows seven days of naltrexone delivery in animals. Purpose the purpose of the current work was to demonstrate delivery of naltrexone for seven days following one microneedle treatment in humans. Methods Human subjects were treated with microneedles, diclofenac (or placebo), and naltrexone. Impedance measurements were used as a surrogate marker to measure micropore formation, and plasma naltrexone concentrations were measured for seven days post-microneedle application. Results Impedance dropped significantly from baseline to post-microneedle treatment, confirming micropore formation. Naltrexone was detected for seven days in Group 1 (diclofenac + naltrexone, n = 6), vs. 72 hours in Group 2 (placebo + naltrexone, n = 2). At study completion, a significant difference in impedance was observed between intact and microneedle-treated skin in Group 1 (confirming the presence of micropores). Conclusion This is the first study demonstrating week-long drug delivery after one microneedle application, which would increase patient compliance and allow delivery of therapies for chronic diseases. PMID:23761054

  4. Photodegradation kinetics, transformation, and toxicity prediction of ketoprofen, carprofen, and diclofenac acid in aqueous solutions.

    PubMed

    Li, Jian; Ma, Li-Yun; Li, Lu-Shuang; Xu, Li

    2017-12-01

    Photodegradation of 3 commonly used nonsteroidal anti-inflammatory drugs, ketoprofen, carprofen, and diclofenac acid, was conducted under ultraviolet (UV) irradiation. The kinetic results showed that the 3 pharmaceuticals obeyed the first-order reaction with decreasing rate constants of 1.54 × 10 -4 , 5.91 × 10 -5 , and 7.78 × 10 -6  s -1 for carprofen, ketoprofen, and diclofenac acid, respectively. Moreover, the main transformation products were identified by ion-pair liquid-liquid extraction combined with injection port derivatization-gas chromatography-mass spectrometry and high-performance liquid chromatography-quadrupole-time of flight mass spectrometric analysis. There were 8, 3, and 6 transformation products identified for ketoprofen, carprofen, and diclofenac acid, respectively. Decarboxylation, dechlorination, oxidation, demethylation, esterification, and cyclization were proposed to be associated with the transformation of the 3 pharmaceuticals. Toxicity prediction of the transformation products was conducted on the EPI Suite software based on ECOSAR model, and the results indicate that some of the transformation products were more toxic than the parent compounds. The present study provides the foundation to understand the transformation behavior of the studied pharmaceuticals under UV irradiation. Environ Toxicol Chem 2017;36:3232-3239. © 2017 SETAC. © 2017 SETAC.

  5. Fast mineralization and detoxification of amoxicillin and diclofenac by photocatalytic ozonation and application to an urban wastewater.

    PubMed

    Moreira, Nuno F F; Orge, Carla A; Ribeiro, Ana R; Faria, Joaquim L; Nunes, Olga C; Pereira, M Fernando R; Silva, Adrián M T

    2015-12-15

    The degradation of two organic pollutants (amoxicillin and diclofenac) in 0.1 mM aqueous solutions was studied by using advanced oxidation processes, namely ozonation, photolysis, photolytic ozonation, photocatalysis and photocatalytic ozonation. Diclofenac was degraded quickly under direct photolysis by artificial light (medium-pressure vapor arc, λ(exc) > 300 nm), while amoxicillin remained very stable. In the presence of ozone, regardless of the type of process, complete degradation of both organic pollutants was observed in less than 20 min. Photolysis or ozonation on their own led to modest values of total organic carbon (TOC) removal (<6% or 41%, respectively in 180 min), while for photocatalysis (no ozone present) a significant fraction of nonoxidizable compounds remained in the treated water (∼15% after 180 min). In the case of photolytic ozonation, the kinetics of TOC removal was slow. In contrast, a relatively fast and complete mineralization of amoxicillin and diclofenac (30 and 120 min, respectively) was achieved when applying the photocatalytic ozonation process. The absence of toxicity of the treated waters was confirmed by growth inhibition assays using two different microorganisms, Escherichia coli and Staphylococcus aureus. Photocatalytic ozonation was also applied to an urban wastewater spiked with both amoxicillin and diclofenac. The parent pollutants were easily oxidized, but the TOC removal was only as much as 68%, mainly due to the persistent presence of oxamic acid in the treated sample. The same treatment allowed the effective degradation of a wide group of micropollutants (pesticides, pharmaceuticals, hormones and an industrial compound) detected in non-spiked urban wastewater. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. New Stability-Indicating RP-HPLC Method for Determination of Diclofenac Potassium and Metaxalone from their Combined Dosage Form

    PubMed Central

    Panda, Sagar Suman; Patanaik, Debasis; Ravi Kumar, Bera V. V.

    2012-01-01

    A simple, precise and accurate isocratic RP-HPLC stability-indicating assay method has been developed to determine diclofenac potassium and metaxalone in their combined dosage forms. Isocratic separation was achieved on a Hibar-C18, Lichrosphere-100® (250 mm × 4.6 mm i.d., particle size 5 μm) column at room temperature in isocratic mode, the mobile phase consists of methanol: water (80:20, v/v) at a flow rate of 1.0 ml/min, the injection volume was 20 μl and UV detection was carried out at 280nm. The drug was subjected to acid and alkali hydrolysis, oxidation, photolysis and heat as stress conditions. The method was validated for specificity, linearity, precision, accuracy, robustness and system suitability. The method was linear in the drug concentration range of 2.5–30 μg/ml and 20–240 μg/ml for diclofenac potassium and metaxalone, respectively. The precision (RSD) of six samples was 0.83 and 0.93% for repeatability, and the intermediate precision (RSD) among six-sample preparation was 1.63 and 0.49% for diclofenac potassium and metaxalone, respectively. The mean recoveries were between 100.99–102.58% and 99.97–100.01% for diclofenac potassium and metaxalone, respectively. The proposed method can be used successfully for routine analysis of the drug in bulk and combined pharmaceutical dosage forms. PMID:22396909

  7. Modulation of Rat Hepatic CYP1A and 2C Activity by Honokiol and Magnolol: Differential Effects on Phenacetin and Diclofenac Pharmacokinetics In Vivo.

    PubMed

    Kim, Sang-Bum; Kim, Kyu-Sang; Ryu, Heon-Min; Hong, Seong-Ho; Kim, Bo-Kyoung; Kim, Dae-Duk; Park, Jin Woo; Yoon, In-Soo

    2018-06-17

    Honokiol (2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol) and magnolol (4-Allyl-2-(5-allyl-2-hydroxy-phenyl)phenol) are the major active polyphenol constituents of Magnolia officinalis (Magnoliaceae) bark, which has been widely used in traditional Chinese medicine (Houpu Tang) for the treatment of various diseases, including anxiety, stress, gastrointestinal disorders, infection, and asthma. The aim of this study was to investigate the direct effects of honokiol and magnolol on hepatic CYP1A and 2C-mediated metabolism in vitro using rat liver microsomes and in vivo using the Sprague-Dawley rat model. Honokiol and magnolol inhibited in vitro CYP1A activity (probe substrate: phenacetin) more potently than CYP2C activity (probe substrate: diclofenac): The mean IC 50 values of honokiol for the metabolism of phenacetin and diclofenac were 8.59 μM and 44.7 μM, while those of magnolol were 19.0 μM and 47.3 μM, respectively. Notably, the systemic exposure (AUC and C max ) of phenacetin, but not of diclofenac, was markedly enhanced by the concurrent administration of intravenous honokiol or magnolol. The differential effects of the two phytochemicals on phenacetin and diclofenac in vivo pharmacokinetics could at least be partly attributed to their lower IC 50 values for the inhibition of phenacetin metabolism than for diclofenac metabolism. In addition, the systemic exposure, CL, and V ss of honokiol and magnolol tended to be similar between the rat groups receiving phenacetin and diclofenac. These findings improve our understanding of CYP-mediated drug interactions with M. officinalis and its active constituents.

  8. Diclofenac delays micropore closure following microneedle treatment in human subjects

    PubMed Central

    Brogden, Nicole K.; Milewski, Mikolaj; Ghosh, Priyanka; Hardi, Lucia; Crofford, Leslie J.; Stinchcomb, Audra L.

    2013-01-01

    Drugs absorbed poorly through the skin are commonly delivered via injection with a hypodermic needle, which is painful and increases the risk of transmitting infectious diseases. Microneedles (MNs) selectively and painlessly permeabilize the outermost skin layer, allowing otherwise skin-impermeable drugs to cross the skin through micron-sized pores and reach therapeutic concentrations. However, rapid healing of the micropores prevents further drug delivery, blunting the clinical utility of this unique transdermal technique. We present the first human study demonstrating that micropore lifetime can be extended following MN treatment. Subjects received one-time MN treatment and daily topical application of diclofenac sodium. Micropore closure was measured with impedance spectroscopy, and area under the admittance–time curve (AUC) was calculated. AUC was significantly higher at MN + diclofenac sodium sites vs. placebo, suggesting slower rates of micropore healing. Colorimetry measurements confirmed the absence of local erythema and irritation. This mechanistic human proof-of-concept study demonstrates that micropore lifetime can be prolonged with simple topical administration of a non-specific cyclooxygenase inhibitor, suggesting the involvement of subclinical inflammation in micropore healing. These results will allow for longer patch wear time with MN-enhanced delivery, thus increasing patient compliance and expanding the transdermal field to a wider variety of clinical conditions. PMID:22929967

  9. Aqueous solubility of diclofenac diethylamine in the presence of pharmaceutical additives: a comparative study with diclofenac sodium.

    PubMed

    Khalil, E; Najjar, S; Sallam, A

    2000-04-01

    Aqueous solubility of diclofenac diethylamine (DDEA), a nonsteroidal anti-inflammatory drug currently formulated as a topical emulgel, was studied in the presence of pharmaceutical additives and compared with diclofenac sodium (DS). Electrolytes at low concentrations exhibited a salting-in effect on DDEA with peak solubility that was attributed to the association of DDEA into micelles, followed by a salting-out effect at higher concentrations, by which structure formation by DDEA molecules increased and precipitation occurred. For DS, which is not capable of forming micelles, the salting-out effect was dominant due to the common ion effect. Cosolvents displayed significant enhancement in solubility of both salts except glycerol, which showed a slight increase in solubility of DDEA and a decrease in solubility of DS due to transformation into the less soluble hydrate form. Ethanol and polyethylene glycol (PEG) 400 cosolvent systems at all concentrations showed positive deviations from the log-linear solubility equation. In the case of propylene glycol (PG) cosolvent systems, negative deviations were observed at low volume fractions of cosolvent, while positive deviations were observed at high volume fractions of cosolvent for DS and DDEA. The parent drug, being less ionizable and highly nonpolar, showed negative deviations up to 90% PG content. Thus, the positive deviations for DS and DDEA could be attributed to the more ionizable carboxylic group and its higher ability for hydrogen bonding at higher fractions of cosolvent. Polyvinylpyrrolidone (PVP) and PEG4000 or PEG6000 enhanced the solubility of DS and DDEA, with PVP exerting higher solubilizing efficiency and DS showing better solubility than DDEA. Solubilities of DS in Tween 80 (T80) and Pluronic F-127 (PF127) aqueous solutions were almost similar, while the solubility of DDEA in the presence of T80 was higher than the solubility in the presence of PF127. DS appeared to be located more in the polyoxyethylene

  10. Efficacy of Combined Ultrasound-and-Microbubbles-Mediated Diclofenac Gel Delivery to Enhance Transdermal Permeation in Adjuvant-Induced Rheumatoid Arthritis in the Rat.

    PubMed

    Liao, Ai-Ho; Chung, Huan-Yu; Chen, Wen-Shiang; Yeh, Ming-Kung

    2016-08-01

    A previous study that investigated the effect of ultrasound (US) on the transdermal permeation of the non-steroidal anti-inflammatory drug diclofenac found that therapeutic US can increase circulation in an inflamed joint and decrease arthritic pain. Transdermal drug delivery has recently been demonstrated by US combined with microbubbles (MB) contrast agent (henceforth referred to as "US-MB"). The present study evaluated the efficacy of US-MB-mediated diclofenac delivery for treating adjuvant-induced rheumatoid arthritis (RA) in rats. RA was induced by injecting 100 μL of complete Freund's adjuvant into the ankle joint of male Sprague-Dawley rats (250-300 g) that were randomly divided into five treatment groups: (i) carbopol gel alone (the control [group C]), (ii) diclofenac-carbopol gel (group D), (iii) US plus carbopol gel (group U), (iv) US plus diclofenac-carbopol gel (group DU) and (v) US-MB plus diclofenac-carbopol gel (group DUB). The ankle width was measured over 10 d using high-frequency (40-MHz) US B-mode and color Doppler-mode imaging, covering the period before and after treatment. Longitudinal US images of the induced RA showed synovitis and neovascularity. Only a small amount of neovascularity was observed after treatment. The recovery rate on day 10 was significantly higher in group DUB (97.7% ± 2.7%, mean ± standard deviation [SD]) than in groups C (1.0% ± 2.7%), D (37.5% ± 4.6%), U (75.5% ± 4.2%) and DU (87.3% ± 5.2%) (p < 0.05). The results obtained indicate that combining US and MB can increase the skin permeability and thereby enhance the delivery of diclofenac sodium gel and thereby inhibit inflammation of the tissues surrounding the arthritic ankle. Color Doppler-mode imaging revealed that US-MB treatment induced a rapid reduction in synovial neoangiogenesis in the arthritic area. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  11. The Clinical Efficacy and Safety of the Sahastara Remedy versus Diclofenac in the Treatment of Osteoarthritis of the Knee: A Double-Blind, Randomized, and Controlled Trial

    PubMed Central

    Pinsornsak, Piya; Kanokkangsadal, Puritat; Itharat, Arunporn

    2015-01-01

    Introduction. The Sahastara (SHT) remedy is a Thai traditional medicine that has been acknowledged in the Thai National List of Essential Medicine and has been used as an alternative medicine to treat knee osteoarthritis. Although SHT remedies have been used in Thai traditional medical practices for a long period of time, there are few reports on their clinical trials. Aim of the Study. To investigate the clinical efficacy and safety of the SHT remedy in treating OA of the knee when compared to diclofenac. Methods. A phase 2, double-blind, randomized, and controlled trial study with a purpose to determine the clinical efficacy and safety of SHT in comparison with diclofenac for the treatment of knee osteoarthritis. Sixty-six patients, ages between 45 and 80 years of age, were randomly allocated into 2 groups. The SHT group received 1,000 mg of SHT powdered capsules 3 times per day, orally before meals, while another group received 25 mg of diclofenac sodium capsules 3 times a day, orally after meals for 28 days. All patients were followed up at 14 and 28 days for the evaluation of the efficacy and safety by using clinical examinations, blood tests, a visual analogue scale (VAS) for pain, and the 100-meter walktime test. Improvement on the quality of life was also assessed by the WOMAC index. Results. There were 31 and 30 patients in SHT and diclofenac groups, respectively, who had completed the study. Both medications have shown to significantly reduce the VAS for pain, and significantly improve the 100-meter walktime test and the WOMAC index score. However, there were no differences in the efficacy between the two groups. The blood chemistry showed no toxicity on renal and/or liver functions after taking SHT for 28 days but the patients who took diclofenac showed significant increases in their AST, ALT, and ALP. Systolic and diastolic blood pressure slightly increased in the diclofenac group but the SHT group did not effect on blood pressure. Conclusions. The

  12. Synergistic interaction between metformin and sulfonylureas on diclofenac-induced antinociception measured using the formalin test in rats

    PubMed Central

    Ortiz, Mario I

    2013-01-01

    BACKGROUND There is evidence that biguanides and sulfonylureas block diclofenac-induced antinociception (DIA) in rat models. However, little is known about the interaction between these hypoglycemics with respect to DIA. OBJECTIVE: To determine whether metformin-sulfonylurea combinations affect DIA during the formalin test. METHODS: Rats received the appropriate vehicle or diclofenac before 1% formaldehyde was injected into the paw. Rats were also pretreated with vehicle, glibenclamide, glipizide, metformin or glibenclamide/metformin and glipizide/metformin combinations before the diclofenac and formaldehyde injections, and the effect on antinociception was assessed. Isobolograms of the combinations were constructed to test for a synergistic interaction. RESULTS: Systemic injection of diclofenac resulted in antinociception during the second phase of the test. Systemic pretreatment with the combinations of glibenclamide (0.56 mg/kg to 10 mg/kg)/metformin (10 mg/kg to 180 mg/kg) and glipizide (0.56 mg/kg to10 mg/kg)/metformin (10 mg/kg to 180 mg/kg) blocked DIA. The derived theoretical effective doses for 50% of subjects (ED50) for the glibenclamide/metformin and glipizide/metformin combinations were 32.52 mg/kg and 32.42 mg/kg, respectively, and were significantly higher than the actual observed experimental ED50 values (7.57 mg/kg and 8.43 mg/kg, respectively). CONCLUSION: Pretreatment with glibenclamide, glipizide or metformin blocked DIA in a dose-dependent manner, and combining either sulfonylurea with metformin produced even greater effects. The observed ED50s for the combinations were approximately fourfold lower than the calculated additive effects. These data indicate that sulfonylureas interact to produce antagonism of DIA. Combination therapy is a common second-line treatment for patients with diabetes and metabolic syndrome, a group that experiences pain from multiple sources. The results suggest that at least some anti-inflammatory agents may not be

  13. Quality evaluation and in vitro interaction studies between levofloxacin 250mg and diclofenac sodium 50mg tablets.

    PubMed

    Fayyaz, Muhammad; Yousuf, Rabia Ismail; Shoaib, Muhammad Harris; Ali, Tariq; Nasiri, Iqbal; Ashraf, Nida

    2015-01-01

    Fluoroquinolones are broad-spectrum antibiotics, work against Gram-positive and Gram-negative bacteria and are a clinically proven option for many resistant infections. Among fluoroquinolones Levofloxacin works best against acute sinusitis, inflammation of the lower airways, acute exacerbation of chronic bronchitis, community acquired pneumonia, complicated urinary tract infection including Pyelonephritis, chronic bacterial prostatitis and skin and soft tissue infection. Levofloxacin is a frequently prescribed antibacterial agent with Diclofenac Sodium for pain management in infectious conditions. The objective of the present work is to evaluate the level of interaction between Levofloxacin and Diclofenac Sodium. In this work market available brands of both drugs were also evaluated for quality.The physiochemical parameters like weight variation, thickness variation, and mechanical strength were determined. Similarly the percentage drug release and content uniformity test were also analyzed; the tested quality attributes were found within the recommended pharmacopeia ranges except brand L(6) that had high drug content 124.629±3.614 while brand L(4) and L(5) were not found similar in pH 1.2. When subjected to model dependent analysis Levofloxacin showed compliance with (first order, Higuchi, Hixson Crowell and Weibull) at pH (1.2, 4.5 and 6.8). However Diclofenac Sodium showed adherence with (first order, Hixson Crowell and Weibull) at pH (1.2, 4.5 and 6.8) but following Higuchi at pH 1.2 and 4.5 only. The interaction studies were also performed spectrophotometrically and simultaneous equation was used to estimate the percentage availability of both the drugs at pH 4.5, 6.8, FaSSGF and FaSSIF. The studies showed that the percent availability of Levofloxacin was increased significantly in FaSSIF i.e. 129.173±0.323 at 45 minutes in the presence of Diclofenac Sodium.

  14. Treatment of acute, non-traumatic pain using a combination of diclofenac-cholestyramine, uridine triphosphate, cytidine monophosphate, and hydroxycobalamin.

    PubMed

    Mibielli, Marco Antonio; Nunes, Carlos Pereira; Cohen, José Carlos; Scussel, Ari Boulanger; Higashi, Rafael; Bendavit, Gabriel Gherman; Oliveira, Lisa; Geller, Mauro

    2010-01-01

    This randomized, controlled, double-blind clinical study in parallel groups evaluated the safety and efficacy of an oral combination diclofenac-cholestyramine, nucleotides (uridine and cytidine) and vitamin B12 versus the oral combination of nucleotides and vitamin B12 in the treatment of acute, non-traumatic pain. Subjects received twice-daily, 10-day oral administration of diclofenac-cholestyramine + uridine + cytidine + vitamin B12 (Group DN, n=40) or uridine + cytidine + vitamin B12 (Group NB, n=41). The primary study endpoint was the number of subjects with VAS reduction of >30mm after 10 days of treatment. Secondary endpoints included the number of patients with improvement >5 points in the Patient Functionality Questionnaire after 10 days of treatment, and the number of subjects presenting adverse events. Treatment with the combination of diclofenac-cholestyramine, nucleotides and Vitamin B12 resulted in a higher number of subjects with VAS score reductions >30mm after 10 days of treatment (87.5% subjects) than in the control group administered nucleotides and Vitamin B12 (51.23% of subjects), (p>0.0006). A significantly higher number of subjects in the DN group (80%) had a score reduction of >5 points in the Patient Functionality Questionnaire at after 10 days of treatment compared to Group NB (29.3%), (p<0.001). The number of subjects presenting AEs did not vary significantly between treatment groups (p=0.587). The combination of diclofenac-cholestyramine with uridine, cytidine and vitamin B12 was well-tolerated over a 10-day treatment period. The combination reduced pain and improved functionality among subjects presenting acute, non-traumatic pain in the lower back, hips, and neck.

  15. Diclofenac delays micropore closure following microneedle treatment in human subjects.

    PubMed

    Brogden, Nicole K; Milewski, Mikolaj; Ghosh, Priyanka; Hardi, Lucia; Crofford, Leslie J; Stinchcomb, Audra L

    2012-10-28

    Drugs absorbed poorly through the skin are commonly delivered via injection with a hypodermic needle, which is painful and increases the risk of transmitting infectious diseases. Microneedles (MNs) selectively and painlessly permeabilize the outermost skin layer, allowing otherwise skin-impermeable drugs to cross the skin through micron-sized pores and reach therapeutic concentrations. However, rapid healing of the micropores prevents further drug delivery, blunting the clinical utility of this unique transdermal technique. We present the first human study demonstrating that micropore lifetime can be extended following MN treatment. Subjects received one-time MN treatment and daily topical application of diclofenac sodium. Micropore closure was measured with impedance spectroscopy, and area under the admittance-time curve (AUC) was calculated. AUC was significantly higher at MN+diclofenac sodium sites vs. placebo, suggesting slower rates of micropore healing. Colorimetry measurements confirmed the absence of local erythema and irritation. This mechanistic human proof-of-concept study demonstrates that micropore lifetime can be prolonged with simple topical administration of a non-specific cyclooxygenase inhibitor, suggesting the involvement of subclinical inflammation in micropore healing. These results will allow for longer patch wear time with MN-enhanced delivery, thus increasing patient compliance and expanding the transdermal field to a wider variety of clinical conditions. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Comparative evaluation of adsorption kinetics of diclofenac and isoproturon by activated carbon.

    PubMed

    Torrellas, Silvia A; Rodriguez, Araceli R; Escudero, Gabriel O; Martín, José María G; Rodriguez, Juan G

    2015-01-01

    Adsorption mechanism of diclofenac and isoproturon onto activated carbon has been proposed using Langmuir and Freundlich isotherms. Adsorption capacity and optimum adsorption isotherms were predicted by nonlinear regression method. Different kinetic equations, pseudo-first-order, pseudo-second-order, intraparticle diffusion model and Bangham kinetic model, were applied to study the adsorption kinetics of emerging contaminants on activated carbon in two aqueous matrices.

  17. Ecotoxicological impact of pharmaceuticals found in treated wastewaters: study of carbamazepine, clofibric acid, and diclofenac.

    PubMed

    Ferrari, Benoît; Paxéus, Nicklas; Lo Giudice, Roberto; Pollio, Antonino; Garric, Jeanne

    2003-07-01

    In four countries (France, Greece, Italy, and Sweden) occurrence in sewage treatment plant (STP) effluents and ecotoxicity of the pharmaceuticals carbamazepine, clofibric acid, and diclofenac were investigated. Bioassays were performed on bacteria, algae, microcrustaceans, and fishes in order to calculate their predicted no-effect concentrations (PNEC) and to perform a first approach of risk characterization. For this aim, risk has been estimated by the predicted environmental concentration/PNEC ratio and the measured environmental concentration/PNEC ratio. First, regarding the PNEC, carbamazepine appears to be the more hazardous compound. Second, even though it is demonstrated that carbamazepine, clofibric acid, and diclofenac have been detected in effluents, only carbamazepine have been detected in all sewage treatment plants with the greatest concentrations. Third, risk quotients greater than unity were calculated only for carbamazepine, suggesting that risk for the water compartment is expected.

  18. Diclofenac vs oxybuprocaine eyedrops for analgesia in paediatric strabismus surgery.

    PubMed

    Morton, N S; Benham, S W; Lawson, R A; McNicol, L R

    1997-01-01

    Forty children undergoing strabismus surgery as day patients were randomly allocated to receive oxybuprocaine 0.4% eyedrops or 0.1% diclofenac eyedrops for perioperative analgesia. A non-invasive anaesthetic technique using the reinforced laryngeal mask airway was used. The study demonstrated that both topical analgesics provided good to excellent analgesia and the anaesthetic technique was associated with a relatively low incidence of nausea and vomiting. Complications were limited to two children who were admitted with persistent postoperative nausea and vomiting.

  19. Relative benefit-risk comparing diclofenac to other traditional non-steroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors in patients with osteoarthritis or rheumatoid arthritis: a network meta-analysis.

    PubMed

    van Walsem, Anneloes; Pandhi, Shaloo; Nixon, Richard M; Guyot, Patricia; Karabis, Andreas; Moore, R Andrew

    2015-03-19

    There is argument over the benefits and risks of drugs for treating chronic musculoskeletal pain. This study compared the efficacy, safety, and tolerability of diclofenac, ibuprofen, naproxen, celecoxib, and etoricoxib for patients with pain caused by osteoarthritis (OA) or rheumatoid arthritis (RA). A systematic literature review used Medline and EMBASE to identify randomised controlled trials. Efficacy outcomes assessed included: pain relief measured by visual analogue scale (VAS); Western Ontario McMaster Universities Arthritis Index (WOMAC) VAS or WOMAC Likert scale; physical functioning measured by WOMAC VAS or Likert scale; and patient global assessment (PGA) of disease severity measured on VAS or 5-point Likert scale. Safety outcomes included: Antiplatelet Trialists' Collaboration (APTC), major cardiovascular (CV) and major upper gastrointestinal (GI) events, and withdrawals. Data for each outcome were synthesized by a Bayesian network meta-analysis (NMA). For efficacy assessments, labelled doses for OA treatment were used for the base case while labelled doses for RA treatment were also included in the sensitivity analysis. Pooled data across dose ranges were used for safety. Efficacy, safety, and tolerability data were found for 146,524 patients in 176 studies included in the NMA. Diclofenac (150 mg/day) was likely to be more effective in alleviating pain than celecoxib (200 mg/day), naproxen (1000 mg/day), and ibuprofen (2400 mg/day), and similar to etoricoxib (60 mg/day); a lower dose of diclofenac (100 mg/day) was comparable to all other treatments in alleviating pain. Improved physical function with diclofenac (100 and 150 mg/day) was mostly comparable to all other treatments. PGA with diclofenac (100 and 150 mg/day) was likely to be more effective or comparable to all other treatments. All active treatments were similar for APTC and major CV events. Major upper GI events with diclofenac were lower compared to naproxen and ibuprofen, comparable to

  20. Degradation and intermediates of diclofenac as instructive example for decomposition of recalcitrant pharmaceuticals by hydroxyl radicals generated with pulsed corona plasma in water.

    PubMed

    Banaschik, Robert; Jablonowski, Helena; Bednarski, Patrick J; Kolb, Juergen F

    2018-01-15

    Seven recalcitrant pharmaceutical residues (diclofenac, 17α-ethinylestradiol, carbamazepine, ibuprofen, trimethoprim, diazepam, diatrizoate) were decomposed by pulsed corona plasma generated directly in water. The detailed degradation pathway was investigated for diclofenac and 21 intermediates could be identified in the degradation cascade. Hydroxyl radicals have been found primarily responsible for decomposition steps. By spin trap enhanced electron paramagnetic resonance spectroscopy (EPR), OH-adducts and superoxide anion radical adducts were detected and could be distinguished applying BMPO as a spin trap. The increase of concentrations of adducts follows qualitatively the increase of hydrogen peroxide concentrations. Hydrogen peroxide is eventually consumed in Fenton-like processes but the concentration is continuously increasing to about 2mM for a plasma treatment of 70min. Degradation of diclofenac is inversely following hydrogen peroxide concentrations. No qualitative differences between byproducts formed during plasma treatment or due to degradation via Fenton-induced processes were observed. Findings on degradation kinetics of diclofenac provide an instructive understanding of decomposition rates for recalcitrant pharmaceuticals with respect to their chemical structure. Accordingly, conclusions can be drawn for further development and a first risk assessment of the method which can also be applied towards other AOPs that rely on the generation of hydroxyl radicals. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Determination of ibuprofen, naproxen and diclofenac in aqueous samples using a multi-template molecularly imprinted polymer as selective adsorbent for solid-phase extraction.

    PubMed

    Madikizela, Lawrence Mzukisi; Chimuka, Luke

    2016-09-05

    This study describes the application of multi-template molecularly imprinted polymer (MIP) as selective sorbent in the solid-phase extraction (SPE) of naproxen, ibuprofen and diclofenac from wastewater and river water. MIP was synthesized at 70°C by employing naproxen, ibuprofen and diclofenac as multi-templates, ethylene glycol dimethacrylate, 2-vinyl pyridine and toluene as cross-linker, functional monomer and porogen, respectively. Wastewater and river water samples (pH 2.5) were percolated through SPE cartridge packed with 50mg of the MIP. The cartridge was washed with 2mL of methanol-water 10:90% (v:v) prior to elution with 2mL of acetic acid-acetonitrile 20:80% (v:v). Quantification of eluted compounds was performed with high performance liquid chromatography equipped with photo diode array detection. The detection limits were 0.15, 1.00 and 0.63μgL(-1) for naproxen, ibuprofen and diclofenac, respectively. Recoveries for naproxen, ibuprofen and diclofenac in deionized water spiked at 5 and 50μgL(-1) were greater than 80%. Ibuprofen was the most frequently detected compound with maximum concentrations of 221, 67.9 and 11.4μgL(-1) in wastewater influent, effluent and river water, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Solid phase microextraction of diclofenac using molecularly imprinted polymer sorbent in hollow fiber combined with fiber optic-linear array spectrophotometry.

    PubMed

    Pebdani, Arezou Amiri; Shabani, Ali Mohammad Haji; Dadfarnia, Shayessteh; Khodadoust, Saeid

    2015-08-05

    A simple solid phase microextraction method based on molecularly imprinted polymer sorbent in the hollow fiber (MIP-HF-SPME) combined with fiber optic-linear array spectrophotometer has been applied for the extraction and determination of diclofenac in environmental and biological samples. The effects of different parameters such as pH, times of extraction, type and volume of the organic solvent, stirring rate and donor phase volume on the extraction efficiency of the diclofenac were investigated and optimized. Under the optimal conditions, the calibration graph was linear (r(2)=0.998) in the range of 3.0-85.0 μg L(-1) with a detection limit of 0.7 μg L(-1) for preconcentration of 25.0 mL of the sample and the relative standard deviation (n=6) less than 5%. This method was applied successfully for the extraction and determination of diclofenac in different matrices (water, urine and plasma) and accuracy was examined through the recovery experiments. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Diclofenac vs oxybuprocaine eyedrops for analgesia in paediatric strabismus surgery.

    PubMed

    Morton, N; Benham, S; Lawson, R; McNICOL, L

    1997-05-01

    Forty children undergoing strabismus surgery as day patients were randomly allocated to receive oxybuprocaine 0.4% eyedrops or 0.1% diclofenac eyedrops for perioperative analgesia. A non-invasive anaesthetic technique using the reinforced laryngeal mask airway was used. The study demonstrated that both topical analgesics provided good to excellent analgesia and the anaesthetic technique was associated with a relatively low incidence of nausea and vomiting. Complications were limited to two children who were admitted with persistent postoperative nausea and vomiting. 1997 Blackwell Science Ltd.

  4. A Review of Topical Diclofenac Use in Musculoskeletal Disease

    PubMed Central

    Nair, Bindu; Taylor-Gjevre, Regina

    2010-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed medications for the treatment of musculoskeletal disorders. Osteoarthritis is the most common form of arthritis in humans and its prevalence rises with age. Oral NSAIDs have potential associated toxicities that must be monitored for and can limit the use of these drugs in certain populations including people of older age. Topical NSAIDs are now being recognized as an option for the treatment strategy of osteoarthritis. We review the efficacy and safety of one of the most common topical NSAIDS, topical diclofenac, for the treatment of osteoarthritis. PMID:27713334

  5. Topical Colchicine Gel versus Diclofenac Sodium Gel for the Treatment of Actinic Keratoses: A Randomized, Double-Blind Study.

    PubMed

    Faghihi, Gita; Elahipoor, Azam; Iraji, Fariba; Behfar, Shadi; Abtahi-Naeini, Bahareh

    2016-01-01

    Introduction. Actinic keratoses (AKs), a premalignant skin lesion, are a common lesion in fair skin. Although destructive treatment remains the gold standard for AKs, medical therapies may be preferable due to the comfort and reliability .This study aims to compare the effects of topical 1% colchicine gel and 3% diclofenac sodium gel in AKs. Materials and Methods. In this randomized double-blind study, 70 lesions were selected. Patients were randomized before receiving either 1% colchicine gel or 3% diclofenac sodium cream twice a day for 6 weeks. Patients were evaluated in terms of their lesion size, treatment complications, and recurrence at 7, 30, 60, and 120 days after treatment. Results. The mean of changes in the size was significant in both groups both before and after treatment (<0.001). The mean lesion size before treatment and at 30, 60, and 120 days was not different between the two groups (p > 0.05). No case of erythema was seen in the colchicine group, while erythema was seen in 22.9% (eight cases) of patients in the diclofenac sodium group (p = 0.005). Conclusions. 1% colchicine gel was a safe and effective medication with fewer side effects and lack of recurrence of the lesion.

  6. Applicational possibilities of linear and non-linear (polynomial) regression and analysis of variance. III. Stability determination of pharmaceutical preparations: stability of diclofenac-sodium in Diclofen injections.

    PubMed

    Arambasić, M B; Jatić-Slavković, D

    2004-05-01

    This paper presents the application of the regression analysis program and the program for comparing linear regressions (modified method for one-way, analysis of variance), writtens in BASIC program language, for instance, determination of content of Diclofenac-Sodium (active ingredient in DIKLOFEN injections, ampules á 75 mg/3 ml). Stability testing of Diclofenac-Sodium was done by isothermic method of accelerated aging at 4 different temperatures (30 degrees, 40 degrees, 50 degrees and 60 degrees C) as a function of time (4 different duration of treatment: (0-155, 0-145, 0-74 and 0-44 days). The decrease in stability (decrease in the mean value of the content of Diclofenac-Sodium (in %), at different temperatures as a function of time, is possible to describe by, linear dependance. According to the value for regression equation values, the times are assessed in which the content of Diclofenac-Sodium (in %) will decrease by 10%, of the initial value. The times are follows at 30 degrees C 761.02 days, at 40 degrees C 397.26 days, at 50 degrees C 201.96 days and at 60 degrees C 58.85 days. The estimated times (in days) in which the mean value for Diclofenac-Sodium content (in %) will by 10% of the initial values, as a junction of time, are most suitably described by 3rd order parabola. Based on the parameter values which describe the 3rd order parabola, the time was estimated in which Diclofenac-Sodium content mean value (in %) will fall by 10% of the initial one at average ambient temperatures of 20 degrees C and 25 degrees C. The times are: 1409.47 days (20 degrees C) and 1042.39 days (25 degrees C). Based on the value for Fischer's coefficien (F), the comparison of trenf of Diclofenac-Sodium content (in %) shows that, under the influence of different temperatures as a function of time, among them, depending on temperature value, there is: statistically very significant difference (P < .05) at 50 degrees C and lower toward 60 degrees C, i.e. statistically

  7. Topical diclofenac epolamine patch 1.3% for treatment of acute pain caused by soft tissue injury

    PubMed Central

    McCarberg, B H; Argoff, C E

    2010-01-01

    Acute pain caused by musculoskeletal disorders is very common and has a significant negative impact on quality-of-life and societal costs. Many types of acute pain have been managed with traditional oral non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 inhibitors (coxibs). Data from prospective, randomised controlled clinical trials and postmarketing surveillance indicate that use of oral traditional NSAIDs and coxibs is associated with an elevated risk of developing gastrointestinal, renovascular and/or cardiovascular adverse events (AEs). Increasing awareness of the AEs associated with NSAID therapy, including coxibs, has led many physicians and patients to reconsider use of these drugs and look for alternative treatment options. Treatment with NSAIDs via the topical route of administration has been shown to provide clinically effective analgesia at the site of application while minimising systemic absorption. The anti-inflammatory and analgesic potency of the traditional oral NSAID diclofenac, along with its physicochemical properties, makes it well suited for topical delivery. Several topical formulations of diclofenac have been developed. A topical patch containing diclofenac epolamine 1.3% (DETP, FLECTOR® Patch), approved for use in Europe in 1993, has recently been approved for use in the United States and is indicated for the treatment of acute pain caused by minor strains, sprains and contusions. In this article, we review the available clinical trial data for this product in the treatment of pain caused by soft tissue injury. PMID:20666849

  8. Diclofenac-Induced Photo-Onycholysis

    PubMed Central

    Al-Kathiri, Lutfi; Al-Asmaili, Abla

    2016-01-01

    Onycholysis is the detachment of the nail plate from the nail bed. If drug-induced, it can be an isolated phenomenon, but it may also accompany or follow a cutaneous phototoxicity reaction due to drug intake and exposure to ultraviolet irradiation. Photo-onycholysis is a rare photosensitivity reaction due to exposure to either a natural or artificial source of light. Many drugs are responsible for this phototoxic reaction, especially tetracyclines, psoralens, chloramphenicol, non-steroidal anti-inflammatory drugs, fluoroquinolones, and, rarely, doxycycline. Any patient given enough of a therapeutic dose of an inducing drug and sufficient light irradiation can develop phototoxic reactions. While there is no need to avoid these drugs completely, precautions should be taken. Here we have reported the case of a patient who developed onycholysis of his fingernails with sparing of the toenails following administration of diclofenac therapy for lower back pain. The onycholysis was associated with a phototoxic reaction. The swellings resolved totally within two days, and the patient started to notice the separation of all fingernail plates from their nail beds. The patient was treated symptomatically. On follow-up, onycholysis had regressed slowly, and the condition recovered totally within three months without any sequelae. PMID:26816569

  9. Design, development, physicochemical, and in vitro and in vivo evaluation of transdermal patches containing diclofenac diethylammonium salt.

    PubMed

    Arora, Priyanka; Mukherjee, Biswajit

    2002-09-01

    In this study, matrix-type transdermal patches containing diclofenac diethylamine were prepared using different ratios of polyvinylpyrrolidone (PVP) and ethylcellulose (EC) by solvent evaporation technique. The drug matrix film of PVP and EC was casted on a polyvinylalcohol backing membrane. All the prepared formulations were subjected to physical studies (moisture content, moisture uptake, and flatness), in vitro release studies and in vitro skin permeation studies. In vitro permeation studies were performed across cadaver skin using a modified diffusion cell. Variations in drug release profiles among the formulations studied were observed. Based on a physicochemical and in vitro skin permeation study, formulation PA4 (PVP/EC, 1:2) and PA5 (PVP/EC, 1:5) were chosen for further in vivo experiments. The antiinflammatory effect and a sustaining action of diclofenac diethylamine from the two transdermal patches selected were studied by inducing paw edema in rats with 1% w/v carrageenan solution. When the patches were applied half an hour before the subplantar injection of carrageenan in the hind paw of male Wistar rats, it was observed that formulation PA4 produced 100% inhibition of paw edema in rats 12 h after carrageenan insult, whereas in the case of formulation PA5, 4% mean paw edema was obtained half an hour after the carrageenan injection and the value became 19.23% 12 h after the carrageenan insult. The efficacy of transdermal patches was also compared with the marketed Voveran gel and it was found that PA4 transdermal patches produced a better result as compared with the Voveran gel. Hence, it can be reasonably concluded that diclofenac diethylamine can be formulated into the transdermal matrix type patches to sustain its release characteristics and the polymeric composition (PVP/EC, 1:2) was found to be the best choice for manufacturing transdermal patches of diclofenac diethylamine among the formulations studied. Copyright 2002 Wiley-Liss, Inc.

  10. Effects of the pharmaceuticals gemfibrozil and diclofenac on biomarker expression in the zebra mussel (Dreissena polymorpha) and their comparison with standardised toxicity tests.

    PubMed

    Quinn, Brian; Schmidt, Wiebke; O'Rourke, Kathleen; Hernan, Robert

    2011-07-01

    Pharmaceuticals, including the lipid regulator gemfibrozil and the non-steroidal anti-inflammatory drug diclofenac have been identified in waste water treatment plant effluents and receiving waters throughout the western world. The acute and chronic toxicity of these compounds was assessed for three freshwater species (Daphnia magna, Pseudokirchneriella subcapitata, Lemna minor) using standardised toxicity tests with toxicity found in the non-environmentally relevant mid mg L(-1) concentration range. For the acute endpoints (IC(50) and EC(50)) gemfibrozil showed higher toxicity ranging from 29 to 59 mg L(-1) (diclofenac 47-67 mg L(-1)), while diclofenac was more toxic for the chronic D. magna 21 d endpoints ranging from 10 to 56 mg L(-1) (gemfibrozil 32-100 mg L(-1)). These results were compared with the expression of several biomarkers in the zebra mussel (Dreissena polymorpha) 24 and 96 h after exposure by injection to concentrations of 21 and 21,000 μg L(-1) corresponding to nominal concentrations of 1 and 1000 μg L(-1). Exposure to gemfibrozil and diclofenac at both concentrations significantly increased the level of lipid peroxidation, a biomarker of damage. At the elevated nominal concentration of 1000 μg L(-1) the biomarkers of defence glutathione transferase and metallothionein were significantly elevated for gemfibrozil and diclofenac respectively, as was DNA damage after 96 h exposure to gemfibrozil. No evidence of endocrine disruption was observed using the alkali-labile phosphate technique. Results from this suite of biomarkers indicate these compounds can cause significant stress at environmentally relevant concentrations acting primarily through oxidation pathways with significant destabilization of the lysosomal membrane and that biomarker expression is a more sensitive endpoint than standardised toxicity tests. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Cost-Effectiveness and Cost-Utility Analysis of Ingenol Mebutate Versus Diclofenac 3% and Imiquimod 5% in the Treatment of Actinic Keratosis in Spain.

    PubMed

    Elías, I; Ortega-Joaquín, N; de la Cueva, P; Del Pozo, L J; Moreno-Ramírez, D; Boada, A; Aguilar, M; Mirada, A; Mosquera, E; Gibbons, C; Oyagüez, I

    2016-01-01

    To perform a cost-effectiveness and cost-utility analysis of ingenol mebutate in the treatment of actinic keratosis in Spain. We used an adapted Markov model to simulate outcomes in a cohort of patients (mean age, 73 years) with actinic keratosis over a 5-year period. The comparators were diclofenac 3% and imiquimod 5%. The analysis was performed from the perspective of the Spanish National Health System based on direct costs (2015 retail price plus value added tax less the mandatory discount). A panel of experts estimated resources, taking unit costs from national databases. An annual discount rate of 3% was applied. Deterministic and probabilistic sensitivity analyses were performed. The effectiveness of ingenol mebutate-with 0.192 and 0.129 more clearances gained in treatments for face and scalp lesions and trunk and extremity lesions, respectively-was superior to diclofenac's. The total costs of treatment with ingenol mebutate were lower at € 551.50 (face and scalp) and € 622.27 (trunk and extremities) than the respective costs with diclofenac (€ 849.11 and € 844.93). The incremental cost-effectiveness and cost-utility ratios showed that ingenol mebutate was a dominant strategy vs diclofenac. Ingenol mebutate also proved to be more effective than imiquimod, based on 0.535 and 0.503 additional clearances, and total costs of € 551.50 and € 527.89 for the two drugs, respectively. The resulting incremental cost-effectiveness ratio was € 728.64 per clearance gained with ingenol mebutate vs imiquimod. Ingenol mebutate was a dominant treatment option vs diclofenac and was efficient vs imiquimod (i.e., more effective at a higher cost, achieving an incremental cost-utility ratio of<€30000/quality-adjusted life-years). Copyright © 2016 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

  12. Efficacy of a comfrey root extract ointment in comparison to a diclofenac gel in the treatment of ankle distortions: results of an observer-blind, randomized, multicenter study.

    PubMed

    Predel, H G; Giannetti, B; Koll, R; Bulitta, M; Staiger, C

    2005-11-01

    In the treatment of minor blunt injuries several topical drugs are known to have anti-inflammatory and analgesic properties. They represent, however, two fundamentally different major pharmacological therapy approaches: the "chemical-synthetical" and the "phytotherapeutical" approach. The main objective of this trial (CODEC_2004) was to compare the efficacy and tolerability of an ointment of Comfrey extract (Extr. Rad. Symphyti) with that of a Diclofenac gel in the treatment of acute unilateral ankle sprain (distortion). In a single-blind, controlled, randomized, parallel-group, multicenter and confirmatory clinical trial outpatients with acute unilateral ankle sprains (n=164, mean age 29.0 years, 47.6% female) received either a 6 cm long ointment layer of Kytta-Salbe f (Comfrey extract) (n=82) or of Diclofenac gel containing 1.16 g of diclofenac diethylamine salt (n=82) for 7 +/- 1 days, four times a day. Primary variable was the area-under-the-curve (AUC) of the pain reaction to pressure on the injured area measured by a calibrated caliper (tonometer). Secondary variables were the circumference of the joint (swelling; figure-of-eight method), the individual spontaneous pain sensation at rest and at movement according to a Visual Analogue Scale (VAS), the judgment of impaired movements of the injured joint by the method of "neutral-zero", consumption of rescue medication (paracetamol), as well as the global efficacy evaluation and the global assessment of tolerability (both by physician and patient, 4 ranks). In this study the primary variable was also to be validated prospectively. It was confirmatorily shown that Comfrey extract is non-inferior to diclofenac. The 95% confidence interval for the AUC (Comfrey extract minus Diclofenac gel) was 19.01-103.09h*N/cm2 and was completely above the margin of non-inferiority. Moreover, the results of the primary and secondary variables indicate that Comfrey extract may be superior to Diclofenac gel.

  13. Comparative effect of topical diclofenac and topical dexamethasone on anterior chamber flare and postoperative pain following rhegmatogenous retinal detachment surgery.

    PubMed

    Ben Yahia, Salim; Kahloun, Rim; Abroug, Nesrine; Kaibi, Imene; Laadhari, Ghassen; Jelliti, Bechir; Khairallah, Moncef

    2016-10-01

    The purpose of this study is to compare the effect of topical diclofenac and topical dexamethasone on anterior chamber flare and postoperative pain following rhegmatogenous retinal detachment (RRD) surgery. This prospective study included 40 eyes of 40 patients treated for RRD. Twenty-eight patients underwent scleral buckling and 12 patients underwent 20-gauge pars plana vitrectomy (PPV). For each surgical procedure, patients were postoperatively randomly divided into two groups: the first group received topical dexamethasone phosphate 0.1 % four times daily for 28 days; the second group received topical diclofenac sodium 0.1 % three times daily for 28 days. The inflammatory reaction in the anterior chamber was measured with laser flare photometry preoperatively and 1, 7, 14, 28, and 90 days postoperatively. Pain level was evaluated with Scott's visual analog scale at day 1, 7, 14, and 28 postoperatively. For patients treated with scleral buckling, there was no significant difference between the two groups regarding mean aqueous flare at day 1 (p = 0.096), day 7 (p = 0.435), day 14 (p = 0.510), day 28 (p = 0.583), and day 90 (p = 0.423). The group who received diclofenac had significantly lower pain score at days 7, 14, and 28 (p = 0.048, p = 0.017, and p = 0.028, respectively). For patients treated with PPV, there was no significant difference between the two groups regarding mean aqueous flare at day 1 (p = 0.400), day 7 (p = 0.728), day 14 (p = 0.843), day 28 (p = 0.939), and day 90 (p = 0.568). Patients who received diclofenac had significantly lower pain score at days 7, 14, and 28 (p = 0.032, p = 0.030, and p = 0.023, respectively). Topical diclofenac seems to be as potent as topical dexamethasone in managing postoperative inflammatory response induced by surgery for RRD with better analgesic effect. Both of them are consequences of blood-aqueous barrier and blood-retinal barrier breakdown.

  14. Efficacy of paracetamol, diclofenac and advice for acute low back pain in general practice: design of a randomized controlled trial (PACE Plus).

    PubMed

    Schreijenberg, M; Luijsterburg, P A J; Van Trier, Y D M; Rizopoulos, D; Koopmanschap, M A; Voogt, L; Maher, C G; Koes, B W

    2017-02-01

    Low back pain is common and associated with a considerable burden to patients and society. There is uncertainty regarding the relative benefit of paracetamol and diclofenac and regarding the additional effect of pain medication compared with advice only in patients with acute low back pain. This trial will assess the effectiveness of paracetamol, diclofenac and placebo for acute low back pain over a period of 4 weeks. Furthermore, this trial will assess the additional effectiveness of paracetamol, diclofenac and placebo compared with advice only for acute low back pain over a period of 4 weeks. The PACE Plus trial is a multi-center, placebo-blinded, superiority randomized controlled trial in primary care, with a follow-up of 12 weeks. Patients with acute low back pain aged 18-60 years presenting in general practice will be included. Patients are randomized into four groups: 1) Advice only (usual care conforming with the clinical guideline of the Dutch College of General Practitioners); 2) Advice and paracetamol; 3) Advice and diclofenac; 4) Advice and placebo. The primary outcome is low back pain intensity measured with a numerical rating scale (0-10). Secondary outcomes include compliance to treatment, disability, perceived recovery, costs, adverse reactions, satisfaction, sleep quality, co-interventions and adequacy of blinding. Between group differences for low back pain intensity will be evaluated using a repeated measurements analysis with linear effects models. An economic evaluation will be performed using a cost-effectiveness analysis with low back pain intensity and a cost-utility analysis with quality of life. Explorative analyses will be performed to assess effect modification by predefined variables. Ethical approval has been granted. Trial results will be released to an appropriate peer-viewed journal. This paper presents the design of the PACE Plus trial: a multi-center, placebo-blinded, superiority randomized controlled trial in primary care that

  15. PENTAZOCINE VERSUS PENTAZOCINE WITH RECTAL DICLOFENAC FOR POSTOPERATIVE PAIN RELIEF AFTER CESAREAN SECTION- A DOUBLE BLIND RANDOMIZED PLACEBO CONTROLLED TRIAL IN A LOW RESOURCE AREA.

    PubMed

    Olateju, Simeon O; Adenekan, Anthony T; Olufolabi, Adeyemi J; Owojuyigbe, Afolabi M; Adetoye, Adedapo O; Ajenifuja, Kayode O; Olowookere, Samuel A; Faponle, Aramide F

    2016-02-01

    The unimodal approach of using pentazocine as post-cesarean section pain relief is inadequate, hence the need for a safer, easily available and more effective multimodal approach. To evaluate the effectiveness of rectal diclofenac combined with intramuscular pentazocine for postoperative pain following cesarean section. In this double blind clinical trial, 130 pregnant women scheduled for cesarean section under spinal anesthesia were randomly assigned to two groups. Group A received 100mg diclofenac suppository and group B received placebo suppository immediately following surgery, 12 and 24h later. Both groups also received intramuscular pentazocine 30mg immediately following surgery and 6 hourly postoperatively in the first 24 h. Postoperative pain was assessed by visual analogue scale at end of surgery and 2, 12 and 24 h after surgery. Patient satisfaction scores were also assessed. One hundred and sixteen patients completed the study. Combining diclofenac and pentazocine had statistically significant reduction in pain intensity at 2, 12, and 24 hours postoperatively compared to pentazocine alone (p <0.05). No significant side effects were noted in both groups. The combined group also had significantly better patient satisfaction scores. The addition of diclofenac suppository to intramuscular pentazocine provides better pain relief after cesarean section and increased patient satisfaction.

  16. Glycerosomes: Use of hydrogenated soy phosphatidylcholine mixture and its effect on vesicle features and diclofenac skin penetration.

    PubMed

    Manca, Maria Letizia; Cencetti, Claudia; Matricardi, Pietro; Castangia, Ines; Zaru, Marco; Sales, Octavio Diez; Nacher, Amparo; Valenti, Donatella; Maccioni, Anna Maria; Fadda, Anna Maria; Manconi, Maria

    2016-09-10

    In this work, diclofenac was encapsulated, as sodium salt, in glycerosomes containing 10, 20 or 30% of glycerol in the water phase with the aim to ameliorate its topical efficacy. Taking into account previous findings, glycerosome formulation was modified, in terms of economic suitability, using a cheap and commercially available mixture of hydrogenated soy phosphatidylcholine (P90H). P90H glycerosomes were spherical and multilamellar; photon correlation spectroscopy showed that obtained vesicles were ∼131nm, slightly larger and more polydispersed than those made with dipalmitoylphosphatidylcholine (DPPC) but, surprisingly, they were able to ameliorate the local delivery of diclofenac, which was improved with respect to previous findings, in particular using glycerosomes containing high amount of glycerol (20 and 30%). Finally, this drug delivery system showed a high in vitro biocompatibility toward human keratinocytes. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Preparation and Physical Characterization of a Diclofenac-Ranitidine Co-precipitate for Improving the Dissolution of Diclofenac.

    PubMed

    Gaitano, Robertino O; Calvo, Natalia L; Narda, Griselda E; Kaufman, Teodoro S; Maggio, Rubén M; Brusau, Elena V

    2016-03-01

    Mixing aqueous solutions of sodium diclofenac (DIC-Na) and ranitidine hydrochloride (RAN·HCl) afforded an off-white solid (DIC-RAN) that was investigated from the microscopic, thermal, diffractometric, spectroscopic, and functional (chemometrics-assisted dissolution) points of view. The solid has a 2:1 (DIC:RAN) molar ratio according to (1)H nuclear magnetic resonance spectroscopy. It is thermally stable, displaying a broad endothermic signal centered at 105°C in the thermogram, and its characteristic reflections in the powder X-ray diffractogram remained unchanged after a 3-month aging period. Scanning electron microscopy micrographs uncovered its morphology, whereas the spectral data suggested an interaction between the carboxylic acid of DIC and the alkyldimethylamino moiety of RAN. The dissolution of DIC-RAN was monitored at different pH values by an ultraviolet/chemometrics procedure, being complete within 5 min at pH 6.8. This compares favorably with the dissolution of a DIC-Na sample of the same particle size. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  18. Synthesis, crystal structure and spectroscopy of bioactive Cd(II) polymeric complex of the non-steroidal anti-inflammatory drug diclofenac sodium: Antiproliferative and biological activity

    NASA Astrophysics Data System (ADS)

    Tabrizi, Leila; Chiniforoshan, Hossein; McArdle, Patrick

    2015-02-01

    The interaction of Cd(II) with the non-steroidal anti-inflammatory drug diclofenac sodium (Dic) leads to the formation of the complex [Cd2(L)41.5(MeOH)2(H2O)]n(L = Dic), 1, which has been isolated and structurally characterized by X-ray crystallography. Diclofenac sodium and its metal complex 1 have also been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines, MCF-7 (breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma), and a mouse fibroblast L-929 cell line. The results of cytotoxic activity in vitro expressed as IC50 values indicated the diclofenac sodium and cadmium chloride are non active or less active than the metal complex of diclofenac (1). Complex 1 was also found to be a more potent cytotoxic agent against T-24 and MCF-7 cancer cell lines than the prevalent benchmark metallodrug, cisplatin, under the same experimental conditions. The superoxide dismutase activity was measured by Fridovich test which showed that complex 1 shows a low value in comparison with Cu complexes. The binding properties of this complex to biomolecules, bovine or human serum albumin, are presented and evaluated. Antibacterial and growth inhibitory activity is also higher than that of the parent ligand compound.

  19. Isolation, identification and molecular docking as cyclooxygenase (COX) inhibitors of the main constituents of Matricaria chamomilla L. extract and its synergistic interaction with diclofenac on nociception and gastric damage in rats.

    PubMed

    Ortiz, Mario I; Fernández-Martínez, Eduardo; Soria-Jasso, Luis Enrique; Lucas-Gómez, Isaac; Villagómez-Ibarra, Roberto; González-García, Martha P; Castañeda-Hernández, Gilberto; Salinas-Caballero, Mireya

    2016-03-01

    Chamomile (Matricaria chamomilla L., Asteraceae) is a medicinal plant widely used as remedy for pain and gastric disorders. The association of non-steroidal anti-inflammatory drugs (NSAIDs) with medicinal plant extracts may increase its antinociceptive activity, permit the use of lower doses and limit side effects. The aim was to isolate and identify the main chemical constituents of Matricaria chamomilla ethanolic extract (MCE) as well as to explore their activity as cyclooxygenase (COX) inhibitors in silico; besides, to examine the interaction between MCE and diclofenac on nociception in the formalin test by isobolographic analysis, and to determine the level of gastric injury in rats. Three terpenoids, α-bisabolol, bisabolol oxide A, and guaiazulene, were isolated and identified by (1)H NMR. Docking simulation predicted COX inhibitory activity for those terpenoids. Diclofenac, MCE, or their combinations produced an antinociceptive effect. The sole administration of diclofenac and the highest combined dose diclofenac-MCE produced significant a gastric damage, but that effect was not seen with MCE alone. An isobologram was constructed and the derived theoretical ED35 for the antinociceptive effect was significantly different from the experimental ED35; hence, the interaction between diclofenac and MCE that mediates the antinociceptive effect is synergist. The MCE contains three major terpenoids with plausible COX inhibitory activity in silico, but α-bisabolol showed the highest affinity. Data suggest that the diclofenac-MCE combination can interact at the systemic level in a synergic manner and may have therapeutic advantages for the clinical treatment of inflammatory pain. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Assessing the impact of diclofenac, ibuprofen and sildenafil citrate (Viagra®) on the fertilisation biology of broadcast spawning marine invertebrates.

    PubMed

    Mohd Zanuri, Norlaila Binti; Bentley, Matthew G; Caldwell, Gary S

    2017-06-01

    Exposure to synthetic chemicals is a key environmental challenge faced by aquatic organisms. The time and dose effects of the pharmaceuticals diclofenac, ibuprofen, and sildenafil citrate on sperm motility and successful fertilisation are studied using the echinoderms, Asterias rubens and Psammechinus miliaris, and the polychaete worm Arenicola marina, all important components of the marine benthos. Motility was reduced for all species when exposed to diclofenac concentrations ≥0.1 μg/L. Exposure to ≥1.0 μg/L of ibuprofen affected only P. miliaris gametes and fertilisation success of A. marina. A. rubens and P. miliaris sperm increased in both percentage motility and swimming velocity when exposed to sildenafil citrate at concentrations ≥18 and ≥ 50 ng/L, respectively. Pre-incubation of sperm with sildenafil citrate significantly increased fertilisation success in A. rubens and P. miliaris but not in A. marina. Pre-incubated A. rubens oocytes fertilised successfully in ibuprofen. According to EU Directive 93/67/EEC, diclofenac is classified as a very toxic substance to gametes of A. rubens, P. miliaris, and A. marina (EC 50  = 100-1000 μg/L) while ibuprofen is classified as very toxic to gametes of P. miliaris but non-toxic to gametes of A. marina (EC 50  > 10,000 μg/L). The present study indicates that diclofenac exposure may have negative impacts on invertebrate reproductive success, whereas ibuprofen potentially may compromise P. miliaris reproduction. This study provides a valuable insight into the mechanisms that allow marine invertebrates to survive and reproduce in contaminated and changing habitats. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Effect of ketorolac and diclofenac on the impairment of endothelium-dependent relaxation induced by reactive oxygen species in rabbit abdominal aorta

    PubMed Central

    Lee, Seung Yoon; Choi, Jin Hwa; Jeon, Woo Jae; Cheong, Mi Ae

    2010-01-01

    Background Reactive oxygen species (ROS) induce lipid peroxidation and tissue damage in endothelium. We studied the influences of ketorolac and diclofenac on ROS effects using the endothelium of rabbit abdominal aorta. Methods Isolated rabbit aortic rings were suspended in an organ bath filled with Krebs-Henseleit (K-H) solution bubbled with 5% CO2 and 95% O2 at 37.5℃. After being stimulated to contract with phenylephrine (PE, 10-6 M), changes in arterial tension were recorded following the cumulative administration of acetylcholine (ACh, 3 × 10-8 to 10-6 M). The percentages of ACh-induced relaxation of aortic rings before and after exposure to ROS, generated by electrolysis of K-H solution, were used as the control and experimental values, respectively. The aortic rings were pretreated with ketorolac or diclofenac at the same concentrations (10-5 M to 3 × 10-4 M), and the effects of these agents were compared with the effects of ROS scavengers: catalase, mannitol, sodium salicylate and deferoxamine and the catalase inhibitor, 3-amino-1,2,4-triazole (3AT). Results Both ketorolac and diclofenac maintained endothlium-dependent relaxation induced by ACh in a dose-related manner inspite of ROS attack (P < 0.05 vs. control value). The 3AT pretreated ketorolac (3 × 10-3 M) group was decreased more significantly than un-pretreated ketorolac (P < 0.05). Conclusions These findings suggest that ketorlac and diclofenac preserve the endothelium-dependent vasorelaxation against the attack of ROS, in a concentration-related manner. One of the endothelial protection mechanisms of ketorolac may be hydrogen peroxide scavenging. PMID:20877705

  2. Effects of topical nasal steroids and diclofenac on the nasal mucosa during hyperbaric oxygen therapy: a double-blind experimental study.

    PubMed

    Vuralkan, Erkan; Cobanoglu, Hatice Bengu; Arslan, Abdullah; Arslan, Selcuk; Mungan, Sevdegul; Tatar, Selcuk; Toklu, Akın Savas

    2014-08-01

    We aimed to evaluate nasal mucosal changes and efficiency of nasal steroids and diclofenac on nasal mucosa during hyperbaric oxygen (HBO) treatment. Forty adult Albino-Wistar rats were randomized into four groups. Group 1 (control group) (n = 10) not exposed to hyperbaric or enhanced oxygen concentrations; group 2 (HBO group) (n = 10) underwent only HBO treatment; group 3 (n = 10) received HBO and intranasal mometasone furoate (10 μl/day); group 4 (n = 10) treated with HBO and diclofenac sodium (10 mg/kg/day ip). Specimens of nasal mucosa were collected after sacrificing and dissection of animals. The specimens were processed for light microscopic evaluation, and then evaluated histopathologically for fibroblastic proliferation and inflammation. Regarding the scores of inflammation, the level of inflammation in the control group was significantly less severe than the other groups (p < 0.05). Evaluation of the fibrosis scores showed that the scores of both groups 2 and 4 were significantly increased (p < 0.05). There were no statistically significant differences between groups 2, 3, and 4 as for fibrosis and inflammation (p > 0.05). Chronic HBO treatment induced mild inflammation of the nasal mucosa. These effects cannot be prevented adequately by administration of nasal steroids and diclofenac.

  3. Determination of diclofenac using electromembrane extraction coupled with stripping FFT continuous cyclic voltammetry.

    PubMed

    Mofidi, Zahra; Norouzi, Parviz; Seidi, Shahram; Ganjali, Mohammad Reza

    2017-06-15

    For the first time, on-line and ultra-sensitive determination of trace amount of diclofenac in whole blood sample was performed by coupling of electromembrane extraction (EME) and stripping fast Fourier transform continuous cyclic voltammetry (SFFTCCV). In SFFTCCV, the potential waveform was continuously applied on a carbon paste electrode and the electrode response was obtained by subtracting the background current and integrating the current in potential range of the analyte oxidation. A central composite design was used for the optimization of the parameters influencing the extraction efficiency. By applying a DC potential of 20 V during 28 min of extraction, diclofenac was migrated from the sample solution (pH 5), into a thin layer of 1-octanol immobilized in the pores of a porous flat sheet membrane and then into the acceptor solution (pH 7). The method presented a good linearity within the range of 5-1000 ng mL -1 with a determination coefficient of 0.993 in whole blood samples. Limits of detection (LOD) and quantification (LOQ) were found to be 1.0 ng mL -1 and 5.0 ng mL -1 respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Manipulating Ratio Spectra for the Spectrophotometric Analysis of Diclofenac Sodium and Pantoprazole Sodium in Laboratory Mixtures and Tablet Formulation

    PubMed Central

    Bhatt, Nejal M.; Chavada, Vijay D.; Sanyal, Mallika; Shrivastav, Pranav S.

    2014-01-01

    Objective. Three sensitive, selective, and precise spectrophotometric methods based on manipulation of ratio spectra, have been developed and validated for the determination of diclofenac sodium and pantoprazole sodium. Materials and Methods. The first method is based on ratio spectra peak to peak measurement using the amplitudes at 251 and 318 nm; the second method involves the first derivative of the ratio spectra (Δλ = 4 nm) using the peak amplitudes at 326.0 nm for diclofenac sodium and 337.0 nm for pantoprazole sodium. The third is the method of mean centering of ratio spectra using the values at 318.0 nm for both the analytes. Results. All the three methods were linear over the concentration range of 2.0–24.0 μg/mL for diclofenac sodium and 2.0–20.0 μg/mL for pantoprazole sodium. The methods were validated according to the ICH guidelines and accuracy, precision, repeatability, and robustness are found to be within the acceptable limit. The results of single factor ANOVA analysis indicated that there is no significant difference among the developed methods. Conclusions. The developed methods provided simple resolution of this binary combination from laboratory mixtures and pharmaceutical preparations and can be conveniently adopted for routine quality control analysis. PMID:24701171

  5. Nephroprotective Effect of the Leaves of Aloe barbadensis (Aloe Vera) against Toxicity Induced by Diclofenac Sodium in Albino Rabbits

    PubMed Central

    Iftikhar, A; Hasan, IJ; Sarfraz, M; Jafri, L; Ashraf, MA

    2015-01-01

    ABSTRACT Background: The present study was designed to evaluate the nephroprotective effect of the leaves of Aloe barbadensis against toxicity induced by diclofenac sodium in albino rabbits. Subjects and Method: Thirty-six healthy albino rabbits were randomly divided into six groups each with six animals. Group 1 served as the untreated control, group 2 was treated only with diclofenac sodium, group 3 with the nephroprotective drug silymarin and groups 4, 5, and 6 were treated with different doses of Aloe barbadensis, ie 200 mg/kg, 400 mg/kg and 600 mg/kg, respectively after being treated with diclofenac sodium. Blood samples were collected after every five days up to fifteen days. Haematological and histopathological parameters were determined by using diagnostic kits. Results: Results of haematological studies showed that use of the powder of Aloe barbadensis normalized the level of different factors eg, white blood cells (WBCs), red blood cells (RBCs), platelet count, packed cell volume (PCV), mean cell volume (MCV) and haemoglobin (Hb) values. Histopathological studies showed that Aloe barbadensis ameliorated pyknotic nuclei in the renal epithelial cells and reduced oxidative stress by increasing the level of catalase and decreasing malondialdehyde (MDA) level. Conclusion: These results have shown that Aloe barbadensis can normalize oxidative stress and can be used as an effective nephroprotective agent against drug-induced nephrotoxicity. PMID:27398602

  6. An activated sludge modeling framework for xenobiotic trace chemicals (ASM-X): assessment of diclofenac and carbamazepine.

    PubMed

    Plósz, Benedek Gy; Langford, Katherine H; Thomas, Kevin V

    2012-11-01

    Conventional models for predicting the fate of xenobiotic organic trace chemicals, identified, and calibrated using data obtained in batch experiments spiked with reference substances, can be limited in predicting xenobiotic removal in wastewater treatment plants (WWTPs). At stake is the level of model complexity required to adequately describe a general theory of xenobiotic removal in WWTPs. In this article, we assess the factors that influence the removal of diclofenac and carbamazepine in activated sludge, and evaluate the complexity required for the model to effectively predict their removal. The results are generalized to previously published cases. Batch experimental results, obtained under anoxic and aerobic conditions, were used to identify extensions to, and to estimate parameter values of the activated sludge modeling framework for Xenobiotic trace chemicals (ASM-X). Measurement and simulation results obtained in the batch experiments, spiked with the diclofenac and carbamazepine content of preclarified municipal wastewater shows comparably high biotransformation rates in the presence of growth substrates. Forward dynamic simulations were performed using full-scale data obtained from Bekkelaget WWTP (Oslo, Norway) to evaluate the model and to estimate the level of re-transformable xenobiotics present in the influent. The results obtained in this study demonstrate that xenobiotic loading conditions can significantly influence the removal capacity of WWTPs. We show that the trace chemical retransformation in upstream sewer pipes can introduce considerable error in assessing the removal efficiency of a WWTP, based only on parent compound concentration measurements. The combination of our data with those from the literature shows that solids retention time (SRT) can enhance the biotransformation of diclofenac, which was not the case for carbamazepine. Model approximation of the xenobiotic concentration, detected in the solid phase, suggest that between

  7. Dissolution stability studies of suspensions of prolonged-release diclofenac microcapsules prepared by the Wurster process: I. Eudragit-based formulation and possible drug-excipient interaction.

    PubMed

    Adeyeye, M C; Mwangi, E; Katondo, B; Jain, A; Ichikawa, H; Fukumori, Y

    2005-06-01

    The aim was to evaluate possible interaction in solid and liquid state of the drug with formulation excipients consequent to very fast drug release of diclofenac-Eudragit prolonged release microcapsules. The microcapsules were prepared by drug layering on calcium carbonate cores and coated with Eudragit RS 30D and L30D-55 as previously reported. Suspension of the microcapsules was prepared using microcrystalline cellulose/sodium carboxymethyl cellulose (Avicel CL-611) as medium. In vitro dissolution testing of the suspension was done, and, based on the dissolution results, possible interaction between diclofenac and Eudragit and Avicel in the medium was studied. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) analyses were performed using 1:1 binary, 1:1:1 ternary mixtures and a ratio equivalent to that in the formulation. The mixtures were prepared by mixing the dispersions--Eudragit RS 30D or L30D-55 with the drug or other components, followed by drying at 60 degrees C for 48 h. Dry mixing was done using the powder equivalents of the polymers, Eudragit RS PO and L100-55, Avicel and calcium carbonate. In vitro dissolution of the suspended microcapsules showed a very fast release after 48 h (T50 = <1 h) compared to the solid microcapsules (T50 = 6 h). DSC curves of the formulation components or microcapsules did not show the characteristic endothermic peak of diclofenac at 287 degrees C. Powder X-ray diffraction of the binary or ternary mixtures of diclofenac and Eudragit polymers indicated reduction, shift or modification of the crystalline peaks of the drug or excipients at 2theta of 12 degrees and 18 degrees , suggestive of interaction. Some changes in drug peak characteristics at 18 degrees and 23 degrees were observed for Avicel/drug mixture, though not significant. The DSC curves of the binary mixture of diclofenac co-dried with liquid forms of Eudragit (i.e. RS 30D or L30D-55) revealed greater interaction compared to the curves of

  8. A comparison of two different formulations of diclofenac sodium 0.1% in the treatment of inflammation following cataract-intraocular lens surgery.

    PubMed

    Mester, Ulrich; Lohmann, Chris; Pleyer, U; Steinkamp, G; Völcker, E; Kruger, H; Raj, Palaniswamy Sunder

    2002-01-01

    To compare the efficacy, tolerability and local tolerance of diclofenac sodium 0.1% containing hydroxypropylgamma cyclodextrin preserved with benzalkonium chloride 0.005% (Voltaren Ophtha CD), with that of diclofenac sodium 0.1% preserved with thiomersal 0.004% (Voltaren Ophtha) in the treatment of inflammation after cataract-intraocular lens surgery. Randomised 2:1, double-masked, parallel-group study in six centres in Germany. 299 patients scheduled to undergo phacoemulsification with posterior chamber intraocular lens implantation. Study medications were instilled four times in the 30 minutes before surgery and four times daily from the first postoperative day. The key efficacy variable was the reduction in anterior chamber flare (photons/millisecond) from day 1 to day 6 to 8. Patients underwent comprehensive ocular examinations, including laser flaremetry (KOWA), preoperatively and postoperatively at days 1, 6 to 8 and 24 to 32. 268 patients (Voltaren Ophtha CD 177, Voltaren Ophtha 91) completed the day 6 to 8 visit without any protocol violations. Reduction in the degree of intraocular inflammation with Voltaren Ophtha CD was equivalent to that achieved with Voltaren Ophtha at the day 6 to 8 [95% confidence interval (CI) -3.07 to +0.54] and day 24 to 32 (95% CI -1.44 to +1.40) visits. Although there was no significant (p = 0.464) difference between the two study groups in patients' global assessment of local tolerance at day 24 to 32, ocular discomfort was significantly (p = 0.023) less with Voltaren Ophtha CD compared with Voltaren Ophtha. Voltaren Ophtha CD was as effective and well tolerated but had less ocular discomfort compared with Voltaren Ophtha in the treatment of ocular inflammation after phacoemulsification with intraocular lens implantation. This new formulation of diclofenac sodium 0.1% may be used as an alternative to the existing formulations of ophthalmic diclofenac sodium 0.1%.

  9. Synthesis, spectroscopic and thermal studies of Mg(II), Ca(II), Sr(II) and Ba(II) diclofenac sodium complexes as anti-inflammatory drug and their protective effects on renal functions impairment and oxidative stress

    NASA Astrophysics Data System (ADS)

    El-Megharbel, Samy M.; Hamza, Reham Z.; Refat, Moamen S.

    2015-01-01

    The main task of our present study is the preparation of newly complexes of Mg(II), Ca(II), Sr(II) and Ba(II) with diclofenac which succeeded to great extent in alleviating the side effects of diclofenac alone and ameliorating the kidney function parameters and antioxidant capacities with respect to diclofenac treated group alone. The Mg(II), Ca(II), Sr(II) and Ba(II) with diclofenac have been synthesized and characterized using infrared, electronic and 1H NMR spectral, thermogravimetric and conductivity measurements. The diclofenac ligand has been found to act as bidentate chelating agent. Diclofenac complexes coordinate through the oxygen's of the carboxyl group. The molar ratio chelation is 1:2 (M2+-dic) with general formula [M(dic)2(H2O)2]ṡnH2O. Antibacterial screening of the alkaline earth metal complexes against Escherichia coli (Gram - ve), Bacillus subtilis (Gram + ve) and anti-fungal (Asperagillus oryzae, Asperagillus niger, Asperagillus flavus) were investigated. The kidney functions in male albino rats were ameliorated upon treatment with metal complexes of dic, which are represented by decreasing the levels of urea and uric acid to be located within normal values. The other looks bright spot in this article is the assessment of antioxidant defense system including SOD, CAT and MDA with the help of Sr2+, Mg2+ and Ca2+-dic complexes. The hormones related to kidney functions and stresses have been greatly ameliorated in groups treated with dic complexes in comparable with dic treated group.

  10. The Concomitant Consumption of Cod Liver Oil Causes a Reduction in the Daily Diclofenac Sodium Usage in Rheumatoid Arthritis Patients: A Pilot Study

    PubMed Central

    Gupta, Vinay Kumar; Khan, Z. Y. Zafer; Ahmad, Mushtaq

    2013-01-01

    Objective: To evaluate whether the concomitant consumption of Cod liver oil can reduce the daily dose of Diclofenac Sodium and probably the risk of the side effects which are associated with it in Rheumatoid Arthritis patients. Material and Methods: This longitudinal, prospective, open label study was conducted from April to September 2012 at Mahatma Gandhi Medical College and Hospital, Jaipur, India. 30 Rheumatoid Arthritis patients who were aged between 19 to 60 years, who fulfilled the inclusion criteria, were enrolled. Each patient was given five Cod liver oil capsules twice a day, for a period of 24 weeks. Each capsule which contained 300 mg of Cod liver oil had Eicosapentaenoic acid-20 mg and Docosahexaenoic acid-30 mg. The patients who took different Nonsteroidal anti-inflammatory drugs daily were switched over to Diclofenac Sodium 50 mg as a single dose, up to a maximum dose of 200 mg per day. The dose of Diclofenac Sodium which was consumed per day and the average daily requirement at different visits were recorded in each patient and they were compared. The patients were assessed for their pain scores by using the Visual Analogue Scale (VAS) at different weeks. In addition, the ‘Subjective Response’ to the pain was evaluated in each patient at the respective visits. The Student’s “t”-test was applied for the analysis of the VAS pain score and for the evaluation of the reduction in the mean daily dose of the Diclofenac Sodium consumption. A probability value of less than 0.05 (p< 0.05) was considered to be statistically significant. Moreover, the results of the ‘Subjective Response’ to the pain were expressed as percentage. Results: A significant decrease (p< 0.05) in the mean VAS pain score from 80.38 ± 6.4 at week 0 to 67.30 ± 5.3 at week 24 was noted in the patients. There was a significant reduction (p<0.05) in mean dose of Diclofenac Sodium consumed from 115.04 ± 24.56 at week 4 to 98.83 ± 22.32 at week 24. Moreover, the percentage

  11. Reducing angiographic cystoid macular edema and blood-aqueous barrier disruption after small-incision phacoemulsification and foldable intraocular lens implantation: multicenter prospective randomized comparison of topical diclofenac 0.1% and betamethasone 0.1%.

    PubMed

    Asano, Sayaka; Miyake, Kensaku; Ota, Ichiro; Sugita, Gentaro; Kimura, Wataru; Sakka, Yuji; Yabe, Nobuyuki

    2008-01-01

    To compare the effectiveness of a topical nonsteroidal drug (diclofenac 0.1%) and a topical steroidal drug (betamethasone 0.1%) in preventing cystoid macular edema (CME) and blood-aqueous barrier (BAB) disruption after small-incision cataract surgery and foldable intraocular lens (IOL) implantation. Shohzankai Medical Foundation Miyake Eye Hospital, Tokyo, Japan. This multicenter interventional double-masked randomized study comprised 142 patients having phacoemulsification and foldable IOL implantation. Seventy-one patients were randomized to receive diclofenac eyedrops and 71, betamethasone eyedrops for 8 weeks postoperatively. The incidence and severity of CME were evaluated by fluorescein angiography. Blood-aqueous barrier disruption was determined by laser flare-cell photometry. Of the patients, 63 were men and 79 were women. Five weeks after surgery, the incidence of fluorescein angiographic CME was lower in the diclofenac group (18.8%) than in the betamethasone group (58.0%) (P<.001). At 1 and 2 weeks, the amount of anterior chamber flare was statistically significantly less in the diclofenac group than in the betamethasone group (P<.05). At 8 weeks, intraocular pressure was statistically significantly higher in the betamethasone group (P = .0003). Diclofenac was more effective than betamethasone in preventing angiographic CME and BAB disruption after small-incision cataract surgery. Thus, nonsteroidal antiinflammatory agents should be considered for routine treatment of eyes having cataract surgery.

  12. Formulation and evaluation of bilayer tablets of metoclopramide hydrochloride and diclofenac sodium.

    PubMed

    Gattani, Surendra G; Khabiya, Sohan S; Amrutkar, Jitendra R; Kushare, Sachin S

    2012-01-01

    The main objective of the present research work was to develop a bilayer tablet of metoclopramide hydrochloride (MTH) and diclofenac sodium (DS) in separate layers to avoid incompatibility and thus to maximize the efficacy of both drugs in combination for the effective treatment of migraine headaches. MTH and DS were formulated as immediate and sustained release layers respectively. In vitro dissolution kinetic studies of an optimized (D10) batch of DS in both sustained release layer and bilayer tablet forms show good linearity of regression coefficient 0.9773 (first order equation). The results reveal that an optimized immediate release layer (M5) of MTH and a sustained release layer (D10) of DS might be suitable for the treatment of migraine by sequential release of the two drugs in a bilayer tablet. Migraine is a type of recurring headache of moderate to severe intensity associated with gastrointestinal, neurological, and autonomic symptoms. In migraine, a combination of pretreatment with antiemetics is required for symptomatic treatment, when nausea and vomiting are severe. In our present research, we have selected the metoclopramide hydrochloride (MTH) active ingredient for study because it has an antiemetic effect and is a prokinetic agent. MTH is more effective to counteract gastric stasis associated with migraine, and it enhances the rate of absorption of non-steroidal anti-inflammatory drugs (NSAIDs). In the present investigation we combine MTH and a second active ingredient, diclofenac sodium, as a formulated bilayer tablet to prevent degradation of MTH.

  13. Diclofenac Salts, VIII. Effect of the Counterions on the Permeation through Porcine Membrane from Aqueous Saturated Solutions.

    PubMed

    Fini, Adamo; Bassini, Glenda; Monastero, Annamaria; Cavallari, Cristina

    2012-09-12

    The following bases: monoethylamine (EtA), diethylamine (DEtA), triethylamine (TEtA), monoethanolamine (MEA), diethanolamine (DEA), triethanolamine (TEA), pyrrolidine (Py), piperidine (Pp), morpholine (M), piperazine (Pz) and their N-2-hydroxyethyl (HE) analogs were employed to prepare 14 diclofenac salts. The salts were re-crystallized from water in order to obtain forms that are stable in the presence of water. Vertical Franz-type cells with a diffusional surface area of 9.62 cm2 were used to study the permeation of these diclofenac salts from their saturated solutions through an internal pig ear membrane. The receptor compartments of the cells contained 100 mL of phosphate buffer (pH 7.4); a saturated solution (5 mL) of each salt was placed in the donor compartment, thermostated at 37 °C. Aliquots were withdrawn at predetermined time intervals over 8 h and then immediately analyzed by HPLC. Fluxes were determined by plotting the permeated amount, normalized for the membrane surface area versus time. Permeation coefficients were obtained dividing the flux values J by the concentration of the releasing phase-that is, water solubility of each salt. Experimental results show that fluxes could be measured when diclofenac salts with aliphatic amines are released from a saturated aqueous solution. Different chemical species (acid, anion, ion pairs) contribute to permeation of the anti-inflammatory agent even though ion-pairs could be hypothesized to operate to a greater extent. Permeation coefficients were found higher when the counterion contains a ring; while hydroxy groups alone do not appear to play an important role, the ring could sustain permeation, disrupting the organized domains of the membrane.

  14. Diclofenac Salts, VIII. Effect of the Counterions on the Permeation through Porcine Membrane from Aqueous Saturated Solutions

    PubMed Central

    Fini, Adamo; Bassini, Glenda; Monastero, Annamaria; Cavallari, Cristina

    2012-01-01

    The following bases: monoethylamine (EtA), diethylamine (DEtA), triethylamine (TEtA), monoethanolamine (MEA), diethanolamine (DEA), triethanolamine (TEA), pyrrolidine (Py), piperidine (Pp), morpholine (M), piperazine (Pz) and their N-2-hydroxyethyl (HE) analogs were employed to prepare 14 diclofenac salts. The salts were re-crystallized from water in order to obtain forms that are stable in the presence of water. Vertical Franz-type cells with a diffusional surface area of 9.62 cm2 were used to study the permeation of these diclofenac salts from their saturated solutions through an internal pig ear membrane. The receptor compartments of the cells contained 100 mL of phosphate buffer (pH 7.4); a saturated solution (5 mL) of each salt was placed in the donor compartment, thermostated at 37 °C. Aliquots were withdrawn at predetermined time intervals over 8 h and then immediately analyzed by HPLC. Fluxes were determined by plotting the permeated amount, normalized for the membrane surface area versus time. Permeation coefficients were obtained dividing the flux values J by the concentration of the releasing phase—that is, water solubility of each salt. Experimental results show that fluxes could be measured when diclofenac salts with aliphatic amines are released from a saturated aqueous solution. Different chemical species (acid, anion, ion pairs) contribute to permeation of the anti-inflammatory agent even though ion-pairs could be hypothesized to operate to a greater extent. Permeation coefficients were found higher when the counterion contains a ring; while hydroxy groups alone do not appear to play an important role, the ring could sustain permeation, disrupting the organized domains of the membrane. PMID:24300300

  15. Diclofenac affects kidney histology in the three-spined stickleback (Gasterosteus aculeatus) at low μg/L concentrations.

    PubMed

    Näslund, Johanna; Fick, Jerker; Asker, Noomi; Ekman, Elisabet; Larsson, D G Joakim; Norrgren, Leif

    2017-08-01

    Diclofenac, a commonly used non-steroidal anti-inflammatory drug, is considered for regulation under the European water framework directive. This is because effects on fish have been reported at concentrations around those regularly found in treated sewage effluents (∼1μg/L). However, a recent publication reports no effects on fish at 320μg/L. In this study, three-spined sticklebacks (Gasterosteus aculeatus) were exposed to 0, 4.6, 22, 82 and 271μg/L diclofenac in flow-through systems for 28days using triplicate aquaria per concentration. At the highest concentration, significant mortalities were observed already after 21days (no mortalities found up to 22μg/L). Histological analysis revealed a significant increase in the proportion of renal hematopoietic tissue (renal hematopoietic hyperplasia) after 28days at the lowest concentration and at all higher concentrations, following a clear dose-response pattern. Skin ulcerations of the jaw were noted by macroscopic observations, primarily at the two highest concentrations. No histological changes were observed in the liver. There was an increase in the relative hepatic mRNA levels of c7 (complement component 7), a gene involved in the innate immune system, at 22μg/L and at all higher concentrations, again following a clear dose-response. The bioconcentration factor was stable across concentrations, but lower than reported for rainbow trout, suggesting lower internal exposure to the drug in the stickleback. In conclusion, this study demonstrates that diclofenac causes histological changes in the three-spined stickleback at low μg/L concentrations, which cause concern for fish populations exposed to treated sewage effluents. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Three-dimensional plotted alginate fibers embedded with diclofenac and bone cells coated with chitosan for bone regeneration during inflammation.

    PubMed

    Lin, Hsin-Yi; Chang, Tsang-Wen; Peng, Tie-Kun

    2018-06-01

    Alginate hydrogel fibers embedded with bone cells and diclofenac were coated with a layer of chitosan hydrogel and made into a porous scaffold by three-dimensional (3D) printing for drug release and bone regeneration. It was hypothesized that the chitosan coating could improve the scaffold's drug retention and release properties and biocompatibility. Macrophage cells were stimulated and cocultured with the scaffold. Tests were conducted to show how the chitosan coating affected the scaffold's drug release efficacy and how the release efficacy affected the cellular activities of stimulated macrophages and bone cells. The bone cells encapsulated in the coated scaffold demonstrated good viability after the acidic/basic coating process. The coating improved the retention and release efficacy of diclofenac and hence significantly inhibited interleukin-6 and tumor necrosis factor-α secretion from macrophages (p < 0.05). The bone cells in the coated sample mineralized more extensively than the control (p < 0.01). They also more actively expressed genes that produce proteins for extracellular matrix remodeling, MMP13, and interacting with the mineral matrix, OPN (both p < 0.01). It is believed that on days 7 and 10, when diclofenac was depleted and the concentrations of inflammatory compounds surged, the coating effectively blocked the harmful compounds and protected the bone cells within the fibers. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1511-1521, 2018. © 2018 Wiley Periodicals, Inc.

  17. Improved Skin Penetration Using In Situ Nanoparticulate Diclofenac Diethylamine in Hydrogel Systems: In Vitro and In Vivo Studies.

    PubMed

    Sengupta, Soma; Banerjee, Sarita; Sinha, Biswadip; Mukherjee, Biswajit

    2016-04-01

    Delivering diclofenac diethylamine transdermally by means of a hydrogel is an approach to reduce or avoid systemic toxicity of the drug while providing local action for a prolonged period. In the present investigation, a process was developed to produce nanosize particles (about 10 nm) of diclofenac diethylamine in situ during the development of hydrogel, using simple mixing technique. Hydrogel was developed with polyvinyl alcohol (PVA) (5.8% w/w) and carbopol 71G (1.5% w/w). The formulations were evaluated on the basis of field emission scanning electron microscopy, texture analysis, and the assessment of various physiochemical properties. Viscosity (163-165 cps for hydrogel containing microsize drug particles and 171-173 cps for hydrogel containing nanosize drug particles, respectively) and swelling index (varied between 0.62 and 0.68) data favor the hydrogels for satisfactory topical applications. The measured hardness of the different hydrogels was uniform indicating a uniform spreadability. Data of in vitro skin (cadaver) permeation for 10 h showed that the enhancement ratios of the flux of the formulation containing nanosize drug (without the permeation enhancer) were 9.72 and 1.30 compared to the formulation containing microsized drug and the marketed formulations, respectively. In vivo plasma level of the drug increased predominantly for the hydrogel containing nanosize drug-clusters. The study depicts a simple technique for preparing hydrogel containing nanosize diclofenac diethylamine particles in situ, which can be commercially viable. The study also shows the advantage of the experimental transdermal hydrogel with nanosize drug particles over the hydrogel with microsize drug particles.

  18. [Indomethacin (indocollyre) versus diclofenac (voltarene) for the control of pain following excimer photoablation].

    PubMed

    Cochener, B; Kling, F; Savary-Le Floch, G; Colin, J

    2000-06-01

    To compare effect of two topical non steroidal anti-inflammatory (NSAI) drugs: Indomethacin (Indocollyre)0.1 %, Chauvin Inc.) and Diclofenac (Voltaren 0.1%, Cibavision) on postoperative pain and epithelial regrowth following surface excimer photoablation. Eighty-six excimer operated patients, were divided in two similar groups depending on the NSAI instilled postoperatively and for 3 days (4 drops daily). No patient was informed of any other available drug. Pain intensity was quantified between 1 and 10 according to an analog scale (reported from 1 to 10 hours, then 4 times a day during 7 days). Complementary medications and functional symptoms were also notified. Biomicroscopic evaluation using fluorescein test was performed to assess reepithelialization. In term of pain, no significative difference was observed between the two groups concerning intensity, associated medications, or numbers of days of discomfort. Controversially, retreated eyes might induce more pain than initial treatments. No delay in epithelial regrowth was noted and the difference between the two groups in functional complaints was no statistically significant. Pain appears to be not related to ablation depth. DISCUSSION- CONCLUSION: Our results are correlated to literature reported data. Introduction of NSAI constitutes a real advent in the care of excimer postoperative pain. Effect of indomethacin seems comparable to diclofenac effect, but might be of interest because of no anesthetic property that might guarantee of no delay in wound healing response.

  19. Diclofenac degradation by heterogeneous photocatalysis with Fe3O4/Ti x O y /activated carbon fiber composite synthesized by ultrasound irradiation

    NASA Astrophysics Data System (ADS)

    Moreno-Valencia, E. I.; Paredes-Carrera, S. P.; Sánchez-Ochoa, J. C.; Flores-Valle, S. O.; Avendaño-Gómez, J. R.

    2017-11-01

    In this work, a photocatalytic system to degrade diclofenac was developed using a composite Fe3O4/Ti x O y on an activated carbon fiber. Diclofenac is widely used as an anti-inflammatory compound worldwide and it is constantly being added as waste in the environment (Heberer 2002 J. Hydrol. 266 175-89), exceeding the permissible maximum concentration in the wastewater (GEO-3 2002 Programa de las Naciones Unidas para el Medio Ambiente; Golet et al 2003 Environ. Sci. Technol. 37 3243-9 Oviedo et al 2010 Environ. Toxicol. Pharmacol. 29 9-43 Le-Minh et al 2010 Water Res. 44 4295-323 Legrini et al 1993 Chem. Rev. 1093 671-98). The composite was synthesized by sol-gel technique with and without ultrasound irradiation (Singh and Nakate 2014 J. Nanopart. 2014 326747). The solids were deposited by ultrasound irradiation on active carbon fiber in order to optimize the diclofenac degradation. The solids were characterized by x-ray diffraction (XRD), nitrogen physisorption (BET), and scanning electron microscopy with EDS microanalysis (SEM-EDS). The crystal size was calculated with the Debye-Scherrer equation, and the band gap values by the diffuse reflectance method. The evaluation process was studied by UV-vis spectroscopy (Rizzoa et al 2009 Water Res. 43 979-88). It was found that in this synthesis method (ultrasound), textural properties such as porosity, specific surface area and morphology depend on the ultrasound irradiation. The proposed system, Fe3O4/titanium oxide hydrate showed better degradation profile than TiO2 anatase phase; the increase of diclofenac degradation was attributed to the textural properties of the composite, it avoids the filtering process since the separation can be achieved by magnetizing and/or decantation.

  20. Effects of low-level laser therapy (LLLT) and diclofenac (topical and intramuscular) as single and combined therapy in experimental model of controlled muscle strain in rats.

    PubMed

    de Paiva Carvalho, Rodrigo Leal; Leal-Junior, Ernesto Cesar Pinto; Petrellis, Maria Carla; Marcos, Rodrigo Labat; de Carvalho, Maria Helena Catelli; De Nucci, Gilberto; Lopes-Martins, Rodrigo Alvaro Brandão

    2013-01-01

    Muscle injuries represent ca 30% of sports injuries and excessive stretching of muscle causes more than 90% of injuries. Currently the most used treatments are nonsteroidal anti-inflammatory drugs (NSAIDs), however, in last years, low-level laser therapy (LLLT) is becoming an interesting therapeutic modality. The aim of this study was to evaluate the effect of single and combined therapies (LLLT, topical application of diclofenac and intramuscular diclofenac) on functional and biochemical aspects in an experimental model of controlled muscle strain in rats. Muscle strain was induced by overloading tibialis anterior muscle of rats. Injured groups received either no treatment, or a single treatment with topical or intramuscular diclofenac (TD and ID), or LLLT (3 J, 810 nm, 100 mW) 1 h after injury. Walking track analysis was the functional outcome and biochemical analyses included mRNA expression of COX-1 and COX-2 and blood levels of prostaglandin E2 (PGE2 ). All treatments significantly decreased COX-1 and COX-2 gene expression compared with injury group (P < 0.05). However, LLLT showed better effects than TD and ID regarding PGE2 levels and walking track analysis (P < 0.05). We can conclude that LLLT has more efficacy than topical and intramuscular diclofenac in treatment of muscle strain injury in acute stage. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

  1. Occurrence of naproxen, ibuprofen, and diclofenac residues in wastewater and river water of KwaZulu-Natal Province in South Africa.

    PubMed

    Madikizela, Lawrence Mzukisi; Chimuka, Luke

    2017-07-01

    The present paper reports a detailed study that is based on the monitoring of naproxen, ibuprofen, and diclofenac in Mbokodweni River and wastewater treatment plants (WWTPs) located around the city of Durban in KwaZulu-Natal Province of South Africa. Target compounds were extracted from water samples using a multi-template molecularly imprinted solid-phase extraction prior to separation and quantification on a high-performance liquid chromatography equipped with photo diode array detector. The analytical method yielded the detection limits of 0.15, 1.00, and 0.63 μg/L for naproxen, ibuprofen, and diclofenac, respectively. Solid-phase extraction method was evaluated for its performance using deionized water samples that were spiked with 5 and 50 μg/L of target compounds. Recoveries were greater than 80% for all target compounds with RSD values in the range of 4.1 to 10%. Target compounds were detected in most wastewater and river water samples with ibuprofen being the most frequently detected pharmaceutical. Maximum concentrations detected in river water for naproxen, ibuprofen, and diclofenac were 6.84, 19.2, and 9.69 μg/L, respectively. The concentrations of target compounds found in effluent and river water samples compared well with some studies. The analytical method employed in this work is fast, selective, sensitive, and affordable; therefore, it can be used routinely to evaluate the occurrence of acidic pharmaceuticals in South African water resources.

  2. Electrospun poly-l-lactide scaffold for the controlled and targeted delivery of a synthetically obtained Diclofenac prodrug to treat actinic keratosis.

    PubMed

    Piccirillo, Germano; Bochicchio, Brigida; Pepe, Antonietta; Schenke-Layland, Katja; Hinderer, Svenja

    2017-04-01

    Actinic Keratosis' (AKs) are small skin lesions that are related to a prolonged sun-damage, which can develop into invasive squamous cell carcinoma (SCC) when left untreated. Effective, specific and well tolerable therapies to cure AKs are still of great interest. Diclofenac (DCF) is the current gold standard for the local treatment of AKs in terms of costs, effectiveness, side effects and tolerability. In this work, an electrospun polylactic acid (PLA) scaffold loaded with a synthetic DCF prodrug was developed and characterized. Specifically, the prodrug was successfully synthetized by binding DCF to a glycine residue via solid phase peptide synthesis (SPPS) and then incorporated in an electrospun PLA scaffold. The drug encapsulation was verified using multiphoton microscopy (MPM) and its scaffold release was spectrophotometrically monitored and confirmed with MPM. The scaffold was further characterized with scanning electron microscopy (SEM), tensile testing and contact angle measurements. Its biocompatibility was verified by performing a cell proliferation assay and compared to PLA scaffolds containing the same amount of DCF sodium salt (DCFONa). Finally, the effect of the electrospun scaffolds on human dermal fibroblasts (HDFs) morphology and metabolism was investigated by combining MPM with fluorescence lifetime imaging microscopy (FLIM). The obtained results suggest that the obtained scaffold could be suitable for the controlled and targeted delivery of the synthesized prodrug for the treatment of AKs. Electrospun scaffolds are of growing interest as materials for a controlled drug delivery. In this work, an electrospun polylactic acid scaffold containing a synthetically obtained Diclofenac prodrug is proposed as a novel substrate for the topical treatment of actinic keratosis. A controlled drug delivery targeted to the area of interest could enhance the efficacy of the therapy and favor the healing process. The prodrug was synthesized via solid phase

  3. Traumeel vs. diclofenac for reducing pain and improving ankle mobility after acute ankle sprain: a multicentre, randomised, blinded, controlled and non-inferiority trial.

    PubMed

    González de Vega, C; Speed, C; Wolfarth, B; González, J

    2013-10-01

    Acute ankle sprains are common and activity limiting injuries, and topical diclofenac gel has proven efficacy in alleviating pain and restoring function. This trial aimed to compare a topical natural agent, Traumeel with topical diclofenac gel (1%) in the management of acute ankle sprain. This prospective, multicentre, randomised, blinded, active-control and non-inferiority study involved 449 physically active adults sustaining unilateral grade 1 or 2 ankle sprain within the past 24 h. Participants were randomised to receive 2 g of Traumeel ointment (T-O) (n = 152) or Traumeel gel (T-G) (n = 150) or diclofenac gel (D-G) (n = 147), administered topically to the ankle three times a day for 14 days, with 6-weeks follow up. Day 7 median percentage reductions in Visual Analogue Scale pain score were 60.6%, 71.1% and 68.9% for the T-O, T-G and D-G groups, respectively. Total pain relief was reported by 12 (8.5%), 7 (5.0%) and 8 (5.9%) participants in each group, respectively. Median improvements in Foot and Ankle Ability Measure Activities of Daily Living subscale score were 26.2, 26.2 and 25.0 points for T-O, T-G and D-G groups, respectively. Mann-Whitney effect sizes and lower bound confidence intervals demonstrated non-inferiority of Traumeel vs. diclofenac for reducing pain and functional improvement. At 6 weeks, participants reported total pain relief and normal functioning. Adverse events (n = 43) were reported by 31/447 participants (6.9%). Treatments were equally well tolerated. T-O and T-G decreased pain and improved joint function to the same extent as D-G in acute ankle sprain, and were well tolerated. © 2013 The Authors. International Journal of Clinical Practice published by John Wiley & Sons Ltd.

  4. Release study of diclofenac from new carbomer gels.

    PubMed

    Bregni, Carlos; Chiappetta, Diego; Faiden, Natalia; Carlucci, Adriana; García, Roberto; Pasquali, Ricardoc

    2008-01-01

    Carbopol gels were prepared using a traditional polymer with mucoadhesive properties (974P). A new Carbomer derivative Ultrez 21 was also evaluated. Mineral oil, as occlusive ingredient, glycerol as humectant and ethanol were included in all the compositions. The feasibility of preparing these formulations with or without a bioadhesive polymer (Polycarbophil AA-1) and a second oil phase with enhancer activity (Miglyol 840) was evaluated. Further characterization including physical stability during a year was carried out. In vitro release behaviour of diclofenac sodium in Franz diffusion cell was evaluated with some selected formulations using an ethanol-water (50% w/w) solution as receptor medium. Addition of Polycarbophil AA-1 increased formulation viscosity and decreased drug release. These types of topical dosage forms could give sustained delivery of drug onto the skin, could tolerate the incorporation of an enhancer, a humectant and an occlusive phase, so they are interesting promises to improve skin absorption of nonsteroidal anti-inflammatory drugs and to prevent side effects associated.

  5. Zn-based porous coordination solid as diclofenac sodium carrier

    NASA Astrophysics Data System (ADS)

    Lucena, Guilherme Nunes; Alves, Renata Carolina; Abuçafy, Marina Paiva; Chiavacci, Leila Aparecida; da Silva, Isabel Cristiane; Pavan, Fernando Rogério; Frem, Regina Célia Galvão

    2018-04-01

    Drug delivery systems produced with biocompatible components can be used to reduce adverse effects and improve therapy efficacy. Most of the carrier materials reported in the literature show poor drug loading and rapid release. However, porous hybrid solids, such as metal-organic frameworks, are well suited to serve as carriers for delivery and imaging applications. In this work, a luminescent and nontoxic porous Zn(II) coordination polymer with 4,4‧-biphenyl-dicarboxylic acid (BPDC) and adenine linkers (BioMOF-Zn) was synthesized by a solvothermal process and characterized by PXRD, TGA, SEM-FEG, and FTIR. Nitrogen adsorption measurements revealed the presence of micropores as well as mesopores in the framework after activation of the material. The blue-emitting BioMOF-Zn exhibited an outstanding loading capacity (1.72 g g-1) and satisfactory release capability (56% after two days) for diclofenac sodium.

  6. Comparison of lignocaine gel-soaked Falope rings vs rectal diclofenac suppository for pain relief in laparoscopic sterilization.

    PubMed

    Sharma, Jai Bhagwan; Ghosh, Bhaswati; Kumar, Praveen; Mittal, Suneeta; Kumar, Sunesh; Roy, Kallol Kumar

    2011-01-01

    To compare the analgesic efficacy of lignocaine gel-soaked Silastic bands compared with rectal diclofenac suppositories in patients undergoing interval laparoscopic sterilization under conscious sedation. Prospective, randomized, controlled, single-blinded, clinical trial. Day-case center in a tertiary care hospital in India. Ninety-six women undergoing interval laparoscopic sterilization using Silastic bands (Yoon rings) randomly allocated by computer-generated random numbers into 3 groups. All women received intravenous sedation with injection diazepam and pentazocine along with local infiltration lignocaine injected at the site of the incision meant for insertion of the single site laparocator. In group 1 (n = 32), the Silastic bands (Falope rings) were presoaked in 2% sterile lignocaine gel; in group 2 (n = 32), women received a 100-mg rectal diclofenac suppository while on the operating table; and women in group 3 received only conventional analgesic. Pain perception was assessed using an 11-point visual analog score just after the procedure while still on the table (zero minutes), at 30 minutes and 1 hour after the procedure, and at discharge. The women in all 3 groups were comparable insofar as age and parity. At zero minutes (while on the operating table), the pain score in all 3 groups was similar. However, the pain scores at 30 and 60 minutes, and at discharge were significantly lower in groups 1 and group 2 compared with group 3. However, 2 women (6.25%) in group 2 and 6 (18.75%) in group 3 required supplemental analgesia within 1 hour, and were administered a 500-mg oral dose of mefenamic acid. The need for further analgesia was significantly lower in groups 1 and 2 compared with group 3 (p = .02). Comparison of groups 1 and 3 revealed that in group 1, the pain scores were significantly lower at 30 minutes (p = .02), 1 hour (p = .005), and at discharge (p = .004). No patients in group 1 requested analgesia, whereas 6 women in group 3 asked for further

  7. Comparison of different advanced degradation processes for the removal of the pharmaceutical compounds diclofenac and carbamazepine from liquid solutions.

    PubMed

    Capodaglio, Andrea G; Bojanowska-Czajka, Anna; Trojanowicz, Marek

    2018-04-18

    Carbamazepine and diclofenac are two examples of drugs with widespread geographical and environmental media proliferation that are poorly removed by traditional wastewater treatment processes. Advanced oxidation processes (AOPs) have been proposed as alternative methods to remove these compounds in solution. AOPs are based on a wide class of powerful technologies, including UV radiation, ozone, hydrogen peroxide, Fenton process, catalytic wet peroxide oxidation, heterogeneous photocatalysis, electrochemical oxidation and their combinations, sonolysis, and microwaves applicable to both water and wastewater. Moreover, processes rely on the production of oxidizing radicals (•OH and others) in a solution to decompose present pollutants. Water radiolysis-based processes, which are an alternative to the former, involve the use of concentrated energy (beams of accelerated electrons or γ-rays) to split water molecules, generating strong oxidants and reductants (radicals) at the same time. In this paper, the degradation of carbamazepine and diclofenac by means of all these processes is discussed and compared. Energy and byproduct generation issues are also addressed.

  8. Sorption of diclofenac and naproxen onto MWCNT in model wastewater treated by H2O2 and/or UV.

    PubMed

    Czech, Bożena; Oleszczuk, Patryk

    2016-04-01

    The application of oxidation processes such as UV and/or H2O2 will change the physicochemical properties of carbon nanotubes (CNT). It may affect the sorption affinity of CNT to different contaminants and then affect their fate in the environment. In the present study the adsorption of two very common used pharmaceuticals (diclofenac and naproxen) onto CNT treated by UV, H2O2 or UV/H2O2 was investigated. Four different adsorption models (Freundlich, Langmuir, Temkin, Dubinin-Radushkevich) were tested. The best fitting of experimental data was observed for Freundlich or Langmuir model. The significant relationships between Q calculated from Langmuir model with O% and dispersity were observed. Kinetics of diclofenac and naproxen followed mainly pseudo-second order indicating for chemisorption limiting step of adsorption. The data showed that the mechanism of sorption was physical or chemical depending on the type of CNT modification. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Analgesic Effect of Topical Sodium Diclofenac before Retinal Photocoagulation for Diabetic Retinopathy: A Randomized Double-masked Placebo-controlled Intraindividual Crossover Clinical Trial.

    PubMed

    Ramezani, Alireza; Entezari, Morteza; Shahbazi, Mohammad Mehdi; Semnani, Yosef; Nikkhah, Homayoun; Yaseri, Mehdi

    2017-04-01

    To evaluate the analgesic effect of topical sodium diclofenac 0.1% before retinal laser photocoagulation for diabetic retinopathy. Diabetic patients who were candidates for peripheral laser photocoagulation were included in a randomized, placebo-controlled, intraindividual, two-period, and crossover clinical trial. At the first session and based on randomization, one eye received topical sodium diclofenac 0.1% and the other eye received an artificial tear drop (as placebo) three times before laser treatment. At the second session, eyes were given the alternate drug. Patients scored their pain using visual analogue scale (max, 10 cm) at both sessions. Patients and the surgeon were blinded to the drops given. Difference of pain level was the main outcome measure. A total of 200 eyes of 100 patients were enrolled. Both treatments were matched regarding the applied laser. Pain sensation based on visual analogue scale was 5.6 ± 3.0 in the treated group and 5.5 ± 3.0 in the control group. The calculated treatment effect was 0.15 (95% confidence interval, -0.27 to 0.58; p = 0.486). The estimated period effect was 0.24 ( p = 0.530) and the carryover effect was not significant ( p = 0.283). Pretreatment with topical sodium diclofenac 0.1% does not have any analgesic effect during peripheral retinal laser photocoagulation in diabetic patients.

  10. Simultaneous extraction and determination of trace amounts of diclofenac from whole blood using supported liquid membrane microextraction and fast Fourier transform voltammetry.

    PubMed

    Mofidi, Zahra; Norouzi, Parviz; Sajadian, Masumeh; Ganjali, Mohammad Reza

    2018-04-01

    A novel, simple, and inexpensive analytical technique based on flat sheet supported liquid membrane microextraction coupled with fast Fourier transform stripping cyclic voltammetry on a reduced graphene oxide carbon paste electrode was used for the extraction and online determination of diclofenac in whole blood. First, diclofenac was extracted from blood samples using a polytetrafluoroethylene membrane impregnated with 1-octanol and then into an acceptor solution, subsequently it was oxidized on a carbon paste electrode modified with reduced graphene oxide nanosheets. The optimal values of the key parameters influencing the method were as follows: scan rate, 6 V/s; stripping potential, 200 mV; stripping time, 5 s; pH of the sample solution, 5; pH of the acceptor solution,7; and extraction time, 240 min. The calibration curves were plotted for the whole blood samples and the method was found to have a good linearity within the range of 1-25 μg/mL with a determination coefficient of 0.99. The limits of detection and quantification were 0.1 and 1.0 μg/mL, respectively. Using this coupled method, the extraction and determination were merged into one step. Accordingly, the speed of detection for sensitive determination of diclofenac in complex samples, such as blood, increased considerably. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Metabolism studies of diclofenac and clofibric acid in activated sludge bioreactors using liquid chromatography with quadrupole - time-of-flight mass spectrometry

    NASA Astrophysics Data System (ADS)

    Kosjek, Tina; Heath, Ester; Pérez, Sandra; Petrović, Mira; Barceló, Damia

    2009-06-01

    SummaryTwo environmentally relevant pharmaceuticals, the non-steroidal antiinflammatory drug, diclofenac and the pharmacologically active metabolite of several serum triglyceride-lowering pharmaceuticals, clofibric acid, were subjected to microbiological transformation in activated sludge bioreactors, and the production of breakdown products was studied. For separation, detection and identification of diclofenac's metabolites a UPLC-(+)ESI-QqToF-MS was employed, which enabled the detection of seven transformation products of diclofenac, all including the diagnostic fragment ion at m/z 214. The chemical structure of one metabolite was proposed, which was produced by dehydratation and lactame formation. Further investigations revealed additional two metabolites, which were isomeric structures with an elemental composition C 13H 10NCl 2; however, their chemical structures were not completely resolved. In addition, another biodegradation product showed an abundant fragment ion at m/z 295, the elemental composition of which was confirmed with a high degree of certainty as C 14H 11NO 2Cl 2. The biodegradation of clofibric acid revealed one metabolite in the (-)ESI-QqToF chromatogram, 4-chlorophenol, which is known to exhibit a higher toxicity than the parent compound. This study confirms that further research is needed on the formation of stable metabolites both during wastewater treatment and in the environment. It also highlights the need for parallel toxicity testing. In addition, this study suggests that more needs to be known about the environmental fate of pharmaceuticals so that we are able to provide a comprehensive risk assessment.

  12. Comparison of placebo and intrauterine lidocaine with/or without rectal diclofenac sodium suppositories used in office endometrial biopsy.

    PubMed

    Kaya, Cengiz; Sener, Elif Bengi; Koksal, Ersin; Ustun, Yasemin Burcu; Celik, Handan; Sahinoglu, Ali Haydar

    2015-01-01

    To compare the effects of intrauterine lidocaine, intrauterine lidocaine plus rectal diclofenac, and a placebo on analgesia and to determine the satisfaction of patients and surgeons in cases of endometrial biopsy. The double-blind, randomised, placebo-controlled study was conducted in the Department of Obstetrics and Gynaecology of the Ondokuz Mayis University, Samsun,Turkey, from April 2013 to January 2014, and comprised patients scheduled for in-office endometrial biopsy.They were divided into three groups: Group P, 5ml of 0.9% saline intrauterine; Group L, 5ml of 2% lidocaine intrauterine; and Group LD, 5ml of 2% lidocaine intrauterine ± 10min before the procedure plus 50mg of rectal diclofenac sodium. Haemodynamic changes and visual analogue scale scores were recorded during the preoperative period, when the cervix was grasped with a tenaculum, immediately after intrauterine instillation, during uterine curettage and at postoperative 10 min. The patient and the surgeon were questioned about their satisfaction 15 min after the procedure. SPSS 21 was used for statistical analysis. The 90 patients in the study were divided into three equal groups of 30(33.33%) each. There were no statistically significant inter-group differences in age, bodyweight, parity, number of postmenopausal patients, haemodynamic parameters and American Society of Anesthesiologists scores (p>0.05 in all categories). In Group P, the visual analogue scale score estimated when the cervix was grasped with the tenaculum was lower when compared with Group L and Group LD (p=0.029 and p=0.007, respectively). At other measurement time points, the scores did not differ between the groups. The groups did not differ with respect to patient and surgeon satisfaction and complication rates (p>0.05). Intrauterine lidocaine or intrauterine lidocaine plus rectal diclofenac application had no effect on visual analogue scale scores, patient satisfaction and vasovagal reaction.

  13. The effect of topical diclofenac 3% and calcitriol 3 μg/g on superficial basal cell carcinoma (sBCC) and nodular basal cell carcinoma (nBCC): A phase II, randomized controlled trial.

    PubMed

    Brinkhuizen, Tjinta; Frencken, Kiki J A; Nelemans, Patty J; Hoff, Marlou L S; Kelleners-Smeets, Nicole W J; Zur Hausen, Axel; van der Horst, Michiel P J; Rennspiess, Dorit; Winnepenninckx, Véronique J L; van Steensel, Maurice A M; Mosterd, Klara

    2016-07-01

    Nonsteroidal anti-inflammatory drugs and vitamin-D derivatives can target signaling pathways activated in basal cell carcinoma (BCC). We investigated the efficacy of topically applied diclofenac sodium 3% gel, calcitriol 3 μg/g ointment, and a combination of both in superficial BCC (sBCC) and nodular BCC. Patients with a primary, histologically proven sBCC (n = 64) or nodular BCC (n = 64) were randomized to topical diclofenac, calcitriol, combination of both, or no topical treatment (control group). After self-application twice daily under occlusion (8 weeks), tumors were excised. Primary outcome was posttreatment expression levels of proliferation (Ki-67) and antiapoptosis (B-cell lymphoma [Bcl-2]) immunohistochemical markers. Secondary outcomes were histologic clearance, adverse events, application-site reactions, and patient compliance. sBCC treated with diclofenac showed a significant decrease in Ki-67 (P < .001) and Bcl-2 (P = .001), and after combination therapy for Ki-67 (P = .012). Complete histologic tumor regression was seen in 64.3% (P = .0003) of sBCC (diclofenac) and 43.8% (P = .007) of sBCC (combination therapy) compared with 0.0% of controls. No significant changes were found in nodular BCC. Application-site reactions were mostly mild to moderate. The sample size was small. Our results suggest that topical diclofenac is a promising new treatment for sBCC. Its mode of action differs from available noninvasive therapies, and thus has an additive value. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  14. The structural and electronical factors that contribute affinity for the time-dependent inhibition of PGHS-1 by indomethacin, diclofenac and fenamates

    NASA Astrophysics Data System (ADS)

    Pouplana, R.; Pérez, C.; Sánchez, J.; Lozano, J. J.; Puig-Parellada, P.

    1999-05-01

    PGHS-1 and PGHS-2 are the targets of nonsteroidal anti- inflammatory drugs (NSAIDs). It appears that the high degree of selectivity for inhibition of PGHS-2 shown by certain compounds is the result of two mechanisms (time-dependent and time-independent inhibition), by which they interact with each isoform. The fenamic acids can be divided into competitive inhibitors of substrate binding and competitive inhibitors that cause time-dependent losses of cyclooxygenase activity. The cyclooxygenase activity was measured by oxygen consumption following preincubation of the enzyme and the inhibitor for increasing periods of time. The rate constants associated with binding inhibition kinetics and structure-activity relationships were calculated for a large number of fenamates, diclofenac and indomethacin. The KI* values are similar but the individual rate constants are markedly different: KI is two-fold lower, and k2 is six-fold slower for diclofenac than for indomethacin. All the active time-dependent compounds show MEPs with a negative conical surface, with their vertex on the minimum of the carboxyl group, which extends around the first aromatic ring to the central region. The conical surface keeps an open angle of 61° or larger, and a close contact surface with the residues Ala527, Ileu523, Val349, and Ser530, in the zones surrounding the bridging amino group and the chlorine atoms for meclofenamate and diclofenac, or in the region around the carbonyl group for indomethacin. The KI* and IC50 values indicate that the interactions that promote the slow binding kinetics must be examined in relation to the reaction energies of formation (ΔHr) of an ionic bond between the deprotonated carboxylic acid group of acid NSAIDs with the monocationic guanidinum group of Arg120, the free energies of solvation in aqueous solution, and the molecular volumes measured. Presumably indomethacin, diclofenac and meclofenamate cause the enzyme to undergo a subtle conformational change to a

  15. An electro-conductive fluid as a responsive implant for the controlled stimuli-release of diclofenac sodium.

    PubMed

    Bijukumar, Divya; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

    2016-11-01

    The purpose of this study was to develop an electro-responsive co-polymeric (ERP) implantable gel from polyethylene glycol (PEG), sodium polystyrene sulphonate (NaPss), polyvinyl alcohol (PVA), and diethyl acetomidomalonate (DAA) for electro-liberation of the model drug diclofenac sodium. Various physicochemical and physicomechanical characterization tests were undertaken on the synthesized drug-free gel (ERP G1) and drug-loaded gel (ERP G2). The ability of the gel to release diclofenac sodium following electrical stimulation was evaluated using a galvanostat while Molecular Mechanics (MM) simulations were performed to elucidate the experimental mechanisms. A stable electro-active gel exhibiting superior cycling stability was produced with desirable rheological properties, rigidity (BHN = 35.4 N ± 0.33 N/mm 2 ; resilience = 10.91 ± 0.11%), thermal properties (T g  ≈ 70 °C; T c  ≈ 200 °C) and homogeneous morphology. "ON-OFF" pursatile gradual drug release (37-94% from t 30 min -t 180   min ) kinetics was observed upon applying electric stimulation intermittently, indicating that drug release from the gel was electrically controlled. Overall, the galvanometric and MM evaluation ascertained the suitability of the PEG/NaPss/PVA ERP-Gel for application as a subcutaneously injectable drug delivery implant.

  16. Downregulation of telomerase activity by diclofenac and curcumin is associated with cell cycle arrest and induction of apoptosis in colon cancer.

    PubMed

    Rana, Chandan; Piplani, Honit; Vaish, Vivek; Nehru, Bimla; Sanyal, S N

    2015-08-01

    Uncontrolled cell proliferation is the hallmark of cancer, and cancer cells have typically acquired damage to genes that directly regulate their cell cycles. The synthesis of DNA onto the end of chromosome during the replicative phase of cell cycle by telomerase may be necessary for unlimited proliferation of cells. Telomerase, a ribonucleoprotein enzyme is considered as a universal therapeutic target of cancer because of its preferential expression in cancer cells and its presence in 90 % of tumors. We studied the regulation of telomerase and telomerase reverse transcriptase catalytic subunit (TERT) by diclofenac and curcumin, alone and also in combination, in 1, 2-dimethylhydrazine dihydrochloride-induced colorectal cancer in rats. The relationship of telomerase activity with tumors suppressor proteins (p51, Rb, p21), cell cycle machinery, and apoptosis was also studied. Telomerase is highly expressed in DMH group and its high activity is associated with increased TERT expression. However, telomerase is absent or is present at lower levels in normal tissue. CDK4, CDK2, cyclin D1, and cyclin E are highly expressed in DMH as assessed by RT-PCR, qRT-PCR, Western blot, and immunofluorescence analysis. Diclofenac and curcumin overcome these carcinogenic effects by downregulating telomerase activity, diminishing the expression of TERT, CDK4, CDK2, cyclin D1, and cyclin E. The anticarcinogenic effects shown after the inhibition of telomerase activity by diclofenac and curcumin may be associated with upregulation of tumor suppressor proteins p51, Rb, and p21, whose activation induces the cells cycle arrest and apoptosis.

  17. Comparison of Intravitreal Bevacizumab and Intravitreal Diclofenac in the Treatment of Diabetic Macular Edema: a 6-month Follow-up

    PubMed Central

    FAGHIHI, Hooshang; YAHYAPOUR, Hanif; MAHMOUDZADEH, Raziyeh; FAGHIHI, Shahin

    2017-01-01

    The aim of this study was to compare the effect of intravitreal diclofenac, a non-steroidal anti-inflammatory drug (NSAID), with that of bevacizumab, a well-known anti-vascular endothelial growth factor (VEGF) drug, in the treatment of diabetic macular edema (DME). Diclofenac was chosen in this study because it has both features of NSAIDs and corticosteroids by inhibiting the cyclooxygenase (COX) and lipoxygenase pathways, respectively. In this non-randomized comparative interventional case series, 64 eyes from 32 patients with bilateral naïve DME were selected and every eye was randomly assigned to intravitreal injection of bevacizumab (IVB) or diclofenac (IVD). After exclusion of some patients because of short follow-up duration or less than two intravitreal injections, finally, 52 eyes from 26 patients were analyzed. Of those, 26 eyes received 500 µg/0.1 mL IVD and 26 eyes received 1.25 mg IVB. After 6 months of follow-up, the results indicated that visual acuity was significantly improved from 0.50 ± 0.13 in IVB and 0.52 ± 0.12 LogMAR in IVD at baseline to 0.2 ± 0.1 and 0.29 ± 0.07, respectively. Central macular thickness (CMT) and macular volume were measured based on spectral-domain optical coherence tomography (OCT) at month 1, 3, and 6. Both groups showed a significant reduction in CMT and macular volume from baseline but there was no significant difference between the IVB and IVD groups. Interestingly, IVD, but not IVB, decreased intraocular pressure (IOP), which is a desirable effect. There was no serious complication due to injections. This study sheds light into the long-term effects of NSAIDs and may support the idea that inflammation suppression by NSAIDs may have the same results as anti-VEGF administration. PMID:29392145

  18. Comparison of Intravitreal Bevacizumab and Intravitreal Diclofenac in the Treatment of Diabetic Macular Edema: a 6-month Follow-up.

    PubMed

    Faghihi, Hooshang; Yahyapour, Hanif; Mahmoudzadeh, Raziyeh; Faghihi, Shahin

    2017-01-01

    The aim of this study was to compare the effect of intravitreal diclofenac, a non-steroidal anti-inflammatory drug (NSAID), with that of bevacizumab, a well-known anti-vascular endothelial growth factor (VEGF) drug, in the treatment of diabetic macular edema (DME). Diclofenac was chosen in this study because it has both features of NSAIDs and corticosteroids by inhibiting the cyclooxygenase (COX) and lipoxygenase pathways, respectively. In this non-randomized comparative interventional case series, 64 eyes from 32 patients with bilateral naïve DME were selected and every eye was randomly assigned to intravitreal injection of bevacizumab (IVB) or diclofenac (IVD). After exclusion of some patients because of short follow-up duration or less than two intravitreal injections, finally, 52 eyes from 26 patients were analyzed. Of those, 26 eyes received 500 µg/0.1 mL IVD and 26 eyes received 1.25 mg IVB. After 6 months of follow-up, the results indicated that visual acuity was significantly improved from 0.50 ± 0.13 in IVB and 0.52 ± 0.12 LogMAR in IVD at baseline to 0.2 ± 0.1 and 0.29 ± 0.07, respectively. Central macular thickness (CMT) and macular volume were measured based on spectral-domain optical coherence tomography (OCT) at month 1, 3, and 6. Both groups showed a significant reduction in CMT and macular volume from baseline but there was no significant difference between the IVB and IVD groups. Interestingly, IVD, but not IVB, decreased intraocular pressure (IOP), which is a desirable effect. There was no serious complication due to injections. This study sheds light into the long-term effects of NSAIDs and may support the idea that inflammation suppression by NSAIDs may have the same results as anti-VEGF administration.

  19. Differential pharmacokinetics of diclofenac potassium for oral solution vs immediate-release tablets from a randomized trial: effect of fed and fasting conditions.

    PubMed

    Chen, Cuiping; Bujanover, Shay; Kareht, Stephanie; Rapoport, Alan M

    2015-02-01

    To compare the pharmacokinetics of, and food effect on, diclofenac potassium delivered as an oral solution vs an immediate-release tablet. Diclofenac potassium for oral solution is the only nonsteroidal anti-inflammatory drug approved as monotherapy for the acute treatment of migraine attacks with or without aura in adults 18 years of age or older. It is formulated with potassium bicarbonate as a buffering agent to raise the pH and consequently increase the aqueous solubility of diclofenac in the acidic environment of the stomach following oral administration. The dosage is 50 mg of powdered diclofenac potassium dissolved in 1 to 2 ounces (30 to 60 mL) of water prior to administration, with dosing time in relation to food intake not specified - this was the case for the pivotal efficacy and safety trials in subjects with acute migraine attacks in which the primary endpoints were achieved. For acute treatment of migraine attacks, rapid onset of pain relief is desirable and is likely related to a rapid appearance of an effective concentration of the drug in the systemic circulation. The rate at which an orally administered drug reaches the blood is affected by both its formulation and the presence of food in the stomach. The present study was designed to investigate the pharmacokinetics of 2 formulations of diclofenac potassium, an immediate-release tablet and an oral solution, and to ascertain the effect of food. This was an open-label, randomized, single-center, crossover trial in healthy volunteers. Subjects were randomized using computer-generated list to 1:1:1:1 ratio. They received a single 50-mg dose of diclofenac potassium in 4 sequences (ABCD, BADC, CDBA, and DCAB) during each of the 4 treatment periods. The 4 treatments were: A, oral solution fasting; B, tablet fasting; C, oral solution fed; and D, tablet fed. There was a ≥7-day washout period between dosing. Blood samples for pharmacokinetic analysis were taken for up to 12 hours post-dose and

  20. Synergistic Interaction of Matricaria Chamomilla Extract with Diclofenac and Indomethacin on Carrageenan-Induced Paw Inflammation in Rats.

    PubMed

    Ortiz, Mario I; Cariño-Cortés, Raquel; Ponce-Monter, Héctor A; González-García, Martha P; Castañeda-Hernández, Gilberto; Salinas-Caballero, Mireya

    2017-11-01

    Preclinical Research The coadministration of non-steroidal anti-inflammatory drugs (NSAIDs) with medicinal plant extracts may increase anti-inflammatory activity, thus permitting the use of lower NSAID doses and limiting the side effects. The aim of this study was to explore the interactions between an ethanolic extract of M. chamomilla extract (MCE) with two NSAIDs, diclofenac and indomethacin on carrageenan-induced paw inflammation and gastric injury in rats. Diclofenac, indomethacin and MCE, or combinations with MCE produced an anti-inflammatory effect. Effective dose (ED) values were estimated for the individual drugs, and isobolograms were constructed. The final experimental ED values were 483.7 mg/kg for diclofenac + MCE combination, and 212.6 mg/kg for indomethacin + MCE. These values were lower (p < 0.05) than the theoretical ED values (1186.9 mg/kg for diclofenac + MCE combination, and 1183.8 mg/kg for indomethacin + MCE). These data suggest that the interactions between NSAIDs and MCE that mediate the anti-inflammatory effects at the systemic level are synergistic and may have therapeutic advantages for the clinical treatment of inflammatory processes. Drug Dev Res 78 : 360-367, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  1. Synthesis and structure of pyridine-functionalized mesoporous SBA-15 organosilicas and their application for sorption of diclofenac

    NASA Astrophysics Data System (ADS)

    Barczak, Mariusz

    2018-02-01

    A series of pyridine-functionalized mesoporous silicas have been prepared for the first time via direct co-condensation of tetraethoxysilane (TEOS) and 2-(2-pyridyl)ethyltrimethoxysilane (PETS) using the block copolymer Pluronic P123 as a structure-directing agent. The obtained materials were fully characterized by a wide range of instrumental techniques and employed as adsorbents for the removal of a diclofenac which is considered a priority hazardous drug. The synthesized materials exhibit a high adsorption capacities and rapid adsorption rates. The structural and adsorption properties depend largely on the relative amount of PETS/TEOS ratio: the gradual degradation of ordered structure and porosity was observed with the increasing amount of PETS. However due to the highest loading of pyridine units the most structurally degraded material had the highest adsorption uptake (631 mg g-1) indicating that the surface chemistry plays - along with porosity - an important role in governing the adsorption process. The experimental adsorption data were modelled using the Langmuir, Freundlich and Langmuir-Freundlich isotherms - among them the Langmuir-Freundlich model turned out to be the most suitable for describing adsorption behaviour of diclofenac onto the materials. The collected data show that the pyridine-functionalized mesoporous silicas can be a promising absorbent of pharmaceuticals.

  2. Comparison of Clinical Efficacies of Preoperatively Initiated Naproxen Sodium-Codeine Phosphate in Combination, Diclofenac Potassium, and Benzydamine Hydrochloride for Pain, Edema, and Trismus After Extraction of Impacted Lower Third Molar: A Randomized Double-Blind Study.

    PubMed

    Cigerim, Levent; Eroglu, Cennet Neslihan

    2018-03-01

    The aim of this study was to compare the clinical efficacies of naproxen sodium-codeine phosphate in combination, benzydamine hydrochloride, and diclofenac potassium for pain, edema, and trismus after lower third molar extraction. Ninety healthy volunteers in whom impacted third molar extraction was indicated were randomly distributed into 3 groups. One hour before the tooth-extraction process, patients were administered one of the following drugs: naproxen sodium, 550 mg, and codeine phosphate, 30 mg, in a tablet; diclofenac potassium, 50 mg, in a coated pill; or benzydamine hydrochloride, 50 mg, in a coated pill. Pain assessment was conducted via a visual analog scale; edema assessment, by measuring the distances between predetermined facial landmarks; and trismus assessment, by measuring interincisal distance. Regarding rescue analgesics (paracetamol, 500 mg), the number and time of use by patients were recorded. Naproxen sodium-codeine phosphate was more effective for pain, edema, and trismus than diclofenac potassium and benzydamine hydrochloride (P < .05). Benzydamine hydrochloride yielded similar clinical responses to diclofenac potassium (P > .05). No drug-related side effects were observed. Naproxen sodium-codeine phosphate constitutes the drug of choice after the extraction of a patient's impacted lower third molar. Benzydamine hydrochloride has similar efficacy to diclofenac potassium, and it can be used as a nonsteroidal anti-inflammatory analgesic drug. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  3. Preparation and in vitro evaluation of guar gum based triple-layer matrix tablet of diclofenac sodium

    PubMed Central

    Chavda, H.V.; Patel, M.S.; Patel, C.N.

    2012-01-01

    The objective of the present study was to design an oral controlled drug delivery system for sparingly soluble diclofenac sodium (DCL) using guar gum as triple-layer matrix tablets. Matrix tablet granules containing 30% (D1), 40% (D2) or 50% (D3) of guar gum were prepared by the conventional wet granulation technique. Matrix tablets of diclofenac sodium were prepared by compressing three layers one by one. Centre layer of sandwich like structure was incorporated with matrix granules containing DCL which was covered on either side by guar gum granule layers containing either 70, 80 or 87% of guar gum as release retardant layers. The tablets were evaluated for hardness, thickness, drug content, and drug release studies. To ascertain the kinetics of drug release, the dissolution profiles were fitted to various mathematical models. The in vitro drug release from proposed system was best explained by the Hopfenberg model indicating that the release of drug from tablets displayed heterogeneous erosion. D3G3, containing 87% of guar gum in guar gum layers and 50% of guar gum in DCL matrix granule layer was found to provide the release rate for prolonged period of time. The results clearly indicate that guar gum could be a potential hydrophilic carrier in the development of oral controlled drug delivery systems. PMID:23181081

  4. A novel spectral resolution and simultaneous determination of multicomponent mixture of Vitamins B1, B6, B12, Benfotiamine and Diclofenac in tablets and capsules by derivative and MCR-ALS

    NASA Astrophysics Data System (ADS)

    Hegazy, Maha A.; Abdelwahab, Nada S.; Fayed, Ahmed S.

    2015-04-01

    A novel method was developed for spectral resolution and further determination of five-component mixture including Vitamin B complex (B1, B6, B12 and Benfotiamine) along with the commonly co-formulated Diclofenac. The method is simple, sensitive, precise and could efficiently determine the five components by a complementary application of two different techniques. The first is univariate second derivative method that was successfully applied for determination of Vitamin B12. The second is Multivariate Curve Resolution using the Alternating Least Squares method (MCR-ALS) by which an efficient resolution and quantitation of the quaternary spectrally overlapped Vitamin B1, Vitamin B6, Benfotiamine and Diclofenac sodium were achieved. The effect of different constraints was studied and the correlation between the true spectra and the estimated spectral profiles were found to be 0.9998, 0.9983, 0.9993 and 0.9933 for B1, B6, Benfotiamine and Diclofenac, respectively. All components were successfully determined in tablets and capsules and the results were compared to HPLC methods and they were found to be statistically non-significant.

  5. A comprehensive strategy in the development of a cyclodextrin-modified microemulsion electrokinetic chromatographic method for the assay of diclofenac and its impurities: Mixture-process variable experiments and quality by design.

    PubMed

    Orlandini, S; Pasquini, B; Caprini, C; Del Bubba, M; Squarcialupi, L; Colotta, V; Furlanetto, S

    2016-09-30

    A comprehensive strategy involving the use of mixture-process variable (MPV) approach and Quality by Design principles has been applied in the development of a capillary electrophoresis method for the simultaneous determination of the anti-inflammatory drug diclofenac and its five related substances. The selected operative mode consisted in microemulsion electrokinetic chromatography with the addition of methyl-β-cyclodextrin. The critical process parameters included both the mixture components (MCs) of the microemulsion and the process variables (PVs). The MPV approach allowed the simultaneous investigation of the effects of MCs and PVs on the critical resolution between diclofenac and its 2-deschloro-2-bromo analogue and on analysis time. MPV experiments were used both in the screening phase and in the Response Surface Methodology, making it possible to draw MCs and PVs contour plots and to find important interactions between MCs and PVs. Robustness testing was carried out by MPV experiments and validation was performed following International Conference on Harmonisation guidelines. The method was applied to a real sample of diclofenac gastro-resistant tablets. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. In-vitro studies of enteric coated diclofenac sodium-carboxymethylcellulose microspheres.

    PubMed

    Arica, B; Arica, M Y; Kaş, H S; Hincal, A A; Hasirci, V

    1996-01-01

    MIcrospheres containing diclofenac sodium (DS) were prepared using carboxymethylcellulose (CMC) as the main support material (1.0, 2.0, 3.0% (w/v)) and aluminum chloride as the crosslinker. Drug to polymer ratios of 1:1, 1:2 and 1:4 were used to obtain a range of microspheres. The microspheres were then coated with an enteric coating material, Eudragit S-100, efficiency, % yield value, particle sizes an in-vitro dissolution behaviour were investigated. The surface of the enteric coated microspheres seemed to be all covered with Eudragit S-100 from scanning electron microscopy observation. It was also observed that increasing the CMC concentration led to an increase in the encapsulation efficiency, % yield value and particle size and decreased the release rate. Eudragit S-100 coating did not significantly alter the size but the release rate was significantly lower even when the lower concentration solution was used.

  7. Effects of the pharmaceuticals gemfibrozil and diclofenac on the marine mussel (Mytilus spp.) and their comparison with standardized toxicity tests.

    PubMed

    Schmidt, Wiebke; O'Rourke, Kathleen; Hernan, Robert; Quinn, Brian

    2011-07-01

    Human pharmaceuticals, like the lipid lowering agent gemfibrozil and the non-steroidal anti-inflammatory drug diclofenac are causing environmental concern. In this study, the marine mussel (Mytilus spp.) was exposed by injection to environmentally relevant and elevated (1 μg/L and 1000 μg/L) concentrations of both compounds and biomarker expression was observed. Gemfibrozil exposure induced biomarkers of stress (glutathione S-transferase and metallothionein) at both concentrations 24h and 96 h after exposure, respectively. Biomarkers of damage (lipid peroxidation (LPO) and DNA damage) were significantly affected, as well as the biomarker for reproduction, alkali-labile phosphate assay, indicating the potential oxidative stress and endocrine disrupting effect of gemfibrozil. Diclofenac significantly induced LPO after 96 h indicating tissue damage. Additionally standard toxicity tests using the marine species Vibrio fischeri, Skeletonema costatum and Tisbe battagliai showed differences in sensitivity to both drugs in the mg/L range. Results indicate a suite of tests should be used to give accurate information for regulation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. The anti-inflammatory drugs diclofenac, naproxen and ibuprofen are found in the bile of wild fish caught downstream of a wastewater treatment plant.

    PubMed

    Brozinski, Jenny-Maria; Lahti, Marja; Meierjohann, Axel; Oikari, Aimo; Kronberg, Leif

    2013-01-02

    Pharmaceutical residues are ubiquitous in rivers, lakes, and at coastal waters affected by discharges from municipal wastewater treatment plants. In this study, the presence of 17 different pharmaceuticals and six different phase I metabolites was determined in the bile of two wild fish species, bream (Abramis brama) and roach (Rutilus rutilus). The fish were caught from a lake that receives treated municipal wastewater via a small river. Prior to analyses, the bile content was enzymatically hydrolyzed to convert the glucuronide metabolites into the original pharmaceuticals or phase I metabolites. The solid phase extracts of hydrolyzates were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the multiple reaction monitoring mode. The anti-inflammatory drug naproxen could be detected in all the six bream and roach bile samples. Diclofenac was found in five of the bream and roach samples, while ibuprofen was detected in three bream and two roach samples. The observed bile concentrations of diclofenac, naproxen, and ibuprofen in bream ranged from 6 to 95 ng mL(-1), 6 to 32 ng mL(-1), and 16 to 34 ng mL(-1), respectively. The corresponding values in roach samples ranged from 44 to 148 ng mL(-1), 11 to 103 ng mL(-1) and 15 to 26 ng mL(-1), respectively. None of the other studied compounds could be detected. The study shows that pharmaceuticals originating from wastewater treatment plant effluents can be traced to the bile of wild bream and roach living in a lake where diclofenac, naproxen, and ibuprofen are present as pollutants.

  9. Comparison of the Effects of Daily Single-Dose Use of Flurbiprofen, Diclofenac Sodium, and Tenoxicam on Postoperative Pain, Swelling, and Trismus: A Randomized Double-Blind Study.

    PubMed

    Kaplan, Volkan; Eroğlu, Cennet Neslihan

    2016-10-01

    The aim of the present study was to compare the effects of daily single-dose use of flurbiprofen, diclofenac sodium, and tenoxicam on pain, swelling, and trismus that occur after surgical extraction of impacted wisdom teeth using local anesthesia. The present study included 3 groups with 30 patients in each group. Those volunteering to participate in this double-blind randomized study (n = 90) were selected from a patient population with an indication for extraction of impacted wisdom teeth. Group 1 patients received 200 mg flurbiprofen, group 2 patients received 100 mg diclofenac sodium, and group 3 patients received 20 mg tenoxicam. All doses were once a day, starting preoperatively. Pain was evaluated postoperatively at 1, 2, 3, 6, 8, and 24 hours and at 2 and 7 days using a visual analog scale (VAS). For comparison with the preoperative measurements, the patients were invited to postoperative follow-up visits 2 and 7 days after extraction to evaluate for swelling and trismus. The statistical analysis was performed using descriptive statistics in SAS, version 9.4 (SAS Institute, Cary, NC), software. Statistical analysis of the pain, swelling, and trismus data was performed using the Kruskal-Wallis, Dunn, and Wilcoxon-Mann-Whitney U tests. The statistical level of significance was accepted at P = .05 and power of 0.80. Clinically, tenoxicam showed better analgesic and anti-inflammatory efficacy compared with diclofenac sodium and, in particular, flurbiprofen. Although the VAS scores in the evaluation of pain showed statistically significant differences at 2 days, no statistically significant difference was found for swelling and trismus. Our study evaluated the analgesic and anti-inflammatory effects with a daily single dose of flurbiprofen, diclofenac sodium, and tenoxicam. Daily 20 mg tenoxicam can be accepted as an adequate and safe option for patients after a surgical procedure. Copyright © 2016 American Association of Oral and Maxillofacial

  10. Nanostructured Diclofenac Sodium Releasing Material

    NASA Astrophysics Data System (ADS)

    Nikkola, L.; Vapalahti, K.; Harlin, A.; Seppälä, J.; Ashammakhi, N.

    2008-02-01

    Various techniques have been developed to produce second generation biomaterials for tissue repair. These include extrusion, molding, salt leaching, spinning etc, but success in regenerating tissues has been limited. It is important to develop porous material, yet with a fibrous structure for it to be biomimetic. To mimic biological tissues, the extra-cellular matrix usually contains fibers in nano scale. To produce nanostructures, self-assembly or electrospinning can be used. Adding a drug release function to such a material may advance applications further for use in controlled tissue repair. This turns the resulting device into a multifunctional porous, fibrous structure to support cells and drug releasing properties in order to control tissue reactions. A bioabsorbable poly(ɛ-caprolactone-co-D,L lactide) 95/5 (PCL) was made into diluted solution using a solvent, to which was added 2w-% of diclofenac sodium (DS). Nano-fibers were made by electrospinning onto substrate. Microstructure of the resulting nanomat was studied using SEM and drug release profiles with UV/VIS spectroscopy. Thickness of the electrospun nanomat was about 2 mm. SEM analysis showed that polymeric nano-fibers containing drug particles form a highly interconnected porous nano structure. Average diameter of the nano-fibers was 130 nm. There was a high burst peak in drug release, which decreased to low levels after one day. The used polymer has slow a degradation rate and though the nanomat was highly porous with a large surface area, drug release rate is slow. It is feasible to develop a nano-fibrous porous structure of bioabsorbable polymer, which is loaded with test drug. Drug release is targeted at improving the properties of biomaterial for use in controlled tissue repair and regeneration.

  11. A novel spectral resolution and simultaneous determination of multicomponent mixture of Vitamins B1, B6, B12, Benfotiamine and Diclofenac in tablets and capsules by derivative and MCR-ALS.

    PubMed

    Hegazy, Maha A; Abdelwahab, Nada S; Fayed, Ahmed S

    2015-04-05

    A novel method was developed for spectral resolution and further determination of five-component mixture including Vitamin B complex (B1, B6, B12 and Benfotiamine) along with the commonly co-formulated Diclofenac. The method is simple, sensitive, precise and could efficiently determine the five components by a complementary application of two different techniques. The first is univariate second derivative method that was successfully applied for determination of Vitamin B12. The second is Multivariate Curve Resolution using the Alternating Least Squares method (MCR-ALS) by which an efficient resolution and quantitation of the quaternary spectrally overlapped Vitamin B1, Vitamin B6, Benfotiamine and Diclofenac sodium were achieved. The effect of different constraints was studied and the correlation between the true spectra and the estimated spectral profiles were found to be 0.9998, 0.9983, 0.9993 and 0.9933 for B1, B6, Benfotiamine and Diclofenac, respectively. All components were successfully determined in tablets and capsules and the results were compared to HPLC methods and they were found to be statistically non-significant. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Short-term tests with a pilot sewage plant and biofilm reactors for the biological degradation of the pharmaceutical compounds clofibric acid, ibuprofen, and diclofenac.

    PubMed

    Zwiener, C; Frimmel, F H

    2003-06-20

    The biodegradation of three active compounds of pharmaceuticals clofibric acid, ibuprofen, and diclofenac was investigated in short-term tests with a pilot sewage plant (PSP) and biofilm reactors (BFR, oxic and anoxic) as model systems for municipal sewage treatment. The PSP was characterized with respect to mixing behavior, the BFR with respect to biofilm content and sorption of the pharmaceutical compounds. The short-term experiments were carried out for 55 h in the PSP and for 48 h in the BFR. The concentration of the pharmaceuticals was in the microgram per liter range in presence of readily biodegradable substances in the milligram per liter range. Therefore, a too short time period and too low concentration to promote adaption of the microorganisms were applied. Under the operating conditions applied the biodegradation of the lipid lowering agent clofibric acid and the analgesic agents ibuprofen and diclofenac in the oxic BFR resembled that in the PSP. Clofibric acid and diclofenac were not eliminated and reached a level of approximately 95% of their initial concentration, whereas the concentration of ibuprofen was decreased to approximately 40% in the PSP and to approximately 35% in the oxic BFR. Both systems showed, therefore, an inherent ability for ibuprofen biodegradation. Elimination in the anoxic BFR resulted in a decrease of the concentration of all three substances to values between 60 and 80% of their initial concentration. In contrast to the PSP acetone revealed as inhibitor in the BFR. In both systems acetone was not degraded in the short-term tests.

  13. Diclofenac salts, part 6: release from lipid microspheres.

    PubMed

    Fini, Adamo; Cavallari, Cristina; Rabasco Alvarez, Antonio M; Rodriguez, Marisa Gonzalez

    2011-08-01

    The release of diclofenac (20%, w/w) was studied from lipidic solid dispersions using three different chemical forms (acid, sodium salt, and pyrrolidine ethanol salt) and two different lipid carriers (Compritol 888 ATO or Carnauba wax) either free or together with varying amounts (10%-30%, w/w) of stearic acid. Microspheres were prepared by ultrasound-assisted atomization of the molten dispersions and analyzed by scanning electron microscopy, differential scanning calorimetry, and hot stage microscopy. The effects of different formulations on the resulting drug release profiles as a function of pH were studied and the results were discussed. The formulation of the 18 systems and the chemical form of the drug were found to strongly affect the mode of the drug release. The solubility of the chemical forms in the lipid mixture is in the following order: pyrrolidine ethanol salt ≫ acid > sodium salt (according to the solubility parameters), and the nature of the systems thus obtained ranges from a matrix, for mutually soluble drug/carrier pairs, to a microcapsule, for pairs wherein mutual solubility is poor. Drug release from microspheres prepared by pure lipids was primarily controlled by diffusion, whereas the release from microspheres containing stearic acid was diffusion/erosion controlled at pH 7.4. Copyright © 2011 Wiley-Liss, Inc.

  14. Predicting the oral pharmacokinetic profiles of multiple-unit (pellet) dosage forms using a modeling and simulation approach coupled with biorelevant dissolution testing: case example diclofenac sodium.

    PubMed

    Kambayashi, Atsushi; Blume, Henning; Dressman, Jennifer B

    2014-07-01

    The objective of this research was to characterize the dissolution profile of a poorly soluble drug, diclofenac, from a commercially available multiple-unit enteric coated dosage form, Diclo-Puren® capsules, and to develop a predictive model for its oral pharmacokinetic profile. The paddle method was used to obtain the dissolution profiles of this dosage form in biorelevant media, with the exposure to simulated gastric conditions being varied in order to simulate the gastric emptying behavior of pellets. A modified Noyes-Whitney theory was subsequently fitted to the dissolution data. A physiologically-based pharmacokinetic (PBPK) model for multiple-unit dosage forms was designed using STELLA® software and coupled with the biorelevant dissolution profiles in order to simulate the plasma concentration profiles of diclofenac from Diclo-Puren® capsule in both the fasted and fed state in humans. Gastric emptying kinetics relevant to multiple-units pellets were incorporated into the PBPK model by setting up a virtual patient population to account for physiological variations in emptying kinetics. Using in vitro biorelevant dissolution coupled with in silico PBPK modeling and simulation it was possible to predict the plasma profile of this multiple-unit formulation of diclofenac after oral administration in both the fasted and fed state. This approach might be useful to predict variability in the plasma profiles for other drugs housed in multiple-unit dosage forms. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Electrochemical incineration of diclofenac in neutral aqueous medium by anodic oxidation using Pt and boron-doped diamond anodes.

    PubMed

    Brillas, Enric; Garcia-Segura, Sergi; Skoumal, Marcel; Arias, Conchita

    2010-04-01

    The degradation of diclofenac, a common non-steroidal anti-inflammatory drug, in aqueous medium has been studied by anodic oxidation (AO) using an undivided cell with a Pt or boron-doped diamond (BDD) anode. Operating without pH regulation, AO with Pt acidifies the solution with precipitation of its protonated form, whereas using BDD, the solution becomes alkaline and only attains partial mineralization. Total incineration of low contents of the drug is feasible by AO with BDD in a neutral buffer medium of pH 6.5. Comparative treatment with Pt gives poor decontamination. The diclofenac decay always follows a pseudo first-order reaction. The increase in current for AO with BDD accelerates the degradative process, but decreases its efficiency. 2-Hydroxyphenylacetic acid, 2,5-dihydroxyphenylacetic acid, 2,6-dichloroaniline and 2,6-dichlorohydroquinone have been identified as aromatic intermediates. For AO with Pt, high amounts of malic, succinic, tartaric and oxalic acids are accumulated in the bulk and the N-derivatives produced are rapidly destroyed with loss of NH4+. When BDD is employed, some carboxylic acids are also accumulated in small extent, with a larger persistence of oxalic and oxamic acids. The process involves the formation of different N-derivatives that slowly release NH4+ and NO3(-) ions. Chloride ion is lost in all cases. 2010 Elsevier Ltd. All rights reserved.

  16. Diclofenac Suppository as a Preemptive Analgesia in Ultrasound-guided Biopsy of Prostate: Randomized Controlled Trial.

    PubMed

    Haroon, Naveed; Ather, M Hammad; Khan, Salma; Kumar, Pirkash; Salam, Basit

    2015-10-01

    To compare preprocedure Diclofenac suppository and Xylocaine gel with Xylocaine gel only in patients undergoing transrectal ultrasound (TRUS)-guided biopsy of prostate for pain. It is a randomized controlled trial conducted on patients undergoing TRUS-guided biopsy for clinical or biochemical suspicion of prostate cancer following a written informed consent and Ethics Review Committee approval. Patients were randomized into 2 groups. Group A included those patients who received Diclofenac suppository 2 hours before in combination with 10 mL of 2% Xylocaine gel 5 minutes before biopsy. Group B received Xylocaine gel only. A visual analog scale was used to measure the pain scores at the time of TRUS probe insertion, just after taking biopsy cores and 2 hours after biopsy. A total of 100 patients were recruited in the study with 50 patients each in group A and B. Mean age of group A was 69.1 ± 10 years and 67.3 ± 8.1 years for group B. The mean pain score for group A and B at the time of probe insertion was 0.08 ± 0.27 and 0.34 ± 0.63 (P = .032), immediately after taking biopsy cores was 1.46 ± 1.15 and 4.68 ± 0.77 (P = .000), and 2 hours after biopsy was 0.14 ± 0.45 vs 2.40 ± 0.81 (P = .000), respectively. The mean pain score at the time of TRUS probe insertion, immediately after taking biopsy cores, and 2 hours after biopsy is statistically significantly higher in group B. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Permanganate oxidation of diclofenac: The pH-dependent reaction kinetics and a ring-opening mechanism.

    PubMed

    Cheng, Hanyang; Song, Dean; Liu, Huijuan; Qu, Jiuhui

    2015-10-01

    In this work, the fate of diclofenac (DCF) during permanganate (Mn(VII)) oxidation was investigated at environmentally relevant pH conditions (from 5 to 9). The batch experiments showed that the kinetics of the Mn(VII)/DCF reaction follows a second-order rate law with an apparent rate constant of 1.57±0.02 M(-1) s(-1) at pH 7 and 20 °C. The half-value of DCF was calculated to be 37.5 min, when the concentration of Mn(VII) (0.4 mM) was 20-fold excess of DCF. The pH-dependence of the reaction kinetics was investigated, and the DCF reactivity with Mn(VII) was found to decrease with increasing pH. The second-order rate constants were then quantitatively described by incorporating the species distribution of DCF. A lower reactivity of the anionic DCF (DCF(-)) in comparison with its neutral counterpart (DCF(0)) was most likely attributable to the interaction between the ionized carboxylate group and amine nitrogen position, which can reduce the nucleophilicity of amine nitrogen by inductive and resonance effects. Moreover, a range of degradation products and the corresponding structures were proposed on the basis of the LC-Q-TOF-MS analysis. A detailed ring-opening reaction mechanism was proposed as follows: Mn(VII) acts as an electrophile to attack the amine moiety, leading to the formation of the primary intermediate products 2,6-dichloroaniline and 5-hydroxy-diclofenac, which can be further transformed. The further degradation proceeded through a multistep process including ring-opening, decarboxylation, hydroxylation, and cyclation reactions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Effects of dose, flow rate, and bile acid on diclofenac disposition in the perfused rat liver.

    PubMed

    Uraki, Misato; Kawase, Atsushi; Matsushima, Yuka; Iwaki, Masahiro

    2016-06-01

    An in situ perfused rat liver system is useful for studying the hepatic disposition of drugs and their metabolites. However, the effects of the perfusion conditions on drug disposition are unclear. We examined the effects of conditions such as flow rate (13 or 26 mL/min) and bile acid on disposition of diclofenac (DF) as a model drug and DF metabolites [diclofenac-1-O-acyl glucuronide (DF-Glu) or 4'-hydroxydiclofenac (DF-4'OH)] in the absence of albumin. DF, DF-Glu, and DF-4'OH concentrations in the perfusate and cumulative amounts of DF-Glu excreted in bile were measured using high-performance liquid chromatography methods. DF in the perfusate was rapidly eliminated as the perfusate flow rate increased. The area under the plasma concentration-time curve from 0 to 60 min (AUC0-60) for DF-Glu and DF-4'OH in a perfusate containing bile acid was lower at a flow rate of 26 and 13 mL/min, respectively. The bile flow rate at 26 mL/min with 24 μM of bile acid in the perfusate was significantly higher (ca. 3.5 times) compared with that at 13 mL/min without bile acid. Cumulative biliary DF-Glu excretion was also dramatically affected by the flow rate and addition of bile acid. This study indicated that the flow rate and bile acid in the perfused rat liver were key factors for bile flow rate and DF, DF-Glu, and DF-4'OH disposition in the absence of albumin.

  19. Efficacy and safety of oral ketamine versus diclofenac to alleviate mild to moderate depression in chronic pain patients: A double-blind, randomized, controlled trial.

    PubMed

    Jafarinia, Morteza; Afarideh, Mohsen; Tafakhori, Abbas; Arbabi, Mohammad; Ghajar, Alireza; Noorbala, Ahmad Ali; Saravi, Maryam Alamdar; Agah, Elmira; Akhondzadeh, Shahin

    2016-11-01

    Ketamine is a glutamate N-methyl-d-aspartate receptor antagonist capable of exerting antidepressive effects in single or repeated intravenous infusions. The objective of this study was to investigate the safety and the efficacy of oral ketamine vs. diclofenac monotherapy in reducing symptoms of mild to moderate depression among patients with chronic pain. This study is a 6-week, randomized, double-blind, controlled, parallel-group trial with two intervention arms (ketamine, fixed daily dosage of 150mg vs. diclofenac, fixed daily dosage of 150mg). Twenty participants in each arm completed the trial program all of whom had two post-baseline measurements at week 3 and week 6. Reduction in depression symptoms was assessed using the Hamilton Depression Rating Scale (HDRS) and the hospital anxiety and depression subscale for depression (HADSDepression) scores at baseline and week 3 and week 6 post-intervention. Significantly lower HDRS scores were observed in the ketamine treatment group as early as 6 weeks post-intervention (P=0.008). By comparison, mean (±standard deviation) HADS depression subscale scores were significantly lower for individuals receiving ketamine compared to diclofenac for both post-baseline measures at week 3 (6.95±1.47 vs. 8.40±1.6, P=0.005) and week 6 (6.20±1.15 vs. 7.35±1.18, p=0.003). The limitations of the present study were its small sample size and the short-term follow-up period. Oral ketamine appears to be a safe and effective option in improving depressive symptoms of patients with chronic pain with mild-to-moderate depression. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Efficacy and safety of diclofenac diethylamine 2.32% gel in acute ankle sprain.

    PubMed

    Predel, Hans-Georg; Hamelsky, Sandra; Gold, Morris; Giannetti, Bruno

    2012-09-01

    Topical diclofenac diethylamine (DDEA) 2.32% gel achieves lasting efficacy in localized pain with two applications per day, while maintaining the favorable safety profile of topical diclofenac and potentially improving convenience and patient compliance. This randomized double-blind controlled study enrolled patients with acute ankle sprain treated with DDEA 2.32% gel two times per day (bid) (n = 80) or three times per day (tid) (n = 80) or placebo (n = 82). Efficacy (including pain and swelling) and local tolerability were evaluated during 8 ± 1 d. By day 5, the reduction in pain on movement (POM) (primary efficacy variable) with DDEA bid and tid (49.1 and 49.7 mm, respectively; 100-mm visual analog scale) was almost double that with placebo (25.4 mm) (P < 0.0001). In patients with severe baseline POM (≥ 80 mm), mean change in POM from baseline to day 5 with DDEA bid or tid was 30-40 mm greater than that with placebo, which was double the difference (15-20 mm) in patients with mild-moderate baseline POM (<80 mm). More than 70% of all DDEA patients experienced ≥ 50% reduction in POM between days 1 and 5 versus 21% of placebo patients (P < 0.0001). By study end (day 8), ankle swelling in patients treated with DDEA (0.3 cm) was one-third that in those treated with placebo (0.9 cm) (P < 0.0001), which had still not achieved the level of ankle joint function seen with DDEA on day 5 (P < 0.0001). At day 5, treatment satisfaction was "good" to "excellent" in almost 90% of DDEA patients but only "good" or "very good" in 23% of placebo patients (P < 0.0001). DDEA 2.32% gel was well tolerated. DDEA 2.32% gel twice daily (applied in the morning and evening) was well tolerated and provided lasting relief from pain, improved function, and reduced symptomatic healing time in uncomplicated ankle sprain.

  1. Multiple response optimization of processing and formulation parameters of Eudragit RL/RS-based matrix tablets for sustained delivery of diclofenac.

    PubMed

    Elzayat, Ehab M; Abdel-Rahman, Ali A; Ahmed, Sayed M; Alanazi, Fars K; Habib, Walid A; Sakr, Adel

    2017-11-01

    Multiple response optimization is an efficient technique to develop sustained release formulation while decreasing the number of experiments based on trial and error approach. Diclofenac matrix tablets were optimized to achieve a release profile conforming to USP monograph, matching Voltaren ® SR and withstand formulation variables. The percent of drug released at predetermined multiple time points were the response variables in the design. Statistical models were obtained with relative contour diagrams being overlaid to predict process and formulation parameters expected to produce the target release profile. Tablets were prepared by wet granulation using mixture of equivalent quantities of Eudragit RL/RS at overall polymer concentration of 10-30%w/w and compressed at 5-15KN. Drug release from the optimized formulation E4 (15%w/w, 15KN) was similar to Voltaren, conformed to USP monograph and found to be stable. Substituting lactose with mannitol, reversing the ratio between lactose and microcrystalline cellulose or increasing drug load showed no significant difference in drug release. Using dextromethorphan hydrobromide as a model soluble drug showed burst release due to higher solubility and formation of micro cavities. A numerical optimization technique was employed to develop a stable consistent promising formulation for sustained delivery of diclofenac.

  2. Photocatalytic degradation of rhodamine B, paracetamol and diclofenac sodium by supported titania-based catalysts from petrochemical residue: effect of doping with magnesium.

    PubMed

    da Silva, William Leonardo; Lansarin, Marla Azário; Dos Santos, João Henrique Z; Silveira, Fernando

    2016-11-01

    Three different lots of a residual Ziegler-Natta catalyst slurry (bearing Ti and Mg) obtained from an industrial petrochemical plant were employed as sources for the photocatalyst supported on silica. The effect of additional magnesium (1.0-25.0 wt% Mg/SiO 2 ) on the photocatalytic properties of the doped materials was investigated. Doping the titania-based photocatalyst with Mg results in a shift in the absorption threshold toward the visible spectrum. The optical band gap energy of the bare supported photocatalyst was in the range of 2.5 eV and shifted to 1.72 eV after 25 wt% Mg doping. The systems were evaluated for the photodegradation of one dye (rhodamine B (RhB)) and two drugs (paracetamol and diclofenac sodium) either under ultraviolet (UV) (365 nm - UVA) or visible radiation, separately. Among the evaluated systems, doping with 25 wt% Mg afforded the highest degradation values for the target molecules under UV and visible radiation (i.e. 87%, 60% and 55% of the RhB, paracetamol and diclofenac under UV, respectively, and 82%, 48.3% and 48% under visible irradiation, respectively).

  3. Bicellar systems for in vitro percutaneous absorption of diclofenac.

    PubMed

    Rubio, L; Alonso, C; Rodríguez, G; Barbosa-Barros, L; Coderch, L; De la Maza, A; Parra, J L; López, O

    2010-02-15

    This work evaluates the effect of different bicellar systems on the percutaneous absorption of diclofenac diethylamine (DDEA) using two different approaches. In the first case, the drug was included in bicellar systems, which were applied on the skin and, in the second case, the skin was treated by applying bicellar systems without drug before to the application of a DDEA aqueous solution. The characterization of bicellar systems showed that the particle size decreased when DDEA was encapsulated. Percutaneous absorption studies demonstrated a lower penetration of DDEA when the drug was included in bicellar systems than when the drug was applied in an aqueous solution. This effect was possibly due to a certain rigidity of the bicellar systems caused by the incorporation of DDEA. The absorption of DDEA on skin pretreated with bicelles increased compared to the absorption of DDEA on intact skin. Bicelles without DDEA could cause certain disorganization of the SC barrier function, thereby facilitating the percutaneous penetration of DDEA subsequently applied. Thus, depending on their physicochemical parameters and on the application conditions, these systems have potential enhancement or retardant effects on percutaneous absorption that result in an interesting strategy, which may be used in future drug delivery applications. Copyright 2009 Elsevier B.V. All rights reserved.

  4. Toxicity of Diclofenac in the Fern Azolla filiculoides and the Lichen Xanthoria parietina.

    PubMed

    Vannini, Andrea; Paoli, Luca; Vichi, Marco; Bačkor, Martin; Bačkorová, Miriam; Loppi, Stefano

    2018-03-01

    This study investigated the occurrence of toxicity, expressed as damage to the photosynthetic apparatus, in the aquatic fern Azolla filiculoides and the lichen Xanthoria parietina following treatments with diclofenac at different concentrations (0.1, 1, 10 and 100 mg/L) and different exposure times (24, 48, 72 and 240 h). Measurements of photosynthetic efficiency, chlorophyll content and chlorophyll degradation indicated dose- and time-dependent toxicity, since significant differences with control samples as well as among treatments, emerged mainly for the highest concentration (100 mg/L) and the longest time (240 h). In addition, also the mycobiont of the lichen X. parietina showed similar toxic effects, expressed as ergosterol content. The absence of relevant alterations at the lowest concentration (0.1 mg/L) suggested a very limited susceptibility of these species to environmentally relevant levels of this pharmaceutical.

  5. In vitro drug interaction of levocetirizine and diclofenac: Theoretical and spectroscopic studies.

    PubMed

    Abo Dena, Ahmed S; Abdel Gaber, Sara A

    2017-06-15

    Levocetirizine dihydrochloride is known to interact with some anti-inflammatory drugs. We report here a comprehensive integrated theoretical and experimental study for the in vitro drug interaction between levocetirizine dihydrochloride (LEV) and diclofenac sodium (DIC). The interaction of the two drugs was confirmed by the molecular ion peak obtained from the mass spectrum of the product. Moreover, FTIR and 1 HNMR spectra of the individual drugs and their interaction product were inspected to allocate the possible sites of interaction. In addition, quantum mechanical DFT calculations were performed to search for the interaction sites and to verify the types of interactions deduced from the spectroscopic studies such as charge-transfer and non-bonding π-π interactions. It was found that the studied drugs interact with each other in aqueous solution via four types of interactions, namely, ion-pair formation, three weak hydrogen bonds, non-bonding π-π interactions and charge-transfer from DIC to LEV. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Diclofenac sodium delivery to the eye: in vitro evaluation of novel solid lipid nanoparticle formulation using human cornea construct.

    PubMed

    Attama, Anthony A; Reichl, Stephan; Müller-Goymann, Christel C

    2008-05-01

    Solid lipid nanoparticles (SLNs) were prepared with a combination of homolipid from goat (goat fat) and phospholipid, and evaluated for diclofenac sodium (DNa) delivery to the eye using bio-engineered human cornea, produced from immortalized human corneal endothelial cells (HENC), stromal fibroblasts and epithelial cells CEPI 17 CL 4. Encapsulation efficiency was high and sustained release of DNa and high permeation through the bio-engineered cornea were achieved. Results obtained in this work showed that permeation of DNa through the cornea construct was improved by formulation as SLN modified with phospholipid.

  7. Microbial transformation of pharmaceuticals naproxen, bisoprolol, and diclofenac in aerobic and anaerobic environments.

    PubMed

    Lahti, Marja; Oikari, Aimo

    2011-08-01

    Although biotransformation is generally considered to be the main process by which to remove pharmaceuticals, both in sewage treatment plants and in aquatic environments, quantitative information on specific compounds is scarce. In this study, the transformations of diclofenac (DCF), naproxen (NPX), and bisoprolol (BSP) were studied under aerobic and anaerobic conditions using inocula taken from activated and digested sludge processes, respectively. Whereas concentration decays were monitored by LC-tandem mass spectrometry, oxygen consumption and methane production were used for the evaluation of the performance of overall conditions. DCF was recalcitrant against both aerobic and anaerobic biotransformation. More than one third of the BSP disappeared under aerobic conditions, whereas only 14% was anaerobically biotransformed in 161 days. Under aerobic conditions, complete removal of NPX was evident within 14 days, but anaerobic transformation was also efficient. Formation of 6-O-desmethylnaproxen, a previously reported aerobic metabolite, was also detected under anaerobic conditions and persisted for 161 days.

  8. Repurposing Drugs in Oncology (ReDO)—diclofenac as an anti-cancer agent

    PubMed Central

    Pantziarka, Pan; Sukhatme, Vidula; Bouche, Gauthier; Meheus, Lydie; Sukhatme, Vikas P

    2016-01-01

    Diclofenac (DCF) is a well-known and widely used non-steroidal anti-inflammatory drug (NSAID), with a range of actions which are of interest in an oncological context. While there has long been an interest in the use of NSAIDs in chemoprevention, there is now emerging evidence that such drugs may have activity in a treatment setting. DCF, which is a potent inhibitor of COX-2 and prostaglandin E2 synthesis, displays a range of effects on the immune system, the angiogenic cascade, chemo- and radio-sensitivity and tumour metabolism. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. Based on this evidence the case is made for further clinical investigation of the anticancer effects of DCF, particularly in combination with other agents - with a range of possible multi-drug and multi-modality combinations outlined in the supplementary materials accompanying the main paper. PMID:26823679

  9. Preparation of diclofenac-imprinted polymer beads for selective molecular separation in water.

    PubMed

    Zhou, Tongchang; Kamra, Tripta; Ye, Lei

    2018-03-01

    Molecular imprinting technique is an attractive strategy to prepare materials for target recognition and rapid separation. In this work, a new type of diclofenac (DFC)-imprinted polymer beads was synthesized by Pickering emulsion polymerization using 2-(dimethylamino)ethyl methacrylate as the functional monomer. The selectivity and capacity of the molecularly imprinted polymers (MIPs) were investigated in aqueous solution. Equilibrium binding results show that the MIPs have a high selectivity to bind DFC in a wide range of pH values. Moreover, in liquid chromatography experiment, the imprinted polymer beads were packed into column to investigate the binding selectivity under nonequilibrium conditions. The retention time of DFC on the MIP column is significantly longer than its structural analogues. Also, retention of DFC on the MIP column was significantly longer than on the nonimprinted polymer column under aqueous condition. As the new MIP beads can be used to achieve direct separation of DFC from water, the synthetic method and the affinity beads developed in this work opened new possibilities for removing toxic chemicals from environmental and drinking water. Copyright © 2017 John Wiley & Sons, Ltd.

  10. Development of reconstitutable suspensions containing diclofenac sodium-loaded microspheres for pediatric delivery.

    PubMed

    Oz, Umut Can; Devrim, Burcu; Bozkır, Asuman; Canefe, Kandemir

    2015-01-01

    Effective clinical utilisation of non-steroidal anti-inflammatory drugs, such as diclofenac sodium (DS) is significantly limited by their ulcerogenic potential and poor bioavailability after oral administration. The objective of this work was to develop reconstitutable pediatric suspensions of DS-loaded microspheres prepared with an acrylic polymer (Eudragit RS) for improved pediatric delivery of DS. The microspheres were prepared by the water-in-oil-in-water or solid-in-oil-in-water emulsion techniques. Enviromental scanning electron microscopy observations clearly showed that microspheres have spherical shape. The drug entrapment efficiency of these microspheres was found 47.96 ± 0.79% to 88.57 ± 0.59% and their average particle sizes were 23.94-60.78 µm, which are within the desired range for the development of suspension formulation. The in vitro dissolution indicated prolonged sustained release of DS over 8 h. The results of preliminary characterisation studies of suspensions show that a liquid pharmaceutical preparation for oral administration capable of providing a sustained release of DS was successfully obtained.

  11. Oxidation of diclofenac by potassium ferrate (VI): reaction kinetics and toxicity evaluation.

    PubMed

    Wang, Yingling; Liu, Haijin; Liu, Guoguang; Xie, Youhai; Gao, Shuyan

    2015-02-15

    The reaction kinetics and toxicity of diclofenac (DCF) oxidation by ferrate (VI) under simulated water disinfection conditions were investigated. Experimental results indicated that the reaction between DCF and Fe(VI) followed first-order kinetics with respect to each reactant. Furthermore, the effects of pH and temperature on DCF oxidation by Fe(VI) were elucidated using a systematic examination. The apparent second-order rate constants (kapp) increased significantly from 2.54 to 11.6M(-1)s(-1), as the pH of the solution decreased from 11.0 to 7.0, and the acid-base equilibriums of Fe(VI) and DCF were proposed to explain the pH dependence of kapp. The acute toxicity of DCF solution during Fe(VI) oxidation was evaluated using a Microtox bioassay. Overall, the DCF degradation process resulted in a rapid increase of the inhibition rate of luminescent bacteria. These toxicity tests suggest that the formation of enhanced toxic intermediates during the Fe(VI) disinfection process may pose potential health risk to consumers. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. A calix[4]arene derivative and its selective interaction with drugs (clofibric acid, diclofenac and aspirin).

    PubMed

    Danil de Namor, Angela F; Al Nuaim, Maan; Villanueva Salas, Jose A; Bryant, Sophie; Howlin, Brendan

    2017-03-30

    The synthesis and characterisation of a partially substituted calix[4]arene, namely, 5,11,17,23-tetra-tert-butyl,25,27-bis[aminoethoxy] 26,28-dihydroxycalix[4]arene are reported. Its interaction with commonly used pharmaceuticals (clofibric acid, diclofenac and aspirin) was investigated by spectroscopic ( 1 H NMR and UV), electrochemical (conductance measurements) and thermal (titration calorimetry) techniques. It is concluded on the basis of the experimental work and molecular simulation studies that the receptor interacts selectively with these drugs. Preliminary studies on the selective extraction of these pharmaceuticals from water by the calix receptor are reported and the potential for a carrier mediated sensor based on this ligand for 'on site' monitoring of pharmaceuticals is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Diclofenac removal from water with ozone and activated carbon.

    PubMed

    Beltrán, Fernando J; Pocostales, Pablo; Alvarez, Pedro; Oropesa, Ana

    2009-04-30

    Diclofenac (DCF) has been treated in water with ozone in the presence of various activated carbons. Activated carbon-free ozonation or single ozonation leads to a complete degradation of DCF in less than 15 min while in the presence of activated carbons higher degradation rates of TOC and DCF are noticeably achieved. Among the activated carbons used, P110 Hydraffin was found the most suitable for the catalytic ozonation of DCF. The influence of pH was also investigated. In the case of the single ozonation the increasing pH slightly increases the TOC removal rate. This effect, however, was not so clear in the presence of activated carbons where the influence of the adsorption process must be considered. Ecotoxicity experiments were performed, pointing out that single ozonation reduces the toxicity of the contaminated water but catalytic ozonation improved those results. As far as kinetics is concerned, DCF is removed with ozone in a fast kinetic regime and activated carbon merely acts as a simple adsorbent. However, for TOC removal the ozonation kinetic regime becomes slow. In the absence of the adsorbent, the apparent rate constant of the mineralization process was determined at different pH values. On the other hand, determination of the rate constant of the catalytic reaction over the activated carbon was not possible due to the effect of mass transfer resistances that controlled the process rate at the conditions investigated.

  14. Layered double hydroxide using hydrothermal treatment: morphology evolution, intercalation and release kinetics of diclofenac sodium

    NASA Astrophysics Data System (ADS)

    Joy, Mathew; Iyengar, Srividhya J.; Chakraborty, Jui; Ghosh, Swapankumar

    2017-12-01

    The present work demonstrates the possibilities of hydrothermal transformation of Zn-Al layered double hydroxide (LDH) nanostructure by varying the synthetic conditions. The manipulation in washing step before hydrothermal treatment allows control over crystal morphologies, size and stability of their aqueous solutions. We examined the crystal growth process in the presence and the absence of extra ions during hydrothermal treatment and its dependence on the drug (diclofenac sodium (Dic-Na)) loading and release processes. Hexagonal plate-like crystals show sustained release with ˜90% of the drug from the matrix in a week, suggesting the applicability of LDH nanohybrids in sustained drug delivery systems. The fits to the release kinetics data indicated the drug release as a diffusion-controlled release process. LDH with rod-like morphology shows excellent colloidal stability in aqueous suspension, as studied by photon correlation spectroscopy.

  15. Lidocaine gel versus combined topical anesthesia using bupivacaine, oxybuprocaine and diclofenac eyedrops in cataract surgery.

    PubMed

    Thill, Michelle; Zeitz, Oliver; Richard, Ines; Richard, Gisbert

    2005-01-01

    To assess the safety and efficacy of two topical anesthesia regimes for cataract surgery. 21 patients received a combination of 4 times bupivacaine 0.5, oxybuprocaine and diclofenac eyedrops, 18 patients were given a single topical application of lidocaine gel 2%. A single intracameral injection of lidocaine 1% was administered to all subjects. The extent to which the surgeon was bothered by patient motility was graded as low in about two thirds of all procedures. Patients reported lower intraoperative pain levels with a single application of lidocaine gel supplemented with intracameral lidocaine than with a fourfold application of the combination topical anesthesia plus intracameral anesthesia. A single application of lidocaine gel 2% combined with intracameral anesthesia provides at least as good analgesia than multiple administration of combined topical anesthesia supplemented with intracameral anesthesia and is equally safe.

  16. Dendrimer-coupled sonophoresis-mediated transdermal drug-delivery system for diclofenac.

    PubMed

    Huang, Bin; Dong, Wei-Jiang; Yang, Gao-Yi; Wang, Wei; Ji, Cong-Hua; Zhou, Fei-Ni

    2015-01-01

    The purpose of the present study was to develop a novel transdermal drug-delivery system comprising a polyamidoamine dendrimer coupled with sonophoresis to enhance the permeation of diclofenac (DF) through the skin. The novel transdermal drug-delivery system was developed by using a statistical Plackett-Burman design. Hairless male Wistar rat skin was used for the DF-permeation study. Coupling media concentration, ultrasound-application time, duty cycle, distance from probe to skin, and a third-generation polyamidoamine-dendrimer concentration were selected as independent variables, while in vitro drug release was selected as a dependent variable. Independent variables were found to be statistically significant (P<0.05). DF gel without dendrimer and ultrasound treatment to skin (passive delivery, run 13) showed 56.69 µg/cm(2) cumulative drug permeated through the skin, while the DF-dendrimer gel without sonophoresis treatment (run 14) showed 257.3 µg/cm(2) cumulative drug permeated through the skin after 24 hours. However, when the same gel was applied to sonophoresis-treated skin, drastic permeation enhancement was observed. In the case of run 3, the cumulative drug that permeated through the skin was 935.21 µg/cm(2). It was concluded that dendrimer-coupled sonophoresis-mediated transdermal drug delivery system has the potential to enhance the permeation of DF through the skin.

  17. Photodegradation of diclofenac in aqueous solution by simulated sunlight irradiation: kinetics, thermodynamics and pathways.

    PubMed

    Zhang, N; Li, J M; Liu, G G; Chen, X L; Jiang, K

    2017-05-01

    Diclofenac (DCF) is one of the most frequently detected pharmaceuticals in various water samples. This paper studied the effects of aquatic environmental factors (pH, temperature and dissolved organic matter) on photodegradation of DCF under simulated sunlight. The results demonstrate that degradation pathways proceed via pseudo first-order kinetics in all cases and the photodegradation of DCF by simulated sunlight. Thermodynamic study indicated that the photodegradation course is spontaneous, exothermic and irreversible. The rate constant gradually increased when the pH increased from 3 to 5, then decreased when the pH increased from 5 to 8, and finally increased when the pH further increased from 8 to 12. Humic acid inhibited the photodegradation of DCF. Three kinds of main degradation products were observed by high performance liquid chromatography/mass spectrometry and the degradation pathways were suggested. A toxicity test using Photobacterium phosphoreum T 3 Sp indicated the generation of some more toxic products than DCF.

  18. Efficacy and safety profile of combination of tramadol-diclofenac versus tramadol-paracetamol in patients with acute musculoskeletal conditions, postoperative pain, and acute flare of osteoarthritis and rheumatoid arthritis: a Phase III, 5-day open-label study

    PubMed Central

    Chandanwale, Ajay S; Sundar, Subramanian; Latchoumibady, Kaliaperumal; Biswas, Swati; Gabhane, Mukesh; Naik, Manoj; Patel, Kamlesh

    2014-01-01

    Objective We aimed to evaluate the safety and efficacy of a fixed-dose combination (FDC) of tramadol and diclofenac versus a standard approved FDC of tramadol and paracetamol, in patients with acute moderate to severe pain. Methods A total of 204 patients with moderate to severe pain due to acute musculoskeletal conditions (n=52), acute flare of osteoarthritis (n=52), acute flare of rheumatoid arthritis (n=50), or postoperative pain (n=50) were enrolled in the study at baseline. Each disease category was then randomized to receive either of two treatments for 5 days: group A received an FDC of immediate-release tramadol hydrochloride (50 mg) and sustained-release diclofenac sodium (75 mg) (one tablet, twice daily), and group B received an FDC of tramadol hydrochloride (37.5 mg) and paracetamol (325 mg) (two tablets every 4–6 hours, up to a maximum of eight tablets daily). The primary efficacy end points were reductions in pain intensity from baseline at day 3 and day 5 as assessed by a Visual Analog Scale (VAS) score. Results Group A showed a significant reduction in the VAS score for overall pain from baseline on day 3 (P=0.001) and day 5 (P<0.0001) as compared with group B. The combination of tramadol-diclofenac resulted in few mild to moderate adverse events (nausea, vomiting, epigastric pain, and gastritis), which required minimal management, without any treatment discontinuation. The number of adverse events in group A was nine (8.82%) compared with 22 (21.78%) in group B, after 5 days of treatment. Conclusion An FDC of tramadol-diclofenac showed a significantly greater reduction in pain intensity and was well tolerated compared with tramadol-paracetamol, resulting in better analgesia in patients suffering from moderate to severe pain due to acute musculoskeletal conditions, postoperative pain following orthopedic surgery, or acute flare of osteoarthritis and rheumatoid arthritis. PMID:25152629

  19. Rapid absorption of diclofenac and acetaminophen after their oral administration to cattle

    PubMed Central

    SAWAGUCHI, Akiyo; SASAKI, Kazuaki; MIYANAGA, Keisuke; NAKAYAMA, Mitsuhiro; NAGASUE, Masato; SHIMODA, Minoru

    2016-01-01

    The oral pharmacokinetics of diclofenac (DF) were evaluated in cattle by analyzing plasma concentration-time data after its intravenous and oral administration in order to propose the oral administration of DF as effective route to avoid long withdraw period. DF was intravenously and orally administered at 1 mg/kg to cattle using a crossover design with a 4-week washout period. Plasma concentrations of DF were determined by a HPLC analysis. The mean absorption time (MAT) and absorption half-life (t1/2ka) were 1.61 ± 0.61 and 1.51 ± 0.38 hr, respectively, and bioavailability was nearly 100%. The oral pharmacokinetics of acetaminophen (AAP) were also evaluated in cattle. Plasma concentrations of AAP were determined by a HPLC analysis. MAT and t1/2ka were 2.85 ± 0.93 and 1.53 ± 0.28 hr, respectively, and bioavailability was approximately 70%. In conclusion, the results of the present study indicate that DF and AAP are rapidly absorbed from the forestomach of cattle. Therefore, the appropriate efficacies of these drugs may be achieved via their oral administration, even in cattle. PMID:27320817

  20. Rapid absorption of diclofenac and acetaminophen after their oral administration to cattle.

    PubMed

    Sawaguchi, Akiyo; Sasaki, Kazuaki; Miyanaga, Keisuke; Nakayama, Mitsuhiro; Nagasue, Masato; Shimoda, Minoru

    2016-10-01

    The oral pharmacokinetics of diclofenac (DF) were evaluated in cattle by analyzing plasma concentration-time data after its intravenous and oral administration in order to propose the oral administration of DF as effective route to avoid long withdraw period. DF was intravenously and orally administered at 1 mg/kg to cattle using a crossover design with a 4-week washout period. Plasma concentrations of DF were determined by a HPLC analysis. The mean absorption time (MAT) and absorption half-life (t 1/2ka ) were 1.61 ± 0.61 and 1.51 ± 0.38 hr, respectively, and bioavailability was nearly 100%. The oral pharmacokinetics of acetaminophen (AAP) were also evaluated in cattle. Plasma concentrations of AAP were determined by a HPLC analysis. MAT and t 1/2ka were 2.85 ± 0.93 and 1.53 ± 0.28 hr, respectively, and bioavailability was approximately 70%. In conclusion, the results of the present study indicate that DF and AAP are rapidly absorbed from the forestomach of cattle. Therefore, the appropriate efficacies of these drugs may be achieved via their oral administration, even in cattle.

  1. Metabolic and Co-Metabolic Transformation of Diclofenac by Enterobacter hormaechei D15 Isolated from Activated Sludge.

    PubMed

    Aissaoui, Salima; Ouled-Haddar, Houria; Sifour, Mohamed; Harrouche, Kamel; Sghaier, Haitham

    2017-03-01

    The presence of non-steroidal anti-inflammatory drugs, such as diclofenac (DCF), in the environment, is an emerging problem due to their harmful effects on non-target organisms, even at low concentrations. We studied the biodegradation of DCF by the strain D15 of Enterobacter hormaechei. The strain was isolated from an activated sludge, and identified as E. hormaechei based on its physiological characteristics and its 16 S RNA sequence. Using HPTLC and GC-MS methods, we demonstrated that this strain metabolized DCF at an elimination rate of 52.8%. In the presence of an external carbon source (glucose), the elimination rate increased to approximately 82%. GC-MS analysis detected and identified one metabolite as 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one; it was produced as a consequence of dehydration and lactam formation reactions.

  2. Adsorption of diclofenac and nimesulide on activated carbon: Statistical physics modeling and effect of adsorbate size

    NASA Astrophysics Data System (ADS)

    Sellaoui, Lotfi; Mechi, Nesrine; Lima, Éder Cláudio; Dotto, Guilherme Luiz; Ben Lamine, Abdelmottaleb

    2017-10-01

    Based on statistical physics elements, the equilibrium adsorption of diclofenac (DFC) and nimesulide (NM) on activated carbon was analyzed by a multilayer model with saturation. The paper aimed to describe experimentally and theoretically the adsorption process and study the effect of adsorbate size using the model parameters. From numerical simulation, the number of molecules per site showed that the adsorbate molecules (DFC and NM) were mostly anchored in both sides of the pore walls. The receptor sites density increase suggested that additional sites appeared during the process, to participate in DFC and NM adsorption. The description of the adsorption energy behavior indicated that the process was physisorption. Finally, by a model parameters correlation, the size effect of the adsorbate was deduced indicating that the molecule dimension has a negligible effect on the DFC and NM adsorption.

  3. Pharmaceutical Product Lead Optimization for Better In vivo Bioequivalence Performance: A case study of Diclofenac Sodium Extended Release Matrix Tablets.

    PubMed

    Shahiwala, Aliasgar; Zarar, Aisha

    2018-01-01

    In order to prove the validity of a new formulation, a considerable amount of effort is required to study bioequivalence, which not only increases the burden of carrying out a number of bioequivalence studies but also eventually increases the cost of the optimization process. The aim of the present study was to develop sustained release matrix tablets containing diclofenac sodium using natural polymers and to demonstrate step by step process of product development till the prediction of in vivo marketed product equivalence of the developed product. Different batches of tablets were prepared by direct compression. In vitro drug release studies were performed as per USP. The drug release data were assessed using model-dependent, modelindependent and convolution approaches. Drug release profiles showed that extended release action were in the following order: Gum Tragacanth > Sodium Alginate > Gum Acacia. Amongst the different batches prepared, only F1 and F8 passed the USP criteria of drug release. Developed formulas were found to fit Higuchi kinetics model with Fickian (case I) diffusion-mediated release mechanism. Model- independent kinetics confirmed that total of four batches were passed depending on the similarity factors based on the comparison with the marketed Diclofenac. The results of in vivo predictive convolution model indicated that predicted AUC, Cmax and Tmax values for batch F8 were similar to that of marketed product. This study provides simple yet effective outline of pharmaceutical product development process that will minimize the formulation development trials and maximize the product success in bioequivalence studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. A cost-effectiveness analysis of celecoxib compared with diclofenac in the treatment of pain in osteoarthritis (OA) within the Swedish health system using an adaptation of the NICE OA model.

    PubMed

    Brereton, Nicholas; Pennington, Becky; Ekelund, Mats; Akehurst, Ronald

    2014-09-01

    Celecoxib for the treatment of pain resulting from osteoarthritis (OA) was reviewed by the Tandvårds- och läkemedelsförmånsverket-Dental and Pharmaceutical Benefits Board (TLV) in Sweden in late 2010. This study aimed to evaluate the incremental cost-effectiveness ratio (ICER) of celecoxib plus a proton pump inhibitor (PPI) compared to diclofenac plus a PPI in a Swedish setting. The National Institute for Health and Care Excellence (NICE) in the UK developed a health economic model as part of their 2008 assessment of treatments for OA. In this analysis, the model was reconstructed and adapted to a Swedish perspective. Drug costs were updated using the TLV database. Adverse event costs were calculated using the regional price list of Southern Sweden and the standard treatment guidelines from the county council of Stockholm. Costs for treating cardiovascular (CV) events were taken from the Swedish DRG codes and the literature. Over a patient's lifetime treatment with celecoxib plus a PPI was associated with a quality-adjusted life year (QALY) gain of 0.006 per patient when compared to diclofenac plus a PPI. There was an increase in discounted costs of 529 kr per patient, which resulted in an incremental cost-effectiveness ratio (ICER) of 82,313 kr ($12,141). Sensitivity analysis showed that treatment was more cost effective in patients with an increased risk of bleeding or gastrointestinal (GI) complications. The results suggest that celecoxib plus a PPI is a cost effective treatment for OA when compared to diclofenac plus a PPI. Treatment is shown to be more cost effective in Sweden for patients with a high risk of bleeding or GI complications. It was in this population that the TLV gave a positive recommendation. There are known limitations on efficacy in the original NICE model.

  5. Biodegradation of Diclofenac by the bacterial strain Labrys portucalensis F11.

    PubMed

    Moreira, Irina S; Bessa, Vânia S; Murgolo, Sapia; Piccirillo, Clara; Mascolo, Giuseppe; Castro, Paula M L

    2018-05-15

    Diclofenac (DCF) is a widely used non-steroidal anti-inflammatory pharmaceutical which is detected in the environment at concentrations which can pose a threat to living organisms. In this study, biodegradation of DCF was assessed using the bacterial strain Labrys portucalensis F11. Biotransformation of 70% of DCF (1.7-34 μM), supplied as the sole carbon source, was achieved in 30 days. Complete degradation was reached via co-metabolism with acetate, over a period of 6 days for 1.7 µM and 25 days for 34 μM of DCF. The detection and identification of biodegradation intermediates was performed by UPLC-QTOF/MS/MS. The chemical structure of 12 metabolites is proposed. DCF degradation by strain F11 proceeds mainly by hydroxylation reactions; the formation of benzoquinone imine species seems to be a central step in the degradation pathway. Moreover, this is the first report that identified conjugated metabolites, resulting from sulfation reactions of DCF by bacteria. Stoichiometric liberation of chlorine and no detection of metabolites at the end of the experiments are strong indications of complete degradation of DCF by strain F11. To the best of our knowledge this is the first report that points to complete degradation of DCF by a single bacterial strain isolated from the environment. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Cyclodextrin Enhances Corneal Tolerability and Reduces Ocular Toxicity Caused by Diclofenac

    PubMed Central

    Abdelkader, Hamdy; Fathalla, Zeinab; Moharram, Hossam; Ali, Taha F. S.

    2018-01-01

    With advances in refractive surgery and demand for cataract removal and lens replacement, the ocular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has increased. One of the most commonly used NSAIDs is diclofenac (Diclo). In this study, cyclodextrins (CDs), α-, β-, γ-, and HP-β-CDs, were investigated with in vitro irritation and in vivo ulceration models in rabbits to reduce Diclo toxicity. Diclo-, α-, β-, γ-, and HP-β-CD inclusion complexes were prepared and characterized and Diclo-CD complexes were evaluated for corneal permeation, red blood cell (RBCs) haemolysis, corneal opacity/permeability, and toxicity. Guest- (Diclo-) host (CD) solid inclusion complexes were formed only with β-, γ-, and HP-β-CDs. Amphipathic properties for Diclo were recorded and this surfactant-like functionality might contribute to the unwanted effects of Diclo on the surface of the eye. Contact angle and spreading coefficients were used to assess Diclo-CDs in solution. Reduction of ocular toxicity 3-fold to16-fold and comparable corneal permeability to free Diclo were recorded only with Diclo-γ-CD and Diclo-HP-β-CD complexes. These two complexes showed faster healing rates without scar formation compared with exposure to the Diclo solution and to untreated groups. This study also highlighted that Diclo-γ-CD and Diclo-HP-β-CD demonstrated fast healing without scar formation. PMID:29636847

  7. Novel chitosan/diclofenac coatings on medical grade stainless steel for hip replacement applications

    NASA Astrophysics Data System (ADS)

    Finšgar, Matjaž; Uzunalić, Amra Perva; Stergar, Janja; Gradišnik, Lidija; Maver, Uroš

    2016-05-01

    Corrosion resistance, biocompatibility, improved osteointegration, as well the prevention of inflammation and pain are the most desired characteristics of hip replacement implants. In this study we introduce a novel multi-layered coating on AISI 316LVM stainless steel that shows promise with regard to all mentioned characteristics. The coating is prepared from alternating layers of the biocompatible polysaccharide chitosan and the non-steroid anti-inflammatory drug (NSAID), diclofenac. Electrochemical methods were employed to characterize the corrosion behavior of coated and uncoated samples in physiological solution. It is shown that these coatings improve corrosion resistance. It was also found that these coatings release the incorporated drug in controlled, multi-mechanism manner. Adding additional layers on top of the as-prepared samples, has potential for further tailoring of the release profile and increasing the drug dose. Biocompatibility was proven on human-derived osteoblasts in several experiments. Only viable cells were found on the sample surface after incubation of the samples with the same cell line. This novel coating could prove important for prolongation of the application potential of steel-based hip replacements, which are these days often replaced by more expensive ceramic or other metal alloys.

  8. Novel chitosan/diclofenac coatings on medical grade stainless steel for hip replacement applications

    PubMed Central

    Finšgar, Matjaž; Uzunalić, Amra Perva; Stergar, Janja; Gradišnik, Lidija; Maver, Uroš

    2016-01-01

    Corrosion resistance, biocompatibility, improved osteointegration, as well the prevention of inflammation and pain are the most desired characteristics of hip replacement implants. In this study we introduce a novel multi-layered coating on AISI 316LVM stainless steel that shows promise with regard to all mentioned characteristics. The coating is prepared from alternating layers of the biocompatible polysaccharide chitosan and the non-steroid anti-inflammatory drug (NSAID), diclofenac. Electrochemical methods were employed to characterize the corrosion behavior of coated and uncoated samples in physiological solution. It is shown that these coatings improve corrosion resistance. It was also found that these coatings release the incorporated drug in controlled, multi-mechanism manner. Adding additional layers on top of the as-prepared samples, has potential for further tailoring of the release profile and increasing the drug dose. Biocompatibility was proven on human-derived osteoblasts in several experiments. Only viable cells were found on the sample surface after incubation of the samples with the same cell line. This novel coating could prove important for prolongation of the application potential of steel-based hip replacements, which are these days often replaced by more expensive ceramic or other metal alloys. PMID:27215333

  9. Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen, and acetylsalicylic acid.

    PubMed

    Cleuvers, Michael

    2004-11-01

    The ecotoxicity of the nonsteroidal anti-inflammatory drugs (NSAIDs) diclofenac, ibuprofen, naproxen, and acetylsalicylic acid (ASA) has been evaluated using acute Daphnia and algal tests. Toxicities were relatively low, with half-maximal effective concentration (EC50) values obtained using Daphnia in the range from 68 to 166 mg L(-1) and from 72 to 626 mg L(-1) in the algal test. Acute effects of these substances seem to be quite improbable. The quantitative structure-activity relationships (QSAR) approach showed that all substances act by nonpolar narcosis; thus, the higher the n-octanol/water partitioning coefficient (log Kow) of the substances, the higher is their toxicity. Mixture toxicity of the compounds could be accurately predicted using the concept of concentration addition. Toxicity of the mixture was considerable, even at concentrations at which the single substances showed no or only very slight effects, with some deviations in the Daphnia test, which could be explained by incompatibility of the very steep dose-response curves and the probit analysis of the data. Because pharmaceuticals in the aquatic environment occur usually as mixtures, an accurate prediction of the mixture toxicity is indispensable for environmental risk assessment.

  10. Lycopene Attenuates Tulathromycin and Diclofenac Sodium-Induced Cardiotoxicity in Mice.

    PubMed

    Abdel-Daim, Mohamed M; Eltaysh, Rasha; Hassan, Azza; Mousa, Shaker A

    2018-01-24

    Recent experiments showed a potential cardiotoxic effect of the macrolide antibiotic (tulathromycin). This study was performed to investigate whether diclofenac sodium (DFS) potentiates the cardiotoxicity of tulathromycin and increases the cardioprotective effects of lycopene against DFS and tulathromycin. Seven groups (eight per group) of adult Swiss albino mice received saline (control), tulathromycin (a single subcutaneous dose of 28 mg/kg/bw on day 14), DFS (a single oral dose of 100 mg/kg/bw on day 14), tulathromycin plus DFS, or lycopene (oral, 10 mg/kg/bw daily for 15 d) combined with tulathromycin, DFS, or both. Compared to the control group, the administration of tulathromycin or DFS (individually or in combination) caused significantly elevated ( p < 0.05) serum levels of Creatine kinase-myocardial B fraction (CK-MB), lactate dehydrogenase, and cardiac-specific troponin-T and tissue levels of nitric oxide and malondialdehyde that were accompanied by significantly decreased tissue reduced glutathione content and glutathione peroxidase, superoxide dismutase, and catalase antioxidant enzyme activity. Upon histopathological and immunohistochemical examination, the mean pathology scores and the percentages of caspase-3-, Bax-, and CK-positive regions were significantly higher in the tulathromycin- and/or DFS-treated groups than in control mice. For all these parameters, the pathological changes were more significant in the tulathromycin-DFS combination group than in mice treated with either drug individually. Interestingly, co-administration of lycopene with tulathromycin and/or DFS significantly ameliorated the changes described above. In conclusion, DFS could potentiate the cardiotoxic effects of tulathromycin, whereas lycopene can serve as a cardioprotective agent against DFS and tulathromycin.

  11. The structural, morphological and thermal properties of grafted pH-sensitive interpenetrating highly porous polymeric composites of sodium alginate/acrylic acid copolymers for controlled delivery of diclofenac potassium

    PubMed Central

    Jalil, Aamir; Khan, Samiullah; Naeem, Fahad; Haider, Malik Suleman; Sarwar, Shoaib; Riaz, Amna; Ranjha, Nazar Muhammad

    2017-01-01

    Abstract In present investigation new formulations of Sodium Alginate/Acrylic acid hydrogels with high porous structure were synthesized by free radical polymerization technique for the controlled drug delivery of analgesic agent to colon. Many structural parameters like molecular weight between crosslinks (M c), crosslink density (M r), volume interaction parameter (v 2,s), Flory Huggins water interaction parameter and diffusion coefficient (Q) were calculated. Water uptake studies was conducted in different USP phosphate buffer solutions. All samples showed higher swelling ratio with increasing pH values because of ionization of carboxylic groups at higher pH values. Porosity and gel fraction of all the samples were calculated. New selected samples were loaded with the model drug (diclofenac potassium).The amount of drug loaded and released was determined and it was found that all the samples showed higher release of drug at higher pH values. Release of diclofenac potassium was found to be dependent on the ratio of sodium alginate/acrylic acid, EGDMA and pH of the medium. Experimental data was fitted to various model equations and corresponding parameters were calculated to study the release mechanism. The Structural, Morphological and Thermal Properties of interpenetrating hydrogels were studied by FTIR, XRD, DSC, and SEM. PMID:29491802

  12. The structural, morphological and thermal properties of grafted pH-sensitive interpenetrating highly porous polymeric composites of sodium alginate/acrylic acid copolymers for controlled delivery of diclofenac potassium.

    PubMed

    Jalil, Aamir; Khan, Samiullah; Naeem, Fahad; Haider, Malik Suleman; Sarwar, Shoaib; Riaz, Amna; Ranjha, Nazar Muhammad

    2017-01-01

    In present investigation new formulations of Sodium Alginate/Acrylic acid hydrogels with high porous structure were synthesized by free radical polymerization technique for the controlled drug delivery of analgesic agent to colon. Many structural parameters like molecular weight between crosslinks ( M c ), crosslink density ( M r ), volume interaction parameter ( v 2, s ), Flory Huggins water interaction parameter and diffusion coefficient ( Q ) were calculated. Water uptake studies was conducted in different USP phosphate buffer solutions. All samples showed higher swelling ratio with increasing pH values because of ionization of carboxylic groups at higher pH values. Porosity and gel fraction of all the samples were calculated. New selected samples were loaded with the model drug (diclofenac potassium).The amount of drug loaded and released was determined and it was found that all the samples showed higher release of drug at higher pH values. Release of diclofenac potassium was found to be dependent on the ratio of sodium alginate/acrylic acid, EGDMA and pH of the medium. Experimental data was fitted to various model equations and corresponding parameters were calculated to study the release mechanism. The Structural, Morphological and Thermal Properties of interpenetrating hydrogels were studied by FTIR, XRD, DSC, and SEM.

  13. Effect of polacrilin potassium as disintegrant on bioavailability of diclofenac potassium in tablets : a technical note.

    PubMed

    Bele, Mrudula H; Derle, Diliprao V

    2012-09-01

    Polacrilin potassium is an ion exchange resin used in oral pharmaceutical formulations as a tablet disintegrant. It is a weakly acidic cation exchange resin. Chemically, it is a partial potassium salt of a copolymer of methacrylic acid with divinyl benzene. It ionizes to an anionic polymer chain and potassium cations. It was hypothesized that polacrilin potassium may be able to improve the permeability of anionic drugs according to the Donnan membrane phenomenon. The effect of polacrilin potassium on the permeability of diclofenac potassium, used as a model anionic drug, was tested in vitro using diffusion cells and in vivo by monitoring serum levels in rats. The amount of drug permeated across a dialysis membrane in vitro was significantly more in the presence of polacrilin potassium. Significant improvement was found in the extent of drug absorption in vivo. It could be concluded that polacrilin potassium may be used as a high-functionality excipient for improving the bioavailability of anionic drugs having poor gastrointestinal permeability.

  14. An insight into the adsorption of diclofenac on different biochars: Mechanisms, surface chemistry, and thermodynamics.

    PubMed

    Lonappan, Linson; Rouissi, Tarek; Kaur Brar, Satinder; Verma, Mausam; Surampalli, Rao Y

    2018-02-01

    Biochars were prepared from feedstocks pinewood and pig manure. Biochar microparticles obtained through grinding were evaluated for the removal of emerging contaminant diclofenac (DCF) and the underlying mechanism were thoroughly studied. Characterization of biochar was carried out using particle size analyzer, SEM, BET, FT-IR, XRD, XPS and zeta potential instrument. Pig manure biochar (BC-PM) exhibited excellent removal efficiency (99.6%) over pine wood biochar (BC-PW) at 500 µg L -1 of DCF (environmentally significant concentration). Intraparticle diffusion was found to be the major process facilitated the adsorption. BC-PW followed pseudo first-order kinetics whereas BC-PM followed pseudo second-order kinetics. Pine wood biochar was largely affected by pH variations whereas for pig manure biochar, pH effects were minimal owing to its surface functional groups and DCF hydrophobicity. Thermodynamics, presence of co-existing ions, initial adsorbate concentration and particles size played substantial role in adsorption. Various isotherms models were also studied and results are presented. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Formulation and evaluation of once-a-day transdermal gels of diclofenac diethylamine.

    PubMed

    Baboota, S; Shakeel, F; Kohli, K

    2006-03-01

    The present study was undertaken to prepare and evaluate transdermal gels of diclofenac diethylamine (DDEA) containing penetration enhancers such as olesan oil and dimethyl sulfoxide (DMSO). Transdermal gels were prepared using different polymers such as carbopol-940, polyvinyl alcohol (PVA), hydroxy propyl methyl cellulose-K(4) M, hydroxy propyl cellulose-M, and sodium carboxy methyl cellulose. The formulated gels were subjected to physicochemical studies, in vitro release studies and in vitro skin permeations studies and were evaluated for drug content, viscosity, extrudability, spreadability, and pH. The in vitro release studies of prepared gels were performed using specially designed Fites cell and in vitro skin permeation studies were performed using keshary-chien diffusion cell through rat skin. Selected formulations were evaluated for their antiinflammatory activity using the carrageenan-induced paw edema in rats. The carbopol-940 and PVA gels containing 10% DMSO showed best in vitro skin permeation of DDEA. In vivo study for the selected formulation showed a sustained reduction in inflammation in the carrageenan induced paw edema in rats. The efficacies of carbopol-940 and PVA gels were also compared with that of the marketed Voveran gel,(R) and it was found that carbopol and PVA gels produced better results than the Voveran gel. (c) 2006 Prous Science. All rights reserved. (c) 2006 Prous Science. All rights reserved.

  16. The physicochemical characterization and in vitro/in vivo evaluation of natural surfactants-based emulsions as vehicles for diclofenac diethylamine.

    PubMed

    Vucinić-Milanković, Nada; Savić, Snezana; Vuleta, Gordana; Vucinić, Slavica

    2007-03-01

    Two sugar-based emulsifiers, cetearyl alcohol & cetearyl glycoside and sorbitan stearate & sucrose cocoate, known as potential promoters of lamellar liquid crystals/gel phases, were investigated in order to formulate an optimal vehicle for amphiphilic drug - diclofenac diethylamine (DDA). Physico-chemical characterization and study of vehicle's physical stability were performed. Then, the in vitro DDA liberation profile, dependent on the mode of drug incorporation to the system, and the in vivo, short-term effects of chosen samples on skin parameters were examined. Droplets size distribution and rheological behavior indicated satisfying physical stability of both types of vehicles. Unexpectedly, the manner of DDA incorporation to the system had no significant influence on DDA release. In vivo study pointed to emulsion's favorable potential for skin hydration and barrier improvement, particularly in cetearyl glycoside-based vehicle.

  17. Sorption and retention of diclofenac on zeolite in the presence of cationic surfactant.

    PubMed

    Sun, Ken; Shi, Yan; Wang, Xiaoyu; Li, Zhaohui

    2017-02-05

    Diclofenac (DC) is one of the most widely prescribed non-steroidal anti-inflammatory drugs and one of the commonly found pharmaceuticals in aquatic environments and wastewater treatment plants. It possesses negative charges when solution pH is greater than its pKa value, while most of the soil components and sediment minerals bear negative charges, too, resulting in a net repulsion between the soil minerals and DC. Surfactant-modified zeolite (SMZ) has been studied extensively over the last 20 years for its effective removal of anionic contaminants tested under different experimental scales. However, its application for the removal of anionic drugs, such as DC, was less reported. This study focused on the sorption of DC by SMZ under different physic-chemical conditions, supplemented with instrumental analyses, in order to elucidate the mechanism of DC sorption by SMZ and to expand the SMZ application further. The results showed that the retention of DC was on the external surfaces of SMZ with extremely fast removal rate. Both anion exchange and partitioning of DC into the adsorbed surfactant micelles (admicelles) were responsible for the extended DC sorption. Interactions of DC with SMZ were facilitated with the benzene ring, the CO, and the CH 2 CH 3 functional groups. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. A Multicenter, Prospective, Randomized Controlled Trial Evaluating the Efficacy of Rectal Diclofenac and Sublingual Nitroglycerin as a Combined Prophylactic Treatment for Post-ERCP Pancreatitis.

    PubMed

    Tomoda, Takeshi; Kato, Hironari; Mizukawa, Sho; Muro, Shinichiro; Akimoto, Yutaka; Uchida, Daisuke; Matsumoto, Kazuyuki; Yamamoto, Naoki; Horiguchi, Shigeru; Tsutsumi, Koichiro; Okada, Hiroyuki

    2016-01-01

    Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP). A preliminary research suggested that the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) with nitroglycerin might reduce the incidence of post-ERCP pancreatitis (PEP) more effectively than NSAIDs alone. We conduct a two-arm, multicenter, prospective, randomized, superiority trial to evaluate the additional effect of nitroglycerin for prevention of PEP. A total of 900 patients randomly receive 50 mg diclofenac suppository either alone or with 5 mg isosorbide dinitrate sublingual tablet. The primary endpoint is the occurrence of PEP. This study will clarify whether NSAIDs plus nitroglycerin can prevent PEP.

  19. Rapid analysis of diclofenac and some of its transformation products in the three-spined stickleback, Gasterosteus aculeatus, by liquid chromatography-tandem mass spectrometry.

    PubMed

    Daniele, Gaëlle; Fieu, Maëva; Joachim, Sandrine; Bado-Nilles, Anne; Baudoin, Patrick; Turies, Cyril; Porcher, Jean-Marc; Andres, Sandrine; Vulliet, Emmanuelle

    2016-06-01

    Pharmaceuticals are emerging organic contaminants ubiquitously present in the environment due to incessant input into the aquatic compartment mainly resulting from incomplete removal in wastewater treatment plants. One of the major preoccupations concerning pharmaceuticals released into surface waters is their potential for bioaccumulation in biota, possibly leading to deleterious effects on ecosystems especially as they could affect a broad variety of organisms living in or depending on the aquatic environment. Thus, the development of accurate and sensitive methods is necessary to detect these compounds in aquatic ecosystems. Considering this need, this study deals with the analytical development of a methodology to quantify traces of diclofenac together with some of its biotic and abiotic transformation products in whole-body tissue of three-spined stickleback. A simple and reliable extraction method based on a modified QuEChERS extraction is implemented on 200 mg of fish. The detection and quantification of the ten target compounds are performed using liquid chromatography-tandem mass spectrometry. The whole process was successfully validated regarding linearity, recovery, repeatability, and reproducibility. The method limits of detection and quantification do not exceed 1 ng/g. To reproduce environmental conditions, we measured the concentration of DCF and its transformation products in three-spined sticklebacks after a 6-month exposure in mesocosms at several levels of DCF ranging from 0.05 to 4.1 μg/L. The phase I metabolite 4'-hydroxydiclofenac was detected in fish samples exposed at the highest DCF concentration. Graphical abstract Analysis of diclofenac and some of its transformation products in the three-spined stickleback, Gasterosteus aculeatus, by QuEChERS extraction followed by LC-MS/MS.

  20. Simultaneous determination of diclofenac potassium and methocarbamol in ternary mixture with guaifenesin by reversed phase liquid chromatography.

    PubMed

    Elkady, Ehab F

    2010-09-15

    New, simple, rapid and precise reversed phase liquid chromatographic (RP-LC) method has been developed for the simultaneous determination of diclofenac potassium (DP) and methocarbamol (MT) in ternary mixture with guaifenesin (GF), degradation product of methocarbamol. Chromatographic separation was achieved on a Symmetry Waters C18 column (150 mm x 4. 6mm, 5 microm). Gradient elution based on phosphate buffer pH (8)-acetonitrile at a flow rate of 1 mL min(-1) was applied. The UV detector was operated at 282 nm for DP and 274 nm for MT and GF. Linearity, accuracy and precision were found to be acceptable over the concentration ranges of 0.05-16, 0.5-160 and 0.5-160 microg mL(-1) for DP, MT and GF, respectively. The optimized method proved to be specific, robust and accurate for the quality control of the cited drugs in pharmaceutical preparation. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  1. The effect of excipients on the release kinetics of diclofenac sodium and papaverine hydrochloride from composed tablets.

    PubMed

    Kasperek, Regina; Trebacz, Hanna; Zimmer, Łukasz; Poleszak, Ewa

    2014-01-01

    For increased analgesic effect, new composed tablets containing diclofenac sodium (DIC) with an addition of papaverine hydrochloride (PAP) were prepared to investigate the mechanism of release of the active substances from tablets with different excipients in eight different formulations. To detect the possible interactions between active substances and excipients differential scanning calorimetry (DSC) was used. A shift of the melting point and enthalpy values of the physical mixtures of tablets components suggested a kind of interaction between components in certain formulations, however, the tabletting process was not disturbed in any of them. Kinetics of drug release from formulations was estimated by zero order, first order and Higuchi and Korsmeyer-Peppas models using results of dissolution of DIC and PAP from tablets. The study revealed that the mechanism of release of active substances was dependent on the excipients contained in tablets and the best fitted kinetics models were obtained for formulations with potentially prolonged release of DIC and PAP.

  2. Photostability and toxicity of finasteride, diclofenac and naproxen under simulating sunlight exposure: evaluation of the toxicity trend and of the packaging photoprotection

    PubMed Central

    2013-01-01

    Background Drugs photostability plays two different opposite roles; a real advantage arises considering the longer expiration time of the drugs while the consequent persistence in the environment involves an obvious negative effect bound to their harmfulness. On this basis we tested the photostability and toxicity of three pharmaceutical active principles: Finasteride, Diclofenac and Naproxen. The pure active principles, as well as commercial drugs containing them, were considered; for the last, the protective effect of the packaging was also evaluated. Samples were irradiated according to the ICH Guidelines for photostability testing (The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use); a simulating sunlight source (a mercury-vapor lamp coupled to a tungsten filament one) was used to cover the wavelength range 300–2000 nm; Temperature, Relative Humidity, Irradiance and Illuminance were maintained constant during the photodegradation. The concentrations of the pharmaceutical active principles during the photodegradation were monitored by HPLC with UV/Vis detector. Toxicity tests were performed by means of an amperometric biosensor based on suspended yeast cells. Since the products obtained by the photodegradation process can result as toxic or more toxic than the original molecules, tests were performed first and after the photodegadation. Results After 90 hours of exposure the concentration resulted lowered by 42.9%, 88.4% and 91% for Finasteride, Naproxen and Diclofenac respectively. Toxicity of the pure active principles follows the same order of the photostability. After photodegradation a contribute of the reaction products was evidenced. Conclusions The simple and cheap analytical procedure here proposed, allowed to obtain not only data on photostability and toxicity of the pure active principles but, even if roughly, also useful information on the reactions kinetic and toxicity of the

  3. Sono-synthesis of solar light responsive S-N-C-tri doped TiO2 photo-catalyst under optimized conditions for degradation and mineralization of Diclofenac.

    PubMed

    Ramandi, Sara; Entezari, Mohammad H; Ghows, Narjes

    2017-09-01

    C-N-S-tri doped TiO 2 anatase phase was synthesized using a facile, effective and novel sonochemical method at low frequency (20kHz) and at room temperature. Titanium butoxide as the titanium precursor and thiourea as the dopant source were used in the synthesis of the photo-catalyst. The effects of important parameters such as thiourea/Ti molar ratio, ultrasound intensity, sonication time and temperature were studied on the synthesis of tri-doped TiO 2 . The XPS results confirmed the presence of N, S, and C in the photo-catalyst. The photo-catalytic efficiency of the synthesized catalyst was studied toward the removal of Diclofenac as a model pharmaceutical organic pollutant. The results confirmed that the photo-catalyst synthesized with narrower band gap energy, shorter sonication time and higher ultrasound intensity leads to a rapid removal of Diclofenac. The effect of operational variables on the photo-catalytic activity of C-N-S tri doped TiO 2 nanoparticles was studied and optimized using the Taguchi method as a statistical technique. Additionally, the degradation process followed the pseudo-first-order kinetics model and the highest apparent rate constant of 0.0632min -1 achieved in 90min. Chemical oxygen demand (COD) analysis confirmed that the mineralization took place completely (100%) under the optimized conditions in 180min. Different scavengers were applied during the degradation process and active species such as OH and O 2 - had key roles in the photo-catalytic process. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Surgical suture braided with a diclofenac-loaded strand of poly(lactic-co-glycolic acid) for local, sustained pain mitigation.

    PubMed

    Huh, Beom Kang; Kim, Byung Hwi; Kim, Se-Na; Park, Chun Gwon; Lee, Seung Ho; Kim, Ka Ryeong; Heo, Chan Yeong; Choy, Young Bin

    2017-10-01

    In this work, we propose a surgical suture that can sustainably release diclofenac (DF) for the local pain relief of surgical wounds. We separately fabricated a DF-loaded strand composed of a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), which was then braided with a surgical suture already in clinical use, i.e., VICRYL™. In this way, the drug-delivery suture presented herein could release DF in a sustained manner for 10days while maintaining the mechanical strength needed for wound closure. According to the in vivo results of an induced-pain animal model, the drug-delivery suture mitigated pain throughout the period of persistent pain. The histological analysis of tissue around the sutures showed that the drug-delivery suture exhibited biocompatibility comparable to that of the VICRYL™ suture in clinical use. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Dielectric relaxation spectroscopy of aqueous solutions of diclofenac potassium over the frequency range of 20 Hz to 2 MHz at 303.15 K temperature

    NASA Astrophysics Data System (ADS)

    Karakthala, J. B.; Vankar, H. P.; Rana, V. A.

    2018-05-01

    The complex relative dielectric function ɛ*(ω) = ɛ' - jɛ″ of aqueous solutions of diclofenac potassium (DK) in the frequency range 20 Hz to 2 MHz at 303.15 K was measured using a precision LCR meter. The electrical/dielectric properties of the solutions samples were represented in terms of complex relative dielectric function ɛ*(ω) real part σ'(ω) of complex ac conductivity and dc conductivity. These types of studies can be used to explore various mechanism contributed in the absorption, transportation of drug through tissues and membranes of body as well as interactions of drug with body fluid and blood plasma.

  6. Modified local diatomite as potential functional drug carrier--A model study for diclofenac sodium.

    PubMed

    Janićijević, Jelena; Krajišnik, Danina; Čalija, Bojan; Vasiljević, Bojana Nedić; Dobričić, Vladimir; Daković, Aleksandra; Antonijević, Milan D; Milić, Jela

    2015-12-30

    Diatomite makes a promising candidate for a drug carrier because of its high porosity, large surface area, modifiable surface chemistry and biocompatibility. Herein, refined diatomite from Kolubara coal basin, which complied with the pharmacopoeial requirements for heavy metals content and microbiological quality, was used as a starting material. Inorganic modification of the starting material was performed through a simple, one-step procedure. Significant increase in adsorbent loading with diclofenac sodium (DS) was achieved after the modification process (∼373mg/g) which enabled the preparation of comprimates containing therapeutic dose of the adsorbed drug. Adsorption of DS onto modified diatomite resulted in the alteration of the drug's XRD pattern and FTIR spectrum. In vitro drug release studies in phosphate buffer pH 7.5 demonstrated prolonged DS release over 8h from comprimates containing DS adsorbed on modified diatomite (up to 37% after 8h) and those containing physical mixture of the same composition (up to 45% after 8h). The results of in vivo toxicity testing on mice pointed on potential safety of both unmodified (starting) and modified diatomite. All these findings favor the application of diatomite as a potential functional drug carrier. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Adsorption of Selected Pharmaceutical Compounds onto Activated Carbon in Dilute Aqueous Solutions Exemplified by Acetaminophen, Diclofenac, and Sulfamethoxazole.

    PubMed

    Chang, E-E; Wan, Jan-Chi; Kim, Hyunook; Liang, Chung-Huei; Dai, Yung-Dun; Chiang, Pen-Chi

    2015-01-01

    The adsorption of three pharmaceuticals, namely, acetaminophen, diclofenac, and sulfamethoxazole onto granular activated carbon (GAC), was investigated. To study competitive adsorption, both dynamic and steady-state adsorption experiments were conducted by careful selection of pharmaceuticals with various affinities and molecular size. The effective diffusion coefficient of the adsorbate was increased with decease in particle size of GAC. The adsorption affinity represented as Langmuir was consistent with the ranking of the octanol-water partition coefficient, K(ow). The adsorption behavior in binary or tertiary systems could be described by competition adsorption. In the binary system adsorption replacement occurred, under which the adsorbate with the smaller K(ow) was replaced by the one with larger K(ow). Results also indicated that portion of the micropores could be occupied only by the small target compound, but not the larger adsorbates. In multiple-component systems the competition adsorption might significantly be affected by the macropores and less by the meso- or micropores.

  8. Adsorption of Selected Pharmaceutical Compounds onto Activated Carbon in Dilute Aqueous Solutions Exemplified by Acetaminophen, Diclofenac, and Sulfamethoxazole

    PubMed Central

    Chang, E.-E.; Wan, Jan-Chi; Liang, Chung-Huei; Dai, Yung-Dun; Chiang, Pen-Chi

    2015-01-01

    The adsorption of three pharmaceuticals, namely, acetaminophen, diclofenac, and sulfamethoxazole onto granular activated carbon (GAC), was investigated. To study competitive adsorption, both dynamic and steady-state adsorption experiments were conducted by careful selection of pharmaceuticals with various affinities and molecular size. The effective diffusion coefficient of the adsorbate was increased with decease in particle size of GAC. The adsorption affinity represented as Langmuir was consistent with the ranking of the octanol-water partition coefficient, K ow. The adsorption behavior in binary or tertiary systems could be described by competition adsorption. In the binary system adsorption replacement occurred, under which the adsorbate with the smaller K ow was replaced by the one with larger K ow. Results also indicated that portion of the micropores could be occupied only by the small target compound, but not the larger adsorbates. In multiple-component systems the competition adsorption might significantly be affected by the macropores and less by the meso- or micropores. PMID:26078989

  9. Development of an osmotic pump system for controlled delivery of diclofenac sodium.

    PubMed

    Emara, L H; Taha, N F; Badr, R M; Mursi, N M

    2012-10-01

    Based on an elementary osmotic pump, controlled release systems of diclofenac sodium (DS) were designed to deliver the drug in a zero-order release pattern. Osmotic pump tablets containing 100 mg DS were prepared and coated with either semipermeable (SPM) or microporous (PM) membranes. The tablet coats were composed of hydrophobic triacetin (TA) or hydrophilic polyethylene glycol 400 (PEG 400) incorporated in cellulose acetate (CA) solution, for SPM and PM, respectively. Variable tablet core compositions such as swelling polymers (PEO and HPMC) and osmotic agents (lactose, NaCl, and KCl) were studied. An optimized, sensitive and well controlled in vitro release design, based on the flow-through cell (FTC), was utilized to discriminate between preparations. The results revealed that the presence of PEG 400 in the coating membrane accelerated the drug release rate, while TA suppressed the release rate of DS. In the case of SPM, the amount of DS released was inversely proportional to the membrane thickness, where 5% (w/w) weight gain gave a higher DS release rate than 10% (w/w). Results of different tablet core compositions revealed that the release rate of DS decreased as PEO molecular weight increased. HPMC K15M showed the lowest DS release rate. The presence of lactose, KCl, or NaCl pronouncedly affected DS release rate depending on polymer type in the core. Scanning electron microscopy (SEM) confirmed formation of pores in the membrane that accounts for faster DS release rate. These results revealed that DS could be formulated as an osmotic pump system with a prolonged, zero-order release pattern.

  10. Geometry of modified release formulations during dissolution--influence on performance of dosage forms with diclofenac sodium.

    PubMed

    Dorożyński, Przemysław; Kulinowski, Piotr; Jamróz, Witold; Juszczyk, Ewelina

    2014-12-30

    The objectives of the work included: presentation of magnetic resonance imaging (MRI) and fractal analysis based approach to comparison of dosage forms of different composition, structure, and assessment of the influence of the compositional factors i.e., matrix type, excipients etc., on properties and performance of the dosage form during drug dissolution. The work presents the first attempt to compare MRI data obtained for tablet formulations of different composition and characterized by distinct differences in hydration and drug dissolution mechanisms. The main difficulty, in such a case stems from differences in hydration behavior and tablet's geometry i.e., swelling, cracking, capping etc. A novel approach to characterization of matrix systems i.e., quantification of changes of geometrical complexity of the matrix shape during drug dissolution has been developed. Using three chosen commercial modified release tablet formulations with diclofenac sodium we present the method of parameterization of their geometrical complexity on the base of fractal analysis. The main result of the study is the correlation between the hydrating tablet behavior and drug dissolution - the increase of geometrical complexity expressed as fractal dimension relates to the increased variability of drug dissolution results. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. A proteomic evaluation of the effects of the pharmaceuticals diclofenac and gemfibrozil on marine mussels (Mytilus spp.): evidence for chronic sublethal effects on stress-response proteins.

    PubMed

    Schmidt, Wiebke; Rainville, Louis-Charles; McEneff, Gillian; Sheehan, David; Quinn, Brian

    2014-03-01

    Human pharmaceuticals (e.g. the lipid regulator gemfibrozil and the non-steroidal anti-inflammatory drug diclofenac) are an emerging environmental threat in the aquatic environment. This study aimed to evaluate sublethal effects of these two commonly found pharmaceuticals on the protein profiles of marine mussels (Mytilus spp.). Mytilus spp. was exposed to environmentally relevant and elevated concentrations (1 and 1000 µg/l respectively) of both drugs for 14 days. In addition, mussels were maintained for seven days post treatment to examine the potential of blue mussels to recover from such an exposure. Differential protein expression signatures (PES) in the digestive gland of mussels were obtained using two-dimensional gel electrophoresis after 7, 14, and 21 days of exposure. Twelve spots were significantly increased or decreased by gemfibrozil and/or diclofenac, seven of which were successfully identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. These proteins were involved in energy metabolism, oxidative stress response, protein folding, and immune responses. Changes in the PES over time suggested that mussels were still experiencing oxidative stress for up to seven days post exposure. In addition, a suite of biomarkers comprising glutathione transferase, lipid peroxidation, and DNA damage were studied. An oxidative stress response was confirmed by biomarker responses. To our knowledge, this is the first investigation using proteomics to assess the potential effects of human pharmaceuticals on a non-target species in an environmentally-relevant model. The successful application of this proteomic approach supports its potential use in pollution biomonitoring and highlights its ability to aid in the discovery of new biomarkers. Copyright © 2013 John Wiley & Sons, Ltd.

  12. Evaluation of PEG and mPEG-co-(PGA-co-PDL) microparticles loaded with sodium diclofenac

    PubMed Central

    Tawfeek, Hesham M.

    2013-01-01

    The aim of this study was to synthesize and evaluate novel biodegradable polyesters namely; poly(ethylene glycol)-Poly(glycerol adipate-co-ω-pentadecalactone), PEG-PGA-co-PDL-PEG, and poly(ethylene glycol methyl ether)-Poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL-PEGme as an alternative sustained release carrier for lung delivery compared with non-PEG containing polymer PGA-co-PDL. The co-polymers were synthesized through lipase catalysis ring opening polymerization reaction and characterized using GPC, FT-IR, 1H-NMR and surface contact angle. Furthermore, microparticles containing a model hydrophilic drug, sodium diclofenac, were prepared via spray drying from a modified single emulsion and characterized for their encapsulation efficiency, geometrical particle size, zeta potential, tapped density, primary aerodynamic diameter, amorphous nature, morphology, in vitro release and the aerosolization performance. Microparticles fabricated from mPEG-co-polymer can be targeted to the lung periphery with an optimum in vitro deposition. Furthermore, a significantly higher in vitro release (p > 0.05, ANOVA/Dunnett’s) was observed with the PEG and mPEG-co-polymers compared to PGA-co-PDL. In addition, these co-polymers have a good safety profile upon testing on human bronchial epithelial, 16HBE14o- cell lines. PMID:24227959

  13. Grafting of GMA and some comonomers onto chitosan for controlled release of diclofenac sodium.

    PubMed

    Sharma, Rajeev Kr; Lalita; Singh, Anirudh P; Chauhan, Ghanshyam S

    2014-03-01

    In order to develop pH sensitive hydrogels for controlled drug release we have graft copolymerized glycidyl methacrylate (GMA) with comonomers acrylic acid, acrylamide and acrylonitrile, onto chitosan (Ch) by using potassium persulphate (KPS) as free radical initiator in aqueous solution. The optimum percent grafting for GMA was recorded for 1g chitosan at [KPS]=25.00 × 10(-3)mol/L, [GMA]=0.756 × 10(-3)mol/L, reaction temperature=60 °C and reaction time=1h in 20 mL H2O. Binary monomers were grafted for five different concentrations at optimum grafting conditions evaluated for GMA alone onto chitosan. The graft copolymers were characterized by FTIR, XRD, TGA and SEM. The swelling properties of chitosan and graft copolymers were investigated at different pH to define their end uses in sustained release of an anti-inflammatory drug, diclofenac sodium. Percent drug release w.r.t. drug loaded in polymeric sample was studied as function of time in buffer solutions of pH 2.0 and 7.4. In vitro release data was analyzed using Fick's Law. Chitosan grafted with binary monomers, GMA-co-AAm and GMA-co-AN showed very good results for sustained release of drug at 7.4 pH. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. In vitro release of diclofenac diethylamine from caprylocaproyl macrogolglycerides based microemulsions.

    PubMed

    Djordjevic, Ljiljana; Primorac, Marija; Stupar, Mirjana

    2005-05-30

    The purpose of the present study was to determine the influence of both formulation parameters and vehicle structure on in vitro release rate of amphiphilic drug diclofenac diethylamine (DDA) from microemulsion vehicles containing PEG-8 caprylic/capric glycerides (surfactant), polyglyceryl-6 dioleate (cosurfactant), isopropyl myristate and water. From the constructed pseudo-ternary phase diagram at surfactant-cosurfactant mass ratio (K(m) 1:1), the optimum oil-to-surfactant-cosurfactant mass ratio values (O/SC 0.67-1.64) for formulation of microemulsions with similar concentrations of hydrophilic, lipophilic and amphiphilic phases (balanced microemulsions) were found. The results of characterization experiments indicated bicontinuous or nonspherical water-continuous internal structure of the selected microemulsion vehicles. Low water/isopropyl myristate apparent partition coefficient for DDA as well as elevated electrical conductivity and apparent viscosity values for the investigated microemulsion formulations containing 1.16% (w/w) of DDA, suggested that the drug molecules was predominantly partitioned in the water phase and most likely selfaggregate and interact with interfacial film. Release of DDA from the selected water-continuous (W/O), oil-continuous (O/W) and balanced microemulsions was investigated using rotating paddle dissolution apparatus modified by addition of enhancer cell. A linear diffusion of DDA through regenerated cellulose membrane was observed for the W/O and O/W formulations with the low content of dispersed phase. Non-linearity of the drug release profile in the case of bicontinuous formulations was related to the more complex distribution of DDA including interactions between the drug and vehicle. The membrane flux value increases from 25.02 microgcm(-2)h(-1) (W/O microemulsion) to 117.94 microgcm(-2)h(-1) (O/W microemulsion) as the water phase concentration increases. Moreover, the obtained flux values for balanced microemulsions (29

  15. Long-term exposure of Mytilus galloprovincialis to diclofenac, Ibuprofen and Ketoprofen: Insights into bioavailability, biomarkers and transcriptomic changes.

    PubMed

    Mezzelani, M; Gorbi, S; Fattorini, D; d'Errico, G; Consolandi, G; Milan, M; Bargelloni, L; Regoli, F

    2018-05-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) represent a growing concern for marine ecosystems due to their ubiquitous occurrence and documented adverse effects on non-target organisms. Despite the remarkable efforts to elucidate bioaccumulation and ecotoxicological potential under short-term conditions, limited and fragmentary information is available for chronic exposures. In this study bioavailability, molecular and cellular effects of diclofenac (DIC), ibuprofen (IBU) and ketoprofen (KET) were investigated in mussels Mytilus galloprovincialis exposed to the realistic environmental concentration of 2.5 μg/L for up to 60 days. Results indicated a significant accumulation of DIC and IBU but without a clear time-dependent trend; on the other hand, KET concentrations were always below the detection limit. Analyses of a large panel of molecular, biochemical and cellular biomarkers highlighted that all investigated NSAIDs caused alterations of immunological parameters, genotoxic effects, modulation of lipid metabolism and changes in cellular turn-over. This study provided the evidence of long-term ecotoxicological potential of NSAIDs, further unraveling the possible hazard for wild marine organisms. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Biotic nitrosation of diclofenac in a soil aquifer system (Katari watershed, Bolivia).

    PubMed

    Chiron, Serge; Duwig, Céline

    2016-09-15

    Up till now, the diclofenac (DCF) transformation into its nitrogen-derivatives, N-nitroso-DCF (NO-DCF) and 5-nitro-DCF (NO2-DCF), has been mainly investigated in wastewater treatment plant under nitrification or denitrification processes. This work reports, for the first time, an additional DCF microbial mediated nitrosation pathway of DCF in soil under strictly anoxic conditions probably involving codenitrification processes and fungal activities. This transformation pathway was investigated by using field observations data at a soil aquifer system (Katari watershed, Bolivia) and by carrying out soil slurry batch experiments. It was also observed for diphenylamine (DPA). Field measurements revealed the occurrence of NO-DCF, NO2-DCF and NO-DPA in groundwater samples at concentration levels in the 6-68s/L range. These concentration levels are more significant than those previously reported in wastewater treatment plant effluents taking into account dilution processes in soil. Interestingly, the p-benzoquinone imine of 5-OH-DCF was also found to be rather stable in surface water. In laboratory batch experiments under strictly anoxic conditions, the transformation of DCF and DPA into their corresponding N-nitroso derivatives was well correlated to denitrification processes. It was also observed that NO-DCF evolved into NO2-DCF while NO-DPA was stable. In vitro experiments showed that the Fisher-Hepp rearrangement could not account for NO2-DCF formation. One possible mechanism might be that NO-DCF underwent spontaneous NO loss to give the resulting intermediates diphenylaminyl radical or nitrenium cation which might evolve into NO2-DCF in presence of NO2 radical or nitrite ion, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Design and Evaluation of Topical Diclofenac Sodium Gel Using Hot Melt Extrusion Technology as a Continuous Manufacturing Process with Kolliphor® P407.

    PubMed

    Pawar, Jaywant; Narkhede, Rajkiran; Amin, Purnima; Tawde, Vaishali

    2017-08-01

    The aim of the present context was to develop and evaluate a Kolliphor® P407-based transdermal gel formulation of diclofenac sodium by hot melt extrusion (HME) technology; central composite design was used to optimize the formulation process. In this study, we have explored first time ever HME as an industrially feasible and continuous manufacturing technology for the manufacturing of gel formulation using Kolliphor® P407 and Kollisolv® PEG400 as a gel base. Diclofenac sodium was used as a model drug. The HME parameters such as feeding rate, screw speed, and barrel temperature were crucial for the semisolid product development, and were optimized after preliminary trials. For the processing of the gel formulation by HME, a modified screw design was used to obtain a uniform product. The obtained product was evaluated for physicochemical characterization such as differential scanning calorimetry (DSC), X-ray diffraction (XRD), pH measurement, rheology, surface tension, and texture profile analysis. Moreover, it was analyzed for general appearance, spreadibility, surface morphology, and drug content. The optimized gel formulation showed homogeneity and transparent film when applied on a glass slide under microscope, pH was 7.02 and uniform drug content of 100.04 ± 2.74 (SD = 3). The DSC and XRD analysis of the HME gel formulation showed complete melting of crystalline API into an amorphous form. The Kolliphor® P407 and Kollisolv® PEG400 formed excellent gel formulation using HME with consistent viscoelastic properties of the product. An improved drug release was found for the HME gel, which showed a 100% drug release than that of a marketed product which showed only 88% of drug release at the end of 12 h. The Flux value of the HME gel was 106 than that of a marketed formulation, which showed only about 60 value, inferring a significant difference (P < 0.05) at the end of 1 h. This study demonstrates a novel application of the hot melt extrusion

  18. [Cardiovascular side effects of non-steroidal anti-inflammatory drugs in the light of recent recommendations. Diclofenac is not more dangerous].

    PubMed

    Horváth, Viktor József; Tabák, Gy Ádám; Szabó, Gergely; Putz, Zsuzsanna; Koós, Csaba Géza; Lakatos, Péter

    2015-03-29

    Among their beneficial effects, non-steroidal anti-inflammatory drugs may also exert several side effects which depend on the dosage and the type of these medications. The most frequent gastrointestinal side effects usually develop shortly after the beginning of their administration, but others such as cardiovascular interactions (which are present much less frequently than gastrointestinal side effects) can also occur after the beginning of drug administration without a latency period. For a long-term treatment, non-steroidal anti-inflammatory drugs are most frequently used in the elderly population where patients typically have high cardiovascular risk and take other medicines, e.g. low dose acetylsalicylic acid that can interact with non-steroidal anti-inflammatory drugs; in this aspect diclofenac may cause less side effects. In this review, the authors briefly review cardiovascular side effects of non-steroidal anti-inflammatory drugs, the processes which potentially influence them, therapeutic consequences and their interaction with acetylsalicylic acid.

  19. Adsorption and removal of clofibric acid and diclofenac from water with MIEX resin.

    PubMed

    Lu, Xian; Shao, Yisheng; Gao, Naiyun; Chen, Juxiang; Zhang, Yansen; Wang, Qiongfang; Lu, Yuqi

    2016-10-01

    This study demonstrates the use of MIEX resin as an efficient adsorbent for the removal of clofibric acid (CA) and diclofenac (DCF). The adsorption performance of CA and DCF are investigated by a batch mode in single-component or bi-component adsorption system. Various factors influencing the adsorption of CA and DCF, including initial concentration, contact time, adsorbent dosage, initial solution pH, agitation speed, natural organic matter and coexistent anions are studied. The Langmuir model can well describe CA adsorption in single-component system, while the Freundlich model gives better fitting in bi-component system. The DCF adsorption can be well fitted by the Freundlich model in both systems. Thermodynamic analyses show that the adsorption of CA and DCF is an endothermic (ΔH(o) > 0), entropy driven (ΔS(o) > 0) process and more randomness exists in the DCF adsorption process. The values of Gibbs free energy (ΔG(o) < 0) indicate the adsorption of DCF is spontaneous but nonspontaneous (ΔG(o) > 0) for CA adsorption. The kinetic data suggest the adsorption of CA and DCF follow the pseudo-first-order model in both systems and the intra-particle is not the unique rate-limiting step. The adsorption process is controlled simultaneously by external mass transfer and surface diffusion according to the surface diffusion modified Biot number (Bis) ranging from 1.06 to 26.15. Moreover, the possible removal mechanism for CA and DCF is respectively proposed based on the ion exchange stoichiometry. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Phospholipids-embedded fully dilutable liquid nanostructures. Part 2: The role of sodium diclofenac.

    PubMed

    Amsalem, Orit; Aserin, Abraham; Garti, Nissim

    2010-12-01

    Complex pseudo-ternary phase diagrams based on sucrose monolaurate (SE), propylene glycol (PG), and phosphatidylcholine (PC) as the "surfactant phase"; triacetin (TA) and decaglycerol ester (10G1CC) as the "oil phase"; and water as the aqueous phase were constructed, into which we solubilized the water-insoluble drug (sodium diclofenac, Na-DFC). In our previous study we demonstrated that the solubilization of Na-DFC in the oil+surfactant phases (prior to diluting it with water), was 90-fold greater than its dissolution in water, and that the system was pH-dependent. The greatest Na-DFC solubilization capacity was obtained at pH 7.2. In this study we examined the effect of the solubilization of Na-DFC in a phosphatidylcholine system using DLS, viscosity, electrical conductivity, SAXS, SD-NMR, and cryo-TEM measurements. It was found that: (1) the system remains micellar after aqueous dilution but with greater polydispersity and greater variety of shapes. We concluded that the structures in the absence of water (but in the presence of PG) were of direct spherical micelles (∼4 nm) mixed with elongated cylindrical micelles (12-140 nm); (2) the aqueous dilution causes fragmentation of the cylinders into smaller spherical micelles; (3) solubilization of Na-DFC behaving like a kosmotropic agent or "structure maker" yields mostly spherical swollen micelles and more ordered systems than in its absence; and (4) Na-DFC is solubilized at the interface of the micelles without swelling the droplets. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. HPTLC and Spectrophotometric Estimation of Febuxostat and Diclofenac Potassium in Their Combined Tablets.

    PubMed

    El-Yazbi, Fawzi A; Amin, Omayma A; El-Kimary, Eman I; Khamis, Essam F; Younis, Sameh E

    2016-08-01

    An accurate, precise, rapid, specific and economic high-performance thin-layer chromatographic (HPTLC) method has been developed for the simultaneous quantitative determination of febuxostat (FEB) and diclofenac potassium (DIC). The chromatographic separation was performed on precoated silica gel 60 GF254 plates with chloroform-methanol 7:3 (v/v) as the mobile phase. The developed plates were scanned and quantified at 289 nm. Experimental conditions including band size, mobile phase composition and chamber-saturation time were critically studied, and the optimum conditions were selected. A satisfactory resolution (Rs = 2.67) with RF 0.48 and 0.69 and high sensitivity with limits of detection of 4 and 7 ng/band for FEB and DIC, respectively, were obtained. In addition, derivative ratio and ratio difference spectrophotometric methods were established for the analysis of such a mixture. All methods were validated as per the ICH guidelines. In the HPTLC method, the calibration plots were linear between 0.01-0.55 and 0.02-0.60 µg/band, for FEB and DIC, respectively. For the spectrophotometric methods, the calibration graphs were linear between 2-14 and 4-18 µg/mL for FEB and DIC, respectively. The simplicity and specificity of the proposed methods suggest their application in quality control analysis of FEB and DIC in their raw materials and tablets. A comparison of the proposed methods with the existing methods is presented. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Nanoemulsion-based gel formulation of diclofenac diethylamine: design, optimization, rheological behavior and in vitro diffusion studies.

    PubMed

    Hamed, Rania; Basil, Marwa; AlBaraghthi, Tamadur; Sunoqrot, Suhair; Tarawneh, Ola

    2016-12-01

    Chronic oral administration of the non-steroidal anti-inflammatory drug, diclofenac diethylamine (DDEA), is often associated with gastrointestinal ulcers and bleeding. As an alternative to oral administration, a nanoemulsion-based gel (NE gel) formulation of DDEA was developed for topical administration. An optimized formulation for the o/w nanoemulsion of oil, surfactant and cosurfactant was selected based on nanoemulsion mean droplet size, clarity, stability, and flowability, and incorporated into the gelling agent Carbopol® 971P. Rheological studies of the DDEA NE gel were conducted and compared to those of conventional DDEA gel and emulgel. The three gels exhibited an elastic behavior, where G' dominated G″ at all frequencies, indicating the formation of strong gels. NE gel exhibited higher G' values than conventional gel and emulgel, which indicated the formation of a stronger gel network. Strat-M® membrane, a synthetic membrane with diffusion characteristics that are well correlated to human skin, was used for the in vitro diffusion studies. The release of DDEA from conventional gel, emulgel and NE gel showed a controlled release pattern over 12 h, which was consistent with the rheological properties of the gels. DDEA release kinetics from the three gels followed super case II transport as fitted by Korsmeyer-Peppas model.

  3. Removal of diclofenac by conventional drinking water treatment processes and granular activated carbon filtration.

    PubMed

    Rigobello, Eliane Sloboda; Dantas, Angela Di Bernardo; Di Bernardo, Luiz; Vieira, Eny Maria

    2013-06-01

    This study was carried out to evaluate the efficiency of conventional drinking water treatment processes with and without pre-oxidation with chlorine and chlorine dioxide and the use of granular activated carbon (GAC) filtration for the removal of diclofenac (DCF). Water treatment was performed using the Jar test with filters on a lab scale, employing nonchlorinated artesian well water prepared with aquatic humic substances to yield 20HU true color, kaolin turbidity of 70 NTU and 1mgL(-1) DCF. For the quantification of DCF in water samples, solid phase extraction and HPLC-DAD methods were developed and validated. There was no removal of DCF in coagulation with aluminum sulfate (3.47mgAlL(-1) and pH=6.5), flocculation, sedimentation and sand filtration. In the treatment with pre-oxidation and disinfection, DCF was partially removed, but the concentration of dissolved organic carbon (DOC) was unchanged and byproducts of DCF were observed. Chlorine dioxide was more effective than chorine in oxidizing DCF. In conclusion, the identification of DCF and DOC in finished water indicated the incomplete elimination of DCF through conventional treatments. Nevertheless, conventional drinking water treatment followed by GAC filtration was effective in removing DCF (⩾99.7%). In the oxidation with chlorine, three byproducts were tentatively identified, corresponding to a hydroxylation, aromatic substitution of one hydrogen by chlorine and a decarboxylation/hydroxylation. Oxidation with chlorine dioxide resulted in only one byproduct (hydroxylation). Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. The effects of gamma irradiation on diclofenac sodium, liposome and niosome ingredients for rheumatoid arthritis

    PubMed Central

    Turker, Selcan; Çolak, Seyda; Korkmaz, Mustafa; Kiliç, Ekrem; Özalp, Meral

    2013-01-01

    The use of gamma rays for the sterilization of pharmaceutical raw materials and dosage forms is an alternative method for sterilization. However, one of the major problems of the radiosterilization is the production of new radiolytic products during the irradiation process. Therefore, the principal problem in radiosterilization is to determine and to characterize these physical and chemical changes originating from high-energy radiation. Parenteral drug delivery systems were prepared and in vitro characterization, biodistribution and treatment studies were done in our previous studies. Drug delivery systems (liposomes, niosomes, lipogelosomes and niogelosomes) encapsulating diclofenac sodium (DFNa) were prepared for the treatment of rheumatoid arthritis (RA). This work complies information about the studies developed in order to find out if gamma radiation could be applied as a sterilization method to DFNa, and the raw materials as dimyristoyl phosphatidylcholine (DMPC), surfactant I [polyglyceryl-3-cethyl ether (SUR I)], dicethyl phosphate (DCP) and cholesterol (CHOL) that are used to prepare those systems. The raw materials were irradiated with different radiation doses (5, 10, 25 and 50 kGy) and physicochemical changes (organoleptic properties pH, UV and melting point), microbiological evaluation [sterility assurance level (SAL), sterility and pyrogen test] and electron spin resonance (ESR) characteristics were studied at normal (25 °C, 60% relative humidity) and accelerated (40 °C, 75% relative humidity) stability test conditions. PMID:24265902

  5. Uptake and metabolism of diclofenac in Typha latifolia--how plants cope with human pharmaceutical pollution.

    PubMed

    Bartha, Bernadett; Huber, Christian; Schröder, Peter

    2014-10-01

    The fate of pharmaceuticals in our environment is a very important issue for environmental and health research. Although these substances have been detected in environmental compartments in low concentration until now, they will pose considerable environmental risk to ecosystems, animals and human due to their biological activity. Alternative plant based removal technologies that make use of some potential wetland species like Phragmites or Typha within traditional wastewater treatment plants have to be established to cope with this "new generation" of pollutants. We investigated uptake and translocation of diclofenac (1mgl(-1)) in the macrophyte Typha latifolia L. during one week exposure in greenhouse experiments. Detoxification products and involved key enzymatic processes were identified. We also examined the oxidative stress induced by the treatment and the defense capacity of the plants. Rapid uptake and effective metabolism were observed, where glycoside and glutathione conjugates represent dominant metabolites. Up to seven-fold induction of glycosyltransferase activity was observed in roots, but not in shoots. Glutathione S-transferase activity was also induced, but to a lower extent. The activity changes of defense enzymes points to oxidative stress in the plants. Our results show that human pharmaceuticals can be metabolized by plants similar to xenobiotics, but that similarities to human metabolism are limited. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Degradation of diclofenac by UV-activated persulfate process: Kinetic studies, degradation pathways and toxicity assessments.

    PubMed

    Lu, Xian; Shao, Yisheng; Gao, Naiyun; Chen, Juxiang; Zhang, Yansen; Xiang, Huiming; Guo, Youluo

    2017-07-01

    Diclofenac (DCF) is the frequently detected non-steroidal pharmaceuticals in the aquatic environment. In this study, the degradation of DCF was evaluated by UV-254nm activated persulfate (UV/PS). The degradation of DCF followed the pseudo first-order kinetics pattern. The degradation rate constant (k obs ) was accelerated by UV/PS compared to UV alone and PS alone. Increasing the initial PS dosage or solution pH significantly enhanced the degradation efficiency. Presence of various natural water constituents had different effects on DCF degradation, with an enhancement or inhibition in the presence of inorganic anions (HCO 3 - or Cl - ) and a significant inhibition in the presence of NOM. In addition, preliminary degradation mechanisms and major products were elucidated using LC-MS/MS. Hydroxylation, decarbonylation, ring-opening and cyclation reaction involving the attack of SO 4 • - or other substances, were the main degradation mechanism. TOC analyzer and Microtox bioassay were employed to evaluate the mineralization and cytotoxicity of solutions treated by UV/PS at different times, respectively. Limited elimination of TOC (32%) was observed during the mineralization of DCF. More toxic degradation products and their related intermediate species were formed, and the UV/PS process was suitable for removing the toxicity. Of note, longer degradation time may be considered for the final toxicity removal. Copyright © 2017. Published by Elsevier Inc.

  7. A new antibacterial silver(I) complex incorporating 2,5-dimethylpyrazine and the anti-inflammatory diclofenac.

    PubMed

    Hamamci Alisir, Sevim; Dege, Necmi

    2016-12-01

    Ag I -containing coordination complexes have attracted attention because of their photoluminescence properties and antimicrobial activities and, in principle, these properties depend on the nature of the structural topologies. A novel two-dimensional silver(I) complex with the anti-inflammatory diclofenac molecule, namely bis{μ-2-[2-(2,6-dichloroanilino)phenyl]acetato-κ 3 O,O':O}bis(μ-2,5-dimethylpyrazine-κ 2 N:N')silver(I), [Ag 2 (C 14 H 10 Cl 2 NO 2 ) 2 (C 6 H 8 N 2 )] n , (I), has been synthesized and characterized by single-crystal X-ray diffraction, revealing that the Ag I ions are chelated by the carboxylate groups of the anionic 2-[2-(2,6-dichloroanilino)phenyl]acetate (dicl) ligand in a μ 3 -η 1 :η 2 coordination mode. Each dicl ligand links three Ag I atoms to generate a one-dimensional infinite chain. Adjacent chains are connected through 2,5-dimethylpyrazine (dmpyz) ligands to form a two-dimensional layer structure parallel to the crystallographic bc plane. The layers are further connected by C-H...π interactions to generate a three-dimensional supramolecular structure. Additionally, the most striking feature is that the structure contains an intramolecular C-H ...Ag anagostic interaction. Furthermore, the title complex has been tested for its in vitro antibacterial activity and is determined to be highly effective on the studied microorganisms.

  8. Influence of water-soluble channeling agents on the release of diclofenac sodium from Irvingia malayana wax matrix tablets.

    PubMed

    Yotsawimonwat, Songwut; Charumanee, Suporn; Kaewvichit, Sayam; Sirithunyalug, Jakkapan; Sirisa-Ard, Panee; Piyamongkol, Sirivipa; Siangwong, Kulthawat

    2017-05-01

    Irvingia malayana wax (IW) is majorly composed of esters of medium chain fatty acids. Its melting point is low and closed to the body temperature. This study aimed at investigating the potential of IW as a matrix-forming agent and evaluate the effect of soluble channeling agents on the release of diclofenac sodium (DS) from IW matrix tablets. The preformulation study by infrared spectroscopy and differential scanning calorimetry showed no incompatibility between IW and DS or soluble channeling agents, namely PEG 4000, PEG 6000 and lactose. IW retarded the release of DS from the matrix tablets more efficiently than carnauba wax due to its greater hydrophobicity and its ability to become partial molten wax at 37° C. Factors affecting the release of DS from IW matrix were drug concentrations, and types and concentrations of channeling agents. The release of DS significantly improved when DS concentration reached approximately 33%. The fast dissolving channeling agent, lactose, could enhance the drug release rate more effectively than PEG 4000 and PEG 6000, respectively. The linear relationship between the DS release rate and the concentration of the chosen channeling agent, PEG 6000, was found (r 2 =0.9866).

  9. Ultrasonic degradation, mineralization and detoxification of diclofenac in water: optimization of operating parameters.

    PubMed

    Naddeo, V; Belgiorno, V; Kassinos, D; Mantzavinos, D; Meric, S

    2010-01-01

    The 20 kHz ultrasound-induced degradation of non-steroidal, anti-inflammatory drug diclofenac (DCF) was investigated. Several operating conditions, such as power density (25-100 W/L), substrate concentration (2.5-80 mg/L), initial solution pH (3.5-11), liquid bulk temperature and the type of sparging gas (air, oxygen, argon), were tested concerning their effect on DCF degradation (as assessed measuring absorbance at 276 nm) and hydroxyl radicals generation (as assessed measuring H(2)O(2) concentration). Sample mineralization (in terms of TOC and COD removal), aerobic biodegradability (as assessed by the BOD(5)/COD ratio) and ecotoxicity to Daphnia magna and Artemia salina were followed too. DCF conversion is enhanced at increased applied power densities and liquid bulk temperatures, acidic conditions and in the presence of dissolved air or oxygen. The reaction rate increases with increasing DCF concentration in the range 2.5-5mg/L but it remains constant in the range 40-80 mg/L, indicating different kinetic regimes (i.e. first and zero order, respectively). H(2)O(2) production rates in pure water are higher than those in DCF solutions, implying that decomposition basically proceeds through hydroxyl radical reactions. Mineralization is a slow process as reaction by-products are more stable than DCF to total oxidation; nonetheless, they are also more readily biodegradable. Toxicity to D. magna increases during the early stages of the reaction and then decreases progressively upon degradation of reaction by-products; nevertheless, complete toxicity elimination cannot be achieved at the conditions in question. Neither the original nor the treated DCF samples are toxic to A. salina.

  10. Ion-exchange selectivity of diclofenac, ibuprofen, ketoprofen, and naproxen in ureolyzed human urine.

    PubMed

    Landry, Kelly A; Sun, Peizhe; Huang, Ching-Hua; Boyer, Treavor H

    2015-01-01

    This research advances the knowledge of ion-exchange of four non-steroidal anti-inflammatory drugs (NSAIDs) - diclofenac (DCF), ibuprofen (IBP), ketoprofen (KTP), and naproxen (NPX) - and one analgesic drug-paracetamol (PCM) - by strong-base anion exchange resin (AER) in synthetic ureolyzed urine. Freundlich, Langmuir, Dubinin-Astakhov, and Dubinin-Radushkevich isotherm models were fit to experimental equilibrium data using nonlinear least squares method. Favorable ion-exchange was observed for DCF, KTP, and NPX, whereas unfavorable ion-exchange was observed for IBP and PCM. The ion-exchange selectivity of the AER was enhanced by van der Waals interactions between the pharmaceutical and AER as well as the hydrophobicity of the pharmaceutical. For instance, the high selectivity of the AER for DCF was due to the combination of Coulombic interactions between quaternary ammonium functional group of resin and carboxylate functional group of DCF, van der Waals interactions between polystyrene resin matrix and benzene rings of DCF, and possibly hydrogen bonding between dimethylethanol amine functional group side chain and carboxylate and amine functional groups of DCF. Based on analysis of covariance, the presence of multiple pharmaceuticals did not have a significant effect on ion-exchange removal when the NSAIDs were combined in solution. The AER reached saturation of the pharmaceuticals in a continuous-flow column at varying bed volumes following a decreasing order of DCF > NPX ≈ KTP > IBP. Complete regeneration of the column was achieved using a 5% (m/m) NaCl, equal-volume water-methanol solution. Results from multiple treatment and regeneration cycles provide insight into the practical application of pharmaceutical ion-exchange in ureolyzed urine using AER.

  11. Design and characterization of diclofenac diethylamine transdermal patch using silicone and acrylic adhesives combination.

    PubMed

    Panchaxari, Dandigi M; Pampana, Sowjanya; Pal, Tapas; Devabhaktuni, Bhavana; Aravapalli, Anil Kumar

    2013-01-07

    The objective of the study was to develop and characterize Diclofenac Diethylamine (DDEA) transdermal patch using Silicone and acrylic adhesives combination. Modified solvent evaporation method was employed for casting of film over Fluoropolymer coated polyester release liner. Initial studies included solubilization of drug in the polymers using solubilizers. The formulations with combination of adhesives were attempted to combine the desirable features of both the adhesives. The effect of the permeation enhancers on the drug permeation were studied using pig ear skin. All the optimized patches were subjected to adhesion, dissolution and stability studies. A 7-day skin irritancy test on albino rabbits and an in vivo anti-inflammatory study on wistar rats by carrageenan induced paw edema method were also performed. The results indicated the high percent drug permeation (% CDP-23.582) and low solubility nature (1%) of Silicone adhesive and high solubility (20%) and low% CDP (10.72%) of acrylic adhesive. The combination of adhesives showed desirable characteristics for DDEA permeation with adequate % CDP and sufficient solubility. Release profiles were found to be dependent on proportion of polymer and type of permeation enhancer. The anti-inflammatory study revealed the sustaining effect and high percentage inhibition of edema of C4/OLA (99.68%). The acute skin irritancy studies advocated the non-irritant nature of the adhesives used. It was concluded that an ideal of combination of adhesives would serve as the best choice, for fabrication of DDEA patches, for sustained effect of DDEA with better enhancement in permeation characteristics and robustness.

  12. Design and characterization of diclofenac diethylamine transdermal patch using silicone and acrylic adhesives combination

    PubMed Central

    2013-01-01

    Background and purpose of the study The objective of the study was to develop and characterize Diclofenac Diethylamine (DDEA) transdermal patch using Silicone and acrylic adhesives combination. Methods Modified solvent evaporation method was employed for casting of film over Fluoropolymer coated polyester release liner. Initial studies included solubilization of drug in the polymers using solubilizers. The formulations with combination of adhesives were attempted to combine the desirable features of both the adhesives. The effect of the permeation enhancers on the drug permeation were studied using pig ear skin. All the optimized patches were subjected to adhesion, dissolution and stability studies. A 7-day skin irritancy test on albino rabbits and an in vivo anti-inflammatory study on wistar rats by carrageenan induced paw edema method were also performed. Results The results indicated the high percent drug permeation (% CDP-23.582) and low solubility nature (1%) of Silicone adhesive and high solubility (20%) and low% CDP (10.72%) of acrylic adhesive. The combination of adhesives showed desirable characteristics for DDEA permeation with adequate % CDP and sufficient solubility. Release profiles were found to be dependent on proportion of polymer and type of permeation enhancer. The anti-inflammatory study revealed the sustaining effect and high percentage inhibition of edema of C4/OLA (99.68%). The acute skin irritancy studies advocated the non-irritant nature of the adhesives used. Conclusion It was concluded that an ideal of combination of adhesives would serve as the best choice, for fabrication of DDEA patches, for sustained effect of DDEA with better enhancement in permeation characteristics and robustness. PMID:23351568

  13. Interaction of two diclofenac acid salts with copolymers of ammoniomethacrylate: effect of additives and release profiles.

    PubMed

    Khalil, E; Sallam, A

    1999-04-01

    The copolymer of ammoniomethacrylate Eudragit RL (ERL) interacted with diclofenac acid salts (sodium and diethylamine salts) in aqueous solutions, forming a complex. Sorption experiments were done in aqueous solutions of either sodium lauryl sulfate (SLS), Tween 20, or Tween 80. The SLS competed strongly with the drug, even at low concentrations, and reduced significantly the amount of drug sorbed by ERL. Tweens at high concentrations exhibited two phase profiles: the sorption phase, which was short and during which drug concentration dropped sharply, and the release phase, during which the drug was released slowly over 24 hr and which was accompanied by dispersion of ERL particles into the colloidal dispersion. The interaction was dependent on temperature, ionic strength, and nature of the additives. The extent of interaction in water and phosphate buffer solutions was in the following order: water > pH 6 > pH 7-8. In-vitro dissolution studies of the dried complex were done over 24 hr. In water, the drug remained bound to the polymer. In aqueous surfactant solutions (SLS, Tween 20, and Tween 80) and phosphate buffer at pH 6.8, a linear relationship between drug concentration and the square root of time was obtained, indicating a matrix diffusion-controlled mechanism. However, 100% release was not reached, and resorption was observed in the phosphate buffer solution.

  14. Application of nanofiltration for the removal of carbamazepine, diclofenac and ibuprofen from drinking water sources.

    PubMed

    Vergili, I

    2013-09-30

    Pharmaceutical active compounds (PhACs) are persistent during the process used to treat drinking water and, because drinking water treatment plants are not specifically designed to remove PhACs, these compounds are found in drinking water. Although there are currently no regulations or drinking water directives for PhACs, precautionary principles suggest ensuring maximal removal of PhACs through improved or existing treatment techniques. This study was designed to investigate the performance of a nanofiltration membrane in cross-flow filtration equipment for the removal of three PhACs [carbamazepine (CBZ), diclofenac (DIC) and ibuprofen (IBU)] that were spiked in water taken from a drinking water treatment plant using surface water. Because of their low solubilities, high log Kow values, low dipole moments and negative charges, higher rejection values were obtained for DIC and IBU. Low to moderate rejection values were most likely due to the small molecular sizes of the PhACs (i.e., MW < MWCO) and the divalent ions present in the raw water. Flux declines obtained from DIC studies was attributed to the adsorption of DIC ions inside the membrane pores, which decreases the flux. The most evident change in the FT-IR spectrum after nanofiltration was the appearance of new intense bands at 1072 cm(-1) and 1011 cm(-1), indicating the deposition of calcium salts on the membrane surface. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Tamarind seed gum-hydrolyzed polymethacrylamide-g-gellan beads for extended release of diclofenac sodium using 32 full factorial design.

    PubMed

    Nandi, Gouranga; Nandi, Amit Kumar; Khan, Najim Sarif; Pal, Souvik; Dey, Sibasish

    2018-07-15

    Development of tamarind seed gum (TSG)-hydrolyzed polymethacrylamide-g-gellan (h-Pmaa-g-GG) composite beads for extended release of diclofenac sodium using 3 2 full factorial design is the main purpose of this study. The ratio of h-Pmaa-g-GG and TSG and concentration of cross-linker CaCl 2 were taken as independent factors with three different levels of each. Effects of polymer ratio and CaCl 2 on drug entrapment efficiency (DEE), drug release, bead size and swelling were investigated. Responses such as DEE and different drug release parameters were statistically analyzed by 3 2 full factorial design using Design-Expert software and finally the formulation factors were optimized to obtain USP-reference release profile. Drug release rate was found to decrease with decrease in the ratio of h-Pmaa-g-GG:TSG and increase in the concentration of Ca 2+ ions in cross-linking medium. The optimized formulation showed DEE of 93.25% and an extended drug release profile over a period of 10h with f 2 =80.13. Kinetic modeling unveiled case-I-Fickian diffusion based drug release mechanism. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Urinary proteomic profiling reveals diclofenac-induced renal injury and hepatic regeneration in mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Swelm, Rachel P.L. van; Laarakkers, Coby M.M.; Pertijs, Jeanne C.L.M.

    Diclofenac (DF) is a widely used non-steroidal anti-inflammatory drug for the treatment of rheumatic disorders, but is often associated with liver injury. We applied urinary proteomic profiling using MALDI-TOF MS to identify biomarkers for DF-induced hepatotoxicity in mice. Female CH3/HeOUJIco mice were treated with 75 mg/kg bw DF by oral gavage and 24 h urine was collected. Proteins identified in urine of DF-treated mice included epidermal growth factor, transthyretin, kallikrein, clusterin, fatty acid binding protein 1 and urokinase, which are related to liver regeneration but also to kidney injury. Both organs showed enhanced levels of oxidative stress (TBARS, p

  17. Diclofenac Sodium 3% in Hyaluronic Acid 2.5% Gel Significantly Diminishes the Actinic Keratosis Area and Severity Index.

    PubMed

    Schmitz, Lutz; Gupta, Girish; Segert, Marc Hanno; Kost, Ricarda; Sternberg, Julia; Gambichler, Thilo; Stockfleth, Eggert; Dirschka, Thomas

    2018-05-23

    Actinic keratosis area and severity index (AKASI) is a new assessment tool to quantify the severity of actinic damage on the head. Thus far, it has not been evaluated in monitoring the efficacy of field-directed topical treatments in actinic keratosis (AK) in routine clinical practice. Thus, the aim of this study was to determine treatment outcomes by using AKASI 3 months after the initiation of topical application of diclofenac sodium 3% in hyaluronic acid 2.5% gel (DFS) in patients with AKs on the head. We performed a retrospective analysis of patients with AKs who had AKASI scores prior to and after treatment with DFS. Of the 24 patients included, 20 (83.3%) showed an improvement in AKASI, 2 (8.3%) a stable AKASI, and 2 (8.3%) a worsening of AKASI after a median (interquartile range) follow-up period of 91.5 days (89.8-104.3). The median AKASI reduction was 31.4% (16.7-59.1). The Wilcoxon test showed significant differences (p = 0.0008) between baseline and posttreatment AKASI values. AKASI is an easy-to-use quantitative tool for assessing the treatment outcome of field-directed therapies. Field-directed therapies of AK should no longer be monitored by assessments based on lesion counts alone. © 2018 S. Karger AG, Basel.

  18. "Real-time" disintegration analysis and D-optimal experimental design for the optimization of diclofenac sodium fast-dissolving films.

    PubMed

    El-Malah, Yasser; Nazzal, Sami

    2013-01-01

    The objective of this work was to study the dissolution and mechanical properties of fast-dissolving films prepared from a tertiary mixture of pullulan, polyvinylpyrrolidone and hypromellose. Disintegration studies were performed in real-time by probe spectroscopy to detect the onset of film disintegration. Tensile strength and elastic modulus of the films were measured by texture analysis. Disintegration time of the films ranged from 21 to 105 seconds whereas their mechanical properties ranged from approximately 2 to 49 MPa for tensile strength and 1 to 21 MPa% for young's modulus. After generating polynomial models correlating the variables using a D-Optimal mixture design, an optimal formulation with desired responses was proposed by the statistical package. For validation, a new film formulation loaded with diclofenac sodium based on the optimized composition was prepared and tested for dissolution and tensile strength. Dissolution of the optimized film was found to commence almost immediately with 50% of the drug released within one minute. Tensile strength and young's modulus of the film were 11.21 MPa and 6, 78 MPa%, respectively. Real-time spectroscopy in conjunction with statistical design were shown to be very efficient for the optimization and development of non-conventional intraoral delivery system such as fast dissolving films.

  19. Formulation and characterization of hydrophilic drug diclofenac sodium-loaded solid lipid nanoparticles based on phospholipid complexes technology.

    PubMed

    Liu, Dongfei; Chen, Li; Jiang, Sunmin; Zhu, Shuning; Qian, Yong; Wang, Fengzhen; Li, Rui; Xu, Qunwei

    2014-03-01

    To successfully prepare the diclofenac sodium (DS)-loaded solid lipid nanoparticles (SLNs), phospholipid complexes (PCs) technology was applied here to improve the liposolubility of DS. Solid lipid nanoparticles (SLNs) loaded with phospholipid complexes (PCs) were prepared by the modified emulsion/solvent evaporation method. DS could be solubilized effectively in the organic solvents with the existence of phospholipid and apparent partition coefficient of DS in PCs increased significantly. X-ray diffraction analysis suggested that DS in PCs was either molecularly dispersed or in an amorphous form. However, no significant difference was observed between the Fourier transform infrared spectroscopy (FT-IR) spectra of physical mixture and that of PCs. Particles with small sizes, narrow polydispersity indexes and high entrapment efficiencies could be obtained with the addition of PCs. Furthermore, according to the transmission electron microscopy, a core-shell structure was likely to be formed. The presence of PCs caused the change of zeta potential and retarded the drug release of SLNs, which indicated that phospholipid formed multilayers around the solid lipid core of SLNs. Both FT-IR and differential scanning calorimetry analysis also illustrated that some weak interactions between DS and lipid materials might take place during the preparation of SLNs. In conclusion, the model hydrophilic drug-DS can be formulated into the SLNs with the help of PCs.

  20. Possible ecological risk of two pharmaceuticals diclofenac and paracetamol demonstrated on a model plant Lemna minor.

    PubMed

    Kummerová, Marie; Zezulka, Štěpán; Babula, Petr; Tříska, Jan

    2016-01-25

    Lemna minor is often used in environmental risk assessment and it can be supposed that usually evaluated parameters will be reliable even for assessing the risk of pharmaceuticals. Subtle changes in duckweed plant number, biomass production, and leaf area size induced by 10-day-exposure to diclofenac (DCF) and paracetamol (PCT) (0.1, 10, and 100 μg/L), excepting 100 μg/L DCF, are in contrast with considerable changes on biochemical and histochemical level. Both drugs caused a decrease in content of photosynthetic pigments (by up to 50%), an increase in non-photochemical quenching (by 65%) and decrease in relative chlorophyll fluorescence decay values (by up to 90% with DCF). Both DCF and especially PCT increased amount of reactive nitrogen and oxygen species in roots. DCF-induced effects included mainly increased lipid peroxidation (by 78%), disturbation in membrane integrity and lowering both oxidoreductase and dehydrogenase activities (by 30%). PCT increased the content of soluble proteins and phenolics. Higher concentrations of both DCF and PCT increased the levels of oxidised ascorbate (by 30%) and oxidised thiols (by up to 84% with DCF). Glutathion-reductase activity was elevated by both pharmaceuticals (nearly by 90%), glutathion-S-transferase activity increased mainly with PCT (by 22%). The early and sensitive indicators of DCF and PCT phytotoxicity stress in duckweed are mainly the changes in biochemical processes, connected with activation of defense mechanisms against oxidative stress. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Electrochemical Selective and Simultaneous Detection of Diclofenac and Ibuprofen in Aqueous Solution Using HKUST-1 Metal-Organic Framework-Carbon Nanofiber Composite Electrode.

    PubMed

    Motoc, Sorina; Manea, Florica; Iacob, Adriana; Martinez-Joaristi, Alberto; Gascon, Jorge; Pop, Aniela; Schoonman, Joop

    2016-10-17

    In this study, the detection protocols for the individual, selective, and simultaneous determination of ibuprofen (IBP) and diclofenac (DCF) in aqueous solutions have been developed using HKUST-1 metal-organic framework-carbon nanofiber composite (HKUST-CNF) electrode. The morphological and electrical characterization of modified composite electrode prepared by film casting was studied by scanning electronic microscopy and four-point-probe methods. The electrochemical characterization of the electrode by cyclic voltammetry (CV) was considered the reference basis for the optimization of the operating conditions for chronoamperometry (CA) and multiple-pulsed amperometry (MPA). This electrode exhibited the possibility to selectively detect IBP and DCF by simple switching the detection potential using CA. However, the MPA operated under optimum working conditions of four potential levels selected based on CV shape in relation to the potential value, pulse time, and potential level number, and order allowed the selective/simultaneous detection of IBP and DCF characterized by the enhanced detection performance. For this application, the HKUST-CNF electrode exhibited a good stability and reproducibility of the results was achieved.

  2. Electrochemical Selective and Simultaneous Detection of Diclofenac and Ibuprofen in Aqueous Solution Using HKUST-1 Metal-Organic Framework-Carbon Nanofiber Composite Electrode

    PubMed Central

    Motoc, Sorina; Manea, Florica; Iacob, Adriana; Martinez-Joaristi, Alberto; Gascon, Jorge; Pop, Aniela; Schoonman, Joop

    2016-01-01

    In this study, the detection protocols for the individual, selective, and simultaneous determination of ibuprofen (IBP) and diclofenac (DCF) in aqueous solutions have been developed using HKUST-1 metal-organic framework-carbon nanofiber composite (HKUST-CNF) electrode. The morphological and electrical characterization of modified composite electrode prepared by film casting was studied by scanning electronic microscopy and four-point-probe methods. The electrochemical characterization of the electrode by cyclic voltammetry (CV) was considered the reference basis for the optimization of the operating conditions for chronoamperometry (CA) and multiple-pulsed amperometry (MPA). This electrode exhibited the possibility to selectively detect IBP and DCF by simple switching the detection potential using CA. However, the MPA operated under optimum working conditions of four potential levels selected based on CV shape in relation to the potential value, pulse time, and potential level number, and order allowed the selective/simultaneous detection of IBP and DCF characterized by the enhanced detection performance. For this application, the HKUST-CNF electrode exhibited a good stability and reproducibility of the results was achieved. PMID:27763509

  3. Optimization and formulation design of gels of Diclofenac and Curcumin for transdermal drug delivery by Box-Behnken statistical design.

    PubMed

    Chaudhary, Hema; Kohli, Kanchan; Amin, Saima; Rathee, Permender; Kumar, Vikash

    2011-02-01

    The aim of this study was to develop and optimize a transdermal gel formulation for Diclofenac diethylamine (DDEA) and Curcumin (CRM). A 3-factor, 3-level Box-Behnken design was used to derive a second-order polynomial equation to construct contour plots for prediction of responses. Independent variables studied were the polymer concentration (X(1)), ethanol (X(2)) and propylene glycol (X(3)) and the levels of each factor were low, medium, and high. The dependent variables studied were the skin permeation rate of DDEA (Y(1)), skin permeation rate of CRM (Y(2)), and viscosity of the gels (Y(3)). Response surface plots were drawn, statistical validity of the polynomials was established to find the compositions of optimized formulation which was evaluated using the Franz-type diffusion cell. The permeation rate of DDEA increased proportionally with ethanol concentration but decreased with polymer concentration, whereas the permeation rate of CRM increased proportionally with polymer concentration. Gels showed a non-Fickian super case II (typical zero order) and non-Fickian diffusion release mechanism for DDEA and CRM, respectively. The design demonstrated the role of the derived polynomial equation and contour plots in predicting the values of dependent variables for the preparation and optimization of gel formulation for transdermal drug release. Copyright © 2010 Wiley-Liss, Inc.

  4. Ecotoxicological impacts of clofibric acid and diclofenac in common carp (Cyprinus carpio) fingerlings: hematological, biochemical, ionoregulatory and enzymological responses.

    PubMed

    Saravanan, Manoharan; Karthika, Subramanian; Malarvizhi, Annamalai; Ramesh, Mathan

    2011-11-15

    Investigation on the toxic effects of pharmaceutical drugs namely clofibric acid (CA) and diclofenac (DCF) were studied in a common carp Cyprinus carpio at different concentrations such as 1, 10 and 100 μg L(-1) for a short-term period of 96 h under static bioassay method. At all concentrations, red blood cell (RBC), plasma sodium (Na(+)), potassium (K(+)), and glutamate oxaloacetate transaminase (GOT) levels were decreased in fish treated with CA and DCF. Contrastingly, white blood cell (WBC), plasma glucose, protein, lactate dehydrogenase (LDH) and gill Na(+)/K(+)-ATPase level were increased. However, a mixed trend was observed in hemoglobin (Hb), hematocrit (Hct), plasma chloride (Cl(-)), mean cellular volume (MCV), mean cellular hemoglobin (MCH), mean cellular hemoglobin concentration (MCHC) and glutamate pyruvate transaminase (GPT) levels. There was a significant (P<0.01 and P<0.05) change in all parameters measured in fish exposed to different concentrations of CA and DCF. In summary, the alterations in hematological, biochemical, ionoregulatory and enzymological parameters can be used as biomarkers in monitoring the toxicity of CA and DCF in aquatic environment. However, more detailed studies on using of specific biomarkers to monitor the human pharmaceuticals are needed. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Biophysical study of the non-steroidal anti-inflammatory drugs (NSAID) ibuprofen, naproxen and diclofenac with phosphatidylserine bilayer membranes.

    PubMed

    Manrique-Moreno, Marcela; Heinbockel, Lena; Suwalsky, Mario; Garidel, Patrick; Brandenburg, Klaus

    2016-09-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) represent an effective pain treatment option and therefore one of the most sold therapeutic agents worldwide. The study of the molecular interactions responsible for their physiological activity, but also for their side effects, is therefore important. This report presents data on the interaction of the most consumed NSAIDs (ibuprofen, naproxen and diclofenac) with one main phospholipid in eukaryotic cells, dimyristoylphosphatidylserine (DMPS). The applied techniques are Fourier-transform infrared spectroscopy (FTIR), with which in transmission the gel to liquid crystalline phase transition of the acyl chains in the absence and presence of the NSAID are monitored, supplemented by differential scanning calorimetry (DSC) data on the phase transition. FTIR in reflection (ATR, attenuated total reflectance) is applied to record the dependence of the interactions of the NSAID with particular functional groups observed in the DMPS spectrum such as the ester carbonyl and phosphate vibrational bands. With Förster resonance energy transfer (FRET) a possible intercalation of the NSAID into the DMPS liposomes and with isothermal titration calorimetry (ITC) the thermodynamics of the interaction are monitored. The data show that the NSAID react in a particular way with this lipid, but in some parameters the three NSAID clearly differ, with which now a clear picture of the interaction processes is possible. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Cyto-genotoxicity and oxidative stress in common carp (Cyprinus carpio) exposed to a mixture of ibuprofen and diclofenac.

    PubMed

    Islas-Flores, Hariz; Manuel Gómez-Oliván, Leobardo; Galar-Martínez, Marcela; Michelle Sánchez-Ocampo, Esmeralda; SanJuan-Reyes, Nely; Ortíz-Reynoso, Mariana; Dublán-García, Octavio

    2017-05-01

    Thirty million people worldwide consume each day nonsteroidal anti-inflammatory drugs (NSAIDs), a heterogeneous group of pharmaceuticals used for its analgesic, antipyretic, and anti-inflammatory properties. Recent studies report high NSAID concentrations in wastewater treatment plant effluents, in surface, ground, and drinking water, and in sediments. NSAIDs are also known to induce toxicity on aquatic organisms. However, toxicity in natural ecosystems is not usually the result of exposure to a single substance but to a mixture of toxic agents, yet only a few studies have evaluated the toxicity of mixtures. The aim of this study was to evaluate the toxicity induced by diclofenac (DCF), ibuprofen (IBP), and their mixture on a species of commercial interest, the common carp Cyprinus carpio. The median lethal concentration of IBP and DCF was determined, and oxidative stress was evaluated using the following biomarkers: lipid peroxidation and activity of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase. Cyto-genotoxicity was evaluated by micronucleus test, comet assay, and the specific activity of caspase-3. Results show that DCF, IBP, and a mixture of these pharmaceuticals induced free radical production, oxidative stress and cyto-genotoxicity in tissues of C. carpio. However, a greater effect was elicited by the mixture than by either pharmaceutical alone in some biomarkers evaluated, particularly in gill. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1637-1650, 2017. © 2017 Wiley Periodicals, Inc.

  7. Effects of exposure to pharmaceuticals (diclofenac and carbamazepine) spiked sediments in the midge, Chironomus riparius (Diptera, Chironomidae).

    PubMed

    Nieto, Elena; Corada-Fernández, Carmen; Hampel, Miriam; Lara-Martín, Pablo A; Sánchez-Argüello, Paloma; Blasco, Julián

    2017-12-31

    Human and veterinary pharmaceuticals and degradation products are continuously introduced into the environment. To date, there is a lack of information about the effects of pharmaceuticals in spiked toxicity tests with non-target organisms. In this study, we have evaluated the effects of exposure to two common pharmaceuticals in the midge Chironomus riparius in spiked sediment experiments. The selected pharmaceuticals are the nonsteroidal anti-inflammatory drug (NSAID): diclofenac (DF) and the anti-depressant drug carbamazepine (CBZ). In order to assess the effects of the pharmaceuticals, a chronic toxicity test with the midge was carried out. The endpoints survival, growth and developmental stage by means of biomass, were measured after 10days, and emergence rates and sex-ratio (male/female) were measured after 21days of exposure. Significant mortality was observed in organisms at day 10 with a 40% of larvae surviving in the highest exposure concentration of CBZ. DF decreased the emergence ratio with respect to the controls in organisms exposed at concentrations of 34.0μg·g -1 whereas CBZ reduced the growth of the midges (30,6% with respect to the control) and induced a significant change in sex-ratio at concentrations of 31.4μg·g -1 . The results obtained in the present study indicate possible adverse effects on aquatic invertebrates, which should be taken into account for environmental risk assessment of pharmaceutical compounds in sediments. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Determination of metoserpate, buquinolate, and diclofenac in pork, eggs, and milk using liquid chromatography-tandem mass spectrometry.

    PubMed

    Park, Jin-A; Abd El-Aty, A M; Zheng, Weijia; Kim, Seong-Kwan; Choi, Jeong-Min; Hacımüftüoğlu, Ahmet; Shim, Jae-Han; Shin, Ho-Chul

    2018-06-01

    In this work, a method was developed for the simultaneous determination of residual metoserpate, buquinolate and diclofenac in pork, milk, and eggs. Samples were extracted with 0.1% formic acid in acetonitrile, defatted with n-hexane, and filtered prior to analysis using liquid chromatography-tandem mass spectrometry. The analytes were separated on a C 18 column using 0.1% acetic acid and methanol as the mobile phase. The matrix-matched calibration curves showed good linearity over a concentration range of 5-50 ng/g with coefficients of determination (R 2 ) ≥0.991. The intra- and inter-day accuracies (expressed as recovery percentage values) calculated using three spiking levels (5, 10, and 20 μg/kg) were 80-108.65 and 74.06-107.15%, respectively, and the precisions (expressed as relative standard deviation) were 2.86-13.67 and 0.05-11.74%, respectively, for the tested drugs determined in various matrices. The limits of quantification (1 and 2 μg/kg) were below the uniform residual level (0.01 mg/kg) set for compounds that have no specific maximum residue limit (MRL). The developed method was tested using market samples and none of the target analytes was detected in any of the samples. The validated method proved to be practicable for detection of the tested analytes in pork, milk, and eggs. Copyright © 2018 John Wiley & Sons, Ltd.

  9. THE PROCESS OF MASS TRANSFER ON THE SOLID-LIQUID BOUNDARY LAYER DURING THE RELEASE OF DICLOFENAC SODIUM AND PAPAVERINE HYDROCHLORIDE FROM TABLETS IN A PADDLE APPARATUS.

    PubMed

    Kasperek, Regina; Zimmer, Lukasz; Poleszak, Ewa

    2016-01-01

    The release study of diclofenac sodium (DIC) and papaverine hydrochloride (PAP) from two formulations of the tablets in the paddle apparatus using different rotation speeds to characterize the process of mass transfer on the solid-liquid boundary layer was carried out. The dissolution process of active substances was described by values of mass transfer coefficients, the diffusion boundary layer thickness and dimensionless numbers (Sh and Re). The values of calculated parameters showed that the release of DIC and PAP from tablets comprising potato starch proceeded faster than from tablets containing HPMC and microcrystalline cellulose. They were obtained by direct dependencies between Sh and Re in the range from 75 rpm to 125 rpm for both substances from all tablets. The description of the dissolution process with the dimensionless numbers make it possible to plan the drug with the required release profile under given in vitro conditions.

  10. Parecoxib sodium in the treatment of postoperative pain after Lichtenstein tension-free mesh inguinal hernia repair.

    PubMed

    Kyriakidis, A V; Perysinakis, I; Alexandris, I; Athanasiou, K; Papadopoulos, Ch; Mpesikos, I

    2011-02-01

    This prospective, randomized, double-blind study compared the analgesic efficacy and safety of parecoxib sodium versus lornoxicam and diclofenac, after Lichtenstein tension-free mesh inguinal hernia repair. Patients were randomly assigned to receive parecoxib 80 mg daily i.v. (Group A), lornoxicam 16 mg daily i.v. (Group B) or diclofenac 150 mg daily i.m. (Group C). Rescue analgesia in all groups consisted of pethidine 25 mg i.m. Pain was measured with an analogue scale (pain intensity score). Patients treated with parecoxib 80 mg reported significantly lower summed pain intensity scores compared with lornoxicam and diclofenac-treated patients. Duration of analgesia was also significantly longer with parecoxib than with lornoxicam and diclofenac. Adverse events were significantly less common in the parecoxib and lornoxicam group, compared with diclofenac group. Multiple-day administration of parecoxib 40 mg twice daily is more effective than equivalent doses of lornoxicam and diclofenac, and generally better tolerated than diclofenac after Lichtenstein tension-free mesh inguinal hernia repair.

  11. Computational insights into the photocyclization of diclofenac in solution: effects of halogen and hydrogen bonding.

    PubMed

    Bani-Yaseen, Abdulilah Dawoud

    2016-08-21

    The effects of noncovalent interactions, namely halogen and hydrogen bonding, on the photochemical conversion of the photosensitizing drug diclofenac (DCF) in solution were investigated computationally. Both explicit and implicit solvent effects were qualitatively and quantitatively assessed employing the DFT/6-31+G(d) and SQM(PM7) levels of theory. Full geometry optimizations were performed in solution for the reactant DCF, hypothesized radical-based intermediates, and the main product at both levels of theories. Notably, in good agreement with previous experimental results concerning the intermolecular halogen bonding of DCF, the SQM(PM7) method revealed different values for d(ClO, Å) and ∠(C-ClO, °) for the two chlorine-substituents of DCF, with values of 2.63 Å/162° and 3.13 Å/142° for the trans and cis orientations, respectively. Employing the DFT/6-31+G(d) method with implicit solvent effects was not conclusive; however, explicit solvent effects confirmed the key contribution of hydrogen and halogen bonding in stabilizing/destabilizing the reactant and hypothesized intermediates. Interestingly, the obtained results revealed that a protic solvent such as water can increase the rate of photocyclization of DCF not only through hydrogen bonding effects, but also through halogen bonding. Furthermore, the atomic charges of atoms majorly involved in the photocyclization of DCF were calculated using different methods, namely Mulliken, Hirshfeld, and natural bond orbital (NBO). The obtained results revealed that in all cases there is a notable nonequivalency in the noncovalent intermolecular interactions of the two chlorine substituents of DCF and the radical intermediates with the solvent, which in turn may account for the discrepancy of their reactivity in different media. These computational results provide insight into the importance of halogen and hydrogen bonding throughout the progression of the photochemical conversion of DCF in solution.

  12. Generic method for the absolute quantification of glutathione S-conjugates: Application to the conjugates of acetaminophen, clozapine and diclofenac.

    PubMed

    den Braver, Michiel W; Vermeulen, Nico P E; Commandeur, Jan N M

    2017-03-01

    Modification of cellular macromolecules by reactive drug metabolites is considered to play an important role in the initiation of tissue injury by many drugs. Detection and identification of reactive intermediates is often performed by analyzing the conjugates formed after trapping by glutathione (GSH). Although sensitivity of modern mass spectrometrical methods is extremely high, absolute quantification of GSH-conjugates is critically dependent on the availability of authentic references. Although 1 H NMR is currently the method of choice for quantification of metabolites formed biosynthetically, its intrinsically low sensitivity can be a limiting factor in quantification of GSH-conjugates which generally are formed at low levels. In the present study, a simple but sensitive and generic method for absolute quantification of GSH-conjugates is presented. The method is based on quantitative alkaline hydrolysis of GSH-conjugates and subsequent quantification of glutamic acid and glycine by HPLC after precolumn derivatization with o-phthaldialdehyde/N-acetylcysteine (OPA/NAC). Because of the lower stability of the glycine OPA/NAC-derivate, quantification of the glutamic acid OPA/NAC-derivate appeared most suitable for quantification of GSH-conjugates. The novel method was used to quantify the concentrations of GSH-conjugates of diclofenac, clozapine and acetaminophen and quantification was consistent with 1 H NMR, but with a more than 100-fold lower detection limit for absolute quantification. Copyright © 2017. Published by Elsevier B.V.

  13. Bacterial β-glucuronidase inhibition protects mice against enteropathy induced by indomethacin, ketoprofen or diclofenac: mode of action and pharmacokinetics

    PubMed Central

    Saitta, Kyle S.; Zhang, Carmen; Lee, Kang Kwang; Fujimoto, Kazunori; Redinbo, Matthew R.; Boelsterli, Urs A.

    2014-01-01

    We have previously demonstrated that a small molecule inhibitor of bacterial β-glucuronidase (Inh-1; [1-((6,8-dimethyl-2-oxo-1,2-dihydroquinolin-3-yl)-3-(4-ethoxyphenyl)-1-(2-hydroxyethyl)thiourea]) protected mice against diclofenac (DCF)-induced enteropathy. Here we report that Inh-1 was equally protective against small intestinal injury induced by other carboxylic acid-containing non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin (10 mg/kg, ip) and ketoprofen (100 mg/kg, ip).Inh-1 provided complete protection if given prior to DCF (60 mg/kg, ip), and partial protection if administered 3-h post-DCF, suggesting that the temporal window of mucosal protection can be extended for drugs undergoing extensive enterohepatic circulation.Pharmacokinetic analysis of Inh-1 revealed an absolute bioavailability (F) of 21% and a short t1/2 of <1 h. This low F was shown to be due to hepatic first-pass metabolism, as confirmed with the pan-CYP inhibitor, 1-aminobenzotriazole.Using the fluorescent probe 5 (and 6)-carboxy-2′,7′-dichlorofluorescein, we demonstrated that Inh-1 did not interfere with hepatobiliary export of glucuronides in gall bladder-cannulated mice.These data are compatible with the hypothesis that pharmacological inhibition of bacterial β-glucuronidase-mediated cleavage of NSAID glucuronides in the small intestinal lumen can protect against NSAID-induced enteropathy caused by locally high concentrations of NSAID aglycones. PMID:23829165

  14. Inhibition of striatal cholinergic interneuron activity by the Kv7 opener retigabine and the nonsteroidal anti-inflammatory drug diclofenac.

    PubMed

    Paz, Rodrigo Manuel; Tubert, Cecilia; Stahl, Agostina; Díaz, Analía López; Etchenique, Roberto; Murer, Mario Gustavo; Rela, Lorena

    2018-05-11

    Striatal cholinergic interneurons provide modulation to striatal circuits involved in voluntary motor control and goal-directed behaviors through their autonomous tonic discharge and their firing "pause" responses to novel and rewarding environmental events. Striatal cholinergic interneuron hyperactivity was linked to the motor deficits associated with Parkinson's disease and the adverse effects of chronic antiparkinsonian therapy like l-DOPA-induced dyskinesia. Here we addressed whether Kv7 channels, which provide negative feedback to excitation in other neuron types, are involved in the control of striatal cholinergic interneuron tonic activity and response to excitatory inputs. We found that autonomous firing of striatal cholinergic interneurons is not regulated by Kv7 channels. In contrast, Kv7 channels limit the summation of excitatory postsynaptic potentials in cholinergic interneurons through a postsynaptic mechanism. Striatal cholinergic interneurons have a high reserve of Kv7 channels, as their opening using pharmacological tools completely silenced the tonic firing and markedly reduced their intrinsic excitability. A strong inhibition of striatal cholinergic interneurons was also observed in response to the anti-inflammatory drugs diclofenac and meclofenamic acid, however, this effect was independent of Kv7 channels. These data bring attention to new potential molecular targets and pharmacological tools to control striatal cholinergic interneuron activity in pathological conditions where they are believed to be hyperactive, including Parkinson's disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Relationship between the structure of Fe-MCM-48 and its activity in catalytic ozonation for diclofenac mineralization.

    PubMed

    Li, Xukai; Chen, Weirui; Tang, Yiming; Li, Laisheng

    2018-05-12

    Fe-MCM-48 catalyst with a three-dimensional cubic pore structure was directly synthesized via a hydrothermal method, and the mineralization efficiency of diclofenac (DCF) in the catalytic ozonation process (Fe-MCM-48/O 3 ) was assessed. X-ray diffraction (XRD), N 2 adsorption desorption, transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) characterizations revealed that Fe existed in the framework of MCM-48, and Fe-MCM-48 possessed a large surface area and a highly ordered cubic mesoporous structure, which could accelerate reactants and products diffusion. Regarding mineralization efficiency, the addition of Fe-MCM-48 significantly improved total organic carbon (TOC) removal, and approximately 49.9% TOC were removed through the Fe-MCM-48/O 3 process at 60 min, which was 2.0 times higher than that in single ozonation. Due to this catalyst's superior structure, Fe-MCM-48 showed the better catalytic activity compared with Fe-MCM-41 and Fe loaded MCM-48 (Fe/MCM-48, Fe existed on the surface of MCM-48). DCF removal in the Fe-MCM-48/O 3 process was primarily based on ozone direct oxidation. The improvement of mineralization efficiency was attributed to the function of generated hydroxyl radicals (•OH), which indicated that the presence of Fe-MCM-48 accelerated ozone decomposition. Moreover, the negatively charged surface of Fe-MCM-48 and the proper pH value of the DCF solution played an essential role in OH generation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Formulation and evaluation of diclofenac controlled release matrix tablets made of HPMC and Poloxamer 188 polymer: An assessment on mechanism of drug release.

    PubMed

    Al-Hanbali, Othman A; Hamed, Rania; Arafat, Mosab; Bakkour, Youssef; Al-Matubsi, Hisham; Mansour, Randa; Al-Bataineh, Yazan; Aldhoun, Mohammad; Sarfraz, Muhammad; Dardas, Abdel Khaleq Yousef

    2018-01-01

    In this study, hydrophilic hydroxypropyl methylcellulose matrices with various concentrations of Poloxamer 188 were used in the development of oral controlled release tablets containing diclofenac sodium. Four formulations of hydrophilic matrix tablets containing 16.7% w/w HPMC and 0, 6.7, 16.7 and 25.0% w/w Poloxamer 188, respectively, were developed. Tablets were prepared by direct compression and characterized for diameter, hardness, thickness, weight and uniformity of content. The influence of various blends of hydroxypropyl methylcellulose and Poloxamer 188 on the in vitro dissolution profile and mechanism of drug release of was investigated. In the four formulations, the rate of drug release decreased with increasing the concentration of Poloxamer 188 at the initial dissolution stages due to the increase in the apparent viscosity of the gel diffusion layer. However, in the late dissolution stages, the rate of drug release increased with increasing Poloxamer 188 concentration due to the increase in wettability and dissolution of the matrix. The kinetic of drug release from the tablets followed non-Fickian mechanism, as predicted by Korsmeyer-Peppas model, which involves diffusion through the gel layer and erosion of the matrix system.

  17. Comparative study between three analgesic agents for the pain management during extracorporeal shock wave lithotripsy.

    PubMed

    Liu, Jianjun; Zang, Yun-Jiang

    2013-09-26

    To compare the clinical efficacy between locally applied diclofenac diethylamine gel, EMLA cream and systemically given diclofenac sodium for the pain relief during extracorporeal shock wave lithotripsy (SWL) using Dornier Delta Compact Lithotripter. One hundred five patients with renal stones were randomly divided in to 3 groups. Group A was given intramuscular diclofenac sodium (1 mg/kg), 45 minutes before the procedure. In group B, 10 gm of eutectic mixture of local anesthetic (EMLA) cream and in group C, 15 gm of diclofenac diethylamine gel was applied locally 45 minutes before the procedure. Ten-score linear and visual analogue scale (VAS) was used to assess the severity of pain during the procedure. Analysis of variance (ANOVA) test was used to compare various parameters and analyzed statistically. All the three groups were not statistically different with respect to age, weight, stone size, number of shock wave delivered and maximum voltage used (P > .05). The mean pain score in group A was 4.48, in group B was 3.60 and in group C was 3.95, which were not significantly different (P = 1.34). Complication like skin lesion was found only in injection diclofenac sodium group whereas cold sensation at the local site was typically found in diclofenac diethylamine gel group. Although not statistically significant, the mean pain score in locally applied analgesic agents (EMLA and diclofenac diethylamine gel) is lower as compared to intramuscularly given diclofenac sodium. Among these two locally acting drugs, diclofenac diethylamine gel is an equally effective alternative to EMLA.

  18. Diclofenac enhances proinflammatory cytokine-induced nitric oxide production through NF-{kappa}B signaling in cultured astrocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kakita, Hiroki; Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601; Department of Neonatology, Aichi Human Service Center Central Hospital, 713-8 Kamiya-Cho, Kasugai 480-0392

    2009-07-01

    Recently, the number of reports of encephalitis/encephalopathy associated with influenza virus has increased. In addition, the use of a non-steroidal anti-inflammatory drug, diclofenac sodium (DCF), is associated with a significant increase in the mortality rate of influenza-associated encephalopathy. Activated astrocytes are a source of nitric oxide (NO), which is largely produced by inducible NO synthase (iNOS) in response to proinflammatory cytokines. Therefore, we investigated whether DCF enhances nitric oxide production in astrocytes stimulated with proinflammatory cytokines. We stimulated cultured rat astrocytes with three cytokines, interleukin-1{beta}, tumor necrosis factor-{alpha} and interferon-{gamma}, and then treated the astrocytes with DCF or acetaminophen (N-acetyl-p-aminophenol:more » APAP). iNOS and NO production in astrocyte cultures were induced by proinflammatory cytokines. The addition of DCF augmented NO production, but the addition of APAP did not. NF-{kappa}B inhibitors SN50 and MG132 inhibited iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. Similarly, NF-{kappa}B p65 Stealth small interfering RNA suppressed iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. LDH activity and DAPI staining showed that DCF induces cell damage in cytokine-stimulated astrocytes. An iNOS inhibitor, L-NMMA, inhibited the cytokine- and DCF-induced cell damage. In conclusion, this study demonstrates that iNOS and NO are induced in astrocyte cultures by proinflammatory cytokines. Addition of DCF further augments NO production. This effect is mediated via NF-{kappa}B signaling and leads to cell damage. The enhancement of DCF on NO production may explain the significant increase in the mortality rate of influenza-associated encephalopathy in patients treated with DCF.« less

  19. Microwave-assisted activated carbon from cocoa shell as adsorbent for removal of sodium diclofenac and nimesulide from aqueous effluents.

    PubMed

    Saucier, Caroline; Adebayo, Matthew A; Lima, Eder C; Cataluña, Renato; Thue, Pascal S; Prola, Lizie D T; Puchana-Rosero, M J; Machado, Fernando M; Pavan, Flavio A; Dotto, G L

    2015-05-30

    Microwave-induced chemical activation process was used to prepare an activated carbon from cocoa shell for efficient removal of two anti-inflammatories, sodium diclofenac (DFC) and nimesulide (NM), from aqueous solutions. A paste was obtained from a mixture of cocoa shell and inorganic components; with a ratio of inorganic: organic of 1 (CSC-1.0). The mixture was pyrolyzed in a microwave oven in less than 10 min. The CSC-1.0 was acidified with a 6 mol L(-1) HCl under reflux to produce MWCS-1.0. The CSC-1.0 and MWCS-1.0 were characterized using FTIR, SEM, N2 adsorption/desorption curves, X-ray diffraction, and point of zero charge (pHpzc). Experimental variables such as initial pH of the adsorbate solutions and contact time were optimized for adsorptive characteristics of MWCS-1.0. The optimum pH for removal of anti-inflammatories ranged between 7.0 and 8.0. The kinetic of adsorption was investigated using general order, pseudo first-order and pseu do-second order kinetic models. The maximum amounts of DCF and NM adsorbed onto MWCS-1.0 at 25 °C are 63.47 and 74.81 mg g(-1), respectively. The adsorbent was tested on two simulated hospital effluents. MWCS-1.0 is capable of efficient removal of DCF and NM from a medium that contains high sugar and salt concentrations. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Enhanced Oxidative and Adsorptive Removal of Diclofenac in Heterogeneous Fenton-like Reaction with Sulfide Modified Nanoscale Zerovalent Iron.

    PubMed

    Su, Yiming; Jassby, David; Song, Shikun; Zhou, Xuefei; Zhao, Hongying; Filip, Jan; Petala, Eleni; Zhang, Yalei

    2018-06-05

    Sulfidation of nanoscale zerovalent iron (nZVI) has shown some fundamental improvements on reactivity and selectivity toward pollutants in dissolved-oxygen (DO)-stimulated Fenton-like reaction systems (DO/S-nZVI system). However, the pristine microstructure of sulfide-modified nanoscale zerovalent iron (S-nZVI) remains uncovered. In addition, the relationship between pollutant removal and the oxidation of the S-nZVI is largely unknown. The present study confirms that sulfidation not only imparts sulfide and sulfate groups onto the surface of the nanoparticle (both on the oxide shell and on flake-like structures) but also introduces sulfur into the Fe(0) core region. Sulfidation greatly inhibits the four-electron transfer pathway between Fe(0) and oxygen but facilitates the electron transfer from Fe(0) to surface-bound Fe(III) and consecutive single-electron transfer for the generation of H 2 O 2 and hydroxyl radical. In the DO/S-nZVI system, slight sulfidation (S/Fe molar ratio = 0.1) is able to nearly double the oxidative removal efficacy of diclofenac (DCF) (from 17.8 to 34.2%), whereas moderate degree of sulfidation (S/Fe molar ratio = 0.3) significantly enhances both oxidation and adsorption of DCF. Furthermore, on the basis of the oxidation model of S-nZVI, the DCF removal process can be divided into two steps, which are well modeled by parabolic and logarithmic law separately. This study bridges the knowledge gap between pollutant removal and the oxidation process of chemically modified iron-based nanomaterials.

  1. Effects of rebamipide on nephrotoxicity associated with selected NSAIDs in rats.

    PubMed

    Wood, Robert C; Wyatt, Jarrett E; Bullins, Kenny W; Hanley, Angela V; Hanley, Gregory A; Denham, James W; Panus, Peter C; Harirforoosh, Sam

    2013-11-15

    Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is primarily limited by renal and gastrointestinal adverse effects. Rebamipide suppresses gastric mucosal injury when administered with NSAIDs. This study aimed to determine rebamipide's influence upon renal effects following concomitant use with celecoxib or diclofenac. On day 0, rats were randomly divided into 6 groups (n≥6). On days 1 and 2, three groups received placebo and three groups were administered rebamipide (30 mg/kg) twice daily. On day 3, the rats treated with placebo received another dose of placebo and ten minutes later a single dose of celecoxib (40 mg/kg), diclofenac (10mg/kg), or placebo, respectively. The rats treated with rebamipide received one more dose of rebamipide and ten minutes later one single dose of celecoxib, diclofenac, or placebo, respectively. Urine and blood samples were collected on days 0, 2, and 3. Sodium and potassium excretion rates decreased significantly in the rats treated with celecoxib, diclofenac, rebamipide plus celecoxib, or rebamipide plus diclofenac on day 3. Blood urea nitrogen (BUN) levels significantly increased in placebo plus diclofenac and rebamipide plus diclofenac groups on day 3. Comparing the two groups, the levels of BUN was significantly higher in the rebamipide plus diclofenac group compared to that of placebo plus diclofenac group. Concomitant administration of rebamipide with either NSAID caused a rise in concentrations of urinary kidney injury molecule-1. Histopathological evaluations revealed an intensified NSAID-induced tubular necrosis by rebamipide. Based upon the results obtained, concomitant administration of rebamipide with NSAIDs enhances the effect of NSAIDs on tubular injury. © 2013 Elsevier B.V. All rights reserved.

  2. Preparation, optimisation and characterisation of novel wound healing film dressings loaded with streptomycin and diclofenac.

    PubMed

    Pawar, H V; Tetteh, J; Boateng, J S

    2013-02-01

    Streptomycin (STP) and diclofenac (DLF) loaded film dressings were prepared by blending Polyox(®) (POL) with four hydrophilic polymers [hydroxypropylmethylcellulose (HPMC), carrageenan (CAR), sodium alginate (SA) or chitosan (CS)] using glycerol (GLY) as plasticiser. The films were characterised by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy, texture analysis (tensile and swelling characteristics) and in vitro dissolution profiles using Franz diffusion cell. SEM showed homogeneous morphology for both blank (BLK) and drug loaded (DL) films. Films prepared by blending of POL with the other polymers showed a reduction in the crystallisation of POL in descending order of SA>CS>HPMC>CAR respectively. DSC and XRD showed no crystalline peaks of STP and DLF suggesting molecular dispersion of both drugs as well as possible drug interaction with negatively charged sulphate ions present in CAR. The DL films did not show any IR bands of both drugs, confirming the DSC and XRD results. POL-CAR-BLK films showed higher tensile strength (12.32±1.40 MPa) than the POL-CAR-DL films (9.52±1.12 MPa). DL films plasticised with 25%w/w GLY revealed soft and tough (tensile strength 1.02±0.28 MPa, % elongation 1031.33±16.23) formulations. The swelling capacities of POL-CAR-BLK and POL-CAR-DL films were (733.17±25.78%) and (646.39±40.39%), increasing to (1072.71±80.30%) and (1051±86.68%) for POL-CAR-BLK-25% GLY and POL-CAR-DL-25% GLY respectively. POL-CAR-DL films showed significantly (n=3, p<0.0318) lower cumulative release of STP and DLF (52.11±1.34, 55.26±2.25) compared to POL-CAR-DL-25% GLY films (60.07±1.56, 63.39±1.92) respectively. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. ADMINISTRATION OF H2 BLOCKERS IN NSAID INDUCED GASTROPATHY IN RATS: effect on histopathological changes in gastric, hepatic and renal tissues.

    PubMed

    Manocha, Sachin; Lal, Dushyant; Venkataraman, Subramanian

    2016-01-01

    Nonsteroidal anti-inflammatory drugs induces gastric mucosal lesions because of its acidic properties. Ranitidine, an H2 receptor antagonist, has proved beneficial in patients with gastric ulcers. The present study was performed to assess the effect of administering ranitidine in Nonsteroidal anti-inflammatory drugs (diclofenac, nimesulide) induced gastropathy, and their effect on the histopathology of stomach, kidney and liver. Diclofenac, nimesulide, and ranitidine were administered in doses of 2, 4, and 6 mg/kg, p.o. once daily for 14 days, and their effect on gastric volume, acidity, mean ulcer number, and gastric pH. In addition, histopathological examination was also performed on sections of stomach, kidney and liver. Following the administration of diclofenac or nimesulide, all the gastric parameters were significantly altered as well as the histopathology of stomach, liver and kidney. In the control group, the renal sections showed normal glomeruli with no thickening of glomerular basement membrane, while in diclofenac alone, nimesulide alone, and ranitidine with nimesulide groups, the thickening of glomerular basement membrane was observed. These alterations were observed to be reversed in the ranitidine with diclofenac group. In the sections from the liver, the control group showed anastomosing plates and cords of cuboidal hepatocytes with round well stained nuclei and abundant cytoplasm. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, mild dilatation of sinusoids is seen coupled with prominence of central vein. In the diclofenac alone and nimesulide alone groups, the proximal and distal convoluted tubules show mild focal tubular necrosis. In the gastric sections, the control group showed several folds forming villi, and the epithelial lining surface of the mucosa. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, the duodenum showed scattered inflammatory cells composed predominantly of lymphocytes. In

  4. Evaluation of the effect of quercetin treatment on CYP2C9 enzyme activity of diclofenac in healthy human volunteers.

    PubMed

    Bedada, Satish Kumar; Neerati, Prasad

    2018-02-01

    The purpose of present study was to evaluate the effect of quercetin on pharmacokinetics of diclofenac sodium (DIC) in healthy volunteers. The open-label, 2 period, sequential study was conducted in 12 healthy volunteers. DIC 100 mg was administered during control and after quercetin phases. Quercetin 500 mg was administered twice daily for 10 days during quercetin phase. Treatment with quercetin significantly enhanced maximum plasma concentration (C max ) , area under the curve (AUC 0-∞ ), and half life, while significantly decreased elimination rate constant (k el ) and apparent oral clearance (CL/F) of DIC compared with control. On the other hand, C max and AUC 0-∞ of 4-hydroxydiclofenac (4-OHDIC) were decreased after quercetin treatment. In addition, geometric mean ratios and 90% confidence intervals for C max and AUC 0-∞ of DIC and 4-OHDIC were both out of the no-effect limits of 0.80-1.25, which indicates a significant pharmacokinetic interaction between quercetin and DIC. Furthermore, quercetin treatment significantly decreased metabolic ratios of C max and AUC 0-∞ suggesting that reduced formation of DIC to 4-OHDIC. The results suggest that quercetin might have inhibited CYP2C9-mediated metabolism of DIC. Accordingly, caution should be taken when quercetin is used in combination with therapeutic drugs metabolized by CYP2C9, and dose adjustment of CYP2C9 substrates may be necessary. Copyright © 2017 John Wiley & Sons, Ltd.

  5. An ultrasensitive electrochemiluminescent immunosensor based on graphene oxide coupled graphite-like carbon nitride and multiwalled carbon nanotubes-gold for the detection of diclofenac.

    PubMed

    Hu, Liuyi; Zheng, Jing; Zhao, Kang; Deng, Anping; Li, Jianguo

    2018-03-15

    In this study, a novel competition-type electrochemiluminescent (ECL) immunosensor for detecting diclofenac (DCF) was fabricated with graphene oxide coupled graphite-like carbon nitride (GO-g-C 3 N 4 ) as signal probe for the first time. The ECL intensity of carboxylated g-C 3 N 4 was significantly enhanced after being combined with graphene oxide (GO) which exhibited excellent charge-transport property. The sensing platform was constructed by multiwalled carbon nanotubes and gold nanoparticles (MWCNTs-AuNPs), which not only provided an effective matrix for immobilizing a large amount of coating antigen but also facilitated the electronic transmission rate to enhance the ECL intensity. Based on the synergistic effect of GO-g-C 3 N 4 and MWCNTs-AuNPs composite, the proposed sensor showed high sensitivity, good stability, and wide linearity for the detection of DCF in the range of 0.005-1000ngmL -1 with a detection limit of 1.7pgmL -1 . Furthermore, the developed immunoassay has been applied to real samples with satisfactory results. Therefore, this work provided a promising method for the detection of DCF and other small molecular compounds in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Preparation of a magnetic N-Fe/AC catalyst for aqueous pharmaceutical treatment in heterogeneous sonication system.

    PubMed

    Zhang, Nan; Zhao, He; Zhang, Guangming; Chong, Shan; Liu, Yucan; Sun, Liyan; Chang, Huazhen; Huang, Ting

    2017-02-01

    High efficiency and facile separation are desirable for catalysts used in water treatment. In this study, a magnetic catalyst (nitrogen doped iron/activated carbon) was prepared and used for pharmaceutical wastewater treatment. The catalyst was characterized using BET, SEM, XRD, VSM and XPS. Results showed that iron and nitrogen were successfully loaded and doped, magnetic Fe 2 N was formed, large amount of active surface oxygen and Fe(II) were detected, and the catalyst could be easily separated from water. Diclofenac was then degraded using the catalyst in ultrasound system. The catalyst showed high catalytic activity with 95% diclofenac removal. Analysis showed that ·OH attack of diclofenac was a main pathway, and then ·OH generation mechanism was clarified. The effects of catalyst dosage, sonication time, ultrasonic density, initial pH, and inorganic anions on diclofenac degradation were studied. Sulfate anion enhanced the degradation of diclofenac. Mechanism in the catalytic ultrasonic process was analyzed and reactions were clarified. Large quantity of oxidants was generated on the catalyst surface, including ·OH, O 2 - , O - and HO 2 ·, which degraded diclofenac efficiently. In the solution and interior of cavitation bubbles, ·OH and "hot spot" effects contributed to the degradation of diclofenac. Reuse of the catalyst was further investigated to enhance its economy, and the catalyst maintained activity after seven uses. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Development of gellan gum containing formulations for transdermal drug delivery: Component evaluation and controlled drug release using temperature responsive nanogels.

    PubMed

    Carmona-Moran, Carlos A; Zavgorodnya, Oleksandra; Penman, Andrew D; Kharlampieva, Eugenia; Bridges, S Louis; Hergenrother, Robert W; Singh, Jasvinder A; Wick, Timothy M

    2016-07-25

    Enhancing skin permeation is important for development of new transdermal drug delivery formulations. This is particularly relevant for non-steroidal anti-inflammatory drugs (NSAIDs). To address this, semisolid gel and solid hydrogel film formulations containing gellan gum as a gelling agent were developed and the effects of penetration enhancers (dimethyl sulfoxide, isopropyl alcohol and propylene glycol) on transport of the NSAID diclofenac sodium was quantified. A transwell diffusion system was used to accelerate formulation development. After 4h, diclofenac flux from a superior formulation of the semisolid gel or the solid hydrogel film was 130±11μg/cm(2)h and 108±7μg/cm(2)h, respectively, and significantly greater than that measured for a currently available diclofenac sodium topical gel (30±4μg/cm(2)h, p<0.05) or solution formulation (44±6μg/cm(2)h, p<0.05) under identical conditions. Over 24h diclofenac transport from the solid hydrogel film was greater than that measured for any new or commercial diclofenac formulation. Entrapment of temperature-responsive nanogels within the solid hydrogel film provides temperature-activated prolonged release of diclofenac. Diclofenac transport was minimal at 22°C, when diclofenac is entrapped within temperature-responsive nanogels incorporated into the solid hydrogel film, but increased 6-fold when the temperature was increased to skin surface temperature of 32°C. These results demonstrate the feasibility of the semisolid gel and solid hydrogel film formulations that can include thermo-responsive nanogels for development of transdermal drug formulations with adjustable drug transport kinetics. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Stability of Atenolol, Clonazepam, Dexamethasone, Diclofenac Sodium, Diltiazem, Enalapril Maleate, Ketoprofen, Lamotrigine, Penicillamine-D, and Thiamine in SyrSpend SF PH4 Oral Suspensions.

    PubMed

    Polonini, Hudson C; Loures, Sharlene; Lima, Luis Claudio; Ferreira, Anderson O; Brandão, Marcos Antônio F

    2016-01-01

    The objective of this study was to evaluate the stability of 10 commonly used active pharmaceutical ingredients compounded in oral suspensions using SyrSpend SF PH4 (atenolol 1.0 and 5.0 mg/mL, clonazepam 0.2 mg/mL, dexamethasone 1.0 mg/mL, diclofenac sodium 5.0 mg/mL, diltiazem 12.0 mg/mL, enalapril maleate 1.0 mg/mL, ketoprofen 20.0 mg/mL, lamotrigine 1.0 mg/mL, penicillamine-D 50.0 mg/mL, thiamine 100 mg/m) and stored both at controlled refrigerated (2°C to 8°C) and room temperature (20°C to 25°C). Stability was assessed by means of measuring percent recovery at varying time points throughout a 90-day period. The quantification of the active pharmaceutical ingredients was performed by a stability-indicating, high-performance liquid chromatographic method. The beyond-use date of the products was found to be at least 90 days for all suspensions (except atenolol 1 mg/mL, which was stable up to 60 days), both for controlled refrigerated temperature and room temperature. This confirms that SyrSpend SF PH4 is a stable suspending vehicle for compounding with a broad range of different active pharmaceutical ingredients.

  9. Pharmacokinetic interactions between rebamipide and selected nonsteroidal anti-inflammatory drugs in rats.

    PubMed

    Cooper, Dustin L; Wood, Robert C; Wyatt, Jarrett E; Harirforoosh, Sam

    2014-03-12

    Nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal and renal side effects. Rebamipide is a mucoprotective agent that reduces gastrointenstinal side effects when administered concomitantly with NSAIDs. In this study, we investigated the pharmacokinetic drug interactions of rebamipide with two selected NSAIDs, celecoxib or diclofenac. Rats were randomly divided into five groups. Two groups received placebo and three groups were administered rebamipide (30 mg/kg) orally twice daily for two days. On day 3, the animals treated with placebo received celecoxib (40 mg/kg) or diclofenac (10mg/kg) and rats receiving rebamipide were administerd rebamipide followed by a single dose of placebo, celecoxib, or diclofenac. To investigate drug protein interactions, blank rat plasma was spiked with known concentrations of rebamipide, diclofenac plus rebamipide, or celecoxib plus rebamipide then dialyzed through a Rapid Equilibrium Dialysis device. AUC (139.70±24.97 μg h/mL), Cmax (42.99±2.98 μg/mL), and CLoral (0.08±0.02 L/h/kg) values of diclofenac in diclofenac plus rebamipide group altered when compared to those of diclofenac treated groups. Treatment with rebamipide showed no significant change in pharmacokinetic parameters of celecoxib treated rats. Cmax (7.80±1.22 μg/mL), AUC (56.46±7.30 μg h/mL), Vd/F (7.55±1.37 L/kg), and CLoral (0.58±0.09 L/h/kg) of rebamipide were significantly altered when diclofenac was co-administered with rebamipide. Pharmacokinetic parameters of rebamipide plus celecoxib group were not significantly different from those of rebamipide group. Plasma protein binding was not affected by concomitant administration of another drug. These results indicate alteration of pharmacokinetic parameters of both rebamipide and diclofenac when co-administered and cannot be explained by a variation in plasma protein binding. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Photocatalytic behaviour of WO3/TiO2-N for diclofenac degradation using simulated solar radiation as an activation source.

    PubMed

    Cordero-García, A; Turnes Palomino, G; Hinojosa-Reyes, L; Guzmán-Mar, J L; Maya-Teviño, L; Hernández-Ramírez, A

    2017-02-01

    In this study, the photocatalytic removal of an emerging contaminant, diclofenac (DCF) sodium, was performed using the nitrogen-doped WO 3 /TiO 2 -coupled oxide catalyst (WO 3 /TiO 2 -N). The catalyst synthesis was accomplished by a sol-gel method using tetrabutyl orthotitanate (C 16 H 36 O 4 Ti), ammonium p-tungstate [(NH 4 ) 10 H 2 W 12 O 42 ·4H 2 O] and ammonium nitrate (NH 4 NO 3 ) as the nitrogen source. For comparison, TiO 2 and WO 3 /TiO 2 were also prepared under similar conditions. Analysis by X-ray diffraction (XRD), N 2 adsorption-desorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM), diffuse reflectance UV-Vis spectroscopy (DRS) and X-ray photoelectron spectroscopy (XPS) were conducted to characterize the synthesized materials. The photocatalytic efficiency of the semiconductors was determined in a batch reactor irradiated with simulated solar light. Residual and mineralized DCF were quantified by high-performance liquid chromatography, total organic carbon analysis and ion exchange chromatography. The results indicated that the tungsten atoms were dispersed on the surface of TiO 2 as WO 3 . The partial substitution of oxygen by nitrogen atoms into the lattice of TiO 2 was an important factor to improve the photocatalytic efficiency of WO 3 /TiO 2 . Therefore, the best photocatalytic activity was obtained with the WO 3 /TiO 2 -N 0.18 catalyst, reaching 100% DCF transformation at 250 kJ m -2 and complete mineralization at 400 kJ m -2 of solar-accumulated energy.

  11. A novel approach for the preparation of highly loaded polymeric controlled release dosage forms of diltiazem HCl and diclofenac sodium.

    PubMed

    Kakish, Hanan F; Tashtoush, Bassam; Ibrahim, Hussein G; Najib, Naji M

    2002-07-01

    In this investigation, modified-release dosage forms of diltiazem HCl (DT) and diclofenac sodium (DS) were prepared. The development work comprised two main parts: (a) loading the drug into ethylene vinyl acetate (EVA) polymer, and (b) generation of a non-uniform concentration distribution of the drug within the polymer matrix. Phase separation technique was successfully used to load DT and DS into the polymer at significantly high levels, up to 81 and 76%, respectively. Size diameter of the resultant microspheres was between 1.6 and 2.0mm. Controlled-extraction of loaded microspheres and high vacuum freeze-drying were used to generate the non-uniform concentration distribution and to immobilize the new drug distribution within the matrix. Parameters controlling the different processes were investigated, and hence optimal processing conditions were used to prepare the dosage forms. Rates of drug release from the two dosage forms in water and in media having different pH were found to be constant for an appreciable length of time (>8h) followed by a slow decline; a characteristic of a non-Fickian diffusion process. Scanning electron microscopy studies suggested that the resultant release behavior was the outcome of the combined effects of the non-uniform distribution of the drug in the matrix and the apparent changes in the pores and surface characteristics of the microspheres. Comparison of release rate-time plots of dissolution data of marketed products with the newly developed dosage forms indicated the ability of the latter to sustain more zero order release.

  12. High-performance thin-layer chromatographic methods for the determination of febuxostat and febuxostat/diclofenac combination in human plasma.

    PubMed

    El-Yazbi, Fawzi A; Amin, Omayma A; El-Kimary, Eman I; Khamis, Essam F; Younis, Sameh E

    2018-06-01

    Two simple, sensitive and specific high-performance thin-layer chromatographic (HPTLC) methods were developed for the determination of febuxostat (FEB) individually, and simultaneously with diclofenac (DIC) in human plasma. Method A presents the first HPTLC-ultraviolet attempt for FEB determination in human plasma. FEB was separated from endogenous plasma components (at hR F  = 70) with ethyl acetate-methanol-water (9:2:1, v/v) mixture as mobile phase and quantified by densitometry at its λ max (315 nm). Method B is considered the first attempt for the simultaneous determination of FEB and DIC in human plasma. A mixture of petroleum ether-chloroform-ethyl acetate-formic acid (7.5:1:2.5:0.25, v/v) was used as the mobile phase. The two drugs were separated at hR F of 39 and 60 for FEB and DIC, respectively. FEB and DIC were quantified by densitometry at their isoabsorptive point (289 nm). FEB calibration plots were linear between 0.1 and 7 μg mL -1 in both methods A and B. In method B, DIC showed linear response in the range of 0.08-8 μg mL -1 . Sample preparation was performed by liquid-liquid extraction using diethyl ether. Both methods did not record any interference from plasma matrix, the studied drugs' metabolites or their decomposition products. They were successfully applied for the determination of the studied drugs in healthy male volunteers after oral administration of FEB or FEB/DIC dosage forms. FEB plasma concentration increased significantly when given with DIC. The proposed methods provided very simple, rapid and cheap approaches that might be attractive for the future pharmacokinetic and bioavailability studies of FEB and/or DIC. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Avian scavengers and the threat from veterinary pharmaceuticals

    PubMed Central

    Cuthbert, Richard J.; Taggart, Mark A.; Prakash, Vibhu; Chakraborty, Soumya S.; Deori, Parag; Galligan, Toby; Kulkarni, Mandar; Ranade, Sachin; Saini, Mohini; Sharma, Anil Kumar; Shringarpure, Rohan; Green, Rhys E.

    2014-01-01

    Veterinary use of the non-steroidal anti-inflammatory drug diclofenac on domesticated ungulates caused populations of resident Gyps vultures in the Indian sub-continent to collapse. The birds died when they fed on carrion from treated animals. Veterinary diclofenac was banned in 2006 and meloxicam was advocated as a ‘vulture-safe’ alternative. We examine the effectiveness of the 2006 ban, whether meloxicam has replaced diclofenac, and the impact of these changes on vultures. Drug residue data from liver samples collected from ungulate carcasses in India since 2004 demonstrate that the prevalence of diclofenac in carcasses in 2009 was half of that before the ban and meloxicam prevalence increased by 44%. The expected vulture death rate from diclofenac per meal in 2009 was one-third of that before the ban. Surveys at veterinary clinics show that diclofenac use in India began in 1994, coinciding with the onset of rapid Gyps declines ascertained from measured rates of declines. Our study shows that one pharmaceutical product has had a devastating impact on Asia's vultures. Large-scale research and survey were needed to detect, diagnose and quantify the problem and measure the response to remedial actions. Given these difficulties, other effects of pharmaceuticals in the environment may remain undetected. PMID:25405963

  14. Integrated Assessment of Diclofenac Biotransformation, Pharmacokinetics, and Omics-Based Toxicity in a Three-Dimensional Human Liver-Immunocompetent Coculture System

    PubMed Central

    Ravindra, Kodihalli C.; Large, Emma; Young, Carissa L.; Rivera-Burgos, Dinelia; Yu, Jiajie; Cirit, Murat; Hughes, David J.; Wishnok, John S.; Lauffenburger, Douglas A.; Griffith, Linda G.

    2017-01-01

    In vitro hepatocyte culture systems have inherent limitations in capturing known human drug toxicities that arise from complex immune responses. Therefore, we established and characterized a liver immunocompetent coculture model and evaluated diclofenac (DCF) metabolic profiles, in vitro–in vivo clearance correlations, toxicological responses, and acute phase responses using liquid chromatography–tandem mass spectrometry. DCF biotransformation was assessed after 48 hours of culture, and the major phase I and II metabolites were similar to the in vivo DCF metabolism profile in humans. Further characterization of secreted bile acids in the medium revealed that a glycine-conjugated bile acid was a sensitive marker of dose-dependent toxicity in this three-dimensional liver microphysiological system. Protein markers were significantly elevated in the culture medium at high micromolar doses of DCF, which were also observed previously for acute drug-induced toxicity in humans. In this immunocompetent model, lipopolysaccharide treatment evoked an inflammatory response that resulted in a marked increase in the overall number of acute phase proteins. Kupffer cell–mediated cytokine release recapitulated an in vivo proinflammatory response exemplified by a cohort of 11 cytokines that were differentially regulated after lipopolysaccharide induction, including interleukin (IL)-1β, IL-1Ra, IL-6, IL-8, IP-10, tumor necrosis factor-α, RANTES (regulated on activation normal T cell expressed and secreted), granulocyte colony-stimulating factor, macrophage colony-stimulating factor, macrophage inflammatory protein-1β, and IL-5. In summary, our findings indicate that three-dimensional liver microphysiological systems may serve as preclinical investigational platforms from the perspective of the discovery of a set of clinically relevant biomarkers including potential reactive metabolites, endogenous bile acids, excreted proteins, and cytokines to predict early drug

  15. Avian scavengers and the threat from veterinary pharmaceuticals.

    PubMed

    Cuthbert, Richard J; Taggart, Mark A; Prakash, Vibhu; Chakraborty, Soumya S; Deori, Parag; Galligan, Toby; Kulkarni, Mandar; Ranade, Sachin; Saini, Mohini; Sharma, Anil Kumar; Shringarpure, Rohan; Green, Rhys E

    2014-11-19

    Veterinary use of the non-steroidal anti-inflammatory drug diclofenac on domesticated ungulates caused populations of resident Gyps vultures in the Indian sub-continent to collapse. The birds died when they fed on carrion from treated animals. Veterinary diclofenac was banned in 2006 and meloxicam was advocated as a 'vulture-safe' alternative. We examine the effectiveness of the 2006 ban, whether meloxicam has replaced diclofenac, and the impact of these changes on vultures. Drug residue data from liver samples collected from ungulate carcasses in India since 2004 demonstrate that the prevalence of diclofenac in carcasses in 2009 was half of that before the ban and meloxicam prevalence increased by 44%. The expected vulture death rate from diclofenac per meal in 2009 was one-third of that before the ban. Surveys at veterinary clinics show that diclofenac use in India began in 1994, coinciding with the onset of rapid Gyps declines ascertained from measured rates of declines. Our study shows that one pharmaceutical product has had a devastating impact on Asia's vultures. Large-scale research and survey were needed to detect, diagnose and quantify the problem and measure the response to remedial actions. Given these difficulties, other effects of pharmaceuticals in the environment may remain undetected. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  16. Solar photolysis versus TiO2-mediated solar photocatalysis: a kinetic study of the degradation of naproxen and diclofenac in various water matrices.

    PubMed

    Kanakaraju, Devagi; Motti, Cherie A; Glass, Beverley D; Oelgemöller, Michael

    2016-09-01

    Given that drugs and their degradation products are likely to occur as concoctions in wastewater, the degradation of a mixture of two nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac (DCF) and naproxen (NPX), was investigated by solar photolysis and titanium dioxide (TiO2)-mediated solar photocatalysis using an immersion-well photoreactor. An equimolar ratio (1:1) of both NSAIDs in distilled water, drinking water, and river water was subjected to solar degradation. Solar photolysis of the DCF and NPX mixture was competitive particularly in drinking water and river water, as both drugs have the ability to undergo photolysis. However, the addition of TiO2 in the mixture significantly enhanced the degradation rate of both APIs compared to solar photolysis alone. Mineralization, as measured by chemical oxygen demand (COD), was incomplete under all conditions investigated. TiO2-mediated solar photocatalytic degradation of DCF and NPX mixtures produced 15 identifiable degradants corresponding to degradation of the individual NSAIDs, while two degradation products with much higher molecular weight than the parent NSAIDs were identified by liquid chromatography mass spectrometry (LC-MS) and Fourier transform-ion cyclotron resonance-mass spectrometry (FT-ICR-MS). This study showed that the solar light intensity and the water matrix appear to be the main factors influencing the overall performance of the solar photolysis and TiO2-mediated solar photocatalysis for degradation of DCF and NPX mixtures.

  17. A novel stability-indicating UPLC method development and validation for the determination of seven impurities in various diclofenac pharmaceutical dosage forms.

    PubMed

    Azougagh, M; Elkarbane, M; Bakhous, K; Issmaili, S; Skalli, A; Iben Moussad, S; Benaji, B

    2016-09-01

    An innovative simple, fast, precise and accurate ultra-high performance liquid chromatography (UPLC) method was developed for the determination of diclofenac (Dic) along with its impurities including the new dimer impurity in various pharmaceutical dosage forms. An Acquity HSS T3 (C18, 100×2.1mm, 1.8μm) column in gradient mode was used with mobile phase comprising of phosphoric acid, which has a pH value of 2.3 and methanol. The flow rate and the injection volume were set at 0.35ml·min(-1) and 1μl, respectively, and the UV detection was carried out at 254nm by using photodiode array detector. Dic was subjected to stress conditions from acid, base, hydrolytic, thermal, oxidative and photolytic degradation. The new developed method was successfully validated in accordance to the International Conference on Harmonization (ICH) guidelines with respect to specificity, limit of detection, limit of quantitation, precision, linearity, accuracy and robustness. The degradation products were well resolved from main peak and its seven impurities, proving the specificity power of the method. The method showed good linearity with consistent recoveries for Dic content and its impurities. The relative percentage of standard deviation obtained for the repeatability and intermediate precision experiments was less than 3% and LOQ was less than 0.5μg·ml(-1) for all compounds. The new proposed method was found to be accurate, precise, specific, linear and robust. In addition, the method was successfully applied for the assay determination of Dic and its impurities in the several pharmaceutical dosage forms. Copyright © 2016 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

  18. Alteration in certain enzymological parameters of an Indian major carp, Cirrhinus mrigala exposed to short- and long-term exposure of clofibric acid and diclofenac.

    PubMed

    Saravanan, Manoharan; Ramesh, Mathan; Petkam, Rakpong

    2013-12-01

    The extensive use of pharmaceuticals in human and veterinary medicine may enter the aquatic environment and pose a serious threat to non-target aquatic organisms like fish. In this study, Indian major carp Cirrhinus mrigala was exposed to different concentrations (1, 10 and 100 μg L⁻¹) of most commonly used pharmaceutical drugs clofibric acid (CA) and diclofenac (DCF) to evaluate its impacts on certain enzymological parameters during short- and long-term exposures. During short-term (96 h) exposure period, plasma glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and gill Na⁺/K⁺-ATPase activity were significantly altered at all concentrations of both the CA- and DCF-treated fish. In long-term exposure (35 days), gill Na⁺/K⁺-ATPase activity was found to be significantly increased at all concentration of CA and DCF exposures throughout the study period (except at the end of 7th day in 10 and 100 µg L⁻¹) . However, a biphasic trend was observed in plasma GOT and GPT activity when compared to the control groups. In both short- and long-term exposure, a significant (P < 0.01 and P < 0.05) changes were observed in all enzymological parameters of fish C. mrigala exposed to different concentrations of CA and DCF. The alterations of these enzymological parameters can be effectively used as potential biomarkers in monitoring of pharmaceutical toxicity in aquatic environment and organisms.

  19. Short and long-term effects of clofibric acid and diclofenac on certain biochemical and ionoregulatory responses in an Indian major carp, Cirrhinus mrigala.

    PubMed

    Saravanan, M; Ramesh, M

    2013-09-01

    Extensive use of pharmaceuticals in human and veterinary medicine and aquaculture practices pose a serious threat to aquatic organisms. In the present investigation, Cirrhinus mrigala an Indian major carp was exposed to different concentrations of clofibric acid (CA) and diclofenac (DCF) and certain biochemical and ionoregulatory responses were assessed under short and long term exposures. During short-term (96h) exposure period, plasma glucose and sodium (Na(+)) levels were increased at all concentrations (1, 10 and 100μgL(-1)) of CA and DCF treated fish. Plasma protein and chloride (Cl(-)) levels were found to be decreased at all concentrations of CA and DCF exposed fish comparatively to control groups. Meanwhile an increase in plasma potassium (K(+)) level was noted in fish exposed to CA treatments alone and in DCF treatments it was decreased. In long-term exposure (35d), plasma Na(+) and Cl(-) levels were found to be significantly increased at all concentration of CA and DCF. However, a biphasic trend was observed in plasma glucose, protein and K(+) levels. In both the treatments, a significant (P<0.01 and P<0.05) changes were observed in all parameters measured in fish exposed to different concentrations of CA and DCF. The results of the present investigation indicate that both the drugs caused significant changes in biochemical and ionoregulatory responses of fish at all concentrations. The alterations of these parameters can be useful in monitoring of pharmaceutical residues present in aquatic environment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Assessing the phototransformation of diclofenac, clofibric acid and naproxen in surface waters: Model predictions and comparison with field data.

    PubMed

    Avetta, Paola; Fabbri, Debora; Minella, Marco; Brigante, Marcello; Maurino, Valter; Minero, Claudio; Pazzi, Marco; Vione, Davide

    2016-11-15

    Phototransformation is important for the fate in surface waters of the pharmaceuticals diclofenac (DIC) and naproxen (NAP) and for clofibric acid (CLO), a metabolite of the drug clofibrate. The goal of this paper is to provide an overview of the prevailing photochemical processes, which these compounds undergo in the different conditions found in freshwater environments. The modelled photochemical half-life times of NAP and DIC range from a few days to some months, depending on water conditions (chemistry and depth) and on the season. The model indicates that direct photolysis is the dominant degradation pathway of DIC and NAP in sunlit surface waters, and potentially toxic cyclic amides were detected as intermediates of DIC direct phototransformation. With modelled half-life times in the month-year range, CLO is predicted to be more photostable than DIC or NAP and to be degraded mainly by reaction with the • OH radical and with the triplet states of chromophoric dissolved organic matter ( 3 CDOM*). The CLO intermediates arising from these processes and detected in this study (hydroquinone and 4-chlorophenol) are, respectively, a chronic toxicant to aquatic organisms and a possible carcinogen for humans. Hydroquinone is formed with only ∼5% yield upon CLO triplet-sensitised transformation, but it is highly toxic for algae and crustaceans. In contrast, the formation yield of 4-chlorophenol reaches ∼50% upon triplet sensitisation and ∼10% by · OH reaction. The comparison of model predictions with field data from a previous study yielded a very good agreement in the case of DIC and, when using 4-carboxybenzophenone as proxy for triplet sensitisation by CDOM, a good agreement was found for CLO as well. In the case of NAP, the comparison with field data suggests that its direct photolysis quantum yield approaches or even falls below the lower range of literature values. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Comparative studies in electrochemical degradation of sulfamethoxazole and diclofenac in water by using various electrodes and phosphate and sulfate supporting electrolytes.

    PubMed

    Sifuna, Fred W; Orata, Francis; Okello, Veronica; Jemutai-Kimosop, Selly

    2016-09-18

    In this study, the electro-oxidation capacities of Na2SO4 and potassium phosphate buffer supporting electrolytes were tested and compared for destruction of the sulfamethoxazole (SMX) and diclofenac (DCF) on platinum (Pt) electrode and graphite carbon electrode in aqueous medium. The suitability of pharmaceutical active compounds (PhACs) for electrochemical oxidation was tested by cyclic voltammetry (CV) technique performed in the potential range -1.5 to +1.5 V versus Ag/AgCl, which confirmed the electro-activity of the selected PhACs. The degradation and mineralization were monitored by ultraviolet (UV)-Vis spectrophotometry and HPLC. 0.1 M Na2SO4 supporting electrolyte was found to be more effective for mineralization of SMX and DCF, with efficiency of 15-30% more than the 0.1 M phosphate buffer supporting electrolyte on the platinum (Pt) and carbon electrodes. The Pt electrode showed better performance in the degradation of the two PhACs while under the same conditions than the carbon electrode for both 0.1 M Na2SO4 and 0.1 M potassium phosphate buffer supporting electrolytes. The SMX and DCF degradation kinetics best fitted the second-order reaction, with rate constants ranging between 0.000389 and 0.006 mol(2) L(-2) min(-1) and correlation coefficient (R(2)) above 0.987. The second-order degradation kinetics indicated that the rate-determining step in the degradation could be a chemical process, thus suggesting the active involvement of electrolyte radical species in the degradation of SMX and DCF. Results obtained from a real field sample showed a more than 98% removal of the PhACs from the wastewater by electrochemical degradation.

  2. [Efficiency of famotidin in prophylaxis of NSAIDs-induced gastropathy: result of multicenter research ZASLON-1 (protection of gastric mucosa from non-steroidal anti-inflammatory drugs].

    PubMed

    Lazebnik, L B; Drozdov, V N; Kim, V A

    2009-01-01

    This article presents results of the first Russian randomized study of NSAID-gastropaty prevention at patients receiving NSAIDS. Results of clinical and endoscopic monitoring of two groups of patients: 1st - 108 patients with AA or RA treated with diclofenac and famotidin and 2nd--116 patients with AA or RA receiving diclofenac treatment only. It was shown that combined use of diclofenac and famotidin reduces to 2.6 times frequency and significantly reduces severity of painful dyspepsia symptoms and antipain manifestations reduces more than twice frequency of erosive-ulcerous lesions of gastric mucosa and duodenum.

  3. In Vitro Model for Hepatotoxicity Studies Based on Primary Human Hepatocyte Cultivation in a Perfused 3D Bioreactor System.

    PubMed

    Knöspel, Fanny; Jacobs, Frank; Freyer, Nora; Damm, Georg; De Bondt, An; van den Wyngaert, Ilse; Snoeys, Jan; Monshouwer, Mario; Richter, Marco; Strahl, Nadja; Seehofer, Daniel; Zeilinger, Katrin

    2016-04-16

    Accurate prediction of the potential hepatotoxic nature of new pharmaceuticals remains highly challenging. Therefore, novel in vitro models with improved external validity are needed to investigate hepatic metabolism and timely identify any toxicity of drugs in humans. In this study, we examined the effects of diclofenac, as a model substance with a known risk of hepatotoxicity in vivo, in a dynamic multi-compartment bioreactor using primary human liver cells. Biotransformation pathways of the drug and possible effects on metabolic activities, morphology and cell transcriptome were evaluated. Formation rates of diclofenac metabolites were relatively stable over the application period of seven days in bioreactors exposed to 300 µM diclofenac (300 µM bioreactors (300 µM BR)), while in bioreactors exposed to 1000 µM diclofenac (1000 µM BR) metabolite concentrations declined drastically. The biochemical data showed a significant decrease in lactate production and for the higher dose a significant increase in ammonia secretion, indicating a dose-dependent effect of diclofenac application. The microarray analyses performed revealed a stable hepatic phenotype of the cells over time and the observed transcriptional changes were in line with functional readouts of the system. In conclusion, the data highlight the suitability of the bioreactor technology for studying the hepatotoxicity of drugs in vitro.

  4. In Vitro Model for Hepatotoxicity Studies Based on Primary Human Hepatocyte Cultivation in a Perfused 3D Bioreactor System

    PubMed Central

    Knöspel, Fanny; Jacobs, Frank; Freyer, Nora; Damm, Georg; De Bondt, An; van den Wyngaert, Ilse; Snoeys, Jan; Monshouwer, Mario; Richter, Marco; Strahl, Nadja; Seehofer, Daniel; Zeilinger, Katrin

    2016-01-01

    Accurate prediction of the potential hepatotoxic nature of new pharmaceuticals remains highly challenging. Therefore, novel in vitro models with improved external validity are needed to investigate hepatic metabolism and timely identify any toxicity of drugs in humans. In this study, we examined the effects of diclofenac, as a model substance with a known risk of hepatotoxicity in vivo, in a dynamic multi-compartment bioreactor using primary human liver cells. Biotransformation pathways of the drug and possible effects on metabolic activities, morphology and cell transcriptome were evaluated. Formation rates of diclofenac metabolites were relatively stable over the application period of seven days in bioreactors exposed to 300 µM diclofenac (300 µM bioreactors (300 µM BR)), while in bioreactors exposed to 1000 µM diclofenac (1000 µM BR) metabolite concentrations declined drastically. The biochemical data showed a significant decrease in lactate production and for the higher dose a significant increase in ammonia secretion, indicating a dose-dependent effect of diclofenac application. The microarray analyses performed revealed a stable hepatic phenotype of the cells over time and the observed transcriptional changes were in line with functional readouts of the system. In conclusion, the data highlight the suitability of the bioreactor technology for studying the hepatotoxicity of drugs in vitro. PMID:27092500

  5. Risk of single and combined exposure of birds to non-steroidal anti-inflammatory drugs and lead.

    PubMed

    Osickova, Jitka; Skochova, Hana; Ondracek, Karel; Kral, Jiri; Damkova, Veronika; Peckova, Lucie; Pohanka, Miroslav; Vitula, Frantisek; Bandouchova, Hana; Pikula, Jiri

    2012-01-01

    Pharmaceuticals and heavy metals such as diclofenac and lead, respectively, have been identified as environmental contaminants toxic to birds and posing serious threats to declining populations of raptors worldwide. The aim of the present study was to test the hypothesis that a sublethal combination of non-steroidal anti-inflammatory drugs and lead induces more pronounced effects than single exposures in birds. A total of 40 Japanese quails (Coturnix coturnix japonica) at the age of 2 months and average weight of 180g were on a random basis divided into four experimental groups of 10 specimens (i.e., control, diclofenac, lead, and lead+diclofenac exposures). Six lead shots in the total weight of 1.5 grams were inserted into the crop on day 0 of the experiment, while a total of 5 mg/kg of diclofenac administered intramuscularly were divided into treatments on days 0 and 5. Group responses were compared using haematology and biochemistry after 10 days. There was no mortality in control and both single and combined diclofenac and lead exposure groups, nor did the birds show any clinical signs of intoxication. Univariate analyses of blood parameters yielded a decrease in haematocrit in birds exposed to both substances when compared with the control, a lower haemoglobin level of the lead-exposed group, increased activity of aspartate aminotransferase in the NSAIDs-exposed group, increased activity of alkaline phosphatase in birds exposed to a combination of diclofenac and lead, and a higher phosphorus level in the lead-exposed group. The principal component analysis revealed no multivariate pattern of responses of blood parameters and did not allow separation of exposure groups from controls when the variables and samples were projected onto a two dimensional space. Results of the present study can enhance understanding of combination toxicity of veterinary drugs and heavy metals in birds, i.e. a scenario that has become environmentally relevant in recent decades

  6. Selective scavenging of intra-mitochondrial superoxide corrects diclofenac-induced mitochondrial dysfunction and gastric injury: A novel gastroprotective mechanism independent of gastric acid suppression.

    PubMed

    Mazumder, Somnath; De, Rudranil; Sarkar, Souvik; Siddiqui, Asim Azhar; Saha, Shubhra Jyoti; Banerjee, Chinmoy; Iqbal, Mohd Shameel; Nag, Shiladitya; Debsharma, Subhashis; Bandyopadhyay, Uday

    2016-12-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat multiple inflammatory diseases and pain but severe gastric mucosal damage is the worst outcome of NSAID-therapy. Here we report that mitoTEMPO, a mitochondrially targeted superoxide (O 2 - ) scavenger protected as well as healed gastric injury induced by diclofenac (DCF), the most commonly used NSAID. Common existing therapy against gastric injury involves suppression of gastric acid secretion by proton pump inhibitors and histamine H 2 receptor antagonists; however, dyspepsia, vitamin B12 deficiency and gastric microfloral dysbalance are the major drawbacks of acid suppression. Interestingly, mitoTEMPO did not inhibit gastric acid secretion but offered gastroprotection by preventing DCF-induced generation of O 2 - due to mitochondrial respiratory chain failure and by preventing mitochondrial oxidative stress (MOS)-mediated mitopathology. MitoTEMPO even restored DCF-stimulated reduced fatty acid oxidation, mitochondrial depolarization and bioenergetic crisis in gastric mucosa. MitoTEMPO also prevented the activation of mitochondrial pathway of apoptosis and MOS-mediated proinflammatory signaling through NF-κB by DCF. Furthermore, mitoTEMPO when administered in rats with preformed gastric lesions expedited the healing of gastric injury and the healed stomach exhibited its normal physiology as evident from gastric acid and pepsin secretions under basal or stimulated conditions. Thus, in contrast to the existing antiulcer drugs, mitochondrially targeted O 2 - scavengers like mitoTEMPO may represent a novel class of gastroprotective molecules that does not affect gastric acid secretion and may be used in combination with DCF, keeping its anti-inflammatory action intact, while reducing its gastrodamaging effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Diclofenac Ophthalmic

    MedlinePlus

    ... to temporarily relieve eye pain and sensitivity to light in patients who are recovering from corneal refractive ... that something is in the eye sensitivity to light blurred or decreased vision teary eyes eye discharge ...

  8. Efficacy and safety of diclofenac diethylamine 1.16% gel in acute neck pain: a randomized, double-blind, placebo-controlled study.

    PubMed

    Predel, Hans-Georg; Giannetti, Bruno; Pabst, Helmut; Schaefer, Axel; Hug, Agnes M; Burnett, Ian

    2013-08-21

    Neck pain (NP) is a common musculoskeletal disorder in primary care that frequently causes discomfort. Non-steroidal anti-inflammatory drugs (NSAIDs) may be used to reduce neck pain and associated inflammation and facilitate earlier recovery. Topical diclofenac diethylamine (DDEA) 1.16% gel is clinically proven to be effective and well tolerated in acute and chronic musculoskeletal conditions, but until now no clinical data existed for its use in acute NP. The aim of this study was to assess the efficacy and safety of DDEA 1.16% gel compared with placebo gel in acute NP. In a randomized, double-blind, placebo-controlled study, patients with acute NP (n = 72) were treated with DDEA 1.16% gel (2 g, 4x/day, for 5 days) or placebo. Efficacy assessments included pain-on-movement (POM), pain-at-rest (PAR), functional neck disability index (NDI) and response to treatment (decrease in POM by 50% after 48 h). Adverse events (AEs) were recorded throughout the study. The primary outcome, POM at 48 h, was statistically significantly lower with DDEA gel (19.5 mm) vs. placebo (56.9 mm) (p < 0.0001), representing a clinically relevant decrease from baseline (75% vs. 23%, respectively). All POM scores were significantly lower with DDEA gel vs. placebo from 1 h, as were PAR and NDI scores from first assessment (24 h) onwards (all p < 0.0001). Response to treatment was significantly higher with DDEA gel (94.4%) vs. placebo (8.3%) (p < 0.0001). There were no AEs with DDEA gel. DDEA 1.16% gel, which is available over-the-counter, was effective and well tolerated in the treatment of acute neck pain. The tools used to assess efficacy suggest that it quickly reduced neck pain and improved neck function. However, questions remain regarding the comparability and validity of such tools. Further studies will help ascertain whether DDEA 1.16% gel offers an alternative treatment option in this common, often debilitating condition. ClinicalTrials.gov identifier: NCT

  9. Fate and Uptake of Pharmaceuticals in Soil–Earthworm Systems

    PubMed Central

    2014-01-01

    Pharmaceuticals present a potential threat to soil organisms, yet our understanding of their fate and uptake in soil systems is limited. This study therefore investigated the fate and uptake of 14C-labeled carbamazepine, diclofenac, fluoxetine, and orlistat in soil–earthworm systems. Sorption coefficients increased in the order of carbamazepine < diclofenac < fluoxetine < orlistat. Dissipation of 14C varied by compound, and for orlistat, there was evidence of formation of nonextractable residues. Uptake of 14C was seen for all compounds. Depuration studies showed complete elimination of 14C for carbamazepine and fluoxetine treatments and partial elimination for orlistat and diclofenac, with greater than 30% of the 14C remaining in the tissue at the end of the experiment. Pore-water-based bioconcentration factors (BCFs), based on uptake and elimination of 14C, increased in the order carbamazepine < diclofenac < fluoxetine and orlistat. Liquid chromatography–tandem mass spectrometry and liquid chromatography–Fourier transform mass spectrometry indicated that the observed uptake in the fluoxetine and carbamazepine treatments was due to the parent compounds but that diclofenac was degraded in the test system so uptake was due to unidentifiable transformation products. Comparison of our data with outputs of quantitative structure−activity relationships for estimating BCFs in worms showed that these models tend to overestimate pharmaceutical BCFs so new models are needed. PMID:24762061

  10. Electro membrane extraction of sodium diclofenac as an acidic compound from wastewater, urine, bovine milk, and plasma samples and quantification by high-performance liquid chromatography.

    PubMed

    Davarani, Saied Saeed Hosseiny; Pourahadi, Ahmad; Nojavan, Saeed; Banitaba, Mohammad Hossein; Nasiri-Aghdam, Mahnaz

    2012-04-13

    Electro membrane extraction (EME) as a new microextraction method was applied for extraction of sodium diclofenac (SDF) as an acidic compound from wastewater, urine, bovine milk and plasma samples. Under applied potential of 20 V during the extraction, SDF migrated from a 2.1 mL of sample solution (1mM NaOH), through a supported liquid membrane (SLM), into a 30 μL acceptor solution (10 mM NaOH), exist inside the lumen of the hollow fiber. The negative electrode was placed in the donor solution, and the positive electrode was placed in the acceptor solution. 1-octanol was immobilized in the pores of a porous hollow fiber of polypropylene as SLM. Then the extract was analyzed by means of high-performance liquid chromatography (HPLC) with UV-detection for quantification of SDF. Best results were obtained using a phosphate running electrolyte (10 mM, pH 2.5). The ranges of quantitation for different samples were 8-500 ngmL(-1). Intra- and inter-day RSDs were less than 14.5%. Under the optimized conditions, the preconcentration factors were between 31 and 66 and also the limit of detections (LODs) ranged from 2.7 ng mL(-1) to 5 ng mL(-1) in different samples. This procedure was applied to determine SDF in wastewater, bovine milk, urine and plasma samples (spiked and real samples). Extraction recoveries for different samples were between 44-95% after 5 min of extraction. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Acupuncture as a complementary therapy to the pharmacological treatment of osteoarthritis of the knee: randomised controlled trial

    PubMed Central

    Vas, Jorge; Méndez, Camila; Perea-Milla, Emilio; Vega, Evelia; Panadero, María Dolores; León, José María; Borge, Miguel Ángel; Gaspar, Olga; Sánchez-Rodríguez, Francisco; Aguilar, Inmaculada; Jurado, Rosario

    2004-01-01

    Objectives To analyse the efficacy of acupuncture as a complementary therapy to the pharmacological treatment of osteoarthritis of the knee, with respect to pain relief, reduction of stiffness, and increased physical function during treatment; modifications in the consumption of diclofenac during treatment; and changes in the patient's quality of life. Design Randomised, controlled, single blind trial, with blinded evaluation and statistical analysis of results. Setting Pain management unit in a public primary care centre in southern Spain, over a period of two years. Participants 97 outpatients presenting with osteoarthritis of the knee. Interventions Patients were randomly separated into two groups, one receiving acupuncture plus diclofenac (n = 48) and the other placebo acupuncture plus diclofenac (n = 49). Main outcome measures The clinical variables examined included intensity of pain as measured by a visual analogue scale; pain, stiffness, and physical function subscales of the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index; dosage of diclofenac taken during treatment; and the profile of quality of life in the chronically ill (PQLC) instrument, evaluated before and after the treatment programme. Results 88 patients completed the trial. In the intention to treat analysis, the WOMAC index presented a greater reduction in the intervention group than in the control group (mean difference 23.9, 95% confidence interval 15.0 to 32.8) The reduction was greater in the subscale of functional activity. The same result was observed in the pain visual analogue scale, with a reduction of 26.6 (18.5 to 34.8). The PQLC results indicate that acupuncture treatment produces significant changes in physical capability (P = 0.021) and psychological functioning (P = 0.046). Three patients reported bruising after the acupuncture sessions. Conclusions Acupuncture plus diclofenac is more effective than placebo acupuncture plus diclofenac for the symptomatic

  12. Mucosal protective agents prevent exacerbation of NSAID-induced small intestinal lesions caused by antisecretory drugs in rats.

    PubMed

    Satoh, Hiroshi; Amagase, Kikuko; Takeuchi, Koji

    2014-02-01

    Antisecretory drugs such as histamine H₂-receptor antagonists and proton pump inhibitors are commonly used for the treatment of upper gastrointestinal mucosal lesions induced by nonsteroidal anti-inflammatory drugs (NSAIDs). However, it has recently been reported that these drugs exacerbate NSAID-induced small intestinal lesions in rats. Unfortunately, there are few effective agents for the treatment of this complication. We examined the effects of mucosal protective agents (MPAs) (misoprostol, irsogladine, and rebamipide) and mucin of porcine stomach on diclofenac-induced intestinal lesions and the exacerbation of the lesions by ranitidine or omeprazole. The effects of the drugs on intestinal motility and mucus distribution/content were also examined. Male Wistar rats (180-220 g) were used. Each drug was administered orally under fed conditions. Diclofenac (1-10 mg/kg) produced multiple lesions in the small intestine dose-dependently. Both ranitidine (30 mg/kg) and omeprazole (100 mg/kg) significantly increased the intestinal lesions induced by low doses (3 and 6 mg/kg) of diclofenac. Misoprostol (0.03-0.3 mg/kg), irsogladine (3-30 mg/kg), and rebamipide (30-300 mg/kg), as well as mucin (30-300 mg/kg) inhibited the formation of intestinal lesions caused by a high dose (10 mg/kg) of diclofenac alone and prevented the exacerbation of diclofenac-induced lesions by antisecretory drugs. Diclofenac (10 mg/kg) markedly increased the intestinal motility and decreased the mucosal mucus, and the decrease of mucus was significantly inhibited by the MPAs. These results indicate the usefulness of the MPAs for the treatment of intestinal lesions induced by NSAIDs alone or by coadministration with antisecretory drugs, and suggest that mucus plays an important role in the protection of intestinal mucosa by the MPAs.

  13. Use of non-steroidal anti-inflammatory drugs that elevate cardiovascular risk: an examination of sales and essential medicines lists in low-, middle-, and high-income countries.

    PubMed

    McGettigan, Patricia; Henry, David

    2013-01-01

    Certain non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., rofecoxib [Vioxx]) increase the risk of heart attack and stroke and should be avoided in patients at high risk of cardiovascular events. Rates of cardiovascular disease are high and rising in many low- and middle-income countries. We studied the extent to which evidence on cardiovascular risk with NSAIDs has translated into guidance and sales in 15 countries. Data on the relative risk (RR) of cardiovascular events with individual NSAIDs were derived from meta-analyses of randomised trials and controlled observational studies. Listing of individual NSAIDs on Essential Medicines Lists (EMLs) was obtained from the World Health Organization. NSAID sales or prescription data for 15 low-, middle-, and high-income countries were obtained from Intercontinental Medical Statistics Health (IMS Health) or national prescription pricing audit (in the case of England and Canada). Three drugs (rofecoxib, diclofenac, etoricoxib) ranked consistently highest in terms of cardiovascular risk compared with nonuse. Naproxen was associated with a low risk. Diclofenac was listed on 74 national EMLs, naproxen on just 27. Rofecoxib use was not documented in any country. Diclofenac and etoricoxib accounted for one-third of total NSAID usage across the 15 countries (median 33.2%, range 14.7-58.7%). This proportion did not vary between low- and high-income countries. Diclofenac was by far the most commonly used NSAID, with a market share close to that of the next three most popular drugs combined. Naproxen had an average market share of less than 10%. Listing of NSAIDs on national EMLs should take account of cardiovascular risk, with preference given to low risk drugs. Diclofenac has a risk very similar to rofecoxib, which was withdrawn from worldwide markets owing to cardiovascular toxicity. Diclofenac should be removed from EMLs.

  14. Toxicological effects of clofibric acid and diclofenac on plasma thyroid hormones of an Indian major carp, Cirrhinus mrigala during short and long-term exposures.

    PubMed

    Saravanan, Manoharan; Hur, Jang-Hyun; Arul, Narayanasamy; Ramesh, Mathan

    2014-11-01

    In the present investigation, the toxicity of most commonly detected pharmaceuticals in the aquatic environment namely clofibric acid (CA) and diclofenac (DCF) was investigated in an Indian major carp Cirrhinus mrigala. Fingerlings of C. mrigala were exposed to different concentrations (1, 10 and 100μgL(-1)) of CA and DCF for a period of 96h (short term) and 35 days (long term). The toxic effects of CA and DCF on thyroid hormones (THs) such as thyroid stimulating hormone (TSH), thyroxine (T4) and triiodothyronine (T3) levels were evaluated. During the short and long-term exposure period TSH level was found to be decreased at all concentrations of CA (except at the end of 14(th) day in 1 and 10μgL(-l) and 21(st) day in 1μgL(-l)) whereas in DCF exposed fish TSH level was found to be increased when compared to control groups. T4 level was found to be decreased at 1 and 100μgL(-l) of CA exposure at the end of 96h. However, T4 level was decreased at all concentrations of CA and DCF during long-term (35 days) exposure period. Fish exposed to all concentrations of CA and DCF had lower level of T3 in both the treatments. These results suggest that both CA and DCF drugs induced significant changes (P<0.01 and P<0.05) on thyroid hormonal levels of C. mrigala. The alterations of these hormonal levels can be used as potential biomarkers in monitoring of pharmaceutical drugs in aquatic organisms. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. New Approaches for Prostate Cancer Combination Therapy

    DTIC Science & Technology

    2007-04-01

    in DU145 cells. Strong inducers of apoptosis included Sulindac sulfide, Finasteride , Diclofenac, Flufenamic acid, Flurbiprofen, Sulindac sulfone and... Finasteride , a selective 5-alpha-reductase inhibitor, is not known to inhibit COX-2, strongly induces MDA-7/IL-24 expression and apoptosis, whereas the...ibuprofen, aspirin, acet- aminophen, and naproxen were obtained from Sigma-Aldrich (St. Louis, MO). Meloxicam, celecoxib, diclofenac, finasteride , and

  16. Permeability Evaluation Through Chitosan Membranes Using Taguchi Design

    PubMed Central

    Sharma, Vipin; Marwaha, Rakesh Kumar; Dureja, Harish

    2010-01-01

    In the present study, chitosan membranes capable of imitating permeation characteristics of diclofenac diethylamine across animal skin were prepared using cast drying method. The effect of concentration of chitosan, concentration of cross-linking agent (NaTPP), crosslinking time was studied using Taguchi design. Taguchi design ranked concentration of chitosan as the most important factor influencing the permeation parameters of diclofenac diethylamine. The flux of the diclofenac diethylamine solution through optimized chitosan membrane (T9) was found to be comparable to that obtained across rat skin. The mathematical model developed using multilinear regression analysis can be used to formulate chitosan membranes that can mimic the desired permeation characteristics. The developed chitosan membranes can be utilized as a substitute to animal skin for in vitro permeation studies. PMID:21179329

  17. Permeability evaluation through chitosan membranes using taguchi design.

    PubMed

    Sharma, Vipin; Marwaha, Rakesh Kumar; Dureja, Harish

    2010-01-01

    In the present study, chitosan membranes capable of imitating permeation characteristics of diclofenac diethylamine across animal skin were prepared using cast drying method. The effect of concentration of chitosan, concentration of cross-linking agent (NaTPP), crosslinking time was studied using Taguchi design. Taguchi design ranked concentration of chitosan as the most important factor influencing the permeation parameters of diclofenac diethylamine. The flux of the diclofenac diethylamine solution through optimized chitosan membrane (T9) was found to be comparable to that obtained across rat skin. The mathematical model developed using multilinear regression analysis can be used to formulate chitosan membranes that can mimic the desired permeation characteristics. The developed chitosan membranes can be utilized as a substitute to animal skin for in vitro permeation studies.

  18. Removal of selected non-steroidal anti-inflammatory drugs (NSAIDs), gemfibrozil, carbamazepine, beta-blockers, trimethoprim and triclosan in conventional wastewater treatment plants in five EU countries and their discharge to the aquatic environment.

    PubMed

    Paxéus, N

    2004-01-01

    The removal of commonly used pharmaceuticals (ibuprofen, naproxen, diclofenac, gemfibrozil, carbamazepine, atenolol, metoprolol and trimethoprim) and a biocide (triclosan) in operating wastewater treatment plants in five EU countries has been studied. Under normal operating conditions the acidic drugs and triclosan were partially removed with removal rates varying from ca. 20 to >95%. The highest removal rate was found for ibuprofen and triclosan (>90%) followed by naproxen (80%), gemfibrozil (55%) and diclofenac (39%). Ibuprofen undergoes an oxidative transformation to corresponding hydroxy- and carboxy-metabolites, which contributes to its high removal rate. Disturbances in the activated sludge process resulted in lower removal rates for all acidic drugs, mostly for diclofenac (<10% removed) but also for ibuprofen (<60% removed). The treatment of wastewaters by activated sludge usually did not result in any practical removal (<10%) of neutral carbamazepine or basic atenolol, metoprolol and trimethoprim. The removal rates of the investigated drugs and triclosan are discussed in terms of mechanisms responsible for their removal. Discharges of carbamazepine, diclofenac, gemfibrozil, naproxen, triclosan and trimethoprim from WWTPs to the aquatic environment, expressed as the average concentration in the effluent and the daily discharged quantity per person served by WWTPs were assessed.

  19. Fate of pharmaceutical compounds in hydroponic mesocosms planted with Scirpus validus.

    PubMed

    Zhang, Dong Qing; Gersberg, Richard M; Hua, Tao; Zhu, Junfei; Goyal, Manish Kumar; Ng, Wun Jern; Tan, Soon Keat

    2013-10-01

    A systematic approach to assess the fate of selected pharmaceuticals (carbamazepine, naproxen, diclofenac, clofibric acid and caffeine) in hydroponic mesocosms is described. The overall objective was to determine the kinetics of depletion (from solution) and plant uptake for these compounds in mesocosms planted with S. validus growing hydroponically. The potential for translocation of these pharmaceuticals from the roots to the shoots was also assessed. After 21 days of incubation, nearly all of the caffeine, naproxen and diclofenac were eliminated from solution, whereas carbamazepine and clofibric acid were recalcitrant to both photodegradation and biodegradation. The fact that the BAFs for roots for carbamazepine and clofibric acid were greater than 5, while the BAFs for naproxen, diclofenac and caffeine were less than 5, implied that the latter two compounds although recalcitrant to biodegradation, still had relatively high potential for plant uptake. Naproxen was sensitive to both photodegradation (30-42%) and biodegradation (>50%), while diclofenac was particularly sensitive (>70%) to photodegradation alone. No significant correlations (p > 0.05) were found between the rate constants of depletion or plant tissue levels of the pharmaceuticals and either log Kow or log Dow. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Efficacy and safety of diclofenac diethylamine 1.16% gel in acute neck pain: a randomized, double-blind, placebo-controlled study

    PubMed Central

    2013-01-01

    Background Neck pain (NP) is a common musculoskeletal disorder in primary care that frequently causes discomfort. Non-steroidal anti-inflammatory drugs (NSAIDs) may be used to reduce neck pain and associated inflammation and facilitate earlier recovery. Topical diclofenac diethylamine (DDEA) 1.16% gel is clinically proven to be effective and well tolerated in acute and chronic musculoskeletal conditions, but until now no clinical data existed for its use in acute NP. The aim of this study was to assess the efficacy and safety of DDEA 1.16% gel compared with placebo gel in acute NP. Methods In a randomized, double-blind, placebo-controlled study, patients with acute NP (n = 72) were treated with DDEA 1.16% gel (2 g, 4x/day, for 5 days) or placebo. Efficacy assessments included pain-on-movement (POM), pain-at-rest (PAR), functional neck disability index (NDI) and response to treatment (decrease in POM by 50% after 48 h). Adverse events (AEs) were recorded throughout the study. Results The primary outcome, POM at 48 h, was statistically significantly lower with DDEA gel (19.5 mm) vs. placebo (56.9 mm) (p < 0.0001), representing a clinically relevant decrease from baseline (75% vs. 23%, respectively). All POM scores were significantly lower with DDEA gel vs. placebo from 1 h, as were PAR and NDI scores from first assessment (24 h) onwards (all p < 0.0001). Response to treatment was significantly higher with DDEA gel (94.4%) vs. placebo (8.3%) (p < 0.0001). There were no AEs with DDEA gel. Conclusions DDEA 1.16% gel, which is available over-the-counter, was effective and well tolerated in the treatment of acute neck pain. The tools used to assess efficacy suggest that it quickly reduced neck pain and improved neck function. However, questions remain regarding the comparability and validity of such tools. Further studies will help ascertain whether DDEA 1.16% gel offers an alternative treatment option in this common, often debilitating condition

  1. Combined effects of aging and in vitro non-steroid anti-inflammatory drugs on kidney and liver mitochondrial physiology.

    PubMed

    Rocha-Rodrigues, Sílvia; Santos-Alves, Estela; Coxito, Pedro M; Marques-Aleixo, Inês; Passos, Emanuel; Guimarães, João T; Martins, Maria J; Oliveira, Paulo J; Magalhães, José; Ascensão, António

    2013-09-03

    Aging and drug-induced side effects may contribute to deteriorate mitochondrial bioenergetics in many tissues, including kidney and liver. One possibility is that the combination of both aging and drug toxicity accelerates the process of mitochondrial degradation, leading to progressive bioenergetic disruption. We therefore analyzed in vitro kidney (KM) and liver (LM) mitochondrial response to salicylate and diclofenac in old and adult animals. Male-Wistar adult (19-wks) and aged (106-wks) rats were used. In vitro endpoints of oxygen consumption and membrane potential were evaluated in non-treated conditions (vehicle) and in the presence of salicylate (0.5mM) and diclofenac (50μM). The susceptibility to calcium-induced permeability transition pore (MPTP) was assessed. Aconitase and C, -SH and MDA contents were measured. Apoptotic signaling was followed by measuring caspase 3, 8 and 9 activities, Bax, Bcl2 and CypD expression. ANT content was semi-quantified. In general, animal age alone compromised KM state 3 and LM ADP lag phase while resulting in decreased resistance to the MPTP. Aging decreased LM CypD and increased Mn-SOD. Kidney caspase 9-like activity was lower in aged group. Salicylate and diclofenac induced KM and LM dysfunction. ADP lag phase in KM was further increased in the aged group in the presence of diclofenac. No further impairments were observed regarding drug toxicity adding to the aging process. Aging impaired KM and LM function despite no detected alterations on oxidative stress and apoptosis. However, aging did not further exacerbate KM and LM frailty induced by salicylate and diclofenac. © 2013.

  2. Potentiation of the antiinflammatory effect of Anacardium occidentale (Linn.) stem-bark aqueous extract by grapefruit juice.

    PubMed

    Ojewole, J A O

    2004-04-01

    In an attempt to scientifically appraise some of the ethnomedical uses of Anacardium occidentale Linn. (family: Anacardiaceae), the present study was undertaken to examine the antiinflammatory effect of the plant's stem-bark aqueous extract in rats. Young adult male Wistar rats weighing 250-300 g were used. The antiinflammatory effect of A. occidentale stem-bark aqueous extract alone and in combination with grapefruit (Citrus paradisi Macf.) juice was investigated on fresh egg albumin-induced rat paw edema. Like diclofenac (100 mg/kg p.o.), aqueous extract of A. occidentale stem-bark (800 mg/kg p.o.) produced time-related, sustained and significant reduction (p < 0.05-0.001) of the fresh egg albumin-induced acute inflammation of the rat hind paw. However, the antiinflammatory effect of the plant extract was found to be approximately 8-15 times less than that of diclofenac. Coadministration of grapefruit juice (5 ml/kg p.o.) with A. occidentale stem-bark aqueous extract (800 mg/kg p.o.) or diclofenac (100 mg/kg p.o.) significantly potentiated (p < 0.05-0.001) the antiinflammatory effects of the crude plant extract and diclofenac on fresh egg albumin-induced rat paw edema. Although A. occidentale stem-bark aqueous extract is less potent than diclofenac as an antiinflammatory agent, the results of this experimental animal study indicate that the plant extract possesses antiinflammatory activity, and thus lend pharmacological support to the folkloric use of the plant in the management and/or control of arthritis and other inflammatory conditions among the Yoruba-speaking people of western Nigeria.

  3. Topical NSAIDs effect on corneal sensitivity.

    PubMed

    Singer, Daniel D; Kennedy, John; Wittpenn, John R

    2015-05-01

    Topical nonsteroidal antiinflammatory drugs (NSAIDs) are administered topically for a variety of ophthalmologic conditions. Brand diclofenac and brand ketorolac were previously shown to have topical anesthetic effects in addition to analgesic effects. Using the same method, we measured similar anesthetic effects of the 4 currently available topical NSAIDs--generic diclofenac, generic ketorolac, brand bromfenac, and brand nepafenac. Baseline corneal sensitivity was measured on 10 healthy adult volunteers with a Cochet-Bonnet esthesiometer. One drop of the agent being studied was applied to the right eye every 5 minutes for a total of 4 drops. Corneal sensitivity was measured immediately after the last topical application and every 15 minutes for 60 minutes. After a 1-week washout period, a different agent was studied until all 4 NSAIDs were evaluated. Corneal sensitivity profiles over time were similar for all NSAIDs. Corneal sensitivity decreased significantly from baseline immediately after topical application remaining flat from 0 to 30 minutes and then rising from 45 to 60 minutes back toward baseline in all treatment groups (P < 0.001). The maximal absolute drop in corneal sensitivity as measured by pressure thresholds was greatest for diclofenac [28.6 mm (95% confidence intervals {CI}, 19.8-37.4)], followed by ketorolac [21.1 mm (95% CI, 15.1-27.1)], bromfenac [16.9 mm (10.7-23.1)], and nepafenac [16.4 mm (95% CI, 12.7-20.1)]. Only diclofenac and nepafenac were statistically different in maximal decrease in sensitivity. All 4 currently available NSAIDs demonstrated anesthetic effects similar to brand diclofenac and brand ketorolac.

  4. Recurrence rates and patient assessed outcomes of 0.5% 5-fluorouracil in combination with salicylic acid treating actinic keratoses.

    PubMed

    Stockfleth, Eggert; Zwingers, Thomas; Willers, Christoph

    2012-01-01

    Actinic keratoses (AK) have been classified as early in situ squamous cell carcinomas and should be treated. To evaluate the clinical benefit of 5-fluorouracil 0.5%/salicylic acid 10.0% (5-FU/SA) versus 3% diclofenac/hyaluronic acid (HA) for the treatment of AK and report patients' assessments of efficacy, tolerability and practicability. Randomised, placebo-controlled, double-blind, parallel-group, multicentre trial. Patients received topical 0.5% 5-FU/SA once daily, its vehicle or diclofenac/HA twice daily for maximum of 12 weeks. Lesion recurrence rates were evaluated at 6 and 12 months after end of treatment (EOT). Patients' assessments were evaluated at 6 weeks, EOT, post-treatment (PT) visit, 6 and 12 months. At 12 months 85.8% of lesions did not recur in the 5-FU/SA group compared to 79.8% (p=0.04419) in the vehicle and 81.0% (p=0.02476) in the diclofenac/HA groups. At PT visit 93.2% patients (n=163/175) in the 5-FU/SA group rated clinical improvement as "very good" or "good" compared to vehicle (66.7%, n=62/93, p<0.0001) and diclofenac/HA (81.6%, n=142/174, p<0.0001). Local side effects (inflammation and burning) were more common with 0.5% FU/SA but in general did not lead to discontinuation of therapy. Overall, patients were satisfied with the therapy. At 12 months, there were no differences in practicability and handling between treatments. Topical 0.5% 5-FU/SA demonstrated superior sustained clinical efficacy versus diclofenac/HA with acceptable tolerability. Patient satisfaction was high.

  5. Study on the Visible-Light Photocatalytic Performance and Degradation Mechanism of Diclofenac Sodium under the System of Hetero-Structural CuBi₂O₄/Ag₃PO₄ with H₂O₂.

    PubMed

    Chen, Xiaojuan; Li, Ning; Xu, Song; Wang, Hailong; Cai, Yumin

    2018-03-28

    Two kinds of CuBi₂O₄/Ag₃PO₄ with different heterojunction structures were prepared based on the combination of hydrothermal and in-situ precipitation methods with surfactant additives (sodium citrate and sodium stearate), and their characteristics were systematically resolved by X-ray Diffraction (XRD), Brunauer-Emmett-Teller (BET), X-ray Photoelectron Spectroscopy (XPS), Scanning Electron Microscope (SEM)/ High-resolution Transmission Electron Microscopy (HRTEM), UV-vis Diffuse Reflectance Spectra (DRS) and Photoluminescence (PL). Meanwhile, the photocatalytic properties of the catalysts were determined for diclofenac sodium (DS) degradation and the photocatalytic mechanism was also explored. The results indicate that both of the two kinds of CuBi₂O₄/Ag₃PO₄ exhibit higher photocatalytic efficiency, mineralization rate, and stability than that of pure CuBi₂O₄ or Ag₃PO₄. Moreover, the catalytic activity of CuBi₂O₄/Ag₃PO₄ can be further enhanced by adding H₂O₂. The free radical capture experiments show that in the pure CuBi₂O₄/Ag₃PO₄ photocatalytic system, the OH • and O₂ •- are the main species participating in DS degradation; however, in the CuBi₂O₄/Ag₃PO₄ photocatalytic system with H₂O₂, all OH • , h ⁺, and O₂ •- take part in the DS degradation, and the contribution order is OH • > h ⁺ > O₂ •- . Accordingly, the photocatalytic mechanism of CuBi₂O₄/Ag₃PO₄ could be explained by the Z-Scheme theory, while the catalysis of CuBi₂O₄/Ag₃PO₄ with H₂O₂ follows the heterojunction energy band theory.

  6. Cell Cycle Target-Based Therapy of Ovarian Cancer

    DTIC Science & Technology

    2008-03-01

    inducers of apoptosis included flufenamic acid, flurbiprofen, celebrex and finasteride , whereas treatment with ibuprofen in low levels of apoptosis...Ibuprofen, Exisulind, Acetaminophen, Naproxen, NS-398, Celecoxib, Diclofenac, Finasteride , Flufenamic acid, Meloxican, Ebselen and Flurbiprofen was...Diclofenac, 50µM Finasteride , 200µM Flufenamic acid, 40µM Meloxican, 50µM Ebselen, 20nM Flurbiprofen or 50µM Sulindac sulfide. Apoptosis was measured 24

  7. Use of Non-Steroidal Anti-Inflammatory Drugs That Elevate Cardiovascular Risk: An Examination of Sales and Essential Medicines Lists in Low-, Middle-, and High-Income Countries

    PubMed Central

    McGettigan, Patricia; Henry, David

    2013-01-01

    Background Certain non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., rofecoxib [Vioxx]) increase the risk of heart attack and stroke and should be avoided in patients at high risk of cardiovascular events. Rates of cardiovascular disease are high and rising in many low- and middle-income countries. We studied the extent to which evidence on cardiovascular risk with NSAIDs has translated into guidance and sales in 15 countries. Methods and Findings Data on the relative risk (RR) of cardiovascular events with individual NSAIDs were derived from meta-analyses of randomised trials and controlled observational studies. Listing of individual NSAIDs on Essential Medicines Lists (EMLs) was obtained from the World Health Organization. NSAID sales or prescription data for 15 low-, middle-, and high-income countries were obtained from Intercontinental Medical Statistics Health (IMS Health) or national prescription pricing audit (in the case of England and Canada). Three drugs (rofecoxib, diclofenac, etoricoxib) ranked consistently highest in terms of cardiovascular risk compared with nonuse. Naproxen was associated with a low risk. Diclofenac was listed on 74 national EMLs, naproxen on just 27. Rofecoxib use was not documented in any country. Diclofenac and etoricoxib accounted for one-third of total NSAID usage across the 15 countries (median 33.2%, range 14.7–58.7%). This proportion did not vary between low- and high-income countries. Diclofenac was by far the most commonly used NSAID, with a market share close to that of the next three most popular drugs combined. Naproxen had an average market share of less than 10%. Conclusions Listing of NSAIDs on national EMLs should take account of cardiovascular risk, with preference given to low risk drugs. Diclofenac has a risk very similar to rofecoxib, which was withdrawn from worldwide markets owing to cardiovascular toxicity. Diclofenac should be removed from EMLs. Please see later in the article for the Editors' Summary

  8. Development and evaluation of natural gum-based extended release matrix tablets of two model drugs of different water solubilities by direct compression.

    PubMed

    Ofori-Kwakye, Kwabena; Mfoafo, Kwadwo Amanor; Kipo, Samuel Lugrie; Kuntworbe, Noble; Boakye-Gyasi, Mariam El

    2016-01-01

    The study was aimed at developing extended release matrix tablets of poorly water-soluble diclofenac sodium and highly water-soluble metformin hydrochloride by direct compression using cashew gum, xanthan gum and hydroxypropylmethylcellulose (HPMC) as release retardants. The suitability of light grade cashew gum as a direct compression excipient was studied using the SeDeM Diagram Expert System. Thirteen tablet formulations of diclofenac sodium (∼100 mg) and metformin hydrochloride (∼200 mg) were prepared with varying amounts of cashew gum, xanthan gum and HPMC by direct compression. The flow properties of blended powders and the uniformity of weight, crushing strength, friability, swelling index and drug content of compressed tablets were determined. In vitro drug release studies of the matrix tablets were conducted in phosphate buffer (diclofenac: pH 7.4; metformin: pH 6.8) and the kinetics of drug release was determined by fitting the release data to five kinetic models. Cashew gum was found to be suitable for direct compression, having a good compressibility index (ICG) value of 5.173. The diclofenac and metformin matrix tablets produced generally possessed fairly good physical properties. Tablet swelling and drug release in aqueous medium were dependent on the type and amount of release retarding polymer and the solubility of drug used. Extended release of diclofenac (∼24 h) and metformin (∼8-12 h) from the matrix tablets in aqueous medium was achieved using various blends of the polymers. Drug release from diclofenac tablets fitted zero order, first order or Higuchi model while release from metformin tablets followed Higuchi or Hixson-Crowell model. The mechanism of release of the two drugs was mostly through Fickian diffusion and anomalous non-Fickian diffusion. The study has demonstrated the potential of blended hydrophilic polymers in the design and optimization of extended release matrix tablets for soluble and poorly soluble drugs by direct

  9. Cell Cycle Target-based Therapy for Ovarian Cancer

    DTIC Science & Technology

    2008-09-01

    induces apoptosis in quiescent ovarian cancer cells. Strong inducers of apoptosis included flufenamic acid, flurbiprofen, celebrex and finasteride ...Thus, a whole panel of NSAIDs including Aspirin, Ibuprofen, Exisulind, Acetaminophen, Naproxen, NS-398, Celecoxib, Diclofenac, Finasteride ...Naproxen, 200µM NS-398, 50µM Celecoxib, 200µM Diclofenac, 50µM Finasteride , 200µM Flufenamic acid, 40µM Meloxican, 50µM Ebselen, 20nM Flurbiprofen or

  10. Disappearance kinetics of solutes from synovial fluid after intra-articular injection.

    PubMed Central

    Owen, S G; Francis, H W; Roberts, M S

    1994-01-01

    1. Five rheumatoid patients with a knee joint effusion participated in the study. An aqueous solution (0.1 to 0.2 ml) containing paracetamol, salicylate, diclofenac and [125I]-albumin was injected into a given joint to yield target concentrations of approximately 20 micrograms ml-1 for diclofenac, salicylate and paracetamol and 10(8) counts ml-1 for [125I]-albumin. 2. Paracetamol, salicylate and diclofenac were analysed in synovial fluid by h.p.l.c. [125I]-albumin was analysed using gamma counting. 3. The clearances (+/- s.d.) obtained for the solutes were [125I]-albumin (0.0053 +/- 0.0019 l h-1), diclofenac (0.0096 +/- 0.0061 l h-1), salicylate (0.024 +/- 0.022 l h-1) and paracetamol (0.055 +/- 0.041 l h-1). The corresponding fractions unbound of these solutes in synovial fluid were 0.0, < or = 0.01, 0.34 +/- 0.09 and 0.85 +/- 0.10, respectively. 4. Diffusion of unbound solute through the synovium is estimated to account for (+/- s.d.) 0.52 +/- 0.08, 0.87 +/- 0.06 and 0.99 +/- 0.01 of the total clearance of diclofenac, salicylate and paracetamol from the joint space, respectively. The remaining proportion of clearance is accounted for by efflux of solute bound to albumin. 5. An expression for the ratio of synovial fluid to total plasma concentrations after systemic administration was developed to include both diffusion of unbound solute and albumin flux. Most solutes appear to satisfy the conditions in which this expression reduces to the limiting case where the unbound concentration of the solute is identical in the synovial fluid and plasma under steady state conditions. PMID:7833225

  11. Effects of reference analgesics and psychoactive drugs on the noxious heat threshold of mice measured by an increasing-temperature water bath.

    PubMed

    Boros, Melinda; Benkó, Rita; Bölcskei, Kata; Szolcsányi, János; Barthó, Loránd; Pethő, Gábor

    2013-12-01

    The study aimed at validating an increasing-temperature water bath suitable for determining the noxious heat threshold for use in mice. The noxious heat threshold was determined by immersing the tail of the gently held awake mouse into a water container whose temperature was near-linearly increased at a rate of 24°C/min. until the animal withdrew its tail, that is, heating attained the noxious threshold. The effects of standard analgesic, neuroleptic and anxiolytic drugs were investigated in a parallel way on both the noxious heat threshold and the psychomotor activity assessed by the open field test. Morphine, diclofenac and metamizol (dipyrone) elevated the heat threshold of mice with minimum effective doses of 6, 30 and 1000 mg/kg i.p., respectively. These doses of morphine and diclofenac failed to induce any remarkable effect on psychomotor activity in the open field test while that of metamizol exerted a profound inhibition. The anxiolytic diazepam and the neuroleptic droperidol at doses evoking a mild and moderate, respectively, psychomotor inhibition failed to alter the heat threshold. Combination of a subliminal dose of morphine (regarding both antinociceptive and psychomotor inhibitory action) with diclofenac, metamizol, diazepam or droperidol at doses also subliminal regarding the thermal antinociceptive effect elevated the noxious heat threshold without major additional effects in the open field test. It is concluded that the increasing-temperature water bath is suitable for studying the thermal antinociceptive effects of morphine and diclofenac as well as the morphine-sparing action of diclofenac, metamizol, droperidol and diazepam. Behavioural testing is recommended when testing analgesics. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

  12. Three Newly Approved Analgesics: An Update

    PubMed Central

    Saraghi, Mana; Hersh, Elliot V.

    2013-01-01

    Since 2008, three new analgesic entities, tapentadol immediate release (Nucynta) diclofenac potassium soft gelatin capsules (Zipsor), and bupivacaine liposome injectable suspension (EXPAREL) were granted US Food and Drug Administration (FDA) approval to treat acute pain. Tapentadol immediate-release is a both a mu-opioid agonist and a norepinephrine reuptake inhibitor, and is indicated for the treatment of moderate to severe pain. Diclofenac potassium soft gelatin capsules are a novel formulation of diclofenac potassium, which is a nonsteroidal anti-inflammatory drug (NSAID), and its putative mechanism of action is through inhibition of cyclooxygenase enzymes. This novel formulation of diclofenac allows for improved absorption at lower doses. Liposomal bupivacaine is a new formulation of bupivacaine intended for single-dose infiltration at the surgical site for postoperative analgesia. Bupivacaine is slowly released from this liposomal vehicle and can provide prolonged analgesia at the surgical site. By utilizing NSAIDs and local anesthetics to decrease the transmission of afferent pain signals, less opioid analgesics are needed to achieve analgesia. Since drug-related adverse events are frequently dose related, lower doses from different drug classes may be employed to reduce the incidence of adverse effects, while producing synergistic analgesia as part of a multimodal analgesic approach to acute pain. PMID:24423420

  13. Diclofenac Transdermal Patch

    MedlinePlus

    ... will be applying the patch. Cut open the envelope containing the patches, cutting on the dotted line ... it. Pull apart the zipper seal on the envelope and remove one patch. Reseal the envelope by ...

  14. The efficacy of Curcuma Longa L. extract as an adjuvant therapy in primary knee osteoarthritis: a randomized control trial.

    PubMed

    Pinsornsak, Piya; Niempoog, Sunyarn

    2012-01-01

    Nonsteroidal anti-inflammatory Drugs (NSAIDs) is one of the most commonly use medication for treatment of knee osteoarthritis which has the analgesic and anti-inflammation by inhibition of prostaglandin synthesis via COX-1 and COX-2 isoenzyme. The problem of prolong using NSAIDs has side effect on kidney, liver and GI system. Curcumin longa extract Curcumin) is the Asian herbal medicine that has the anti-inflammatory effect by down regulate activation of NF-kappaB and proinflammatory cytokines such as Tumor Necrotic Factor-alpha, Interleukin-1, Interleukin-8, and Nitric Oxide Syntase. Many research data had advocate for the combination therapy which can increase safety and efficacy with less side effect compare with monotherapy regimen especially when the medicine has the different mechanism of action. The present study is the double blind prospective randomized control trial to evaluate the efficacy of curcumin as an adjuvant therapy of diclofenac in primary knee osteoarthritis. 44 patients were randomized to take NSAIDs (diclofenac) 75 mg/d with placebo and the other 44 took NSAIDs (diclofenac) 75 mg/d with curcumin 1,000 mg/d for 3 months. The authors evaluated the Visual Analog Scale (VAS) for pain and Knee Injury and Osteoarthritis Outcome Score (KOOS) every month for 3 months. At the end of study 36 patients were completed for the first group and 37 for the study group. There was no difference in VAS [p-value = 0.923 (F = 0.009)]. The KOOS was analyzed in 5 categories symptom, pain, function in daily living, function in sport and recreation and knee related quality of life. The curcumin with diclofenac group had tendency to be better in Pain and Function in daily living, but there were no statistic different in all group [p-value = 0.412 (F = 0.683), p-value = 0.814 (F = 0.056), p-value = 0.446 (F = 0.589), p-value = 0.224 (F = 1.511) and p-value = 0.938 (F = 0.006)]. In conclusion, the adjuvant therapy ofcurcumin with diclofenac has the potential beneficial

  15. Removal of pharmaceuticals from wastewater by biological processes, hydrodynamic cavitation and UV treatment.

    PubMed

    Zupanc, Mojca; Kosjek, Tina; Petkovšek, Martin; Dular, Matevž; Kompare, Boris; Širok, Brane; Blažeka, Željko; Heath, Ester

    2013-07-01

    To augment the removal of pharmaceuticals different conventional and alternative wastewater treatment processes and their combinations were investigated. We tested the efficiency of (1) two distinct laboratory scale biological processes: suspended activated sludge and attached-growth biomass, (2) a combined hydrodynamic cavitation-hydrogen peroxide process and (3) UV treatment. Five pharmaceuticals were chosen including ibuprofen, naproxen, ketoprofen, carbamazepine and diclofenac, and an active metabolite of the lipid regulating agent clofibric acid. Biological treatment efficiency was evaluated using lab-scale suspended activated sludge and moving bed biofilm flow-through reactors, which were operated under identical conditions in respect to hydraulic retention time, working volume, concentration of added pharmaceuticals and synthetic wastewater composition. The suspended activated sludge process showed poor and inconsistent removal of clofibric acid, carbamazepine and diclofenac, while ibuprofen, naproxen and ketoprofen yielded over 74% removal. Moving bed biofilm reactors were filled with two different types of carriers i.e. Kaldnes K1 and Mutag BioChip™ and resulted in higher removal efficiencies for ibuprofen and diclofenac. Augmentation and consistency in the removal of diclofenac were observed in reactors using Mutag BioChip™ carriers (85%±10%) compared to reactors using Kaldnes carriers and suspended activated sludge (74%±22% and 48%±19%, respectively). To enhance the removal of pharmaceuticals hydrodynamic cavitation with hydrogen peroxide process was evaluated and optimal conditions for removal were established regarding the duration of cavitation, amount of added hydrogen peroxide and initial pressure, all of which influence the efficiency of the process. Optimal parameters resulted in removal efficiencies between 3-70%. Coupling the attached-growth biomass biological treatment, hydrodynamic cavitation/hydrogen peroxide process and UV treatment

  16. [Pharmacological analysis of anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation].

    PubMed

    Gapeev, A B; Lushnikov, K V; Shumilina, Iu V; Chemeris, N K

    2006-01-01

    The anti-inflammatory effect of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR, 42.0 GHz, 0.1 mW/cm2) was compared with the action of the known anti-inflammatory drug sodium diclofenac and the antihistamine clemastine on acute inflammatory reaction in NMRI mice. The local inflammatory reaction was induced by intraplantar injection of zymosan into the left hind paw. Sodium diclofenac in doses of 2, 3, 5, 10, and 20 mg/kg or clemastine in doses of 0.02, 0.1, 0.2, 0.4, and 0.6 mg/kg were injected intraperitoneally 30 min after the initiation of inflammation. The animals were whole-body exposed to EHF EMR for 20 min at 1 h after the initiation of inflammation. The inflammatory reaction was assessed over 3 - 8 h after the initiation by measuring the footpad edema and hyperthermia of the inflamed paw. Sodium diclofenac in doses of 5 - 20 mg/kg reduced the exudative edema on the average by 26% as compared to the control. Hyperthermia of the inflamed paw decreased to 60% as the dose of was increased diclofenac up to 20 mg/kg. EHF EMR reduced both the footpad edema and hyperthermia by about 20%, which was comparable with the effect of a single therapeutic dose of diclofenac (3 - 5 mg/kg). The combined action of diclofenac and the exposure to the EHF EMR caused a partial additive effect. Clemastine in doses of 0.02-0.4 mg/kg it did not cause any significant effects on the exudative edema, but in a dose of 0.6 mg/kg it reduced edema by 14 - 22% by 5 - 8 h after zymosan injection. Clemastine caused a dose-dependent increase in hyperthermia of inflamed paw at doses of 0.02-0.2 mg/kg and did not affect the hyperthermia at doses of 0.4 and 0.6 mg/kg. The combined action of clemastine and EHF EMR exposure caused a dose-dependent abolishment of the anti-inflammatory effect of EHF EMR. The results obtained suggest that both arachidonic acid metabolites and histamine are involved in the realization of anti-inflammatory effects of low-intensity

  17. New Approaches for Prostate Cancer Combination Therapy

    DTIC Science & Technology

    2008-04-01

    5 times whereas Finasteride , Diclofenac and Sulindac Sulfone 5 can be reduced 2 times when compared with the solvent controls, and still resulting...Flufenamic acid and Sulindac Sulfide; 20, 10, 5 and 2nM Flurbiprofen; 50, 25,10 and 5 µM Finasteride ; 200, 100,50 and 25 µM NS-398 and Sulindac...Diclofenac, Sulindac Sulfide, Finasteride and NS398 and NF-B inhibitors 6-Amino-4-(4-phenoxyphenylethylamino) quinazoline and IKK- 2 inhibitor SC-514

  18. Analysis of drug metabolism activities in a miniaturized liver cell bioreactor for use in pharmacological studies.

    PubMed

    Hoffmann, Stefan A; Müller-Vieira, Ursula; Biemel, Klaus; Knobeloch, Daniel; Heydel, Sandra; Lübberstedt, Marc; Nüssler, Andreas K; Andersson, Tommy B; Gerlach, Jörg C; Zeilinger, Katrin

    2012-12-01

    Based on a hollow fiber perfusion technology with internal oxygenation, a miniaturized bioreactor with a volume of 0.5 mL for in vitro studies was recently developed. Here, the suitability of this novel culture system for pharmacological studies was investigated, focusing on the model drug diclofenac. Primary human liver cells were cultivated in bioreactors and in conventional monolayer cultures in parallel over 10 days. From day 3 on, diclofenac was continuously applied at a therapeutic concentration (6.4 µM) for analysis of its metabolism. In addition, the activity and gene expression of the cytochrome P450 (CYP) isoforms CYP1A2, CYP2B6, CYP2C9, CYP2D6, and CYP3A4 were assessed. Diclofenac was metabolized in bioreactor cultures with an initial conversion rate of 230 ± 57 pmol/h/10(6) cells followed by a period of stable conversion of about 100 pmol/h/10(6) cells. All CYP activities tested were maintained until day 10 of bioreactor culture. The expression of corresponding mRNAs correlated well with the degree of preservation. Immunohistochemical characterization showed the formation of neo-tissue with expression of CYP2C9 and CYP3A4 and the drug transporters breast cancer resistance protein (BCRP) and multidrug resistance protein 2 (MRP2) in the bioreactor. In contrast, monolayer cultures showed a rapid decline of diclofenac conversion and cells had largely lost activity and mRNA expression of the assessed CYP isoforms at the end of the culture period. In conclusion, diclofenac metabolism, CYP activities and gene expression levels were considerably more stable in bioreactor cultures, making the novel bioreactor a useful tool for pharmacological or toxicological investigations requiring a highly physiological in vitro representation of the liver. Copyright © 2012 Wiley Periodicals, Inc.

  19. Improved WOMAC score following 16-week treatment with bromelain for knee osteoarthritis.

    PubMed

    Kasemsuk, Thitima; Saengpetch, Nadhaporn; Sibmooh, Nathawut; Unchern, Supeenun

    2016-10-01

    Treatment with bromelain-containing enzyme preparation for 3-4 weeks is effective for treatment of knee osteoarthritis (OA). Here, we aimed to assess 16-week treatment with bromelain in mild-to-moderate knee OA patients. We performed a randomized, single-blind, active-controlled pilot study. Forty knee OA patients were randomized to receive oral bromelain (500 mg/day) or diclofenac (100 mg/day). Primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) analyzed by Wilcoxon signed rank test. Secondary outcome was the short-form 36 (SF-36). Plasma malondialdehyde (MDA) and nitrite were measured as oxidative stress markers. There was no difference in WOMAC and SF-36 scores compared between bromelain and diclofenac groups after 4 weeks. At week 4, the improvement of total WOMAC and pain subscales from baseline was observed in both groups; however, two patients given diclofenac had adverse effects leading to discontinuation of diclofenac. However, observed treatment difference was inconclusive. At week 16 of bromelain treatment, the patients had improved total WOMAC scores (12.2 versus 25.5), pain subscales (2.4 versus 5.6), stiffness subscales (0.8 versus 2.0), and function subscales (9.1 versus 17.9), and physical component of SF-36 (73.3 versus 65.4) as compared with baseline values. OA patients had higher plasma MDA, nitrite, and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated whole blood but lower plasma α-tocopherol than control subjects. Plasma MDA and LPS-stimulated PGE2 production were decreased at week 16 of bromelain treatment. Bromelain has no difference in reducing symptoms of mild-to-moderate knee OA after 4 weeks when compared with diclofenac.

  20. Influence of different recombinant systems on the cooperativity exhibited by cytochrome P4503A4.

    PubMed

    Zhang, Z; Li, Y; Shou, M; Zhang, Y; Ngui, J S; Stearns, R A; Evans, D C; Baillie, T A; Tang, W

    2004-05-01

    1. The in vitro cooperativity exhibited by cytochrome P450 (CYP) 3A4 is influenced by the nature of the recombinant system in which the phenomenon is studied. Diclofenac, piroxicam and R-warfarin were used as model substrates, and quinidine was the effector. 2. The 5-, 5'- and 10-hydroxylation of diclofenac, piroxicam and R-warfarin, respectively, were enhanced five- to sevenfold by quinidine in human liver microsomal incubations. Whereas these cooperative drug interactions were apparent in incubations with CYP3A4 expressed in human lymphoblast cells, similar phenomena were not observed with the enzyme expressed in insect cells. 3. Insect cell microsomes were treated with a detergent and CYP3A4 was solubilized into a buffer medium. In incubations with CYP3A4 'freed' from its host membrane, the 5-hydroxylation of diclofenac increased with increasing quinidine concentrations, reaching a maximal eightfold elevation relative to controls. The metabolism of piroxicam and warfarin was similarly enhanced by quinidine. 4. Kinetically, enhancement by quinidine of the 5-hydroxylation of diclofenac in incubations with solubilized CYP3A4 was characterized by increases in the rate of metabolism with little change in the substrate-binding affinity. Conversely, the 3-hydroxylation of quinidine was not affected by diclofenac. 5. The data suggest that certain properties of CYP3A4 are masked by expression of the protein in insect cells and reinforce the concept that the enzyme possesses multiple binding domains. The absence of cooperative drug interactions with quinidine when CYP3A4 was expressed in insect cells might be due to an absence of enzyme conformation changes on quinidine binding, or the inability of quinidine to gain access to a putative effector-binding domain. 6. Caution should be exercised when comparing models for CYP3A4 cooperativity derived from different recombinant preparations of the enzyme.

  1. Status of hormones and painkillers in wastewater effluents across several European states-considerations for the EU watch list concerning estradiols and diclofenac.

    PubMed

    Schröder, P; Helmreich, B; Škrbić, B; Carballa, M; Papa, M; Pastore, C; Emre, Z; Oehmen, A; Langenhoff, A; Molinos, M; Dvarioniene, J; Huber, C; Tsagarakis, K P; Martinez-Lopez, E; Pagano, S Meric; Vogelsang, C; Mascolo, G

    2016-07-01

    Present technologies for wastewater treatment do not sufficiently address the increasing pollution situation of receiving water bodies, especially with the growing use of personal care products and pharmaceuticals (PPCP) in the private household and health sector. The relevance of addressing this problem of organic pollutants was taken into account by the Directive 2013/39/EU that introduced (i) the quality evaluation of aquatic compartments, (ii) the polluter pays principle, (iii) the need for innovative and affordable wastewater treatment technologies, and (iv) the identification of pollution causes including a list of principal compounds to be monitored. In addition, a watch list of 10 other substances was recently defined by Decision 2015/495 on March 20, 2015. This list contains, among several recalcitrant chemicals, the painkiller diclofenac and the hormones 17β-estradiol and 17α-ethinylestradiol. Although some modern approaches for their removal exist, such as advanced oxidation processes (AOPs), retrofitting most wastewater treatment plants with AOPs will not be acceptable as consistent investment at reasonable operational cost. Additionally, by-product and transformation product formation has to be considered. The same is true for membrane-based technologies (nanofiltration, reversed osmosis) despite of the incredible progress that has been made during recent years, because these systems lead to higher operation costs (mainly due to higher energy consumption) so that the majority of communities will not easily accept them. Advanced technologies in wastewater treatment like membrane bioreactors (MBR) that integrate biological degradation of organic matter with membrane filtration have proven a more complete elimination of emerging pollutants in a rather cost- and labor-intensive technology. Still, most of the presently applied methods are incapable of removing critical compounds completely. In this opinion paper, the state of the art of European WWTPs is

  2. Evaluation of aquatic plants for removing polar microcontaminants: a microcosm experiment.

    PubMed

    Matamoros, Víctor; Nguyen, Loc Xuan; Arias, Carlos A; Salvadó, Victòria; Brix, Hans

    2012-08-01

    Microcosm wetland systems (5 L containers) planted with Salvinia molesta, Lemna minor, Ceratophyllum demersum, and Elodea canadensis were investigated for the removal of diclofenac, triclosan, naproxen, ibuprofen, caffeine, clofibric acid and MCPA. After 38 days of incubation, 40-99% of triclosan, diclofenac, and naproxen were removed from the planted and unplanted reactors. In covered control reactors no removal was observed. Caffeine and ibuprofen were removed from 40% to 80% in planted reactors whereas removals in control reactors were much lower (2-30%). Removal of clofibric acid and MCPA were negligible in both planted and unplanted reactors. The findings suggested that triclosan, diclofenac, and naproxen were removed predominantly by photodegradation, whereas caffeine and naproxen were removed by biodegradation and/or plant uptake. Pseudo-first-order removal rate constants estimated from nonlinear regressions of time series concentration data were used to describe the contaminant removals. Removal rate constants ranged from 0.003 to 0.299 d(-1), with half-lives from 2 to 248 days. The formation of two major degradation products from ibuprofen, carboxy-ibuprofen and hydroxy-ibuprofen, and a photodegradation product from diclofenac, 1-(8-Chlorocarbazolyl)acetic acid, were followed as a function of time. This study emphasizes that plants contribute to the elimination capacity of microcontaminants in wetlands systems through biodegradation and uptake processes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Compound-Specific Stable Isotope Fractionation of Pesticides and Pharmaceuticals in a Mesoscale Aquifer Model.

    PubMed

    Schürner, Heide K V; Maier, Michael P; Eckert, Dominik; Brejcha, Ramona; Neumann, Claudia-Constanze; Stumpp, Christine; Cirpka, Olaf A; Elsner, Martin

    2016-06-07

    Compound-specific isotope analysis (CSIA) receives increasing interest for its ability to detect natural degradation of pesticides and pharmaceuticals. Despite recent laboratory studies, CSIA investigations of such micropollutants in the environment are still rare. To explore the certainty of information obtainable by CSIA in a near-environmental setting, a pulse of the pesticide bentazone, the pesticide metabolite 2,6-dichlorobenzamide (BAM), and the pharmaceuticals diclofenac and ibuprofen was released into a mesoscale aquifer with quasi-two-dimensional flow. Concentration breakthrough curves (BTC) of BAM and ibuprofen demonstrated neither degradation nor sorption. Bentazone was transformed but did not sorb significantly, whereas diclofenac showed both degradation and sorption. Carbon and nitrogen CSIA could be accomplished in similar concentrations as for "traditional" priority pollutants (low μg/L range), however, at the cost of uncertainties (0.4-0.5‰ (carbon), 1‰ (nitrogen)). Nonetheless, invariant carbon and nitrogen isotope values confirmed that BAM was neither degraded nor sorbed, while significant enrichment of (13)C and in particular (15)N corroborated transformation of diclofenac and bentazone. Retardation of diclofenac was reflected in additional (15)N sorption isotope effects, whereas isotope fractionation of transverse dispersion could not be identified. These results provide a benchmark on the performance of CSIA to monitor the reactivity of micropollutants in aquifers and may guide future efforts to accomplish CSIA at even lower concentrations (ng/L range).

  4. Occurrence and distribution of selected pharmaceuticals and personal care products in aquatic environments: a comparative study of regions in China with different urbanization levels.

    PubMed

    Chen, Hong; Li, Xiaojuan; Zhu, Saichang

    2012-07-01

    We analyzed and compared the distributions of 13 target pharmaceuticals in different water samples from the Hangzhou metropolitan area and Linan County, Southeast China. Sampling was conducted in five hospitals, two wastewater treatment plants (WWTPs), and Qiantang River. Samples were concentrated by solid-phase extraction and PPCP concentrations were determined by UPLC-MS/MS. Trimethoprim, erythromycin A dihydrate, norfloxacin, ofloxacin, diclofenac sodium, and atenolol were the most frequently detected pharmaceuticals in hospital effluents. Most of the pharmaceutical concentrations in hospital effluents were higher than those in the WWTP influents. Although both WWTPs adopt the anaerobic-aerobic-anoxic treatment process, the removal rates for pharmaceuticals, such as trimethoprim and diclofenac sodium, were completely different. Meanwhile, erythromycin A dihydrate, ofloxacin, penicillin-G, cephalexin, cefazolin, ibuprofen, and diclofenac sodium were detected in Qiantang River. These results indicate that hospitals are more concentrated sources of pharmaceuticals than WWTPs, and the WWTPs are not the only route of entry of pharmaceuticals into aquatic environments in these two regions.

  5. Study of Nephrotoxic Potential of Acetaminophen in Birds

    PubMed Central

    Jayakumar, K.; Mohan, K.; Swamy, H. D. Narayana; Shridhar, N. B.; Bayer, M. D.

    2010-01-01

    The present study was designed to evaluate the effect of acetaminophen on kidneys of birds by comparison with diclofenac that is used as positive control. The birds of Group I served as negative control and received normal saline, whereas Group II birds received diclofenac injection (2.5 mg/kg IM) and Group III birds received acetaminophen injection (10 mg/kg IM) for a period of seven days daily. The birds treated with diclofenac showed severe clinical signs of toxicity accompanied with high mortality and significant increase (P<0.001) in serum creatinine and uric acid concentration. The creatinine and uric acid concentrations were consistent with gross and histopathological findings. The negative control and acetaminophen-treated groups showed no adverse clinical signs, serum creatinine and uric acid concentrations were normal, and no gross or histopathological changes in kidneys were observed. Thus, it was concluded that acetaminophen can be used for treatment in birds without any adverse effect on kidneys. PMID:21170252

  6. Effects of anti-inflammatory compounds on sulfur mustard injured cells: Recommendations and caveats suggested by in vitro cell culture models.

    PubMed

    Menacher, Georg; Steinritz, Dirk; Schmidt, Annette; Popp, Tanja; Worek, Franz; Gudermann, Thomas; Thiermann, Horst; Balszuweit, Frank

    2018-09-01

    Sulfur mustard (SM) is a vesicant agent who had its first military use 100 years ago, in Ypres. Since then it has been used in several conflicts like the Iran-Iraq war in the 1980s. The use of SM in Syria 2015 indicated the still existing threat. Despite decades of research no causal antidote against SM intoxication is available, so far. A SM intoxication is accompanied by necrosis, apoptosis and inflammation. To counteract the SM-induced inflammation, glucocorticoids and non-steroidal anti-inflammatory compounds (NSAIDs) are recommended. Aim of this study was to evaluate the efficacy of the anti-inflammatory compounds dexamethasone, ibuprofen and diclofenac in vitro. For that purpose, two different cell culture models were used. Firstly, a monoculture of keratinocytes (HaCaT) and secondly, an established co-culture of keratinocytes (HaCaT) and immunocompetent cells (THP-1) to identify the role of immune cells in the process and to mimic the dermal physiology more closely. Both models were challenged with different SM concentrations (100, 200 and 300μM) and treated with different anti-inflammatory compounds one hour after the SM exposure. Analytical analysis of necrosis (ToxiLight), apoptosis (CDDE) and inflammation (IL-6 and -8 ELISAs) followed 24h thereafter. Dexamethasone provided small but consistent protective effects in the monoculture. For the reduction of apoptosis, 3μM dexamethasone was sufficient. The most effective reduction regarding interleukin (IL) production was found with 6μM dexamethasone. Protective effects were less pronounced in co-culture, which implies, that the protective effects of dexamethasone are rather generic and not due to a modulation of the immune cells. Against our expectations, ibuprofen strongly amplified apoptosis and necrosis in SM exposed cells in the monoculture as well as the co-culture. Therefore, use of ibuprofen for treatment of SM intoxication should at least be considered most critically, if not even regarded as

  7. Non-Steroidal Anti-Inflammatory Drug Use and the Risk of Acute Myocardial Infarction in the General German Population: A Nested Case-Control Study.

    PubMed

    Thöne, Kathrin; Kollhorst, Bianca; Schink, Tania

    2017-09-01

    Use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with an increased relative risk of acute myocardial infarction (AMI), but the label warnings refer particularly to patients with cardiovascular risk factors. The magnitude of relative AMI risk for patients with and without cardiovascular risk factors varies between studies depending on the drugs and doses studied. The aim of our study was to estimate population-based relative AMI risks for individual and widely used NSAIDs, for a cumulative amount of NSAID use, and for patients with and without a prior history of cardiovascular risk factors. Based on data from the German Pharmacoepidemiological Research Database (GePaRD) of about 17 million insurance members from four statutory health insurance providers, for the years 2004-2009, a nested case-control study was conducted within a cohort of 3,476,931 new NSAID users classified into current, recent, or past users. Up to 100 controls were matched to each case by age, sex, and length of follow-up using risk set sampling. Multivariable conditional logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Duration of NSAID use was calculated by the cumulative amount of dispensed defined daily doses (DDDs), and stratified analyses were conducted for potential effect modifiers. Overall, 17,236 AMI cases were matched to 1,714,006 controls. Elevated relative AMI risks were seen for current users of fixed combinations of diclofenac with misoprostol (OR 1.76, 95% CI 1.26-2.45), indometacin (1.69, 1.22-2.35), ibuprofen (1.54, 1.43-1.65), etoricoxib (1.52, 1.24-1.87), and diclofenac (1.43, 1.34-1.52) compared with past use. A low cumulative NSAID amount was associated with a higher relative AMI risk for ibuprofen, diclofenac, and indometacin. The relative risk associated with current use of diclofenac, fixed combinations of diclofenac with misoprostol, etoricoxib, and ibuprofen was highest in the younger age group

  8. Changes in mechanical, chemical, and thermal sensitivity of the cornea after topical application of nonsteroidal anti-inflammatory drugs.

    PubMed

    Acosta, M Carmen; Berenguer-Ruiz, Leticia; García-Gálvez, Alberto; Perea-Tortosa, David; Gallar, Juana; Belmonte, Carlos

    2005-01-01

    In addition to their well-known anti-inflammatory actions, some of the nonsteroidal anti-inflammatory drugs (NSAIDs) appear to have an analgesic effect. In human subjects, the changes in threshold and intensity of sensations evoked by mechanical, chemical, and thermal stimulation of the cornea induced by topical administration of two commercial NSAIDs, diclofenac sodium (Voltaren; Novartis, Basel, Switzerland) and flurbiprofen (Ocuflur; Allergan, Irvine, CA), were studied. Corneal sensitivity was measured in 10 young, healthy subjects with a gas esthesiometer. Chemical (10%-70% CO2 in air), mechanical (0-264 mL/min), and thermal (corneal temperature changes between -4.5 degrees C and +3 degrees C around the normal value) stimuli were applied to the center of the cornea. The intensity and perceived magnitude of the psychophysical attributes of the evoked sensation were scored at the end of the pulse in a 10-cm, continuous visual analog scale (VAS). The threshold was expressed as the stimulus intensity that evoked a VAS score >0.5. Sensitivity was measured in both eyes of each subject on two separate days, one without treatment and the other 30 minutes after topical application of 0.03% flurbiprofen (seven subjects) or 0.1% diclofenac sodium (six subjects). Diclofenac attenuated significantly all the sensation parameters evoked by high-intensity mechanical, chemical, and thermal stimuli. Flurbiprofen produced a slight reduction of the sensations evoked by mechanical and chemical stimulation that became significant only for the irritation caused by chemical stimuli of maximum intensity (70% CO2). None of the drugs modified significantly the detection threshold of the different stimuli. Flurbiprofen had a very limited effect on sensations evoked by corneal stimulation, whereas diclofenac reduced the intensity of sensations evoked by stimuli of different modality, suggesting a mild local anesthetic effect of this drug on all types of corneal sensory fibers. Such

  9. Phytoremediation of pharmaceuticals--preliminary study.

    PubMed

    Kotyza, Jan; Soudek, Petr; Kafka, Zdenĕk; Vanĕk, Toás

    2010-03-01

    Phytoremediation of selected pharmaceuticals (diclofenac, ibuprofen, and acetaminophen) using Armoracia rusticana and Linum usitatissimum cell cultures and by hydroponically cultivated Lupinus albus, Hordeum vulgaris, and Phragmites australis plants in laboratory conditions is described. During in vitro experiments, the best results for acetaminophen were achieved using Armoracia rusticana hairy root cultures, where 100% of the starting amount was removed from the media during eight days. Total removal of ibuprofen and diclofenac was achieved using a Linum usitatissimum suspension culture after one and six days, respectively. In the hydroponic arrangement, the best results were achieved for Lupinus, where acetaminophen was totally removed from media during two or four days in concentrations of 0.1 or 0.2 mM, respectively. The best effectiveness of ibuprofen removal (50% of starting amount) was found in case of Phragmites. Effectiveness of all tested plants for diclofenac removal was low. The best removal was achieved using Phragmites in the case of 0.2 mM concentration-67% of the starting amount and Hordeum for 0.1 mM starting concentration, 56%.

  10. Transformation and Removal Pathways of Four Common PPCP/EDCs in Soil

    PubMed Central

    Dodgen, LK; Li, J; Wu, X; Lu, Z; Gan, JJ

    2014-01-01

    Pharmaceutical and personal care products (PPCPs) and endocrine disrupting chemicals (EDCs) enter the soil environment via irrigation with treated wastewater, groundwater recharge, and land application of biosolids. The transformation and fate of PPCP/EDCs in soil affects their potential for plant uptake and groundwater pollution. This study examined four PPCP/EDCs (bisphenol A, diclofenac, naproxen, and 4-nonylphenol) in soil by using 14C-labeling and analyzing mineralization, extractable residue, bound residue, and formation of transformation products. At the end of 112 d of incubation, the majority of 14C-naproxen and 14C-diclofenac was mineralized to 14CO2, while a majority of 14C-bisphenol A and 14C-nonylphenol was converted to bound residue. After 112 d, the estimated half-lives of the parent compounds were only 1.4 – 5.4 d. However a variety of transformation products were found and several for bisphenol A and diclofenac were identified, suggesting the need to consider degradation intermediates in soils impacted by PPCP/EDCs. PMID:24997388

  11. Diclofenac in municipal wastewater treatment plant: quantification using laser diode thermal desorption--atmospheric pressure chemical ionization--tandem mass spectrometry approach in comparison with an established liquid chromatography-electrospray ionization-tandem mass spectrometry method.

    PubMed

    Lonappan, Linson; Pulicharla, Rama; Rouissi, Tarek; Brar, Satinder K; Verma, Mausam; Surampalli, Rao Y; Valero, José R

    2016-02-12

    Diclofenac (DCF), a prevalent non-steroidal anti-inflammatory drug (NSAID) is often detected in wastewater and surface water. Analysis of the pharmaceuticals in complex matrices is often laden with challenges. In this study a reliable, rapid and sensitive method based on laser diode thermal desorption/atmospheric pressure chemical ionization (LDTD/APCI) coupled with tandem mass spectrometry (MS/MS) has been developed for the quantification of DCF in wastewater and wastewater sludge. An established conventional LC-ESI-MS/MS (liquid chromatography-electrospray ionization-tandem mass spectrometry) method was compared with LDTD-APCI-MS/MS approach. The newly developed LDTD-APCI-MS/MS method reduced the analysis time to 12s in lieu of 12 min for LC-ESI-MS/MS method. The method detection limits for LDTD-APCI-MS/MS method were found to be 270 ng L(-1) (LOD) and 1000 ng L(-1) (LOQ). Furthermore, two extraction procedures, ultrasonic assisted extraction (USE) and accelerated solvent extraction (ASE) for the extraction of DCF from wastewater sludge were compared and ASE with 95.6 ± 7% recovery was effective over USE with 86 ± 4% recovery. The fate and partitioning of DCF in wastewater (WW) and wastewater sludge (WWS) in wastewater treatment plant was also monitored at various stages of treatment in Quebec Urban community wastewater treatment plant. DCF exhibited affinity towards WW than WWS with a presence about 60% of DCF in WW in contrary with theoretical prediction (LogKow=4.51). Copyright © 2016 Elsevier B.V. All rights reserved.

  12. A comparative study to evaluate ultrasound-guided transversus abdominis plane block versus ilioinguinal iliohypogastric nerve block for post-operative analgesia in adult patients undergoing inguinal hernia repair.

    PubMed

    Kamal, Kirti; Jain, Parul; Bansal, Teena; Ahlawat, Geeta

    2018-04-01

    Both transversus abdominis plane (TAP) block and combined ilioinguinal-iliohypogastric (IIN/IHN) blocks are used routinely under ultrasound (USG) guidance for postoperative pain relief in patients undergoing inguinal hernia surgery. This study compares USG guided TAP Vs IIN/IHN block for post-operative analgesic efficacy in adults undergoing inguinal hernia surgery. Sixty adults aged 18 to 60 with American Society of Anesthesiologsts' grade I or II were included. After general anaesthesia, patients in Group I received USG guided unilateral TAP block using 0.75% ropivacaine 3 mg/kg (maximum 25 mL) and those in Group II received IIN/IHN block using 10 mL 0.75% ropivacaine. Postoperative rescue analgesia was with tramadol (intravenous) IV ± diclofenac IV in the first 4 h followed by oral diclofenac subsequently. Total analgesic consumption in the first 24 h was the primary objective, intraoperative haemodynamics, number of attempts and time required for performing the block as well as the postoperative pain scores were also evaluated. Time to first analgesic request was 319.8 ± 115.2 min in Group I and 408 ± 116.4 min in Group II ( P = 0.005). Seven patients (23.33%) in Group I and two (6.67%) in Group II required tramadol in first four hours. No patient in either groups received diclofenac IV. The average dose of tablet diclofenac was 200 ± 35.96 mg in Group I and 172.5 ± 34.96 mg in Group II ( P = 0. 004). USG guided IIN/IHN block reduces the postoperative analgesic requirement compared to USG guided TAP block.

  13. Characterization of caprylocaproyl macrogolglycerides based microemulsion drug delivery vehicles for an amphiphilic drug.

    PubMed

    Djordjevic, Ljiljana; Primorac, Marija; Stupar, Mirjana; Krajisnik, Danina

    2004-03-01

    Microemulsion systems composed of water, isopropyl myristate, PEG-8 caprylic/capric glycerides (Labrasol), and polyglyceryl-6 dioleate (Plurol Oleique), were investigated as potential drug delivery vehicles for an amphiphilic model drug (diclofenac diethylamine). Pseudo-ternary phase diagram of the investigated system, at constant surfactant/cosurfactant mass ratio (Km 4:1) was constructed at room temperature by titration, and the oil-to-surfactant/cosurfactant mass ratios (O/SC) that exhibit the maximum in the solubilization of water were found. This allowed the investigation of the continuous structural inversion from water-in-oil to oil-in-water microemulsions on dilution with water phase. Furthermore, electrical conductivity (sigma) of the system at Km 1:4, and O/SC 0.250 was studied, and the percolation phenomenon was observed. Conductivity and apparent viscosity (eta') measurement results well described colloidal microstructure of the selected formulations, including gradual changes during their formation. Moreover, sigma, eta', and pH values of six selected microemulsion vehicles which differ in water phase volume fraction (phi(w)) at the selected Km and O/SC values, were measured. In order to investigate the influence of the amphiphilic drug on the vehicle microstructures, each system was formulated with 1.16% (w/w) diclofenac diethylamine. Electrical conductivity, and eta' of the investigated systems were strongly affected by drug incorporation. The obtained results suggest that diclofenac diethylamine interacts with the specific microstructure of the investigated vehicles, and that the different drug release kinetics from these microemulsions may be expected. The investigated microemulsions should be very interesting as new drug carrier systems for dermal application of diclofenac diethylamine.

  14. Energy metabolism and biotransformation as endpoints to pre-screen hepatotoxicity using a liver spheroid model

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xu Jinsheng; Purcell, Wendy M.

    2006-10-15

    The current study investigated liver spheroid culture as an in vitro model to evaluate the endpoints relevant to the status of energy metabolism and biotransformation after exposure to test toxicants. Mature rat liver spheroids were exposed to diclofenac, galactosamine, isoniazid, paracetamol, m-dinitrobenzene (m-DNB) and 3-nitroaniline (3-NA) for 24 h. Pyruvate uptake, galactose biotransformation, lactate release and glucose secretion were evaluated after exposure. The results showed that pyruvate uptake and lactate release by mature liver spheroids in culture were maintained at a relatively stable level. These endpoints, together with glucose secretion and galactose biotransformation, were related to and could reflect themore » status of energy metabolism and biotransformation in hepatocytes. After exposure, all of the test agents significantly reduced glucose secretion, which was shown to be the most sensitive endpoint of those evaluated. Diclofenac, isoniazid, paracetamol and galactosamine reduced lactate release (P < 0.01), but m-DNB increased lactate release (P < 0.01). Diclofenac, isoniazid and paracetamol also reduced pyruvate uptake (P < 0.01), while galactosamine had little discernible effect. Diclofenac, galactosamine, paracetamol and m-DNB also reduced galactose biotransformation (P < 0.01), by contrast, isoniazid did not. The metabolite of m-DNB, 3-NA, which served as a negative control, did not cause significant changes in lactate release, pyruvate uptake or galactose biotransformation. It is concluded that pyruvate uptake, galactose biotransformation, lactate release and glucose secretion can be used as endpoints for evaluating the status of energy metabolism and biotransformation after exposure to test agents using the liver spheroid model to pre-screen hepatotoxicity.« less

  15. Behavior of pharmaceuticals in waste water treatment plant in Japan.

    PubMed

    Matsuo, H; Sakamoto, H; Arizono, K; Shinohara, R

    2011-07-01

    The fate of pharmaceuticals in a wastewater treatment plant (WWTP) in Kumamoto, Japan with activated sludge treatment is reported. Selected pharmaceuticals were detected in influent. Results from the present study confirmed that Acetaminophen, Amoxicillin, Ampicillin and Famotidine were removed at a high rate (>90% efficiency). In contrast, removal efficiency of Ketoprofen, Losartan, Oseltamivir, Carbamazepine, and Diclofenac was relatively low (<50%). The selected pharmaceuticals were also detected in raw sludge. In digestive process, Indomethacin, Atenolol, Famotidine, Trimethoprim and Cyclofosamide were removed at a high (>70% efficiency). On the other hand, removal of Carbamazepine, Ketoprofen and Diclofenac was not efficient (<50%).

  16. Comparative evaluation of effect of preoperative alprazolam and diclofenac potassium on the success of inferior alveolar, Vazirani-Akinosi, and Gow-Gates techniques for teeth with irreversible pulpitis: Randomized controlled trial

    PubMed Central

    Shetkar, Pratibha; Jadhav, Ganesh Ranganath; Mittal, Priya; Surapaneni, Saikalyan; Kalra, Dheeraj; Sakri, Mohan; Basavaprabhu, A

    2016-01-01

    Introduction: In teeth with irreversible pulpitis, successful local anesthesia is hard to achieve irrespective of the amount of local anesthesia and technique used. Such cases can be managed by concoction of pre-medications like anxiolytics, analgesics and effective local anesthesia. This double-blind, placebo-controlled study was planned to evaluate the effect of oral administration of alprazolam and diclofenac potassium on the success rate of inferior alveolar nerve block (IANB), Gow-Gates (GG) and Vazirani-Akinosi (VA) techniques for the root canal treatment of mandibular molars with irreversible pulpitis. Method: 198 emergency patients with symptomatic irreversible pulpitis were randomly divided into three groups as – A, B and C receiving IANB, GG or V-A respectively using 2% lidocaine with 1: 100,000 epinephrine. These groups were sub-divided into sub-groups I and II as control and pre-medication groups. Patients who did not react to the stimulus made by an explorer between the canine and first premolar and showing subjective lip and tongue numbness were included in the study. Result: All sub-groups showed statistically significant reduction in VAS score. However sub-groups V and VI (that is GG with and without pre-medication respectively) showed best improvement in initial severe pain in mandibular molars with irreversible pulpitis. Moreover, all pre-medication sub-groups showed better pain control compared to respective control groups. Conclusion: It was concluded that use of pre-medications in the form of combination of anxiolytics and analgesics improves the success rate of local anesthesia in teeth with irreversible pulpitis. Use of anxiolytics eases the patient in endodontic emergencies. Also use of GG along with pre-medication is the best method for effective pain management of acute pain in irreversible pulpitis. PMID:27656053

  17. Perioperative bromelain reduces pain and swelling and improves quality of life measures after mandibular third molar surgery: a randomized, double-blind, placebo-controlled clinical trial.

    PubMed

    Majid, Omer Waleed; Al-Mashhadani, Bashar Adil

    2014-06-01

    The purpose of the present study was to compare the effect of oral bromelain (4 × 250 mg) versus oral diclofenac sodium (4 × 25 mg) on pain, swelling, trismus, and quality of life (QOL) after surgical removal of impacted lower third molars. A randomized, double-blind, placebo-controlled study was planned. The sample included patients requiring extraction under local anesthesia of a single partial bony impacted mandibular third molar. The patients were randomly distributed into 1 of 3 groups: bromelain, diclofenac, and placebo. Treatment started 1 day before surgery and continued for 4 days. The predictor variable was the type of the drug given to the patients. The outcome variables were pain, swelling, and trismus, which were measured at 1, 3, and 7 days postoperatively. The other study variables included QOL measures to assess the patients' perception regarding the effect of surgery on their well-being and daily activities. A validated questionnaire was used to measure QOL. The data were analyzed using analysis of variance, multiple measures analysis of variance, or Pearson's χ(2) test, as appropriate. P < .05 was considered significant. A total of 45 subjects requiring surgical removal of a single impacted mandibular third molar under local anesthesia were included in the present study. The bromelain and diclofenac groups both showed a significant reduction in pain compared with the placebo group at all intervals (P < .05). Diclofenac also resulted in a significant reduction of swelling at 3 and 7 days, and bromelain resulted in an insignificant reduction. A nonsignificant reduction in trismus occurred in both treatment groups compared with the placebo group. Both treatment groups also showed a significant difference in the effect on QOL in most subscales and total scores (P < .05). The effect was comparable between the 2 treatment groups for all parameters and at all intervals. The results of our study have shown that oral bromelain is an effective therapy to

  18. Photodegradation of pharmaceutical persistent pollutants using hydroxyapatite-based materials.

    PubMed

    Márquez Brazón, E; Piccirillo, C; Moreira, I S; Castro, P M L

    2016-11-01

    Pharmaceutical persistent pollutants pose a serious threat to the environment. The aim of this study was to use, for the first time, hydroxyapatite-based biomaterials as photocatalysts to degrade micropollutants. Diclofenac and fluoxetine were selected for these initial tests. Hydroxyapatite (Ca10(PO4)(OH)2, HAp) is one of the most commonly used biomaterials/bioceramics, being a major constituent of bone. In this work sustainable HAp-based materials of marine origin, obtained from cod fish bones, were used; these photocatalysts were previously fully studied and characterised. Both single-phase HAp and HAp-titania multicomponent materials (1 wt% TiO2) were employed as UV light photocatalysts, the latter showing better performance, indicated by higher degradation rates of both compounds. The HAp-titania photocatalyst showed excellent degradation of both persistent pollutants, the maximum degradation performance being 100% for fluoxetine and 92% for diclofenac, with pollutant and photocatalyst concentrations of 2 ppm and 4 g/L, respectively. Variations in features such as pollutant and photocatalyst concentrations were investigated, and results showed that generally fluoxetine was degraded more easily than diclofenac. The photocatalyst's crystallinity was not affected by the photodegradation reaction; indeed the material exhibited good photostability, as the degradation rate did not decrease when the material was reused. Tests were also performed using actual treated wastewater; the photocatalyst was still effective, even if with lower efficiency (-20% and -4% for diclofenac and fluoxetine, respectively). TOC analysis showed high but incomplete mineralisation of the pollutants (maximum 60% and 80% for DCF and FXT, respectively). Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Non-invasive diagnosis and monitoring of actinic cheilitis with reflectance confocal microscopy.

    PubMed

    Ulrich, M; González, S; Lange-Asschenfeldt, B; Roewert-Huber, J; Sterry, W; Stockfleth, E; Astner, S

    2011-03-01

    Actinic cheilitis (AC) represents the equivalent of actinic keratosis on the lip. Various treatment modalities are available and the efficacy of diclofenac in hyaluronic acid has recently been described. Reflectance confocal microscopy (RCM) is a non-invasive imaging technique which has recently been applied for the diagnosis of actinic keratoses. Herein, we describe the applicability of RCM for the diagnosis of AC and for monitoring of treatment response of AC to diclofenac in hyaluronic acid. Ten Caucasian patients with clinical suspicion for AC were included in this study. To obtain a non-invasive diagnosis, RCM was performed at baseline, followed by biopsy and respective confocal-histopathological correlation. Six patients with a histological diagnosis of AC were treated with diclofenac in hyaluronic acid, whereby monitoring was performed by RCM. Reflectance confocal microscopy was able to correctly identify 6/7 cases of AC and 3/3 cases of benign lesions. The most important RCM criteria for diagnosis of AC were cellular atypia at the stratum spinosum and granulosum with atypical honeycomb pattern. One patient with AC was misclassified as inflammatory cheilitis by RCM as it showed marked inflammatory response and lacked clear signs of cellular atypia on RCM imaging. Following topical treatment with diclofenac gel, 5/6 patients (83%) showed a good treatment response with regression of dysplasia on consecutive RCM examination. Reflectance confocal microscopy is a promising tool for the non-invasive diagnosis and monitoring of actinic cheilitis. However, marked inflammation represents a potential diagnostic pitfall. In this regard, biopsy should be performed in doubtful cases. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

  20. Investigating the chlorination of acidic pharmaceuticals and by-product formation aided by an experimental design methodology.

    PubMed

    Quintana, José Benito; Rodil, Rosario; López-Mahía, Purificación; Muniategui-Lorenzo, Soledad; Prada-Rodríguez, Darío

    2010-01-01

    The degradation of seven acidic drugs and two metabolites during chlorination was investigated by liquid chromatography-mass spectrometry (LC-MS). A triple-quadrupole (QqQ) system was used to follow the time course of the pharmaceuticals and by-products, while a quadrupole time-of-flight (Q-TOF) system was also used for the identification of the by-products. Under strong chlorination conditions (10mg/L Cl(2), 24h), only four of the target compounds were significantly degraded: salicylic acid, naproxen, diclofenac and indomethacine. The degradation kinetics of these four compounds were investigated at different concentrations of chlorine, bromide and pH by means of a Box-Behnken experimental design. Depending on these factors, measured pseudo-first order half-lives were in the ranges: 23-573h for salicylic acid, 13-446min for naproxen, 5-328min for diclofenac and 0.4-13.4min for indomethacine. Also, it was observed that chlorine concentration was the overall most significant factor, followed by the bromide concentration (except for indomethacine), resulting in increased degradation kinetics as they are increased. The degradation path of salicylic acid, naproxen and diclofenac consisted of aromatic substitution of one or two hydrogens by chlorine and/or bromide. Moreover, for diclofenac, two other by-products corresponding to a decarboxylation/hydroxylation pathway from the monohalogenated products were also identified. On the other hand, indomethacine degradation did not lead to halogenation products but to oxidation ones. The investigation of these by-products in real samples by LC-MS/MS (QqQ) showed that the halogenated derivates of salicylic acid occurred in all the drinking water and wastewater samples analysed.

  1. Shear-induced hydrodynamic cavitation as a tool for pharmaceutical micropollutants removal from urban wastewater.

    PubMed

    Zupanc, Mojca; Kosjek, Tina; Petkovšek, Martin; Dular, Matevž; Kompare, Boris; Širok, Brane; Stražar, Marjeta; Heath, Ester

    2014-05-01

    In this study, the removal of clofibric acid, ibuprofen, naproxen, ketoprofen, carbamazepine and diclofenac residues from wastewater, using a novel shear-induced cavitation generator has been systematically studied. The effects of temperature, cavitation time and H2O2 dose on removal efficiency were investigated. Optimisation (50°C; 15 min; 340 mg L(-1) of added H2O2) resulted in removal efficiencies of 47-86% in spiked deionised water samples. Treatment of actual wastewater effluents revealed that although matrix composition reduces removal efficiency, this effect can be compensated for by increasing H2O2 dose (3.4 g L(-1)) and prolonging cavitation time (30 min). Hydrodynamic cavitation has also been investigated as either a pre- or a post-treatment step to biological treatment. The results revealed a higher overall removal efficiency of recalcitrant diclofenac and carbamazepine, when hydrodynamic cavitation was used prior to as compared to post biological treatment i.e., 54% and 67% as compared to 39% and 56%, respectively. This is an important finding since diclofenac is considered as a priority substance to be included in the EU Water Framework Directive. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Non-Ablative Fractional Laser to Facilitate Transdermal Delivery.

    PubMed

    Ganti, Sindhu S; Banga, Ajay K

    2016-11-01

    The advances in laser technology have led to its rapidly expanding applications in dermatology. This study aims at the novel use of a non-ablative fractional laser to enhance transdermal permeation of diclofenac sodium and sumatriptan succinate. The effects of the laser on skin were characterized visually with dye binding, scanning electron microscopy, pore permeability index, and histology. In vitro transdermal permeation of drugs through laser treated and untreated human dermatomed skin was analyzed over 24 h and quantified by HPLC. Drug transport through untreated skin resulted in transdermal delivery of 72.61 μg/cm 2 ± 50.35 and 22.80 ± 0.64 μg/cm 2 of diclofenac sodium and sumatriptan succinate, respectively. Laser treatment of skin significantly increased (p < 0.005) delivery of diclofenac sodium to 575.66 ± 207.18 μg/cm 2 and sumatriptan succinate to 498.32 ± 97.54 μg/cm 2 . This is a first of its kind study that demonstrates the use of 1410 nm non-ablative fractional laser to enhance transdermal permeation of 2 small molecular weight drugs. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  3. Rapid and Sensitive Reverse-phase High-performance Liquid Chromatography Method for Estimation of Ketorolac in Pharmaceuticals Using Weighted Regression

    PubMed Central

    Dubey, S. K.; Duddelly, S.; Jangala, H.; Saha, R. N.

    2013-01-01

    A reliable, rapid and sensitive isocratic reverse phase high-performance liquid chromatography method has been developed and validated for assay of ketorolac tromethamine in tablets and ophthalmic dosage forms using diclofenac sodium as an internal standard. An isocratic separation of ketorolac tromethamine was achieved on Oyster BDS (150×4.6 mm i.d., 5 μm particle size) column using mobile phase of methanol:acetonitrile:sodium dihydrogen phosphate (20 mM; pH 5.5) (50:10:40, %v/v) at a flow rate of 1.0 ml/min. The eluents were monitored at 322 nm for ketorolac and at 282 nm for diclofenac sodium with a photodiode array detector. The retention times of ketorolac and diclofenac sodium were found to be 1.9 min and 4.6 min, respectively. Response was a linear function of drug concentration in the range of 0.01-15 μg/ml (R2=0.994; linear regression model using weighing factor 1/x2) with a limit of detection and quantification of 0.002 μg/ml and 0.007 μg/ml, respectively. The % recovery and % relative standard deviation values indicated the method was accurate and precise. PMID:23901166

  4. Exploring the intermolecular interactions acting in solvent-modified MEKC by Molecular Dynamics and NMR: The effect of n-butanol on the separation of diclofenac and its impurities.

    PubMed

    Caprini, Claudia; Pasquini, Benedetta; Melani, Fabrizio; Del Bubba, Massimo; Giuffrida, Alessandro; Calleri, Enrica; Orlandini, Serena; Furlanetto, Sandra

    2018-02-05

    An integrated approach involving CE experiments, Molecular Dynamics (MD) simulations and two-dimensional NOE spectroscopy (2D-NOESY) experiments was employed to elucidate the intermolecular interactions and the separation mechanisms involved in a solvent-modified MEKC method for the simultaneous determination of diclofenac sodium and its impurities. The CE findings indicated that the addition of n-butanol (nBuOH) to the SDS micellar solution played a primary role for controlling the partitioning into the mixed micelles and the migration of the analytes and that the presence of nBuOH as cosurfactant was compulsory for achieving the complete separation of the compounds. The different capacity factors of the analytes were calculated and a change in solute association with the mixed micelle when changing the SDS/nBuOH molar ratio was highlighted. The optimal SDS/nBuOH molar ratio for the electrophoretic separation was 1:8. On the other hand, both MD simulations and NMR experiments indicated that the most favorable molar ratio for the formation of mixed SDS/nBuOH micelles was 1:2. These results suggested that probably there is an excess of nBuOH in the background electrolyte, both as free molecules and in form of aggregates, which is able to interact with the analytes, and thus may compete with mixed micelles for the considered compounds. The calculated values of gain in potential energy of the analytes when included in mixed micelles were in agreement with the observed migration order of the compounds. The role of methyl-β-cyclodextrin (MβCyD) in the background electrolyte was also investigated, since the addition of this CyD to the solvent-modified MEKC system was found to be useful to reduce the analysis time. MD simulations and 2D-NOESY spectra highlighted the formation of inclusion complexes with MβCyD not only with the analytes, but also with SDS. MβCyD may lower the availability of both SDS and nBuOH for forming micelles and mostly may compete with the mixed

  5. Assessing the removal of pharmaceuticals and personal care products in a full-scale activated sludge plant.

    PubMed

    Salgado, R; Marques, R; Noronha, J P; Carvalho, G; Oehmen, A; Reis, M A M

    2012-06-01

    This study aimed to investigate the removal mechanisms of pharmaceutical active compounds (PhACs) and musks in a wastewater treatment plant (WWTP). Biological removal and adsorption in the activated sludge tank as well as the effect of UV radiation used for disinfection purposes were considered when performing a mass balance on the WWTP throughout a 2-week sampling campaign. Solid-phase extraction (SPE) was carried out to analyse the PhACs in the influent and effluent samples. Ultrasonic solvent extraction was used before SPE for PhACs analysis in sludge samples. PhAC extracts were analysed by LC-MS. Solid-phase microextraction of liquid and sludge samples was used for the analysis of musks, which were detected by GC-MS. The fluxes of the most abundant compounds (13 PhACs and 5 musks) out of 79 compounds studied were used to perform the mass balance on the WWTP. Results show that incomplete removal of diclofenac, the compound that was found in the highest abundance, was observed via biodegradation and adsorption, and that UV photolysis was the main removal mechanism for this compound. The effect of adsorption to the secondary sludge was often negligible for the PhACs, with the exceptions of diclofenac, etofenamate, hydroxyzine and indapamide. However, the musks showed a high level of adsorption to the sludge. UV radiation had an important role in reducing the concentration of some of the target compounds (e.g. diclofenac, ibuprofen, clorazepate, indapamide, enalapril and atenolol) not removed in the activated sludge tank. The main removal mechanism of PhACs and musks studied in the WWTP was most often biological (45%), followed by adsorption (33%) and by UV radiation (22%). In the majority of the cases, the WWTP achieved >75% removal of the most detected PhACs and musks, with the exception of diclofenac.

  6. Pes Anserine Bursitis in Symptomatic Osteoarthritis Patients: A Mesotherapy Treatment Study.

    PubMed

    Saggini, Raoul; Di Stefano, Alexandra; Dodaj, Ira; Scarcello, Laura; Bellomo, Rosa Grazia

    2015-08-01

    Pes anserine bursitis strongly affects quality of life in patients with osteoarthritis. Treatment includes nonsteroidal anti-inflammatory drugs (NSAIDs), physiotherapy, and injections of corticosteroid, with highly variable responses; recovery can take 10 days to 36 months. Mesotherapy is a minimally invasive technique consisting of subcutaneous injections of bioactive substances. The goal is to modulate the pharmacokinetics of the injected substance and prolong the effects at a local level. To evaluate the effects of mesotherapy with diclofenac for anserine bursitis associated with knee osteoarthritis. One hundred and seventeen patients with anserine bursitis associated with grade II Kellgren-Lawrence knee osteoarthritis, assessed by clinical, radiographic, and ultrasonographic examination, were evaluated and treated. They were randomly divided into two groups (A, mesotherapy; B, control). Group A completed nine sessions of mesotherapy with sodium diclofenac (25 mg/1 mL; Akis®, IBSA, Lugano, Switzerland), 1 mL for each session, three times per week. Group B received 21 oral administrations of sodium diclofenac (50 mg; Voltaren®, Novartis, Parsippany, NJ), once a day for 3 weeks. Primary outcome measures were pain intensity assessed by visual analogue scale (VAS), along with ability to perform activities of daily living, ability to participate in sports, level of pain, symptoms, and quality of life, as assessed by the Knee injury and Osteoarthritis Outcome Score. These measures were performed before and after the treatment period and at 30 and 90 days' follow up. In both groups pain level decreased significantly after the treatment period. Ultrasonography showed a reduction of the hypoechoic area related to anserine bursitis only in group A. Administration of conventional NSAIDs (diclofenac) by mesotherapy is effective in managing anserine bursitis in knee osteoarthritis in the short term and mid-term. These observations could be of interest for efforts

  7. The Safety and Pharmacokinetics of Carprofen, Flunixin and Phenylbutazone in the Cape Vulture (Gyps coprotheres) following Oral Exposure.

    PubMed

    Fourie, Tamsyn; Cromarty, Duncan; Duncan, Neil; Wolter, Kerri; Naidoo, Vinny

    2015-01-01

    The following study evaluates the overt toxic potential of carprofen (CRP), flunixin (FXN) and phenylbutazone (PBZ) in Old world vultures in relation to historic toxicity data for diclofenac and ketoprofen, with the Cape vulture (Gyps coprotheres) being the indicator species. The toxic potential of a single oral dose of CRP (11.5 mg/kg), FXN (1 mg/kg),PBZ (1.7 mg/kg) or water was evaluated by means of a four-way parallel study (n = 2), as means of ascertaining if these drugs were as toxic as diclofenac in the vulture. No unscheduled deaths or pathological lesions were noted following exposure. Clinical signs of lethargy and depression were, however, noted in one CRP, two FXN and one PBZ treated birds. Mild reversible inhibition of UA excretion was evident in all three groups, although UA remained within the population reference interval in contrast to the effects previously described for diclofenac and ketoprofen. All treatment groups had a drug concentration responsive increase in alanine transferase activity. CRP, FXN and PBZ were characterised by a maximum plasma concentration (Cmax) of 1051.8 ± 620.7 ng/ml, 335.9 ± 36.3 ng/ml and 11150 ± 2474.9 ng/ml at 4 ± 4.3, 0.45 ± 0.02 and 5.3 ± 5.2 hours (Tmax) respectively and a half-life of elimination of 13.3 ±5, 1.8±1 and 18.7 ±11.4 hours respectively. While we could not demonstrate a lethal effect of the tested substances, the presence of toxic clinical signs, clinical pathological changes and/or long half-lives of elimination suggests that all three drugs have a potential for toxicity in a larger population or on repeat administration. In conclusion while the studied substances were not as overtly toxic as diclofenac, they are of safety concern.

  8. The Safety and Pharmacokinetics of Carprofen, Flunixin and Phenylbutazone in the Cape Vulture (Gyps coprotheres) following Oral Exposure

    PubMed Central

    Fourie, Tamsyn; Cromarty, Duncan; Duncan, Neil; Wolter, Kerri; Naidoo, Vinny

    2015-01-01

    The following study evaluates the overt toxic potential of carprofen (CRP), flunixin (FXN) and phenylbutazone (PBZ) in Old world vultures in relation to historic toxicity data for diclofenac and ketoprofen, with the Cape vulture (Gyps coprotheres) being the indicator species. The toxic potential of a single oral dose of CRP (11.5 mg/kg), FXN (1 mg/kg),PBZ (1.7 mg/kg) or water was evaluated by means of a four-way parallel study (n = 2), as means of ascertaining if these drugs were as toxic as diclofenac in the vulture. No unscheduled deaths or pathological lesions were noted following exposure. Clinical signs of lethargy and depression were, however, noted in one CRP, two FXN and one PBZ treated birds. Mild reversible inhibition of UA excretion was evident in all three groups, although UA remained within the population reference interval in contrast to the effects previously described for diclofenac and ketoprofen. All treatment groups had a drug concentration responsive increase in alanine transferase activity. CRP, FXN and PBZ were characterised by a maximum plasma concentration (Cmax) of 1051.8 ± 620.7 ng/ml, 335.9 ± 36.3 ng/ml and 11150 ± 2474.9 ng/ml at 4 ± 4.3, 0.45 ± 0.02 and 5.3 ± 5.2 hours (Tmax) respectively and a half-life of elimination of 13.3 ±5, 1.8±1 and 18.7 ±11.4 hours respectively. While we could not demonstrate a lethal effect of the tested substances, the presence of toxic clinical signs, clinical pathological changes and/or long half-lives of elimination suggests that all three drugs have a potential for toxicity in a larger population or on repeat administration. In conclusion while the studied substances were not as overtly toxic as diclofenac, they are of safety concern. PMID:26512724

  9. Durapain in symptomatic treatment of severe acute pain: a post-marketing, prospective, multicenter, observational study – PRIME study

    PubMed Central

    Shah, Kshitij; Chaudhari, Omvijay B; Gupta, Palash; Chaudhuri, R Hom; Kamilya, Ranjan; Kulkarni, Shreedhar S; Subbaiah, S; Sorathia, Zubair H; Billa, Gauri

    2017-01-01

    Objective To assess the effectiveness, overall tolerability, and gastrointestinal (GI) tolerability of Durapain (fixed dose combination of tramadol hydrochloride immediate release [50 mg] and diclofenac sodium sustained release [75 mg]) in symptomatic treatment of severe acute pain in physician’s routine clinical practice. Materials and methods In this prospective, multicenter, observational, post-marketing study, adult patients (aged 18–60 years) with severe acute pain were treated with tramadol hydrochloride/diclofenac sodium as per approved prescribing information. Evaluation was done at base-line, day 2, and day 5. Primary end point was pain intensity difference from baseline to day 5. Results A total of 351 patients (mean age 44.2 years; male 43%; female 57%) were included. The mean pain score was reduced from 9.2±1.09 at baseline to 2.8±1.73 at day 5 (p<0.0001). The number of patients with severe intensity of pain reduced from 100% at baseline to 18.3% at day 2 and 6.96% at day 5. According to the patient assessment, 68.36% of patients reported tolerability as “very good to good”, whereas according to physician’s assessment, “very good to good” tolerability was reported in 68.27% of patients. Five (1.43 %) patients discontinued the study because of adverse drug reaction. Five patients developed nine GI-related events of moderate intensity. Two patients developed three adverse reactions (burning sensation in urine, giddiness, and urine retention) other than GI events. No serious adverse drug reactions were reported during the study period. Conclusion Tramadol hydrochloride/diclofenac sodium is an effective and well-tolerated treatment in Indian patients with severe acute pain. Treatment with tramadol hydrochloride/diclofenac sodium provides significant pain relief on day 2 and maintained until day 5 without any serious adverse reactions. PMID:28579825

  10. Delivering safe and effective analgesia for management of renal colic in the emergency department: a double-blind, multigroup, randomised controlled trial.

    PubMed

    Pathan, Sameer A; Mitra, Biswadev; Straney, Lahn D; Afzal, Muhammad Shuaib; Anjum, Shahzad; Shukla, Dharmesh; Morley, Kostantinos; Al Hilli, Shatha A; Al Rumaihi, Khalid; Thomas, Stephen H; Cameron, Peter A

    2016-05-14

    The excruciating pain of patients with renal colic on presentation to the emergency department requires effective analgesia to be administered in the shortest possible time. Trials comparing intramuscular non-steroidal anti-inflammatory drugs with intravenous opioids or paracetamol have been inconclusive because of the challenges associated with concealment of randomisation, small sample size, differences in outcome measures, and inadequate masking of participants and assessors. We did this trial to develop definitive evidence regarding the choice of initial analgesia and route of administration in participants presenting with renal colic to the emergency department. In this three-treatment group, double-blind, randomised controlled trial, adult participants (aged 18-65 years) presenting to the emergency department of an academic, tertiary care hospital in Qatar, with moderate to severe renal colic (Numerical pain Rating Scale ≥ 4) were recruited. With the use of computer-generated block randomisation (block sizes of six and nine), participants were assigned (1:1:1) to receive diclofenac (75 mg/3 mL intramuscular), morphine (0.1 mg/kg intravenous), or paracetamol (1 g/100 mL intravenous). Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants achieving at least a 50% reduction in initial pain score at 30 min after analgesia, assessed by intention-to-treat analysis and per-protocol analysis, which included patients where a calculus in the urinary tract was detected with imaging. This trial is registered with ClinicalTrials.gov, number NCT02187614. Between Aug 5, 2014, and March 15, 2015, we randomly assigned 1645 participants, of whom 1644 were included in the intention-to-treat analysis (547 in the diclofenac group, 548 in the paracetemol group, and 549 in the morphine group). Ureteric calculi were detected in 1316 patients, who were analysed as the per-protocol population (438 in

  11. Study on the Visible-Light Photocatalytic Performance and Degradation Mechanism of Diclofenac Sodium under the System of Hetero-Structural CuBi2O4/Ag3PO4 with H2O2

    PubMed Central

    Chen, Xiaojuan; Li, Ning; Xu, Song; Cai, Yumin

    2018-01-01

    Two kinds of CuBi2O4/Ag3PO4 with different heterojunction structures were prepared based on the combination of hydrothermal and in-situ precipitation methods with surfactant additives (sodium citrate and sodium stearate), and their characteristics were systematically resolved by X-ray Diffraction (XRD), Brunauer–Emmett–Teller (BET), X-ray Photoelectron Spectroscopy (XPS), Scanning Electron Microscope (SEM)/ High-resolution Transmission Electron Microscopy (HRTEM), UV-vis Diffuse Reflectance Spectra (DRS) and Photoluminescence (PL). Meanwhile, the photocatalytic properties of the catalysts were determined for diclofenac sodium (DS) degradation and the photocatalytic mechanism was also explored. The results indicate that both of the two kinds of CuBi2O4/Ag3PO4 exhibit higher photocatalytic efficiency, mineralization rate, and stability than that of pure CuBi2O4 or Ag3PO4. Moreover, the catalytic activity of CuBi2O4/Ag3PO4 can be further enhanced by adding H2O2. The free radical capture experiments show that in the pure CuBi2O4/Ag3PO4 photocatalytic system, the OH• and O2•− are the main species participating in DS degradation; however, in the CuBi2O4/Ag3PO4 photocatalytic system with H2O2, all OH•, h+, and O2•− take part in the DS degradation, and the contribution order is OH• > h+ > O2•−. Accordingly, the photocatalytic mechanism of CuBi2O4/Ag3PO4 could be explained by the Z-Scheme theory, while the catalysis of CuBi2O4/Ag3PO4 with H2O2 follows the heterojunction energy band theory. PMID:29597267

  12. A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis.

    PubMed

    Chandran, Binu; Goel, Ajay

    2012-11-01

    Curcumin is known to possess potent antiinflammatory and antiarthritic properties. This pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty-five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events. Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large-scale trials to validate these findings in patients with RA and other arthritic conditions. Copyright © 2012 John Wiley & Sons, Ltd.

  13. Amphiphilic Polyurethane Hydrogels as Smart Carriers for Acidic Hydrophobic Drugs.

    PubMed

    Fonseca, Lucas P; Trinca, Rafael B; Isabel Felisberti, Maria

    2018-05-14

    Amphiphilic hydrogels are widely reported as systems with great potential for controlled drug release. Nevertheless, the majority of studies make use of functionalization or attachment of drugs to the polymer chains. In this study, we propose a strategy of combining amphiphilic polyurethanes with pH-responsive drugs to develop smart drug carriers. While the amphiphilic character of the polymer imparts an efficient load of hydrophobic and hydrophilic drugs, the drug's characteristics determine the selectivity of the medium delivery. Drug loading and release behavior as well as hydrolytic degradation of chemically crosslinked polyurethane hydrogels based on PEG and PCL-triol (PU (polyurethane) hydrogels) synthesized by an easy one-pot route were studied. PU hydrogels have been shown to successfully load the hydrophobic acidic drug sodium diclofenac, reaching a partition coefficient of 8 between the most hydrophobic PU and diclofenac/ethanol solutions. Moreover, an oral administration simulation was conducted by changing the environment from an acidic to a neutral medium. PU hydrogels release less than 5 % of the drug in an acidic medium; however, in a PBS pH 7.4 solution, diclofenac is delivered in a sustained fashion for up to 40 hours, achieving 80% of cumulative release. Copyright © 2018. Published by Elsevier B.V.

  14. Polyox and carrageenan based composite film dressing containing anti-microbial and anti-inflammatory drugs for effective wound healing.

    PubMed

    Boateng, Joshua S; Pawar, Harshavardhan V; Tetteh, John

    2013-01-30

    Polyethylene oxide (Polyox) and carrageenan based solvent cast films have been formulated as dressings for drug delivery to wounds. Films plasticised with glycerol were loaded with streptomycin (30%, w/w) and diclofenac (10%, w/w) for enhanced healing effects in chronic wounds. Blank and drug loaded films were characterised by texture analysis (for mechanical and mucoadhesive properties), scanning electron microscopy, differential scanning calorimetry, X-ray diffraction and Fourier transform infrared spectroscopy. In addition, swelling, in vitro drug release and antibacterial studies were conducted to further characterise the films. Both blank and drug loaded films showed a smooth, homogeneous surface morphology, excellent transparency, high elasticity and acceptable tensile (mechanical) properties. The drug loaded films showed a high capacity to absorb simulated wound fluid and significant mucoadhesion force which is expected to allow effective adherence to and protection of the wound. The films showed controlled release of both streptomycin and diclofenac for 72 h. These drug loaded films produced higher zones of inhibition against Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli compared to the individual drugs zones of inhibition. Incorporation of streptomycin can prevent and treat chronic wound infections whereas diclofenac can target the inflammatory phase of wound healing to relieve pain and swelling. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Multi-functional polyelectrolyte multilayer films: combining mechanical resistance, biodegradability and bioactivity

    PubMed Central

    Schneider, Aurore; Vodouhê, Constant; Richert, Ludovic; Francius, Gregory; Le Guen, Erell; Schaaf, Pierre; Voegel, Jean-Claude; Frisch, Benoît; Picart, Catherine

    2008-01-01

    Cross-linked polyelectrolyte multilayer films (CL PEM) have an increased rigidity and are mechanically more resistant than native (e.g. uncrosslinked) films. However, they are still biodegradable, which make them interesting candidates for biomedical applications. In this study, CL PEM films have been explored for their multifunctional properties as i) mechanically resistant ii) biodegradable and iii) bioactive films. Toward this end, we investigated drug loading into CL chitosan/hyaluronan (CHI/HA) and poly(L-lysine)/hyaluronan (PLL/HA) films by simple diffusion of the drugs. Sodium diclofenac and paclitaxel were chosen as model drugs and were successfully loaded into the films. The effect of varying the number of layers in the (CHI/HA) films as well as the cross-linker concentration on diclofenac loading were studied. Diclofenac was released from the film in about ten hours. Paclitaxel was also found to diffuse within CL films. Its activity was maintained after loading in the CL films and cellular viability could be reduced by about 55% over three days. Such simple approach may be applied to other types of cross-linked films and to other drugs. These results prove that it is possible to design multifunctional multilayer films that combine mechanical resistance, biodegradability and bioactivity properties into a single PEM architecture. PMID:17206799

  16. The hepatic safety and tolerability of the cyclooxygenase-2 selective NSAID celecoxib: pooled analysis of 41 randomized controlled trials.

    PubMed

    Soni, Paresh; Shell, Briton; Cawkwell, Gail; Li, Chunming; Ma, Hong

    2009-08-01

    To assess the hepatic safety and tolerability of celecoxib versus placebo and three commonly prescribed nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). This was a retrospective, pooled analysis of a 41-study dataset involving patients with osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, chronic low back pain, and Alzheimer's disease. Criteria for selection of studies were: (1) Randomized, parallel-group design and planned treatment duration of > or =2 weeks (2) > or =1 placebo or NSAID comparator (3) > or =1 arm with celecoxib at total daily dose of > or =200 mg (4) Data available as of October 31, 2004 Data were pooled by treatment and subject from the safety analysis population of included studies. Treatment-emergent hepatobiliary adverse events (AEs) were compared for celecoxib <200 mg/day (943 patients), 200 mg/day (12 008 patients), 400 mg/day (7380 patients), and 800 mg/day (4602 patients); placebo (4057 patients); diclofenac 100-150 mg/day (7639 patients); naproxen 1000 mg/day (2953 patients); and ibuprofen 2400 mg/day (2484 patients). Hepatobiliary laboratory abnormalities were also analyzed. There were no cases of liver failure, treatment-related liver transplant, or treatment-related hepatobiliary death. Incidence of serious hepatic AEs was low, with 13 (0.05%) serious hepatic AEs among 24 933 celecoxib-treated patients, and 16 (0.21%) among 7639 diclofenac-treated patients. No patients receiving celecoxib or any nonselective NSAID met criteria for Hy's rule (alanine aminotransferase [ALT] > or =3 x upper limit of normal [ULN] with bilirubin > or =2 x ULN). The incidence of notable (> or =5 x ULN) and severe (> or =10 x ULN) ALT elevations was similar for all treatment groups except diclofenac. Significantly fewer hepatobiliary AEs were reported for celecoxib (any dose; 1.11%) than for diclofenac (vs. 4.24%, p < 0.0001); for ibuprofen (vs. 1.53%, p = 0.06) and placebo (vs. 0.89%, p = 0.21) the incidence of AEs was comparable to

  17. 21 CFR 524.590 - Diclofenac.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... inflammation associated with osteoarthritis in tarsal, carpal, metacarpophalangeal, metatarsophalangeal, and proximal interphalangeal (hock, knee, fetlock and pastern) joints. (3) Limitations. Do not use in horses...

  18. [Prevention of NSAID gastropathy: the difference between a coxibs and the addition of a PPI].

    PubMed

    Lems, Willem F; Kuipers, Ernst J

    2010-01-01

    Several strategies are available for the prevention of NSAID gastropathy: the addition of misoprostol or proton pump inhibitors (PPIs) to conventional NSAIDs, or selective use of cyclo-oxygenase 2 inhibitors, the 'coxibs'. The recently published CONDOR study was a randomized trial comparing celecoxib with omeprazole in patients at high risk for NSAID gastropathy. A statistically significant reduction in the primary endpoint was found: hazard ratio: 4.3 (95% CI: 2.6-6.7; p < 0.0001). However, the reduction was largely based on a higher incidence of anaemia in the diclofenac plus omeprazole group. The study has strengths and weaknesses. The most important conclusion is that the nature of the gastro-protective effects of celecoxib and diclofenac/misoprostol are different.

  19. Influence of ionic strength, anions, cations, and natural organic matter on the adsorption of pharmaceuticals to silica.

    PubMed

    Bui, Tung Xuan; Choi, Heechul

    2010-08-01

    The adsorption of four wide-use pharmaceuticals (carbamazepine, diclofenac, ibuprofen, and ketoprofen) onto a porous silica was investigated under varied ionic strengths, different anions, divalent cations (Ca(2+) and Mg(2+)), trivalent cations (Al(3+) and Fe(3+)), and natural organic matter (NOM). The experiments demonstrated that at a given pH the adsorption was most affected by ionic strength, trivalent cations, and properties of pharmaceuticals. The increase of ionic strength resulted in an increase in the adsorption of ketoprofen, but a decrease in the adsorption of carbamazepine. Trivalent metal cations made intense increases in the adsorption of three acidic pharmaceuticals, which could be due to the formation of inner-sphere complex of the cations on the surface and/or complexation of the pharmaceuticals with both surface and aqueous metal species. It was found that the adsorption of carbamazepine was not affected by divalent and trivalent cations, whereas the adsorption of diclofenac was solely impacted by the presence of Al(3+). Moreover, divalent cations at low concentration could slightly enhance the adsorption of ibuprofen and ketoprofen, whereas NOM caused a reduction in the adsorption of the tested pharmaceuticals except for diclofenac. These results suggest that ionic strength, divalent cations, trivalent cations, and NOM are notable factors affecting the adsorption of pharmaceuticals and thus the ultimate fate of pharmaceuticals in the aqueous environment. Copyright 2010 Elsevier Ltd. All rights reserved.

  20. Rapid degradation, mineralization and detoxification of pharmaceutically active compounds in aqueous solution during pulsed corona discharge treatment.

    PubMed

    Singh, Raj Kamal; Philip, Ligy; Ramanujam, Sarathi

    2017-09-15

    In the present study, plasma generated by pulsed corona discharge was used for the degradation of diclofenac, carbamazepine and ciprofloxacin. Pollutants in aqueous solution were plasma treated under two categories: single and mixed pollutant condition. Mixed pollutant condition showed an antagonistic behaviour and thus the degradation time was higher for mixed condition compared to the single condition. At different voltage and frequencies, degradation efficiency followed the trend, diclofenac>carbamazepine>ciprofloxacin. Acidic pH slightly favoured the degradation process whereas in presence of radical scavengers (HCO 3 - , CO 3 2- and humic acid) the degradation yield was significantly decreased. With an input power of 101.5 W, complete degradation was achieved within 4-16 min of plasma treatment for pharmaceutical's concentrations of 1-10 mg/L. As the pollutant concentration increased from 1 to 10 mg/L, the pseudo first order rate constant decreased, while yield increased. Complete degradation pathway of diclofenac, carbamazepine and ciprofloxacin in plasma treatment process are proposed by identifying the intermediates using LC-MS analysis. TOC analysis confirmed 80% mineralization within 10 min of plasma treatment for higher pharmaceutical's concentrations of 10 mg/L. The microalgae ecotoxicity study and disc diffusion test confirmed the complete detoxification of PACs that took place after 6 min of plasma treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Chronic Prosopis Glandulosa Treatment Blunts Neutrophil Infiltration and Enhances Muscle Repair after Contusion Injury

    PubMed Central

    George, Cindy; Smith, Carine; Isaacs, Ashwin W.; Huisamen, Barbara

    2015-01-01

    The current treatment options for soft tissue injuries remain suboptimal and often result in delayed/incomplete recovery of damaged muscle. The current study aimed to evaluate the effects of oral Prosopis glandulosa treatment on inflammation and regeneration in skeletal muscle after contusion injury, in comparison to a conventional treatment. The gastrocnemius muscle of rats was subjected to mass-drop injury and muscle samples collected after 1-, 3 h, 1- and 7 days post-injury. Rats were treated with P. glandulosa (100 mg/kg/day) either for 8 weeks prior to injury (up until day 7 post-injury), only post-injury, or with topically applied diclofenac post-injury (0.57 mg/kg). Neutrophil (His48-positive) and macrophage (F4/80-positive) infiltration was assessed by means of immunohistochemistry. Indicators of muscle satellite cell proliferation (ADAM12) and regeneration (desmin) were used to evaluate muscle repair. Chronic P. glandulosa and diclofenac treatment (p < 0.0001) was associated with suppression of the neutrophil response to contusion injury, however only chronic P. glandulosa treatment facilitated more effective muscle recovery (increased ADAM12 (p < 0.05) and desmin (p < 0.001) expression), while diclofenac treatment had inhibitory effects on repair, despite effective inhibition of neutrophil response. Data indicates that P. glandulosa treatment results in more effective muscle repair after contusion. PMID:25625816

  2. Multifunctional medicated lyophilised wafer dressing for effective chronic wound healing.

    PubMed

    Pawar, Harshavardhan V; Boateng, Joshua S; Ayensu, Isaac; Tetteh, John

    2014-06-01

    Wafers combining weight ratios of Polyox with carrageenan (75/25) or sodium alginate (50/50) containing streptomycin and diclofenac were prepared to improve chronic wound healing. Gels were freeze-dried using a lyophilisation cycle incorporating an annealing step. Wafers were characterised for morphology, mechanical and in vitro functional (swelling, adhesion, drug release in the presence of simulated wound fluid) characteristics. Both blank (BLK) and drug-loaded (DL) wafers were soft, flexible, elegant in appearance and non-brittle in nature. Annealing helped to improve porous nature of wafers but was affected by the addition of drugs. Mechanical characterisation demonstrated that the wafers were strong enough to withstand normal stresses but also flexible to prevent damage to newly formed skin tissue. Differences in swelling, adhesion and drug release characteristics could be attributed to differences in pore size and sodium sulphate formed because of the salt forms of the two drugs. BLK wafers showed relatively higher swelling and adhesion than DL wafers with the latter showing controlled release of streptomycin and diclofenac. The optimised dressing has the potential to reduce bacterial infection and can also help to reduce swelling and pain associated with injury due to the anti-inflammatory action of diclofenac and help to achieve more rapid wound healing. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  3. Pes Anserine Bursitis in Symptomatic Osteoarthritis Patients: A Mesotherapy Treatment Study

    PubMed Central

    Di Stefano, Alexandra; Dodaj, Ira; Scarcello, Laura; Bellomo, Rosa Grazia

    2015-01-01

    Abstract Background: Pes anserine bursitis strongly affects quality of life in patients with osteoarthritis. Treatment includes nonsteroidal anti-inflammatory drugs (NSAIDs), physiotherapy, and injections of corticosteroid, with highly variable responses; recovery can take 10 days to 36 months. Mesotherapy is a minimally invasive technique consisting of subcutaneous injections of bioactive substances. The goal is to modulate the pharmacokinetics of the injected substance and prolong the effects at a local level. Objective: To evaluate the effects of mesotherapy with diclofenac for anserine bursitis associated with knee osteoarthritis. Methods: One hundred and seventeen patients with anserine bursitis associated with grade II Kellgren-Lawrence knee osteoarthritis, assessed by clinical, radiographic, and ultrasonographic examination, were evaluated and treated. They were randomly divided into two groups (A, mesotherapy; B, control). Group A completed nine sessions of mesotherapy with sodium diclofenac (25 mg/1 mL; Akis®, IBSA, Lugano, Switzerland), 1 mL for each session, three times per week. Group B received 21 oral administrations of sodium diclofenac (50 mg; Voltaren®, Novartis, Parsippany, NJ), once a day for 3 weeks. Primary outcome measures were pain intensity assessed by visual analogue scale (VAS), along with ability to perform activities of daily living, ability to participate in sports, level of pain, symptoms, and quality of life, as assessed by the Knee injury and Osteoarthritis Outcome Score. These measures were performed before and after the treatment period and at 30 and 90 days' follow up. Results: In both groups pain level decreased significantly after the treatment period. Ultrasonography showed a reduction of the hypoechoic area related to anserine bursitis only in group A. Conclusion: Administration of conventional NSAIDs (diclofenac) by mesotherapy is effective in managing anserine bursitis in knee osteoarthritis in the short term and

  4. Rationale of combination therapy with antioxidants in medical management of Peyronie’s disease: results of clinical application

    PubMed Central

    Paulis, Gianni; Paulis, Andrea; Romano, Gennaro; Barletta, Davide; Fabiani, Andrea

    2017-01-01

    Peyronie’s disease (PD) is a connective tissue disorder involving the tunica albuginea of the corpora cavernosa of the penis. We have published several studies describing a “combined therapy” for PD patients, but the present study aims to clearly demonstrate how the association between various antioxidants in PD treatment can significantly increase the likelihood of therapeutic success. We used the following substances: silymarin, ginkgo biloba, vitamin E, bilberry, topical diclofenac sodium, and pentoxifylline (PTX). We analyzed the therapeutic impact and possible side effects of one or more antioxidants in patients with early-stage PD. To clearly prove that it is possible to achieve better results when combining more than one agent, we designed this study with five treatment groups, corresponding, respectively, to the administration of a single oral antioxidant; two oral antioxidants; three oral antioxidants; five oral antioxidants + local diclofenac; and five oral antioxidants + local diclofenac + PTX by perilesional injection. One hundred and twenty patients were assigned to five groups of treatment designed according to the abovementioned study aim. Outcomes after 6 months of treatment showed that combined antioxidant therapy is effective in treating PD. Statistical analysis showed significant differences between the treatment groups with regard to: improvement and disappearance of penile pain; percentage of reduction in the volume of penile plaque; reduction in penile curvature; recovery of erectile function in patients with erectile dysfunction; increase in the International Index of Erectile Function score; and reduction of psychosexual impact. Furthermore, we observed that the clinical efficacy of combined therapy is greater when topical use of diclofenac gel and perilesional injection of PTX are added to oral treatment with more than one antioxidant. Although several articles have already been published reporting the effectiveness of combined

  5. The effects of the topical administration of non-steroidal anti-inflammatory drugs on corneal epithelium and corneal sensitivity in normal subjects.

    PubMed

    Aragona, P; Tripodi, G; Spinella, R; Laganà, E; Ferreri, G

    2000-04-01

    To study the changes in the corneal epithelium and corneal sensitivity of healthy subjects after the topical administration of non-steroidal anti-inflammatory drugs (NSAIDs; diclofenac, indomethacin, flurbiprofen and ketorolac) frequently used in ocular therapy. A double-masked parallel clinical study was undertaken on 90 subjects (45 men, 45 women; Caucasian; age 21-46 years, mean +/- SD 27.1 +/- 5 years). The subjects were divided into six groups: group 1 was treated with placebo, group 2 with 0.1% diclofenac, group 3 with 0.1% indomethacin, group 4 with 0.03% flurbiprofen, group 5 with 0.5% ketorolac and group 6 with 0.4% oxybuprocaine. One eye was randomly treated with the study drug and the fellow eye was treated with placebo. The medications were instilled four times, at 5 min intervals. Assessment of the corneal epithelium was carried out by vital fluorescein stain before instillation and 5, 15, 30 and 60 min after instillation of the last drop. Subjective burning sensation was assessed by asking participants to rate burning on a scale from 0 (none) to 3 (severe). After 1 week, assessment of corneal sensitivity was carried out by the Cochet-Bonnet method, repeating the above scheme of instillation and measurement times. None of the study drugs, with the exception of oxybuprocaine, produced evident epithelial damage. All the drugs caused a mean burning sensation greater than the placebo. The diclofenac-treated group showed a statistically significant decrease in corneal sensitivity (p < 0.001) at the measurement carried out 15 min after instillation of the last drop and lasting up to the end of the study, when the corneal anaesthesia was similar to that induced by the topical anaesthetic treatment. No significant changes were demonstrated for the other NSAIDs when compared either with the placebo-treated eyes or with the fellow eyes. Despite a similar mechanism of action and analgesic activity to the other NSAIDs tested, diclofenac was able to induce a

  6. Selection of non-steroidal anti-inflammatory drug and treatment regimen for sulfur mustard-induced cutaneous lesions.

    PubMed

    Plahovinsak, Jennifer L; Buccellato, Matthew A; Reid, Frances M; Graham, John S

    2016-09-01

    The inflammatory process plays an important role in sulfur mustard (HD) injury and HD pathogenesis, suggesting that anti-inflammatory treatments applied as soon as possible following HD injury may reduce tissue damage and accelerate healing. This study used the HD dermal weanling swine model to investigate the efficacy of two non-steroidal anti-inflammatory drugs, capsaicin and diclofenac, when applied in combination with the steroid, clobetasol. The therapeutic regimen was also investigated with respect to initiation of treatment post-exposure, frequency and duration. Yorkshire-cross pigs were randomly assigned to experimental groups, corresponding to all combinations of treatment (capsaicin with clobetasol or diclofenac with clobetasol), onset time (1, 2 or 4 h post-exposure), treatment duration (1, 3 or 5 days) and frequency of applications (2, 3 or 4 per day). For each animal, two sites on the ventral abdomen were exposed to 400 μL of neat HD for 8 min to achieve superficial dermal (SD) lesions and two sites were exposed to 400 μL neat HD for 30 min to achieve deep dermal (DD) lesions. Each treatment regimen was tested against a SD and a DD injury. Untreated SD and DD lesion sites served as within-animal controls. Assessments, up to one week post-challenge, included digital photographs, clinical assessments (lesion size measurements and modified Draize scoring), transepidermal water loss (TEWL), reflectance colorimetry and histopathologic evaluations that included an estimate for depth of injury and wound healing parameters. Diclofenac plus clobetasol treatment resulted in significant reductions in lesion contracture and modified Draize scores, increased barrier function (decreased TEWL), and increased healing as determined by histopathology for both SD and DD injury when compared with untreated sites and sites treated with capsaicin plus clobetasol. An increased duration of treatment from 1 to 5 days was most commonly associated with decreased

  7. Improving sustained drug delivery from ophthalmic lens materials through the control of temperature and time of loading.

    PubMed

    Topete, Ana; Oliveira, Andreia S; Fernandes, A; Nunes, T G; Serro, A P; Saramago, B

    2018-05-30

    Although the possibility of using drug-loaded ophthalmic lens to promote sustained drug release has been thoroughly pursued, there are still problems to be solved associated to the different alternatives. In this work, we went back to the traditional method of drug loading by soaking in the drug solution and tried to optimize the release profiles by changing the temperature and the time of loading. Two materials commercially available under the names of CI26Y and Definitive 50 were chosen. CI26Y is used for intraocular lenses (IOLs) and Definitive 50 for soft contact lenses (SCLs). Three drugs were tested: an antibiotic, moxifloxacin, and two anti-inflammatories, diclofenac and ketorolac. Sustained drug release from CI26Y disks for, at least 15 days, was obtained for moxifloxacin and diclofenac increasing the loading temperature up to 60 °C or extending the loading time till two months. The sustained release of ketorolac was limited to about 8 days. In contrast, drug release from Definitive 50 disks could not be improved by changing the loading conditions. An attempt to interpret the impact of the loading conditions on the drug release behavior was done using solid-state NMR and differential scanning calorimetry. These studies suggested the establishment of reversible, endothermic interactions between CI26Y and the drugs, moxifloxacin and diclofenac. The loading temperature had a slight effect on the mechanical and optical properties of drug loaded CI26Y samples, which still kept adequate properties to be used as IOL materials. The in vivo efficacy of CI26Y samples, drug loaded at 60 °C for two weeks, was predicted using a simplified mathematical model to estimate the drug concentration in the aqueous humor. The estimated concentrations were found to comply with the therapeutic needs, at least, for moxifloxacin and diclofenac. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Oxidation of non-steroidal anti-inflammatory drugs with aqueous permanganate.

    PubMed

    Rodríguez-Álvarez, Tania; Rodil, Rosario; Quintana, José Benito; Triñanes, Sara; Cela, Rafael

    2013-06-01

    Potassium permanganate is a strong oxidant widely used in drinking water treatment, that can react with organic micropollutants. Thus, the oxidation kinetics and transformation route of seven non-steroidal anti-inflammatory drugs (NSAIDs) upon reaction with potassium permanganate was investigated. A liquid chromatography-quadrupole-time-of-flight-mass spectrometry (LC-Q-TOF-MS) system was used to follow the time course of pharmaceuticals concentrations and for the identification of their by-products. Under strong oxidation conditions (2 mg L(-1) KMnO4, 24 h), only two NSAIDs were significantly degraded: indomethacine and diclofenac. The degradation kinetics of these two drugs was investigated at different concentrations of permanganate, chlorides, phosphates and sample pH by means of a full factorial experimental design. Depending on these factors, half-lives were in the range: 2-270 h for indomethacine and 3-558 h for diclofenac, equivalent to apparent second order constants between 0.65 and 9.5 M(-1) s(-1) and 0.27 and 7.4 M(-1) s(-1), respectively. Permanganate concentration was the most significant factor on NSAIDs oxidation kinetics, but the pH also played a significant role in diclofenac reaction, being faster at acidic pH. In the case of indomethacine, the dose of permanganate seemed also to play an autocatalytic effect. The use of an accurate-mass high resolution LC-Q-TOF-MS system permitted the identification of a total of 13 by-products. The transformation path of these drugs consisted mainly of hydroxylations, decarboxylations and oxidation of aromatic double bonds, with ring opening. The software predicted toxicity of these products indicates that they are expected not to be more toxic than the NSAIDs, with the exception of two indomethacine by-products. Reaction in real samples was slower and/or incomplete for both pharmaceuticals, depending on the organic matter content of the sample. However, still all transformation products could be detected for

  9. Fucus Vesiculosus

    MedlinePlus

    ... type of brown seaweed. People use the whole plant to make medicine. People use Fucus vesiculosus for ... diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ...

  10. Natural remedies for non-steroidal anti-inflammatory drug-induced toxicity.

    PubMed

    Simon, Jerine Peter; Evan Prince, Sabina

    2017-01-01

    The liver is an important organ of the body, which has a vital role in metabolic functions. The non-steroidal anti-inflammatory drug (NSAID), diclofenac causes hepato-renal toxicity and gastric ulcers. NSAIDs are noted to be an agent for the toxicity of body organs. This review has elaborated various scientific perspectives of the toxicity caused by diclofenac and its mechanistic action in affecting the vital organ. This review suggests natural products are better remedies than current clinical drugs against the toxicity caused by NSAIDs. Natural products are known for their minimal side effects, low cost and availability. On the other hand, synthetic drugs pose the danger of adverse effects if used frequently or over a long period. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Mediated effect of ultrasound treated Diclofenac on mussel hemocytes: First evidence for the involvement of respiratory burst enzymes in the induction of DCF-mediated unspecific mode of action.

    PubMed

    Toufexi, Eirini; Dailianis, Stefanos; Vlastos, Dimitris; Manariotis, Ioannis D

    2016-06-01

    The present study investigates the toxic behavior of diclofenac (DCF) before and after its ultrasound (US) treatment, as well as the involvement of intracellular target molecules, such as NADPH oxidase and NO synthase, in the DCF-induced adverse effects on hemocytes of mussel Mytilus galloprovincialis. In this context, appropriate volumes (350 and 500mL) of DCF solutions (at concentrations of 2, 2.5, 5 and 10mgL(-1)) were treated under different ultrasound operating conditions (frequency at 582 and 862kHz, electric power density at 133 and 167W) for assessing US method efficiency. In parallel, DCF and US DCF-mediated cytotoxic (in terms of cell viability measured with the use of neutral red uptake/NRU method), oxidative (in terms of superoxide anions/(.)O2(-), nitric oxides such as NO2(-) and lipid peroxidation products, such as malondialdehyde/MDA content) and genotoxic (DNA damage measured by the use of Comet assay method) effects were investigated in hemocytes exposed for 1h to 5, 10 and 100ngL(-1) and 1, 10 and 20μgL(-1) of DCF. The involvement of NADPH oxidase and NO synthase to the DCF-induced toxicity was further investigated by the use of 10μΜ L-NAME, a NO synthase inhibitor and 10μΜ DPI, a NADPH oxidase inhibitor. According to the results, 350mL of 2mgL(-1) DCF showed higher degradation (>50%) under 167W electric power density and frequency at 862kHz for 120min, compared to degradation in all other cases, followed by a significant elimination of its toxicity. Specifically, US DCF-treated hemocytes showed a significant attenuation of DCF-mediated cytotoxic, oxidative and genotoxic effects, which appeared to be caused by NADPH oxidase and NO synthase activation, since their inhibition was followed by a significant elimination of (.)O2(-) and NO2(-) generation and the concomitant oxidative damage within cells. The results of the present study showed for the first time that unspecific mode of action of DCF, associated with the induction of NADPH oxidase

  12. Uptake from water, biotransformation, and biliary excretion of pharmaceuticals by rainbow trout.

    PubMed

    Lahti, Marja; Brozinski, Jenny-Maria; Jylhä, Antti; Kronberg, Leif; Oikari, Aimo

    2011-06-01

    An urgent need exists to assess the exposure of fish to pharmaceuticals. The aim of the present study was to assess the uptake and metabolism of waterborne pharmaceuticals in rainbow trout (Oncorhynchus mykiss). A further objective was to determine the possibility of monitoring exposure to low levels of pharmaceuticals by bile assays. Rainbow trout were exposed for 10 d under flow-through conditions to mixtures of five pharmaceuticals (diclofenac, naproxen, ibuprofen, bisoprolol, and carbamazepine) at high and low concentrations. The low concentration was used to mimic the conditions prevailing in the vicinity of the discharge points of wastewater treatment plants. The uptake and the bioconcentration were determined by blood plasma and bile analyses. The average bioconcentration factor in plasma ranged from below 0.1 for bisoprolol to 4.9 for diclofenac, the values being approximately similar at low and high ambient concentrations. The biotransformation of diclofenac, naproxen, and ibuprofen was considered efficient, because several metabolites could be detected in concentrations clearly exceeding those of the unmetabolized compounds. The glucuronides were the dominant metabolites for all three pharmaceuticals. The total bioconcentration in the bile was two to four orders of magnitude higher than in the plasma. The results of this work show that the exposure of fish to pharmaceuticals in environmentally relevant concentrations may be monitored by blood plasma and bile analyses, the latter allowing detection at markedly lower ambient concentration. Copyright © 2011 SETAC.

  13. COX-2 and SCD, markers of inflammation and adipogenesis, are related to disease activity in Graves' ophthalmopathy.

    PubMed

    Vondrichova, Tereza; de Capretz, Annika; Parikh, Hemang; Frenander, Christofer; Asman, Peter; Aberg, Magnus; Groop, Leif; Hallengren, Bengt; Lantz, Mikael

    2007-06-01

    Inflammation and adipogenesis are two parallel processes with increased activity in severe Graves' ophthalmopathy. The aim of this work was to define target genes for therapeutic intervention in adipogenesis and inflammation in Graves' ophthalmopathy. Orbital tissue was obtained from patients with ophthalmopathy in acute or chronic phase undergoing orbital surgery to study gene expression followed by the study of potential intervention mechanisms in preadipocytes. Clinic of Endocrinology, University Hospital, Malmö, Sweden. Patients in acute severe or in chronic phase of ophthalmopathy. Lateral orbital decompression in acute phase and restorative surgery in chronic phase. In vitro treatment of preadipocytes with rosiglitazone and diclofenac. Gene expression in intraorbital tissue or preadipocytes and differentiation of preadipocytes. A marker of adipose tissue, stearoyl-coenzyme A desaturase (SCD), and the proinflammatory gene, cyclooxygenase-2 (COX-2), were overexpressed in patients in active phase compared to the chronic phase of ophthalmopathy. In growth-arrested preadipocytes stimulated with rosiglitazone, COX-2 expression increased temporarily within 1 hour and decreased to undetectable levels after 48 hours. In contrast, SCD and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) expression increased continuously from day 2 to day 7 during adipogenesis. Diclofenac, an inhibitor of cyclooxygenases with antagonistic effects on PPAR-gamma, reduced the number of mature adipocytes by approximately 50%. We conclude that inflammation and adipogenesis decrease with a decrease in activity of ophthalmopathy and that the nonsteroidal antiinflammatory drug diclofenac inhibits adipogenesis. This may represent a putative future treatment of endocrine ophthalmopathy.

  14. Therapeutic effect of methanolic extract of Laportea aestuans (L.) Chew, on oxidative stress in the brain of male Wistar rats

    NASA Astrophysics Data System (ADS)

    Elizabeth, Omotosho Omolola; Olawumi, Ogunlade Oladipupo

    2018-04-01

    The aim of this study was to assess the effect of diclofenac-induced oxidative stress in the brain of Wistar rats. The experiment was carried out using thirty-six rats. Six groups contained six rats in each. The first group being the control group received 1ml of gum acacia which is the vehicle. Groups 2 to 6 were induced with oxidative stress by oral administration of 40 mg/kg body weight of diclofenac and pretreated as follows: group 2 received only diclofenac, group 3 with 200 mg/kg body weight of methanolic extract of Laportea aestuans (L.) Chew, group 4 with 400 mg/kg body weight of Laportea aestuans extract, group 5 with 800 mg/kg body weight of Laportea aestuans and group 6 with 50 mg/kg body weight of cimetidine. The pretreatment was carried out for a period of seven days after which oxidative stress was induced. The animals were thereafter sacrificed and brain was excised. Antioxidant enzymes and molecules such as superoxide dismutase, catalase, glutathione, levels of malondialdehyde and protein carbonyl were assayed by standard methods. The results showed significant increases in glutathione level and activities of catalase, superoxide dismutase and significant decrease in lipid peroxidation and protein carbonyl in groups 3 to 5 when compared to group 2. This shows that the methanolic extract of Laportea aestuans has a protective effect on the brain against oxidative stress.

  15. Parecoxib Increases Blood Pressure Through Inhibition of Cyclooxygenase-2 Messenger RNA in an Experimental Model.

    PubMed

    Vértiz-Hernández, Ángel Antonio; Martínez-Morales, Flavio; Valle-Aguilera, Roberto; López-Sánchez, Pedro; Villalobos-Molina, Rafael; Pérez-Urizar, José

    2015-01-01

    Cyclooxygenase-2 selective inhibitors have been developed to alleviate pain and inflammation; however, the use of a selective cyclooxygenase-2 inhibitor is associated with mild edema, hypertension, and cardiovascular risk. To evaluate, in an experimental model in normotensive rats, the effect of treatment with parecoxib in comparison with diclofenac and aspirin and L-NAME, a non-selective nitric oxide synthetase, on mean arterial blood pressure, and cyclooxygenase-1 and -2 messenger RNA and protein expression in aortic tissue. Rats were treated for seven days with parecoxib (10 mg/kg/day), diclofenac (3.2 mg/kg/day), aspirin (10 mg/kg/day), or L-NAME (10 mg/kg/day). Mean arterial blood pressure was evaluated in rat tail; cyclooxygenase-1 and -2 were evaluated by reverse transcription-polymerase chain reaction and Western blot analysis in aortic tissue. Parecoxib and L-NAME, but not aspirin and diclofenac, increased mean arterial blood pressure by about 50% (p < 0.05) without changes in cardiac frequency. Messenger RNA cyclooxygenase-1 expression in aortic tissue was not modified with any drug (p < 0.05). L-NAME and parecoxib treatment decreased messenger RNA cyclooxygenase-2 and cyclooxygenase-2 (p < 0.05). While cyclooxygenase-1 protein decreased with the three drugs tested but not with L-NAME (p < 0.05), the cyclooxygenase-2 protein decreased only with aspirin and parecoxib (p < 0.05). Parecoxib increases the blood pressure of normotensive rats by the suppression of COX-2 gene expression, which apparently induced cardiovascular control.

  16. Managing Osteoarthritis Pain with Medicines: A Review of the Research for Adults

    MedlinePlus

    ... much you buy at one time. When you shop around for the best price, you should also consider the quality of the product. 7 Wholesale Prices of Prescription Analgesics Drug Name NSAIDs Celecoxib Ibuprofen Diclofenac Naproxen Etodolac Meloxicam ...

  17. Synthesis and anti-inflammatory activity of some benzofuran and benzopyran-4-one derivatives.

    PubMed

    Ragab, Fatma Abd El-Fattah; Eid, Nahed Mahmoud; Hassan, Ghaneya Sayed; Nissan, Yassin Mohammed

    2012-01-01

    New series of furosalicylic acids 3a-c, furosalicylanilides 6a-n, furobenzoxazines 8a-f, 1-benzofuran-3-arylprop-2-en-1-ones 12a,b, 6-(aryl-3-oxoprop-1-enyl)-4H-chromen-4-ones 16a-c and 6-[6-aryl-2-thioxo-2,5-dihydropyrimidin-4-yl]-4H-chromen-4-ones 17a-c were synthesized. Anti-inflammatory activity evaluation was performed using carrageenan-induced paw edema model in rats and prostaglandin E(2) (PGE(2)) synthesis inhibition activity. Some of the tested compounds revealed comparable activity with less ulcerogenic effect than Diclofenac at a dose 100 mg/kg. All the synthesized compounds were docked on the active site of cyclooxygenase-2 (COX-2) enzyme and most of them showed good interactions with the amino acids of the active site comparable to the interactions exhibited by Diclofenac.

  18. Abacavir induces arterial thrombosis in a murine model.

    PubMed

    Collado-Diaz, Victor; Andujar, Isabel; Sanchez-Lopez, Ainhoa; Orden, Samuel; Blanch-Ruiz, María Amparo; Martinez-Cuesta, María Angeles; Blas-García, Ana; Esplugues, Juan V; Álvarez, Ángeles

    2018-01-16

    The effects of abacavir were evaluated in a validated model of arterial thrombosis. The role of ATP-P2X7-receptors and the actions of two vascular-damaging agents (diclofenac or rofecoxib) and other NRTIs were also analysed. Abacavir dose-dependently promoted thrombus formation. This effect was reversed by a P2X7-receptor antagonist and was non-existent in P2X7 KO mice. The effects of abacavir were similar to those of diclofenac and rofecoxib. Other NRTIs had no thrombosis-related effects. Abacavir promotes arterial thrombosis through interference with purinergic signalling, suggesting a possible biological mechanism for the clinical association of abacavir with cardiovascular diseases. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  19. Yerba Mate

    MedlinePlus

    Mate is a plant. The leaves are used to make medicine. Mate is used as a stimulant to relieve mental and physical tiredness ( ... diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ...

  20. Effects of photobiomodulation therapy and topical non-steroidal anti-inflammatory drug on skeletal muscle injury induced by contusion in rats-part 2: biochemical aspects.

    PubMed

    Tomazoni, Shaiane Silva; Frigo, Lúcio; Dos Reis Ferreira, Tereza Cristina; Casalechi, Heliodora Leão; Teixeira, Simone; de Almeida, Patrícia; Muscara, Marcelo Nicolas; Marcos, Rodrigo Labat; Serra, Andrey Jorge; de Carvalho, Paulo de Tarso Camillo; Leal-Junior, Ernesto Cesar Pinto

    2017-11-01

    Muscle injuries trigger an inflammatory process, releasing important biochemical markers for tissue regeneration. The use of non-steroidal anti-inflammatory drugs (NSAIDs) is the treatment of choice to promote pain relief due to muscle injury. NSAIDs exhibit several adverse effects and their efficacy is questionable. Photobiomodulation therapy (PBMT) has been demonstrated to effectively modulate inflammation induced from musculoskeletal disorders and may be used as an alternative to NSAIDs. Here, we assessed and compared the effects of different doses of PBMT and topical NSAIDs on biochemical parameters during an acute inflammatory process triggered by a controlled model of contusion-induced musculoskeletal injury in rats. Muscle injury was induced by trauma to the anterior tibial muscle of rats. After 1 h, rats were treated with PBMT (830 nm, continuous mode, 100 mW of power, 35.71 W/cm 2 ; 1, 3, and 9 J; 10, 30, and 90 s) or diclofenac sodium (1 g). Our results demonstrated that PBMT, 1 J (35.7 J/cm 2 ), 3 J (107.1 J/cm 2 ), and 9 J (321.4 J/cm 2 ) reduced the expression of tumor necrosis factor alpha (TNF-α) and cyclooxygenase-2 (COX-2) genes at all assessed times as compared to the injury and diclofenac groups (p < 0.05). The diclofenac group showed reduced levels of COX-2 only in relation to the injury group (p < 0.05). COX-2 protein expression remained unchanged with all therapies except with PBMT at a 3-J dose at 12 h (p < 0.05 compared to the injury group). In addition, PBMT (1, 3, and 9 J) effectively reduced levels of cytokines TNF-α, interleukin (IL)-1β, and IL-6 at all assessed times as compared to the injury and diclofenac groups (p < 0.05). Thus, PBMT at a 3-J dose was more effective than other doses of PBMT and topical NSAIDs in the modulation of the inflammatory process caused by muscle contusion injuries.