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1

Morphine Oral  

MedlinePLUS

... relieve moderate to severe pain. Morphine extended-release tablets and capsules are only used to relieve severe ( ... use of other pain medications. Morphine extended-release tablets and capsules should not be used to treat ...

2

Oral diacetylmorphine (heroin) yields greater morphine bioavailability than oral morphine: bioavailability related to dosage and prior opioid exposure  

PubMed Central

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTVenosclerosis prevents many opioid addicts in heroin substitution programmes from injecting intravenously, which makes consideration of other routes of administration necessary.Even high doses of oral diacetylmorphine are completely converted to morphine presystemically.Morphine bioavailability in heroin addicts after high-dose oral diacetylmorphine administration is considerably higher than expected based on prior data obtained with relatively low oral diacetylmorphine or morphine doses in healthy subjects or patients receiving treatment for pain (64–72% vs. 20–25%). WHAT THIS STUDY ADDSMorphine influx into systemic circulation is more rapid after oral diacetylmorphine than after oral morphine, resulting in earlier and more than double maximal concentrations.In opioid-dependent people, bioavailability of morphine from oral doses of diacetylmorphine is also 37% higher than that of oral morphine.Morphine bioavailability is two and 1.5 times higher in chronic users than in opioid-naive subjects after low oral doses of diacetylmorphine or morphine, respectively.Oral absorption of morphine from diacetylmorphine is dose dependent, i.e. bioavailability increases with diacetylmorphine dose. AIMS In the Swiss heroin substitution trials, patients are treated with self-administered diacetylmorphine (heroin). Intravenous administration is not possible in patients that have venosclerosis. Earlier studies have demonstrated that oral diacetylmorphine may be used, although it is completely converted to morphine presystemically. Morphine bioavailability after high-dose oral diacetylmorphine is considerably higher than would be predicted from low-dose trials. The aim was to investigate whether the unexpectedly high bioavailability is due to a difference in the drug examined, and whether it depends on previous exposure or on dose. METHODS Opioid-naive healthy volunteers and dependent patients from the Swiss heroin trials (n = 8 per group) received low doses of intravenous and oral deuterium-labelled morphine and diacetylmorphine, respectively. Patients also received a high oral diacetylmorphine dose. RESULTS The maximum plasma concentration (Cmax) of morphine was twofold higher after oral diacetylmorphine than after morphine administration in both groups. However, morphine bioavailability was considerably higher in chronic users [diacetylmorphine 45.6% (95% confidence interval 40.0, 51.3), morphine 37.2% (30.1, 44.3)] than in naive subjects [diacetylmorphine 22.9% (16.4, 29.4), morphine 23.9% (16.5, 31.2)] after low oral doses (48.5 µmol) of either diacetylmorphine or morphine. Morphine clearance was similar in both groups. Moreover, oral absorption of morphine from diacetylmorphine was found to be dose dependent, with bioavailability reaching 64.2% (55.3, 73.1) for high diacetylmorphine doses (1601 µmol). CONCLUSIONS Oral absorption of opioids is substance-, dose- and patient collective-dependent, suggesting that there may be a saturation of first-pass processes, the exact mechanism of which is not yet understood. PMID:18945270

Halbsguth, Ulrike; Rentsch, Katharina M; Eich-Höchli, Dominique; Diterich, Isabel; Fattinger, Karin

2008-01-01

3

Effect of premedication with controlled-release oral morphine on postoperative pain. A comparison with intramuscular morphine.  

PubMed

Thirty fit patients presenting for elective total hip replacement were randomly allocated to receive a premedication of 60 or 90 mg controlled-release oral morphine or 15 mg intramuscular morphine. Postoperative analgesia was assessed using on-demand intravenous pethidine supplementation requirements. In 15 patients free plasma morphine concentrations were measured. Both 60 and 90 mg controlled-release oral morphine led to a reduced pethidine requirement compared to the intramuscular group but the reduction was not statistically different. PMID:4014620

Slowey, H F; Reynolds, A D; Mapleson, W W; Vickers, M D

1985-05-01

4

Rifampin reduces oral morphine absorption: a case of transdermal buprenorphine selection based on morphine pharmacokinetics.  

PubMed

A 51-year-old male was referred to the Stratton Veterans Affairs Medical Center Pain Service after hospital admission for endocarditis with a history of heroin use and chronic low back pain. During his hospital stay he experienced a reduction in his serum morphine level ostensibly as a result of concomitant rifampin administration. We hypothesize that diminished absorption was from rifampin-mediated intestinal P-glycoprotein induction, ultimately decreasing serum free morphine and metabolites. The case became more complex in an attempt to balance managed pain, history of substance abuse, completion of antibiotic therapy, and a reasonable pain regimen upon discharge. Ultimately, the patient was titrated onto a buprenorphine transdermal patch, the initiation of which was based on serum free morphine and an extrapolated oral morphine dose by calculation. PMID:23216174

Fudin, Jeffrey; Fontenelle, Dania Vanesta; Payne, Annette

2012-12-01

5

Direct conversion from oral morphine to transdermal fentanyl: a multicenter study in patients with cancer pain  

Microsoft Academic Search

Direct conversion from oral morphine to transdermal fentanyl with a ratio of oral morphine\\/transdermal fentanyl (100:1 mg) daily was examined in patients with cancer pain. Patients with a ‘stable and low level of cancer pain’ receiving a constant dosage of sustained release morphine during a pre-study phase of 6 days were included in the study. Initial fentanyl dosage was calculated

Barbara Donner; Michael Zenz; Michael Tryba; Michael Strumpf

1996-01-01

6

Oral morphine in cancer patients: in vivo kinetics and in vitro hepatic glucuronidation.  

PubMed Central

The kinetics of morphine and formation of the main metabolite, morphine-3-glucuronide (M3G) after single and intravenous doses of morphine were studied in six cancer patients and compared with the formation rate of M3G in vitro in microsomes isolated from liver biopsies obtained from the same patients at palliative laparotomy. The results showed that high formation rates of M3G in vitro in microsomes isolated from liver biopsies were associated both with high apparent oral clearance values and high M3G/morphine AUC (area under the concentration vs time curve) ratios as measured in vivo in the same patients. In accordance with previous results marked interindividual differences were seen in the kinetics of morphine; the oral bioavailability varied between 30 and 69% and the systemic plasma clearance between 18.6 and 34.0 ml min-1 kg-1. This variation correlated with the variation in morphine metabolism as assessed in vitro. In vivo, a high M3G/morphine AUC ratio predicted a high oral clearance. Hepatic UDP-glucuronyl transferase activity is thus an important determinant of the in vivo kinetics of orally administered morphine. PMID:3994897

Säwe, J; Kager, L; Svensson Eng, J O; Rane, A

1985-01-01

7

Start of oral morphine to cancer patients: effective serum morphine concentrations and contribution from morphine-6-glucuronide to the analgesia produced by morphine  

Microsoft Academic Search

Objective: To investigate the serum concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) and the\\u000a relationships between serum concentrations and clinical effects associated with start of morphine treatment in cancer patients.\\u000a \\u000a \\u000a \\u000a Methods: Forty patients with malignant disease and intolerable pain on weak opioids (codeine\\/dextropropoxyphen) were included. After\\u000a a wash-out period, titration with immediate-release (IR) morphine was started. When a stable

P. Klepstad; S. Kaasa; P. C. Borchgrevink

2000-01-01

8

Morphine and codeine in oral fluid after controlled poppy seed administration.  

PubMed

Opiates are an important drug class in drug testing programmes. Ingestion of poppy seeds containing morphine and codeine can yield positive opiate tests and mislead result interpretation in forensic and clinical settings. Multiple publications evaluated urine opiate concentrations following poppy seed ingestion, but only two addressed oral fluid (OF) results; neither provided the ingested morphine and codeine dosage. We administered two 45?g raw poppy seed doses, each containing 15.7?mg morphine and 3.1?mg codeine, 8?h apart to 17 healthy adults. All OF specimens were screened by on-site OF immunoassay Draeger DrugTest 5000, and confirmed with OF collected with Oral-Eze® device and quantified by liquid chromatography-tandem mass spectrometry (1?µg/L morphine and codeine limits of quantification). Specimens (n?=?459) were collected before and up to 32?h after the first dose. All specimens screened positive 0.5?h after dosing and remained positive for 0.5-13?h at Draeger 20?µg/L morphine cut-off. Maximum OF morphine and codeine concentrations (Cmax ) were 177 and 32.6?µg/L, with times to Cmax (Tmax ) of 0.5-1?h and 0.5-2.5?h post-dose, respectively. Windows of detection after the second dose extended at least 24?h for morphine and to 18?h for codeine. After both doses, the last morphine positive OF result was 1?h with 40?µg/L 2004 proposed US Substance Abuse and Mental Health Services Administration cut-off, and 0.5?h with 95?µg/L cut-off, recently recommended by the Driving under the Influence of Drugs and Medicines project. Positive OF morphine results are possible 0.5-1?h after ingestion of 15.7?mg of morphine in raw poppy seeds, depending on the cut-off employed. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25345619

Concheiro, Marta; Newmeyer, Matthew N; da Costa, Jose Luiz; Flegel, Ron; Gorelick, David A; Huestis, Marilyn A

2014-10-24

9

Oral administration of morphine versus ibuprofen to manage postfracture pain in children: a randomized trial  

PubMed Central

Background: Recent warnings from Health Canada regarding codeine for children have led to increased use of nonsteroidal anti-inflammatory drugs and morphine for common injuries such as fractures. Our objective was to determine whether morphine administered orally has superior efficacy to ibuprofen in fracture-related pain. Methods: We used a parallel group, randomized, blinded superiority design. Children who presented to the emergency department with an uncomplicated extremity fracture were randomly assigned to receive either morphine (0.5 mg/kg orally) or ibuprofen (10 mg/kg) for 24 hours after discharge. Our primary outcome was the change in pain score using the Faces Pain Scale — Revised (FPS-R). Participants were asked to record pain scores immediately before and 30 minutes after receiving each dose. Results: We analyzed data from 66 participants in the morphine group and 68 participants in the ibuprofen group. For both morphine and ibuprofen, we found a reduction in pain scores (mean pre–post difference ± standard deviation for dose 1: morphine 1.5 ± 1.2, ibuprofen 1.3 ± 1.0, between-group difference [?] 0.2 [95% confidence interval (CI) ?0.2 to 0.6]; dose 2: morphine 1.3 ± 1.3, ibuprofen 1.3 ± 0.9, ? 0 [95% CI ?0.4 to 0.4]; dose 3: morphine 1.3 ± 1.4, ibuprofen 1.4 ± 1.1, ? ?0.1 [95% CI ?0.7 to 0.4]; and dose 4: morphine 1.5 ± 1.4, ibuprofen 1.1 ± 1.2, ? 0.4 [95% CI ?0.2 to 1.1]). We found no significant differences in the change in pain scores between morphine and ibuprofen between groups at any of the 4 time points (p = 0.6). Participants in the morphine group had significantly more adverse effects than those in the ibuprofen group (56.1% v. 30.9%, p < 0.01). Interpretation: We found no significant difference in analgesic efficacy between orally administered morphine and ibuprofen. However, morphine was associated with a significantly greater number of adverse effects. Our results suggest that ibuprofen remains safe and effective for outpatient pain management in children with uncomplicated fractures. Trial registration: ClinicalTrials.gov, no. NCT01690780. PMID:25349008

Poonai, Naveen; Bhullar, Gina; Lin, Kangrui; Papini, Adam; Mainprize, David; Howard, Jocelyn; Teefy, John; Bale, Michelle; Langford, Cindy; Lim, Rodrick; Stitt, Larry; Rieder, Michael J.; Ali, Samina

2014-01-01

10

Morphine mouthwash for the management of oral mucositis in patients with head and neck cancer  

PubMed Central

Background: Oral mucositis is a debilitating side effect of cancer treatment for which there is not much successful treatments at yet. We evaluated the effectiveness of topical morphine compared with a routine mouthwash in managing cancer treatment-induced mucositis. Materials and Methods: Thirty head and neck cancer patients with severe mucositis (World Health Organization Grade III or IV) were randomized into the morphine and magic mouthwash groups. Patients received morphine sulfate 2% or magic solution (contained magnesium aluminum hydroxide, viscous lidocaine, and diphenhydramine), 10 ml for every 3 h, six times a day, for 6 days. Both groups received same dietary and oral hygiene instructions and care. Mucositis was graded at baseline and every 3 days after treatment. Patients’ satisfaction and drug effect maintenance were also evaluated. Results: Twenty-eight patients (mean age of 49.5 ± 13.2 years, 63.3% female) completed the trial; 15 in the morphine group and 13 in the magic group. There was a decrease in mucositis severity in both of the morphine (P < 0.001) and magic (P = 0.049) groups. However, at the 6th day, more reduction was observed in mucositis severity in the morphine compared with magic group (P = 0.045). Drug effect maintenance was similar between the two groups, but patients in the morphine group were more satisfied by their treatments than those in the magic group (P = 0.008). Conclusions: Topical morphine is more effective and more satisfactory to patients than the magic mouthwash in reducing severity of cancer treatment-induced oral mucositis. More studies with larger sample size and longer follow-up are required in this regard. PMID:25789270

Sarvizadeh, Mostafa; Hemati, Simin; Meidani, Mohsen; Ashouri, Moghtada; Roayaei, Mahnaz; Shahsanai, Armindokht

2015-01-01

11

Fast disintegrating tablets of nisoldipine for intra-oral administration.  

PubMed

Nisoldipine is a calcium channel blocker with low and variable oral bioavailability. This was attributed to slow dissolution and presystemic metabolism. Accordingly, the objective of this work was to enhance the dissolution rate of nisoldipine to formulate fast disintegrating tablets with rapid dissolution. Binary solid dispersions (SD) were prepared for the drug with hydroxypropyl methyl cellulose E5 (HPMC), polyvinylpyrrolidone (PVP), Pluronic F68 or polyethylene glycol 6000 (PEG 6000). SD formation increased the dissolution rate compared to pure drug with the corresponding physical mixtures failing to provide the same dissolution enhancement. This indicates that the SD enhanced dissolution is not due to the solubilizing effect of the polymer and can be due to physical change in the drug crystal which was confirmed by thermal analysis. SD with HPMC and PVP were selected for preparation of fast disintegrating tablets as they liberated most of the drug in the first 5?min. HPMC-based tablets disintegrated rapidly and released most of the drug in the first 2?min which correlated with the corresponding SD. In contrast, PVP-based tablets disintegrated slowly with gradual dissolution. This can be attributed to the binding effect of PVP. The study developed fast disintegrating tablet for intra-oral administration. PMID:23841582

El Maghraby, Gamal M; Elsergany, Ramy N

2014-09-01

12

Stability of benzocaine formulated in commercial oral disintegrating tablet platforms.  

PubMed

Pharmaceutical excipients contain reactive groups and impurities due to manufacturing processes that can cause decomposition of active drug compounds. The aim of this investigation was to determine if commercially available oral disintegrating tablet (ODT) platforms induce active pharmaceutical ingredient (API) degradation. Benzocaine was selected as the model API due to known degradation through ester and primary amino groups. Benzocaine was either compressed at a constant pressure, 20 kN, or at pressure necessary to produce a set hardness, i.e., where a series of tablets were produced at different compression forces until an average hardness of approximately 100 N was achieved. Tablets were then stored for 6 months under International Conference on Harmonization recommended conditions, 25°C and 60% relative humidity (RH), or under accelerated conditions, 40°C and 75% RH. Benzocaine degradation was monitored by liquid chromatography-mass spectrometry. Regardless of the ODT platform, no degradation of benzocaine was observed in tablets that were kept for 6 months at 25°C and 60% RH. After storage for 30 days under accelerated conditions, benzocaine degradation was observed in a single platform. Qualitative differences in ODT platform behavior were observed in physical appearance of the tablets after storage under different temperature and humidity conditions. PMID:23990120

Köllmer, Melanie; Popescu, Carmen; Manda, Prashanth; Zhou, Leon; Gemeinhart, Richard A

2013-12-01

13

[Impact of slow-release oral morphine on drug abusing habits in Austria].  

PubMed

A well-established possibility to treat opiate addiction is the participation in opiate maintenance treatment programmes. For this purpose the opioids methadone and buprenorphine have been evaluated and are used nowadays in many countries. However, since 1998 also the use of slow-release oral morphine (SROM) has been legally permitted in Austria. Our data show that these morphine preparations are frequently abused and are dominating the black market in the meantime. Especially the intravenous consumption of SROM goes along with highly dangerous side effects that exceed the risks of needle sharing alone. Special galenics are supposed to ensure a 24 h effect of the otherwise quickly metabolised morphine. If dissolved and injected, insoluble contents such as talcum cause microembolisms, leading to severe damages of the inner organs. Furthermore, SROM, i.e. a drug prescribed by physicians, has been proved to be the main responsible substance in most drug related deaths since its permission and has nearly replaced heroin. Forensic physicians play a major role in the profound examination of these cases, including extensive toxicological analyses and interpretation of results. For instance, a differentiation between a recent morphine and heroin consumption is certainly possible, provided appropriate methods are used. A reliable estimation of the current situation of drug abusing habits is a premise for adequate therapeutic offers and preventive measures. Thus, well-founded and comparable data have to be collected. To facilitate data report a standardized report form has been developed that includes an obligatory statement regarding morphine or heroin consumption. This should help to enlighten the ongoing discussion on the role of SRM in drug abuse cases. Our results indicate that the prescription of SROM in opiate maintenance therapy has to be handled very strictly and should be reserved for special patients only. A slackening of the Austrian law concerning SROM is therefore objected. PMID:20605006

Beer, Beate; Rabl, Walter; Libiseller, Kathrin; Giacomuzzi, Salvatore; Riemer, Yvonne; Pavlic, Marion

2010-01-01

14

Orally disintegrating mini-tablets (ODMTs)--a novel solid oral dosage form for paediatric use.  

PubMed

The new European regulations on paediatric medicines and recent WHO recommendations have induced an increased need for research into novel child-appropriate dosage forms. The aim of this study was the development of orally disintegrating mini-tablets (ODMTs) as a suitable dosage form for paediatric patients. The suitability of five commercially available ready-to-use tableting excipients, Ludiflash, Parteck ODT, Pearlitol Flash, Pharmaburst 500 and Prosolv ODT, to be directly compressed into mini-tablets, with 2 mm in diameter, was examined. All of the excipients are based on co-processed mannitol. Drug-free ODMTs and ODMTs with a child-appropriate dose of hydrochlorothiazide were investigated. ODMTs could be produced with all investigated excipients. ODMTs with a sufficient crushing strength >7 N and a low friability <1% could be obtained, as well as ODMTs with a short simulated wetting test-time <5 s. ODMTs made of Ludiflash showed the best results with crushing strengths from 7.8 N up to 11.8 N and excellent simulated wetting test-times from 3.1 s to 5.0 s. For each excipient, ODMTs with accordance to the pharmacopoeial specification content uniformity could be obtained. The promising results indicate that orally disintegrating mini-tablets may serve as a novel platform technology for paediatrics in future. PMID:21324357

Stoltenberg, I; Breitkreutz, J

2011-08-01

15

Oral malodor reduction by a palatal mucoadhesive tablet containing herbal formulation  

Microsoft Academic Search

Objective: The aim of the present study was to test the effect of a palatal mucoadhesive tablet containing an herbal formulation on oral malodor production and volatile sulfide compound (VSC) levels, and to evaluate its antimicrobial activity. Methods: A total of 56 healthy young volunteers participated in experiments 1 and 2. The palatal adhesive tablets were prepared with different active

Nir Sterer; Shada Nuas; Boaz Mizrahi; Chen Goldenberg; Ervin I. Weiss; Abraham Domb; Michael Perez Davidi

2008-01-01

16

77 FR 1695 - Determination That AVALIDE (Hydrochlorothiazide and Irbesartan), Oral Tablets, 25 Milligrams/300...  

Federal Register 2010, 2011, 2012, 2013, 2014

...irbesartan), oral tablets, 25 mg/300 mg, were withdrawn from sale for reasons of safety or effectiveness. In addition, Lupin Pharmaceuticals, Inc. submitted a citizen petition dated November 10, 2011 (Docket No. FDA-2011-P-0822),...

2012-01-11

17

The Influence of Formulation and Manufacturing Process Parameters on the Characteristics of Lyophilized Orally Disintegrating Tablets  

PubMed Central

Gelatin is a principal excipient used as a binder in the formulation of lyophilized orally disintegrating tablets. The current study focuses on exploiting the physicochemical properties of gelatin by varying formulation parameters to determine their influence on orally disintegrating tablet (ODT) characteristics. Process parameters, namely pH and ionic strength of the formulations, and ball milling were investigated to observe their effects on excipient characteristics and tablet formation. The properties and characteristics of the formulations and tablets which were investigated included: glass transition temperature, wettability, porosity, mechanical properties, disintegration time, morphology of the internal structure of the freeze-dried tablets, and drug dissolution. The results from the pH study revealed that adjusting the pH of the formulation away from the isoelectric point of gelatin, resulted in an improvement in tablet disintegration time possibly due to increase in gelatin swelling resulting in greater tablet porosity. The results from the ionic strength study revealed that the inclusion of sodium chloride influenced tablet porosity, tablet morphology and the glass transition temperature of the formulations. Data from the milling study showed that milling the excipients influenced formulation characteristics, namely wettability and powder porosity. The study concludes that alterations of simple parameters such as pH and salt concentration have a significant influence on formulation of ODT. PMID:24310589

Jones, Rhys J.; Rajabi-Siahboomi, Ali; Levina, Marina; Perrie, Yvonne; Mohammed, Afzal R.

2011-01-01

18

Evaluation of coprocessed disintegrants produced from tapioca starch and mannitol in orally disintegrating paracetamol tablet.  

PubMed

The study evaluated two novel coprocessed excipients (with two methods) as disintegrants in an orally disintegrating paracetamol tablet formulation. The tablets produced were assessed for mechanical properties with the use of friability and tensile strength while the release properties were assessed with wetting time, water absorption ratio, disintegration time and dissolution profile. The results obtained showed that the methods of coprocessing and disintegrant incorporation influenced the activities of the disintegrants. The novel disintegrant enhanced the mechanical properties of the tablets containing them as shown by lower friability and higher tensile strength of the tablets. The result further showed that the rate and amount of water absorbed, type of disintegrant and the method of disintegrant incorporation influenced the total amount of paracetamol released. The study concluded that the novel disintegrants will be effective in the formulation of orally disintegrating paracetamol tablets. PMID:25362809

Adeoye, Oluwatomide; Alebiowu, Gbenga

2014-01-01

19

Proniosomal oral tablets for controlled delivery and enhanced pharmacokinetic properties of acemetacin.  

PubMed

Free-flowing proniosomal powders of acemetacin (AC) were prepared using the slurry method and maltodextrin as carrier. Positively charged proniosomes composed of 70:20:10 of Span 60/cholesterol (Chol)/stearylamine (SA), respectively, were successively compressed into tablets using direct compression method. The tablets were characterized for weight variability, friability, hardness, drug content uniformity, and dissolution properties. The in vivo evaluation of the prepared proniosomes (powder or tablet forms) after oral administration was investigated by the determination of AC and its active metabolite indomethacin (IND) in the blood of albino rabbits. Results indicated that the increase of Chol from 10% to 20% markedly reduced the efflux of the drug. Further Chol addition from 30% to 50% led to increased AC release rates. The proniosome tablets of AC showed greater hardness and disintegration time and less friability than AC plain tablets. The dissolution of proniosomal tablets indicated a lower drug release percentage compared to powdered proniosomes and AC plain tablets. The mean pharmacokinetic parameters of AC and IND from different formulations indicated increased t 1/2 and area under the curve (AUC) of both AC and IND for proniosomal tablets compared with both proniosomal powders and AC plain tablets. This study suggested the formulation of AC proniosomal powder into tablets to control and extend its pharmacologic effects. PMID:25319057

Shehata, Tamer M; Abdallah, Marwa H; Ibrahim, Mahmoud Mokhtar

2015-04-01

20

Breakthrough cancer pain: a randomized trial comparing oral transmucosal fentanyl citrate (OTFC ®) and morphine sulfate immediate release (MSIR ®)  

Microsoft Academic Search

Oral transmucosal fentanyl citrate (OTFC®; Actiq®) is a drug delivery formulation used for management of breakthrough cancer pain. Previous studies with open-label comparisons indicated OTFC was more effective than patients’ usual opioid for breakthrough pain. The objective of this study was to compare OTFC and morphine sulfate immediate release (MSIR®) for management of breakthrough pain in patients receiving a fixed

Paul H Coluzzi; Lee Schwartzberg; John D Conroy; Steve Charapata; Mason Gay; Michael A Busch; Jana Chavez; Jeri Ashley; Dixie Lebo; Maureen McCracken; Russell K Portenoy

2001-01-01

21

Comparison of rectal diazepam and subcutaneous morphine-scopolamine administration for outpatient sedation in minor oral surgery.  

PubMed

In a randomized cross-over study on sedation in outpatient oral surgery, subcutaneous administration of morphine-scopolamine was compared with rectal administration of diazepam. The mean dose of morphine was 0.13 mg kg-1 (range 0.13-0.24) and of diazepam 0.57 mg kg-1 (range 0.50-0.71). Apprehension, the determining factor for patients' preference for sedation method, the recovery from sedation and the postoperative course were studied. Both methods produced the desired effects. For diazepam, the effect was scored higher by the patient than the nurse observer and for morphine-scopolamine the opposite was found. Postoperative pain and patients' preference for sedation did not differ between the methods and the determining factor for the patients' preference for sedation method was the experience of stronger tranquilization. Side-effects such as prolonged recovery, nausea, dizziness, and dysphoria were frequent during the postoperative course after the morphine-scopolamine sedation but were not seen during diazepam sedation. Thus, rectal administration of diazepam should be preferred to morphine and scopolamine for sedation in minor oral surgery performed under local anesthesia. PMID:4072591

Lundgren, S

1985-10-01

22

Oral heroin in opioid-dependent patients: pharmacokinetic comparison of immediate and extended release tablets  

PubMed Central

In diacetylmorphine prescription programs for heavily dependent addicts, diacetylmorphine is usually administered intravenously, but this may not be possible due to venosclerosis or when heroin abuse had occurred via non-intravenous routes. Since up to 25% of patients administer diacetylmorphine orally, we characterised morphine absorption after single oral doses of immediate and extended release diacetylmorphine in 8 opioid addicts. Plasma concentrations were determined by liquid chromatography-mass spectrometry. Non-compartmental methods and deconvolution were applied for data analysis. Mean (±SD) immediate and extended release doses were 719 ± 297 mg and 956 ± 404 mg, with high absolute morphine bioavailabilities of 56% to 61%, respectively. Immediate release diacetylmorphine caused rapid morphine absorption, peaking at 10 to 15 min. Morphine absorption was considerably slower and more sustained for extended release diacetylmorphine, with only ~30% of maximal immediate release absorption being reached after 10 min and maintained for 3 to 4 h, with no relevant food interaction. The relative extended to immediate release bioavailability was calculated to be 86% by non-compartmental analysis and 93% by deconvolution analysis. Thus, immediate and extended release diacetylmorphine produce the intended morphine exposures. Both are suitable for substitution treatments. Similar doses can be applied if used in combination or sequentially. PMID:19084595

Perger, Ludwig; Rentsch, Katharina M.; Kullak-Ublick, Gerd A.; Verotta, Davide; Fattinger, Karin

2009-01-01

23

Postoperative Intravenous Morphine Consumption, Pain Scores, and Side Effects with Perioperative Oral Controlled-Release Oxycodone After Lumbar Discectomy  

Microsoft Academic Search

BACKGROUND: Oral opioid formulations contribute to postoperative analgesia. In this study, we evaluated the perioperative application of oral controlled-release oxyc- odone to reduce postoperative IV morphine consumption and opioid side effects after lumbar discectomy. METHODS: Forty patients scheduled for elective lumbar discectomy over 1 or 2 levels were included in this prospective, randomized, double-blind, placebo-controlled study. Every 12 h patients

Stephan Blumenthal; Kan Min; Michael Marquardt; Alain Borgeat

2007-01-01

24

Prolonged release (PR) oxycodone & naloxone (TarginactTM) fixed combination oral tablets for severe chronic pain  

Microsoft Academic Search

Summary • A fixed dose oral prolonged release (PR) oxycodone and prolonged release (PR) naloxone combination tablet is a new preparation for the treatment of severe pain which can only be adequately managed by opioid analgesics. • Naloxone has been added to counteract opioid induced constipation. The bioavailability of naloxone after oral ad- ministration is <3% because of first pass

Katie Smith

25

Efficacy of oral powder compared with chewable tablets for lanthanum carbonate administration in hemodialysis patients.  

PubMed

Lanthanum carbonate (LC) has been administered in a chewable tablet form for patients with hyperphosphatemia undergoing dialysis. However, some patients have difficulty chewing the tablets. LC oral powder has recently been released in Japan. The purpose of this study was to clarify the efficacy of LC oral powder form compared with that of chewable tablet form. The efficacy and safety of LC oral powder was retrospectively assessed in hemodialysis patients who switched from chewable tablet form to oral powder form without dose modification. Thirty-six patients (mean age, 66.8 ± 10.5 years; male, 64%; 39% with diabetes; mean duration of dialysis treatment, 99.2 ± 95.6 months) were enrolled in this study between June and July of 2012. Changes in clinical data and adverse events after the switch to oral powder form were investigated. The average dose of LC was 1180 ± 520 mg/day. Serum phosphorus levels were significantly decreased after the switch from chewable tablet form to oral powder form (5.3 ± 1.7 mg/dL at baseline vs. 4.9 ± 1.2 mg/dL at after 1 month after, P = 0.038). In contrast, no significant differences were observed in serum calcium and parathyroid hormone levels. Furthermore, no significant differences were evident in weight gain after the switch to oral powder form (2.5 ± 1.2 kg at baseline vs. 2.4 ± 1.1 kg at 1 month after the switch, P = 0.29). No serious adverse events were recorded. Our results suggest that LC is more effective in oral powder form than chewable tablet form for hemodialysis patients. PMID:24134326

Sakurada, Tsutomu; Oishi, Daisuke; Shibagaki, Yugo; Yasuda, Takashi; Kimura, Kenjiro

2013-10-01

26

Long-Term High-dose Oral Morphine in Phantom Limb Pain with No Addiction Risk  

PubMed Central

Chronic phantom limb pain (PLP) is a type of neuropathic pain, which is located in the missing/amputated limb. Phantom pain is difficult to treat as the exact basis of pain mechanism is still unknown. Various methods of treatment for PLP have been described, including pharmacological (NSAIDs, opioids, antiepileptic, antidepressants) and non-pharmacological (TENS, sympathectomy, deep brain stimulation and motor cortex stimulation). Opioids are used for the treatment of neuropathic pain and dose of opioid is determined based on its effect and thus there is no defined ceiling dose for opioids. We report a case where a patient receiving high-dose oral morphine for chronic cancer pain did not demonstrate signs of addiction. PMID:25709194

Kumar, Vinod; Garg, Rakesh; Bharati, Sachidanand Jee; Gupta, Nishkarsh; Bhatanagar, Sushma; Mishra, Seema; Balhara, Yatan Pal Singh

2015-01-01

27

Development and evaluation of orally disintegrating tablets (ODTs) containing Ibuprofen granules prepared by hot melt extrusion.  

PubMed

In the current study Ibuprofen was embedded in a methacrylate copolymer (Eudragit® EPO) matrix to produce solid dispersions by hot-melt extrusion (HME) processing. The obtained granules were incorporated in orally disintegrating tablets (ODTs). The tablets were developed by varying the ratio of superdisintegrants such as sodium croscarmellose and crosslinked polyvinylpyrrolidone grades while a direct compression process was used to compress the ODTs under various compaction forces to optimize tablet robustness. The properties of the compressed tablets which included porosity, hardness, friability and dissolution profiles were further evaluated and compared with Nurofen® Meltlet ODTs. The taste and sensory evaluation in human volunteers demonstrated excellence in masking the bitter active and improved tablet palatability. PMID:21592751

Gryczke, Andreas; Schminke, Silke; Maniruzzaman, Mohammed; Beck, Julien; Douroumis, Dennis

2011-09-01

28

Oral Disintegration Tablets of Stavudine for HIV Management: A New Technological Approach.  

PubMed

Stavudine oral disintegration tablets were formulated to minimize the bitter taste and to reduce the first-pass hepatic metabolism. The various precompression parameters like the angle of repose, bulk density, compressibility index and Hausner's ratio were determined for the powder blend. In this study, 14 formulations of stavudine oral disintegration tablet were prepared by direct compression method. The tablets were evaluated for weight variation, percentage friability, disintegration time, hardness, wetting time and water absorption ratio. The in vitro dissolution study results of the batch S1 (stavudine+crospovidone+sodium starch glycollate) are encouraging as highest dissolution rate (99.2% in 100 min) and lowest time of disintegration (56 s) was achieved. The in vivo drug release studies were carried out in rabbits and the relative bioavailability of formulation S1 was found to be 2.83 times greater than that of conventional tablets. PMID:23798782

Sankar, V; Ramakrishna, B; Devi, P Shalini; Karthik, S

2012-11-01

29

Orally disintegrating films and mini-tablets-innovative dosage forms of choice for pediatric use.  

PubMed

Oral drug delivery is a non-invasive and therefore a very convenient route of administration. Orally disintegrating dosage forms, like soluble films and (mini-)tablets, appear promising for use in the pediatric population. New guidance for the development of pediatric medicines has been published, which provides considerations on how pediatric products should be designed. However, most of the considerations leave a lot of room for interpretations. Bearing in mind the different aspects discussed in the latest guideline, the use of orally disintegrating films and tablets, in particular, small-sized tablets, is discussed and reflected upon by providing evidence from the scientific literature. The available dosage forms for children are various and examples of currently licensed products for use in the pediatric population were compiled. Aspects such as the appropriateness for pediatrics, the choice of excipients, the opportunities for modified drug release preparations or fixed-dose combinations, the acceptability and palatability, and also limitations were discussed with respect to the new dosage forms of orally disintegrating films and mini-tablets. This paper points out that innovation in pediatric medicines are planned and should be encouraged; however, supported by the regulatory guidance, only general considerations are provided. Nevertheless, the guideline summarizes multiple points to consider during the development of medicines for pediatric use. Considering the scientific evidence and the regulatory guidance, orally disintegrating dosage forms, like soluble films and (mini-)tablets, offer an innovative solution for pediatric drug delivery. PMID:25739913

Preis, Maren

2015-04-01

30

Comparative efficacy and safety of long-acting risperidone and risperidone oral tablets  

Microsoft Academic Search

A double-blind study of long-acting injectable risperidone and oral risperidone tablets was conducted in 640 patients with schizophrenia. All patients received flexible doses of 1–6 mg of oral risperidone for 8 weeks. Doses were stable during weeks 5–8. At the end of week 8, symptomatically stable patients were randomly assigned to receive long-acting risperidone (active injections, dummy oral) or continued

Pierre Chue; Marielle Eerdekens; Ilse Augustyns; Bernard Lachaux; Peter Mol?an; Lars Eriksson; H. Pretorius; Anthony S. David

2005-01-01

31

Chitosan-based mucoadhesive tablets for oral delivery of ibuprofen.  

PubMed

Chitosan and its half-acetylated derivative have been compared as excipients in mucoadhesive tablets containing ibuprofen. Initially the powder formulations containing the polymers and the drug were prepared by either co-spray drying or physical co-grinding. Polymer-drug interactions and the degree of drug crystallinity in these formulations were assessed by infrared spectroscopy and differential scanning calorimetry. Tablets were prepared and their swelling and dissolution properties were studied in media of various pHs. Mucoadhesive properties of ibuprofen-loaded and drug-free tablets were evaluated by analysing their detachment from pig gastric mucosa over a range of pHs. Greater polymer-drug interactions were seen for spray-dried particles compared to co-ground samples and drug loading into chitosan-based microparticles (41%) was greater than the corresponding half-acetylated samples (32%). Swelling and drug release was greater with the half-acetylated chitosan tablets than tablets containing the parent polymer and both tablets were mucoadhesive, the extent of which was dependent on substrate pH. The results illustrate the potential sustained drug delivery benefits of both chitosan and its half-acetylated derivative as mucoadhesive tablet excipients. PMID:22842627

Sogias, Ioannis A; Williams, Adrian C; Khutoryanskiy, Vitaliy V

2012-10-15

32

Day-long reduction of oral malodor by a palatal mucoadhesive tablet containing herbal formulation.  

PubMed

Previous research has shown the oral malodor reducing abilities of an herbal formulation delivered using a palatal mucoadhesive tablet. The aim of the present study was to test the day-long effect of this preventive treatment on oral malodor reduction as compared with placebo and commercial mouthwash. Forty young healthy subjects (mean age, 25.8 ± 1.8 yrs, 19 females) presenting with oral malodor were randomly assigned to use one of the three tested products: herbal mucoadhesive tablets, placebo mucoadhesive tablets and a commercial mouthwash. Following baseline measurements, subjects were instructed to use the products in the evening of the same day and the following morning. Baseline and follow-up measurements were conducted in the afternoon and included odor judge scores (two judges), volatile sulfide compounds (VSC) levels using a sulfide monitor (Halimeter™) and saliva sample for ?-galactosidase activity assay. The herbal mucoadhesive tablet caused a significant reduction in malodor scores (p = 0.004), VSC levels (p = 0.002) and ?-galactosidase assay (p = 0.02) as compared to the placebo, and reduced malodor level to below the clinical threshold (mean odor judge score of 1.7). These results demonstrate the efficacy of the herbal formulation delivered using a mucoadhesive tablet for day-long prevention of oral malodor. PMID:23519054

Sterer, N; Ovadia, O; Weiss, E I; Perez Davidi, M

2013-06-01

33

Analyses of beverage remains in drug rape cases revealing drug residues--the possibility of contamination from drug concentrated oral fluid or oral cavity contained tablets.  

PubMed

In drug-facilitated sexual assault (DFSA) cases, drug residues may be detected in beverage remains found in cups or glasses known to have been used by the victims. In this small naturalistic study, the possibility of beverages being contaminated, either by drug concentrated oral fluid or by oral cavity contained tablets, was investigated. Analysis of residues from cups containing soft drinks was performed by immunoassay and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Beverage with both added tablets and spiked oral fluid was investigated, as well as simulation of swallowing tablets. Only the residues from added tablets were positive with immunoassay, while drugs were detectable in all cups using more sensitive UPLC-MS/MS. In conclusion, the possibility of detecting drug residues in beverages due to a contamination, from either drug concentrated oral fluid or oral cavity contained tablets at a time of consumption, should be kept in mind when performing sensitive analysis. PMID:24117495

Øiestad, Elisabeth L; Karinen, Ritva; Christophersen, Asbjørg S; Vindenes, Vigdis; Bachs, Liliana

2014-01-01

34

Stability of cilazapril in pediatric oral suspensions prepared from commercially available tablet dosage forms.  

PubMed

Abstract: Cilazapril is a drug commonly used in management of heart failure in pediatric population. On pharmaceutical market it is available only in inconvenient for pediatric use tablet dosage forms. Until now, no oral liquid formulation containing cilazapril has been evaluated. Therefore, the aim of this study was to prepare easy to made and palatable 1 mg/mL oral liquid formulation with cilazapril (with consideration of original and generic cilazapril tablet and different packages) and subsequent investigation of physicochemical stability of these suspensions. Formulations were compounded using cilazapril obtained from original or generic cilazapril marketed tablet formulations and Ora-Blend" suspending agent. Stability of prepared suspensions stored in closed amber glass or amber plastic PET bottles in the temperature of 298 K was estimated throughout 28 day shelf-life period. Chemical stability was assessed by HPLC cilazapril stability indicating method. Physical stability was evaluated by appearance, taste, smell, pH and theological assessments. Cilazapril oral suspensions at concentration of 1 mg/mL demonstrated satisfactory stability over 28 day long storage at room temperature. Cilazapril concentrations remained within acceptable limit (+/- 10%) stored in closed amber bottles made of glass or PET material. Moreover, suspensions physical properties remained unaffected. Cilazapril - Ora-Blend* pediatric oral liquid is easy to made, palatable and stable when stored at room temperature for 28 days. Stability of cilazapril oral liquid remains unchanged while using cilazapril tablets produced by different manufacturers and bottles made of amber glass or PET material. PMID:25272892

Stanisz, Beata J; Paszun, Sylwia K; Zalewska, Anna

2014-01-01

35

The bioavailability of cefpodoxime proxetil tablets relative to an oral solution.  

PubMed

The bioavailability of cefpodoxime proxetil tablets relative to an oral solution of cefpodoxime proxetil in a sucrose/alcohol/citric acid vehicle was studied in 11 healthy volunteers in a randomized, crossover study. Fasted subjects took one cefpodoxime proxetil 100 mg tablet or 50 mL of a 2 mg mL-1 cefpodoxime proxetil oral solution on two separate occasions. In a third study period, all subjects took a 100 mg dose of the oral solution with a high-fat meal to investigate the effect of food on cefpodoxime proxetil absorption from the oral solution. Serial blood samples were obtained over a 24 h period, and urine was collected for 48 h after dosing. Cefpodoxime concentrations in plasma and in urine were determined using HPLC methods. The bioavailability of cefpodoxime proxetil tablets relative to the oral solution was 82%, as determined from AUC ratios. There was no difference in the rate of cefpodoxime absorption between dosage forms. Food had no effect on the extent of drug absorption from the oral solution but did result in delayed absorption. These results suggest that complete dissolution of cefpodoxime proxetil is critical for optimal bioavailability. PMID:7548778

Borin, M T; Forbes, K K; Hughes, G S

1995-05-01

36

Tablets containing a cysteine protease, actinidine, reduce oral malodor: a crossover study.  

PubMed

Tongue coating (TC) mainly consists of protein mostly from exfoliated epithelial cells. Until now, to reduce TC accumulation, only mechanical measures have been available, and the procedure involves unpleasant side effects, such as gagging reflex or carcinogenesis related to mechanical stimulation. We expected that protease might be effective in reducing the accumulation of TC causing oral malodor. The purpose of this study was to determine the effect of long-term use of candy tablets containing protease, actinidine, on both TC accumulation and concentration of volatile sulfur compounds (VSCs) in mouth air. We employed 14 subjects aged 24 to 54 years old for this study, and conducted a double-blind randomized crossover trial. The subjects sucked the tablets containing actinidine three times a day until the sixth day after starting the study. The tablets without actinidine were utilized as a placebo. Measurements of VSC concentration and TC accumulation were carried out before and after chewing tablets on the first day, and also on the seventh day. The levels of VSC and TC significantly (p < 0.05) decreased after tablets were taken on the first day in both the test and placebo groups. There was a statistically significant decrease (p < 0.05) in VSC after seven days of use only in the test group. The results of the study suggest that the tablets containing actinidine had an accumulative effect in reducing VSC in mouth air with long-term use. PMID:22368260

Nohno, K; Yamaga, T; Kaneko, N; Miyazaki, H

2012-03-01

37

Development and testing of bioadhesive, fluoride-containing slow-release tablets for oral use.  

PubMed

The bioadhesive characteristics of tablets for oral use made from modified starch, polyacrylic acid (PAA), polyethylene glycol (PEG) and sodium carboxymethylcellulose (CMC) were investigated. Adhesion force and energy were determined in-vitro and maximal adhesion time was evaluated in-vivo in human subjects. In-vitro, PAA showed the best bioadhesive properties, followed by modified maize starch and PEG with a mol. wt of 300,000-400,000 daltons. The presence of 0.1 mg of fluoride as NaF did not lead to significant differences in adhesion force and energy for the same formulation. The in-vivo bioadhesion was not strongly correlated to the in-vitro data. PAA, despite its excellent adhesion, proved to be irritating to the mucosa. PEG with a mol, wt of 200,000 daltons was subject to erosion. CMC showed good bioadhesive properties but the mechanical strength of the tablets was low. Modified maize starch tablets containing 5% (w/w) PAA and PEG with a mol. wt of 300,000 daltons proved to be the most suitable formulations for a fluoride-slow-release tablet with bioadhesive properties. In-vitro, the tablets released all of the fluoride within the 8 h period, with a high initial release. The release rate was related to the water absorption rate of the tablets. The PAA-containing formulations and the CMC formulations had the fastest release. In-vivo, fluoride levels with a minimum of 150 and a maximum of 1000 micrograms mL-1 were maintained for 8 h in the oral cavity. These fluoride levels were sustained significantly longer than those obtained with the administration of fourfold the amount of fluoride in the form of a fluoride-containing toothpaste. The release characteristics in-vivo exhibited a high variation. The use of bioadhesive polymers in oral pharmacotherapy seems promising. PMID:1682457

Bottenberg, P; Cleymaet, R; de Muynck, C; Remon, J P; Coomans, D; Michotte, Y; Slop, D

1991-07-01

38

The Relative Potency of Oral Transmucosal Fentanyl Citrate Compared with Intravenous Morphine in the Treatment of Moderate to Severe Postoperative Pain  

Microsoft Academic Search

Pharmacokinetic studies have shown that oral trans- mucosal absorption of fentanyl is relatively rapid com- pared with gastrointestinal absorption, and it results in increased bioavailability. We designed this study to es- tablish the relative potency of oral transmucosal fenta- nyl citrate (OTFC) compared with IV morphine in 133 postoperative patients. The morning after surgery, pa- tients randomly received one dose

J. Lance Lichtor; Ferne B. Sevarino; Girish P. Joshi; Michael A. Busch; Earl Nordbrock; Brian Ginsberg

1999-01-01

39

Early pregnancy termination with intravaginally administered sodium chloride solution–moistened misoprostol tablets: Historical comparison with mifepristone and oral misoprostol  

Microsoft Academic Search

Objective: The purpose of this study was to compare the abortifacient effect of intravaginally administered moistened misoprostol tablets with that of the combination regimen of mifepristone and oral misoprostol. Study Design: One hundred women at ?56 days’ gestation received 800 ?g misoprostol intravaginally in the form of sodium chloride solution–moistened tablets. The dose was repeated 24 hours later if a

John K. Jain; Karen R. Meckstroth; Daniel R. Mishell

1999-01-01

40

Development and optimization of buspirone oral osmotic pump tablet.  

PubMed

The aim of the current study was to design a porous osmotic pump-based drug delivery system for controlling the release of buspirone from the delivery system. The osmotic pump was successfully developed using symmetric membrane coating. The core of the tablets was prepared by direct compression technique and coated using dip-coating technique. Drug release from the osmotic system was studied using USP paddle type apparatus. The effect of various processing variables such as the amount of osmotic agent, the amount of swellable polymer, concentration of the core former, concentration of the plasticizer, membrane thickness, quantum of orifice on drug release from osmotic pump were evaluated. Different kinetic models (zero order, first order and Higuchi model) were applied to drug release data in order to establish the kinetics of drug release. It was found that the drug release was mostly affected by the amount of NaCl as osmotic agent, the swellable polymer; hydroxy propyl methyl cellulose (HPMC), the amount of PEG-400 and cellulose acetate in the coating solution and thickness of the semipermeable membrane. The optimized formulation released buspirone independent of pH and orifice quantum at the osmogen amount of 42%, hydrophilic polymer of 13% and pore size of 0.8 mm on the tablet surface. The drug release of osmotic formulation during 24 h showed zero order kinetics and could be suggested that this formulation as a once-daily regimen improves pharmacokinetic parameters of the drug and enhances patient compliance. PMID:25657794

Derakhshandeh, K; Berenji, M Ghasemnejad

2014-01-01

41

A Novel Multilayered Multidisk Oral Tablet for Chronotherapeutic Drug Delivery  

PubMed Central

A Multilayered Multidisk Tablet (MLMDT) comprising two drug-loaded disks enveloped by three drug-free barrier layers was developed for use in chronotherapeutic disorders, employing two model drugs, theophylline and diltiazem HCl. The MLMDT was designed to achieve two pulses of drug release separated by a lag phase. The polymer disk comprised hydroxyethylcellulose (HEC) and ethylcellulose (EC) granulated using an aqueous dispersion of EC. The polymeric barrier layers constituted a combination of pectin/Avicel (PBL) (1st barrier layer) and hydroxypropylmethylcellulose (HPMC) (HBL1 and HBL2) as the 2nd and 3rd barrier layers, respectively. Sodium bicarbonate was incorporated into the diltiazem-containing formulation for delayed drug release. Erosion and swelling studies confirmed the manner in which the drug was released with theophylline formulations exhibiting a maximum swelling of 97% and diltiazem containing formulations with a maximum swelling of 119%. FTIR spectra displayed no interactions between drugs and polymers. Molecular mechanics simulations were undertaken to predict the possible orientation of the polymer morphologies most likely affecting the MLMDT performance. The MLMDT provided two pulses of drug release, separated by a lag phase, and additionally it displayed desirable friability, hardness, and uniformity of mass indicating a stable formulation that may be a desirable candidate for chronotherapeutic drug delivery. PMID:24024200

Khan, Zaheeda; Choonara, Yahya E.; du Toit, Lisa C.; Ndesendo, Valence M. K.; Pillay, Viness

2013-01-01

42

Impact of active ingredients on the swelling properties of orally disintegrating tablets prepared by microwave treatment.  

PubMed

The impact of different active pharmaceutical ingredients (APIs) loading on the properties of orally disintegrating tablets (ODTs) prepared according to our previously reported microwave (MW) treatment process was evaluated using famotidine (FAM), acetaminophen (AAP), and ibuprofen (IBU). None of the APIs interrupted the tablet swelling during the MW treatment and the tablet hardness were improved by more than 20 N. MW treatment, however, led to a significant increase in the disintegration time of the ODTs containing IBU, but it had no impact on that of the ODTs containing FAM or AAP. This increased disintegration time of the ODTs containing IBU was attributed to the relatively low melting point of IBU (Tm=76 °C), with the IBU particles melting during the MW treatment to form agglomerates, which interrupted the penetration of water into the tablets and delayed their disintegration. The effects of the MW treatment on the chemical stability and dissolution properties of ODTs were also evaluated. The results revealed that MW treatment did not promote the degradations of FAM and AAP or delay their release from the ODTs, while dissolution of the ODTs containing IBU delayed by MW treatment. Based on these results, the MW method would be applicable to the preparation of ODTs containing APIs with melting points higher than 110 °C. PMID:24709215

Sano, Syusuke; Iwao, Yasunori; Kimura, Susumu; Noguchi, Shuji; Itai, Shigeru

2014-07-01

43

Orally disintegrating tablet of novel salt of antiepileptic drug: formulation strategy and evaluation.  

PubMed

The aim of present research was to design and evaluate orally disintegrating tablet (ODT) of novel lamotrigine-cyclamate salt. Box-Behnken response surface methodology was selected to design the optimized formulation. The independent factors selected were tablet hardness (X1), disintegrant (X2) and lubricant (X3) levels, and responses chosen were disintegration time (DT, Y1), friability (Y2), T50 (Y3), and T90 (Y4). The tablets were also characterized for drug uniformity by near infrared chemical imaging (NIR-CI) and taste masking evaluation by electronic tongue. All the selected independent variables were statistically (p<0.05) effect the Y1 while Y2, Y3, and Y4 affected only by X2. The optimized ODT was found to meet the regulatory requirement of DT and friability specification. The NIR-CI images indicated uniform distribution of active and inactive ingredients within the tablets. The electronic tongue results were analyzed by principle component analysis (PCA). It indicated that novel salt of lamotrigine and its ODT formulation have a taste similar to cyclamic acid which is indicated by close proximity on PCA score plot, lower Euclidean distance, and high discrimination index values. Furthermore, these parameters were very close to ODT placebo formulation. On the other hand, lamotrigine, its ODT, and placebo formulation were far from each other. In summary, lamotrigine salt provides another avenue for pediatric friendly formulation for children and will enhance patience compliance. PMID:23800704

Rahman, Ziyaur; Siddiqui, Akhtar; Khan, Mansoor A

2013-11-01

44

Bioequivalence of Ondansetron Oral Soluble Film 8 mg (ZUPLENZ) and Ondansetron Orally Disintegrating Tablets 8 mg (ZOFRAN) in Healthy Adults.  

PubMed

Oral formulations of ondansetron are used to prevent nausea and vomiting associated with chemotherapy, radiotherapy, and surgery. An oral soluble film formulation of ondansetron (OND OSF) was developed using MonoSol Rx's proprietary PharmFilm technology and was formulated to dissolve rapidly on the tongue, without the need for water. This product provides an oral antiemetic treatment option for patients who experience difficulty swallowing. The purpose of this study was to compare the bioequivalence of OND OSF 8 mg (ZUPLENZ, Monosol Rx, Warren, NJ) with ondansetron orally disintegrating tablets (OND ODT) 8 mg (ZOFRAN, GlaxoSmithKline, Research Triangle Park). In 3 individual open-label, randomized studies, healthy adult subjects received a single dose of OND OSF 8 mg and a single dose of OND ODT 8 mg, under fasted conditions (study 1, n = 48), fed conditions (study 2, n = 48), and fasted with and without water (study 3, n = 18). Each dosing period was followed by a 3- or 7-day washout period. Ondansetron pharmacokinetics were assessed predose to 24 hours postdose for the single 8-mg doses of OND OSF and OND ODT. All analyses were conducted on natural log-transformed pharmacokinetic parameters for OND OSF and OND ODT. Under both fasted and fed conditions, the 90% confidence interval for the comparisons of OND OSF and OND ODT plasma ondansetron area under the curve from time 0 to the last measured concentration (AUC0-t), area under the concentration vs. time curve from time 0 to infinity (AUC0-?), and maximum plasma concentration (Cmax) were within the 80%-125% range, indicating bioequivalence between the formulations. With features designed to make it portable and easy to take, OND OSF 8 mg provides an alternative treatment option, particularly for patients with dysphagia and others who find it difficult to take oral tablets. PMID:25581856

Dadey, Eric

2015-01-01

45

Effects of Orally Administered Lactoferrin and Lactoperoxidase-Containing Tablets on Clinical and Bacteriological Profiles in Chronic Periodontitis Patients  

PubMed Central

This study was undertaken to evaluate the effect of oral administration of lactoferrin (LF) and lactoperoxidase-(LPO-)containing tablet on periodontal condition. Seventy-two individuals with chronic periodontitis were randomly assigned to take either bovine LF and LPO-containing tablets (test group, n = 37) or control tablets (control group, n = 35) every day for 12 weeks. Periodontal parameters and levels of subgingival plaque bacteria, human and bovine LF, and endotoxin in gingival crevicular fluid (GCF) were evaluated at baseline, 1 week, 4 weeks, and 12 weeks. Significant differences were observed in GCF levels of bovine LF between the test and control groups throughout the study (P < .05). However, clinical and bacteriological parameter values proved comparable between the two groups at 1 week to 12 weeks. Therefore, the effect of oral administration of LF and LPO-containing tablets might be weak on periodontal and bacteriological profile in this study. PMID:21747858

Shimizu, Eiju; Kobayashi, Tetsuo; Wakabayashi, Hiroyuki; Yamauchi, Koji; Iwatsuki, Keiji; Yoshie, Hiromasa

2011-01-01

46

Sufentanil Sublingual Tablet System vs. Intravenous Patient-Controlled Analgesia with Morphine for Postoperative Pain Control: A Randomized, Active-Comparator Trial  

PubMed Central

Background Problems with intravenous patient-controlled analgesia (IV PCA) are well known, including invasive route of delivery and pump programming errors. The primary objective of this study was to evaluate patient satisfaction with a novel sublingual sufentanil PCA system (sufentanil sublingual tablet system 15 mcg with a 20-minute lockout interval; SSTS) to IV PCA morphine sulfate 1 mg with a 6-minute lockout interval (IV PCA MS) for the management of acute postoperative pain. Methods This was a randomized, open-label, 48-hour non-inferiority study with optional extension to 72 hours at 26 U.S. sites enrolling patients scheduled for elective major open abdominal or orthopedic (hip or knee replacement) surgery. The primary outcome measure was the proportion of patients who responded “good” or “excellent” (collectively “success”) at the 48-hour timepoint on the Patient Global Assessment of method of pain control (PGA48). Results A total of 357 patients received study drug and 78.5% vs. 65.6% of patients achieved PGA48 “success” for SSTS vs. IV PCA MS, respectively, demonstrating non-inferiority (P < 0.001 using the one-side Z-test against the non-inferiority margin) as well as statistical superiority for treatment effect (P = 0.007). Patients using SSTS reported more rapid onset of analgesia and patient and nurse ease of care and satisfaction scores were higher than IV PCA MS. Adverse events were similar between the 2 groups; however, SSTS had fewer patients experiencing oxygen desaturations below 95% compared to IV PCA MS (P = 0.028). Conclusions Sufentanil sublingual tablet system is a promising new analgesic technology that may address some of the concerns with IV PCA. PMID:25155134

Melson, Timothy I; Boyer, David L; Minkowitz, Harold S; Turan, Alparslan; Chiang, Yu-Kun; Evashenk, Mark A; Palmer, Pamela P

2014-01-01

47

Coated dextrin microcapsules of amlodipine incorporable into orally disintegrating tablets for geriatric patients.  

PubMed

To improve oral absorption and patient compliance when using amlodipine, novel coated dextrin microcapsules incorporable into orally disintegrating tablets (ODT's) were investigated. Amlodipine-loaded dextrin microcapsules (ADM) were prepared by spray-drying a mixture of amlodipine free base dissolved in ethanol and aqueous dextrin solution. The ADM were suspended in Eudragit(®) EPO solution in ethanol and subsequently spray-dried to collect coated ADM (CADM). The ADM or CADM were blended with ODT excipients and then directly compressed into ODTs. The ADM and CADM used were both spherical with smooth surfaces and had mean particle sizes of 13.3 and 18.5?m, respectively. Amlodipine was dispersed in an amorphous state and was readily encapsulated within ADM or CADM. Unlike the ADM, the tableted CADM remained intact without rupture during tableting, which was consistent with no loss of ethanol (0.82%) entrapped in the ODTs containing the CADM (ODTs-CADM). The amlodipine content appeared to be uniformly maintained as designed in all the dextrin microcapsules and ODTs. The ODTs-CADM compressed with 3kp of hardness showed acceptable ODT characteristics: fast disintegration time (29.8s) and low friability (0.1%). Drug dissolution from the ODTs-CADM was much faster than that of amlodipine free base itself at both pH 1.2 and 6.8 over the tested time. CADM demonstrated significantly higher plasma concentrations (2.7 fold in AUC0-24h and 2.5 fold in Cmax) in SD rats than did amlodipine free base. These results indicate that CADM substantially increased the oral absorption of amlodipine and can be incorporated into ODTs while maintaining their original physicochemical features. The dextrin microcapsules coated using Eudragit(®) EPO may be applied to the development of an amlodipine ODT formulation for improving geriatric patient compliance. PMID:25458788

Jang, Dong-Jin; Bae, Soo Kyung; Oh, Euichaul

2014-10-01

48

Development of orally disintegrating tablets comprising controlled-release multiparticulate beads  

PubMed Central

Melperone is an atypical antipsychotic agent that has shown a wide spectrum of neuroleptic properties, particularly effective in the treatment of senile dementia and Parkinson’s-associated psychosis, and is marketed in Europe as an immediate-release (IR) tablet and syrup. An orally disintegrating tablet (ODT) dosage form would be advantageous for patients who experience difficulty in swallowing large tablets or capsules or those who experience dysphagia. Controlled-release (CR) capsule and ODT formulations containing melperone HCl were developed with target in vitro release profiles suitable for a once-daily dosing regimen. Both dosage forms allow for the convenient production of dose-proportional multiple strengths. Two ODT formulations exhibiting fast and medium release profiles and one medium release profile capsule formulation (each 50?mg) were tested in vivo using IR syrup as the reference. The two medium release formulations were shown to be bioequivalent to each other and are suitable for once-daily dosing. Based on the analytical and organoleptic test results, as well as the blend uniformity and in-process compression data at various compression forces using coated beads produced at one-tenth (1/10) commercial scale, both formulations in the form of CR capsules and CR ODTs have shown suitability for progression into further clinical development. PMID:22356215

2012-01-01

49

Preparation and evaluation of taste-masked donepezil hydrochloride orally disintegrating tablets.  

PubMed

The purpose of this research was to prepare and evaluate a non-bitter donepezil hydrochloride (DH) orally disintegrating tablet (ODT) for enhanced patient compliance. Taste masking was done by preparing microspheres with different ratios of drug and Eudragit EPO using spray drying method. The entrapment of the drug into microspheres was confirmed by scanning electron microscope (SEM) and X-ray powder diffraction. It was found that microspheres with a drug-polymer ratio of 1 : 2 could mask the taste obviously by inhibiting the release of DH in simulated salivary fluid. Microspheres-loaded tablets containing Polyplasdone NF and Low substituted Hydroxypropyl Cellulose (L-HPC) both at a 10% level showed rapid disintegration, in vitro (15.5 s) and in vivo (19.8 s), which were faster than that of marketed tablets (36.7, 41.3 s, respectively). Results from taste evaluation in human volunteers revealed that the ODTs with taste-masked microspheres had significantly enhanced palatability. Dissolution in vitro and pharmacokinetics in rats were evaluated for the tested ODTs compared to the donepezil hydrochloride commercial product (ARICEPT). Both tablets showed comparable dissolution patterns in vitro and similar area under curve from 0 to 24 h (AUC(0-24)), C(max) and T(max) of DH in vivo to each other, suggesting that the tested ODTs might give the similar drug efficacy in rats compared to that of ARICEPT. Thus, it was concluded that DH ODTs with masked taste were obtained by Eudragit EPO-based microspheres, drug loaded microspheres neither decreased the bioavailability nor delayed the release of DH. PMID:20686233

Yan, Yi-Dong; Woo, Jong Soo; Kang, Joon Heok; Yong, Chul Soon; Choi, Han-Gon

2010-01-01

50

Evidence-based nanoscopic and molecular framework for excipient functionality in compressed orally disintegrating tablets.  

PubMed

The work investigates the adhesive/cohesive molecular and physical interactions together with nanoscopic features of commonly used orally disintegrating tablet (ODT) excipients microcrystalline cellulose (MCC) and D-mannitol. This helps to elucidate the underlying physico-chemical and mechanical mechanisms responsible for powder densification and optimum product functionality. Atomic force microscopy (AFM) contact mode analysis was performed to measure nano-adhesion forces and surface energies between excipient-drug particles (6-10 different particles per each pair). Moreover, surface topography images (100 nm2-10 µm2) and roughness data were acquired from AFM tapping mode. AFM data were related to ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal analysis using DSC and TGA, disintegration testing, Heckel and tabletability profiles. The study results showed a good association between the adhesive molecular and physical forces of paired particles and the resultant densification mechanisms responsible for mechanical strength of tablets. MCC micro roughness was 3 times that of D-mannitol which explains the high hardness of MCC ODTs due to mechanical interlocking. Hydrogen bonding between MCC particles could not be established from both AFM and FTIR solid state investigation. On the contrary, D-mannitol produced fragile ODTs due to fragmentation of surface crystallites during compression attained from its weak crystal structure. Furthermore, AFM analysis has shown the presence of extensive micro fibril structures inhabiting nano pores which further supports the use of MCC as a disintegrant. Overall, excipients (and model drugs) showed mechanistic behaviour on the nano/micro scale that could be related to the functionality of materials on the macro scale. PMID:25025427

Al-Khattawi, Ali; Alyami, Hamad; Townsend, Bill; Ma, Xianghong; Mohammed, Afzal R

2014-01-01

51

Formulation and evaluation of a novel matrix-type orally disintegrating Ibuprofen tablet.  

PubMed

Orally disintegrating tablets (ODTs) are capable of turning quickly into a liquid dosage form in contact with the saliva, thus possessing the advantages of both the solid dosage forms particularly stability and liquid dosage forms specially ease of swallowing and pre-gastric absorption of drug. The aim of this study was to prepare a novel matrix-type buccal fast disintegrating ibuprofen tablet formulation using special polymers, water soluble excipients, super-disintegrants and quickly soluble granules. For this purpose different tablet formulations of ibuprofen were prepared. The amount of ibuprofen in each formulation was 100 mg. Eight groups of formulation were prepared (A-H series), accounting for a total number of 45 formulations. Formulations prepared were examined in terms of different physicochemical tests including powder/granule flowability, appearance, thickness, uniformity of weight, hardness, friability and disintegration time. Results of formulation F22a (in series F), was found to be acceptable, making it the chosen formulation for further studies. Then, by adding various flavorants and sweeteners to this formulation, complementary series of formulations, named G and H, were prepared. Following the comparison of their taste with each other through asking 10 volunteers, the most suitable formulation regarding the taste, being formulation F22s, was chosen as the ultimate formulation. This formulation had PVP, ibuprofen and croscarmellose as the intra-granular components and xylitol and saccharin as the extra-granular ingredients. Formulation F22s was found to be acceptable in terms of physicochemical tests conducted, showing quick disintegration within the buccal cavity, appropriate hardness and rather low friability. Hence formulation F22s was selected as the final formulation. PMID:24250378

Tayebi, Hoda; Mortazavi, Seyed Alireza

2011-01-01

52

Evidence-Based Nanoscopic and Molecular Framework for Excipient Functionality in Compressed Orally Disintegrating Tablets  

PubMed Central

The work investigates the adhesive/cohesive molecular and physical interactions together with nanoscopic features of commonly used orally disintegrating tablet (ODT) excipients microcrystalline cellulose (MCC) and D-mannitol. This helps to elucidate the underlying physico-chemical and mechanical mechanisms responsible for powder densification and optimum product functionality. Atomic force microscopy (AFM) contact mode analysis was performed to measure nano-adhesion forces and surface energies between excipient-drug particles (6-10 different particles per each pair). Moreover, surface topography images (100 nm2–10 µm2) and roughness data were acquired from AFM tapping mode. AFM data were related to ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal analysis using DSC and TGA, disintegration testing, Heckel and tabletability profiles. The study results showed a good association between the adhesive molecular and physical forces of paired particles and the resultant densification mechanisms responsible for mechanical strength of tablets. MCC micro roughness was 3 times that of D-mannitol which explains the high hardness of MCC ODTs due to mechanical interlocking. Hydrogen bonding between MCC particles could not be established from both AFM and FTIR solid state investigation. On the contrary, D-mannitol produced fragile ODTs due to fragmentation of surface crystallites during compression attained from its weak crystal structure. Furthermore, AFM analysis has shown the presence of extensive micro fibril structures inhabiting nano pores which further supports the use of MCC as a disintegrant. Overall, excipients (and model drugs) showed mechanistic behaviour on the nano/micro scale that could be related to the functionality of materials on the macro scale. PMID:25025427

Al-khattawi, Ali; Alyami, Hamad; Townsend, Bill; Ma, Xianghong; Mohammed, Afzal R.

2014-01-01

53

Mucoadhesive elementary osmotic pump tablets of trimetazidine for controlled drug delivery and reduced variability in oral bioavailability.  

PubMed

Abstract The objectives of this work was preparation and evaluation of the mucoadhesive elementary osmotic pump tablets of trimetazidine hydrochloride to achieve desired controlled release action and augmentation of oral drug absorption. The drug-loaded core tablets were prepared employing the suitable tableting excipients and coated with polymeric blend of ethyl cellulose and hydroxypropyl methylethylcellulose E5 (4:1). The prepared tablets were characterized for various quality control tests and in vitro drug release. Evaluation of drug release kinetics through model fitting suggested the Fickian mechanism of drug release, which was regulated by osmosis and diffusion as the predominant mechanism. Evaluation of mucoadhesion property using texture analyzer suggested good mucoadhesion potential of the developed osmotic systems. Solid state characterization using Fourier-transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction spectroscopy confirmed the absence of any physiochemical incompatibilities between drug and excipients. Scanning electron microscopy analysis showed the smooth surface appearance of the coated tablets with intact polymeric membrane without any fracture. In vivo pharmacokinetic studies in rabbits revealed 3.01-fold enhancement in the oral bioavailability vis-à-vis the marketed formulation (Vastarel MR®). These studies successfully demonstrate the bioavailability enhancement potential of the mucoadhesive elementary osmotic pumps as novel therapeutic systems for other drugs too. PMID:24669975

Alam, Naushad; Beg, Sarwar; Rizwan, Mohammad; Ahmad, Akifa; Ahmad, Farhan Jalees; Ali, Asgar; Aqil, Mohammad

2014-03-26

54

Effect of granule properties on rough mouth feel and palatability of orally disintegrating tablets.  

PubMed

In this study, we evaluated the palatability of orally disintegrating tablets (ODTs) containing core granules with different particle sizes, coating, and types of materials using visual analog scales (VAS). Tableting the core granules into ODTs reduced rough mouth feel and improved overall palatability compared to the ingestion of core granules alone. Moreover, the evaluation performed immediately after spitting out ODTs demonstrated differences in rough mouth feel between ODTs containing placebo and core granules. Rough mouth feel was found to be significantly more intense with core granules with particle sizes ?200?m. Since ODTs may contain taste-masked particles, palatability of ODTs containing coated core granules was also evaluated. Although coating with polymers impairs palatability, it was improved by coating the outer layer with d-mannitol. The effects on palatability of materials constituting core granules were also evaluated, with reduced rough mouth feel observed with core granules composed of water-soluble additives. Based on these data, receiver operating characteristic analysis was performed to determine the threshold VAS scores at which the subjects felt roughness and discomfort. In addition, the threshold particle size of the core granule contained within the ODT required for feeling roughness was determined to be 244?m. This study elucidated the effect of the properties of masking particles on the rough mouth feel and palatability of ODTs. PMID:25681720

Kimura, Shin-Ichiro; Uchida, Shinya; Kanada, Ken; Namiki, Noriyuki

2015-04-30

55

Bioequivalence assay between orally disintegrating and conventional tablet formulations in healthy volunteers.  

PubMed

The purpose of this study was to evaluate bioequivalence of two commercial 8 mg tablet formulations of ondansetrona available in the Brazilian market. In this study, a simple, rapid, sensitive and selective liquid chromatography-tandem mass spectrometry method is described for the determination of ondansetron in human plasma samples. The method was validated over a concentration range of 2.5-60 ng/ml and used in a bioequivalence trial between orally disintegrating and conventional tablet ondansetron formulations, to assess its usefulness in this kind of study. Vonau flash (Biolab Sanus Farmacêutica, Brazil, as test formulations) and Zofran (GlaxoSmithKline, Brazil, as reference formulation) were evaluated following a single 8 mg dose to 23 healthy volunteers of both genders. The dose was administered after an overnight fast according to a two-way crossover design. Bioequivalence between the products was determinated by calculating 90% confidence interval (90% CI) for the ratio of C(max), AUC(0-t) and AUC(0-infinity) values for the test and reference products, using logarithmically transformed data. The 90% confidence interval for the ratio of C(max) (87.5-103.8%), AUC(0-t) (89.3-107.2%) and AUC(0-infinity) (89.7-106.0%) values for the test and reference products is within the 80-125% interval, proposed by FDA, EMEA and ANVISA. It was concluded that two ondansetron formulations are bioequivalent in their rate and extent of absorption. PMID:18848869

Armando, Yara Popst; Schramm, Simone Grigoleto; Silva, Marina de Freitas; Kano, Eunice Kazue; Koono, Eunice Emiko Mori; Porta, Valentina; Serra, Cristina Helena dos Reis

2009-01-21

56

Preparation and evaluation of an orally fast disintegrating tablet formulation containing a hydrophobic drug.  

PubMed

Orally fast disintegrating tablets (FDTs or ODTs) have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. Although the FDT area has passed its infancy, as shown by a large number of commercial products on the market, there are still many aspects to improve in the FDT formulations. Despite advances in the FDT technologies, formulation of hydrophobic drugs is still a challenge, especially when the amount of drug is high. In this study, a new solution is being developed to incorporate higher doses of a model hydrophobic drug; meloxicam, without affecting the fast disintegrating properties of the formulation. In order to enhance the solubilization of meloxicam in FDT formulations, ? cyclodextrin inclusion complex of the drug is prepared and FDTs containing meloxicam--? cyclodextrin inclusion complex (F1 A and F2 A) were compared and evaluated with the FDTs containing pure meloxicam (F1 and F2) by means of in vitro quality control tests. PMID:24295202

Comoglu, Tansel; Unal, Burcu

2015-01-01

57

Predicting orally disintegrating tablets formulations of ibuprophen tablets: an application of the new SeDeM-ODT expert system.  

PubMed

This article provides a new innovative tool for pharmaceutical preformulation to predict whether a disintegrant excipient or mixture of powder containing API+excipients is suitable to obtain a bucodispersible tablet by direct compression or not. This innovative tool is the new model SeDeM-ODT that provides the Index of Good Compressibility and Bucodispersibility (IGCB index), which is based on the previous SeDeM expert system that indicates the aptitude of a powder to be compressed. The IGCB index is composed of six main factors (from 15 pharmaceutical raw parameters), which indicate whether a mixture of powder has the aptitude to be compressed by direct compression and at the same time indicates whether these tablets are suitable to be used as a bucodispersible tablet (disintegration time lower than 3 min). PMID:22245156

Aguilar-Díaz, Johnny Edward; García-Montoya, Encarna; Suñe-Negre, José María; Pérez-Lozano, Pilar; Miñarro, Montserrat; Ticó, José Ramón

2012-04-01

58

Formulation and In-vitro Evaluation of Orally Disintegrating Tablets of Olanzapine-2-Hydroxypropyl-?-Cyclodextrin Inclusion Complex  

PubMed Central

The aim of this study was to design orally disintegrating tablets of Olanzapine and to complex Olanzapine with 2-hydroxypropyl-?- cyclodextrin with special emphasis on disintegration and dissolution studies. Phase solubility studies demonstrated the formation of 1:1 molar inclusion complex by kneading method. Tablets were prepared by using superdisintegrants namely, sodium starch glycolate, croscarmellose sodium, crospovidone, tulsion 339, and indion 414. Complex was characterized using infrared spectroscopy, drug content estimation, saturated solubility study, diffrerential scanning calorimetry and X-ray diffractometry. 5% w/w croscarmellose sodium showed the minimum disintegration time 39 ± 1.76 sec and in-vitro drug release 99.19 ± 0.18% within 6 min. In general, solubility of Olanzapine can be improved by complexing with 2-hydroxypropyl-?- cyclodextrin. Croscarmellose sodium can be used for faster disintegration of tablets. PMID:24381598

Ajit Shankarrao, Kulkarni; Dhairysheel Mahadeo, Ghadge; Pankaj Balavantrao, Kokate

2010-01-01

59

In vivo evaluation of thiolated chitosan tablets for oral insulin delivery.  

PubMed

Chitosan-6-mercaptonicotinic acid (chitosan-6-MNA) is a thiolated chitosan with strong mucoadhesive properties and a pH-independent reactivity. This study aimed to evaluate the in vivo potential for the oral delivery of insulin. The comparison of the nonconjugated chitosan and chitosan-6-MNA was performed on several studies such as mucoadhesion, release, and in vivo studies. Thiolated chitosan formulations were both about 80-fold more mucoadhesive compared with unmodified ones. The thiolated chitosan tablets showed a sustained release for 5 h for the polymer of 20 kDa and 8 h for the polymer of 400 kDa. Human insulin was quantified in rats' plasma by means of ELISA specific for human insulin with no cross-reactivity with the endogenous insulin. In vivo results showed thiolation having a tremendous impact on the absorption of insulin. The absolute bioavailabilities were 0.73% for chitosan-6-MNA of 20 kDa and 0.62% for chitosan-6-MNA 400 kDa. The areas under the concentration-time curves (AUC) of chitosan-6-MNA formulations compared with unmodified chitosan were 4.8-fold improved for the polymer of 20 kDa and 21.02-fold improved for the polymer of 400 kDa. The improvement in the AUC with regard to the most promising aliphatic thiomer was up to 6.8-fold. Therefore, chitosan-6-MNA represents a promising excipient for the oral delivery of insulin. PMID:25139279

Millotti, Gioconda; Laffleur, Flavia; Perera, Glen; Vigl, Claudia; Pickl, Karin; Sinner, Frank; Bernkop-Schnürch, Andreas

2014-10-01

60

Formulation strategy and evaluation of nanocrystal piroxicam orally disintegrating tablets manufacturing by freeze-drying.  

PubMed

Piroxicam (PRX) is a non-steroidal anti-inflammatory drug characterized by a poor water solubility and consequently by a low oral bioavailability. In this work, different nanocrystal orally disintegrating tablets (ODT) were prepared to enhance piroxicam dissolution rate and saturation solubility. PRX nanocrystals were prepared by means of high pressure homogenization technique using poloxamer 188 as stabilizer. Three different ODTs were prepared with the same nanosuspension using different excipients in order to study their effect on the PRX dissolution properties. PRX nanocrystal size and zeta potential were determined by photon correlation spectroscopy. Additional characterization of PRX nanocrystal ODT was carried out by infrared spectroscopy, X-ray powder diffractometry, differential scanning calorimetry. Dissolution study was performed in distilled water (pH 5.5) and compared with PRX coarse suspension ODT, PRX/poloxamer 188 physical mixture, bulk PRX samples and a PRX commercial ODT. All PRX nanocrystal ODT formulations showed a higher drug dissolution rate than coarse PRX ODT. PRX nanocrystal ODT prepared using gelatin or croscarmellose as excipient showed a higher PRX dissolution rate compared with the commercial formulation and ODT prepared using xanthan gum. Overall results confirmed that improved PRX dissolution rate is due to the increased surface-to-volume ratio due to the nanosized drug particle but also revealed the important role of different excipients used. PMID:24680963

Lai, Francesco; Pini, Elena; Corrias, Francesco; Perricci, Jacopo; Manconi, Maria; Fadda, Anna Maria; Sinico, Chiara

2014-06-01

61

Effect of food on the comparative pharmacokinetics of modified-release morphine tablet formulations: Oramorph SR and MST Continus  

PubMed Central

The relative bioavailability and pharmacokinetic profiles of Oramorph SR (OSR) and MST Continus (MST), were evaluated by a randomized, four-way cross-over study in 24 healthy, male volunteers given single oral (30?mg) doses whilst fasting or after a high-fat breakfast. Mean Cmax, tmax, AUC(0,24h), AUC and tlag were significantly greater in fed compared with fasting subjects. Overall relative bioavailability of the two formulations (log AUC), was within the acceptable 80–125% limits for bioequivalence both fed and fasting. Mean fasting Cmax for OSR was greater than MST (P<0.05) but there was no difference between formulations in mean fed Cmax. No statistically significant difference between OSR and MST was found for other parameters nor in the incidence of adverse events. These results suggest that OSR and MST are bioequivalent and that if patients were to transfer between formulations, dosage adjustment would be unnecessary, irrespective of their meal schedules or food intake. PMID:8735684

DRAKE, J.; KIRKPATRICK, C. T.; ALIYAR, C. A.; CRAWFORD, F. E.; GIBSON, P.; HORTH, C. E.

1996-01-01

62

High-Amylose Sodium Carboxymethyl Starch Matrices: Development and Characterization of Tramadol Hydrochloride Sustained-Release Tablets for Oral Administration  

PubMed Central

Substituted amylose (SA) polymers were produced from high-amylose corn starch by etherification of its hydroxyl groups with chloroacetate. Amorphous high-amylose sodium carboxymethyl starch (HASCA), the resulting SA polymer, was spray-dried to obtain an excipient (SD HASCA) with optimal binding and sustained-release (SR) properties. Tablets containing different percentages of SD HASCA and tramadol hydrochloride were produced by direct compression and evaluated for dissolution. Once-daily and twice-daily SD HASCA tablets containing two common dosages of tramadol hydrochloride (100?mg and 200?mg), a freely water-soluble drug, were successfully developed. These SR formulations presented high crushing forces, which facilitate further tablet processing and handling. When exposed to both a pH gradient simulating the pH variations through the gastrointestinal tract and a 40% ethanol medium, a very rigid gel formed progressively at the surface of the tablets providing controlled drug-release properties. These properties indicated that SD HASCA was a promising and robust excipient for oral, sustained drug-release, which may possibly minimize the likelihood of dose dumping and consequent adverse effects, even in the case of coadministration with alcohol. PMID:25006518

Nabais, Teresa; Leclair, Grégoire

2014-01-01

63

Influence of Prosolv and Prosolv:Mannitol 200 direct compression fillers on the physicomechanical properties of atorvastatin oral dispersible tablets.  

PubMed

Abstract The objective of the present study was to evaluate the influence of Prosolv® and Prosolv®: Mannitol 200 direct compression (DC) fillers on the physicomechanical characteristics of oral dispersible tablets (ODTs) of crystalline atorvastatin calcium. ODTs were formulated by DC and were analyzed for weight uniformity, hardness, friability, drug content, disintegration and dissolution. Three disintegration time (DT) test methods; European Pharmacopoeia (EP) method for conventional tablets (Method 1), a modification of this method (Method 2) and the EP method for oral lyophilisates (Method 3) were compared as part of this study. All ODTs showed low weight variation of <2.5%. Prosolv® only ODTs showed the highest tablet hardness of ?73?N, hardness decreased with increasing mannitol content. Friability of all formulations was <1% although friability of Prosolv®:Mannitol ODTs was higher than for pure Prosolv®. DT of all ODTs was <30?s. Method 2 showed the fastest DT. Method 3 was non-discriminatory giving a DT of 13-15?s for all formulations. Atorvastatin dissolution from all ODTs was >60% within 5?min despite the drug being crystalline. Prosolv® and Prosolv®:Mannitol-based ODTs are suitable for ODT formulations by DC to give ODTs with high mechanical strength, rapid disintegration and dissolution. PMID:24397821

Gowda, Veeran; Pabari, Ritesh M; Kelly, John G; Ramtoola, Zebunnissa

2014-01-01

64

Preparation and evaluation of orally disintegrating tablets containing vitamin e as a model fat-soluble drug.  

PubMed

The purpose of the present study was to develop orally disintegrating tablets (ODTs) containing fat-soluble drugs that disintegrate rapidly while having appropriate tablet strength. We chose vitamin E (VE) as a model drug; d-?-tocopheryl acetate, as the oily VE (VE-OI), and d-?-tocopheryl acid succinate, as the powder VE (VE-PO), were used. The oily VE was added directly to ODTs (VE-OI ODTs) and also used for the preparation of two types of VE granule, i.e., granules prepared using adsorption to calcium silicate (VE-FL granules) and granules prepared using spray-drying with gelatin (VE-SD granules); each type of granule was added to ODTs (VE-FL ODTs and VE-SD ODTs). Powder VE was added directly to ODTs (VE-PO ODTs). Various VE ODTs were prepared using these four additional methods with varying amounts of VE per tablet and were evaluated with respect to their manufacturability, physicochemical characteristics, and stability. It was demonstrated that a tablet porosity of 30% to 35% and tensile strength of 7?kg/cm(2) or greater are required to provide VE ODTs with rapid disintegration and appropriate tablet strength, and that VE-SD granules and powder VE are suitable forms of VE to be added. When stability tests of VE-SD ODTs and VE-PO ODTs were performed, VE-PO ODTs exhibited prolongation of disintegration time and increased tensile strength, whereas VE-SD ODTs showed none of these changes. These changes were thought to be attributable to a decrease in the pore size of VE-PO ODTs resulting from the softening and migration of powder VE under hot storage conditions. PMID:25757486

Ikematsu, Yasuyuki; Uchida, Shinya; Namiki, Noriyuki

2015-01-01

65

Formulation and evaluation of meloxicam oral disintegrating tablet with dissolution enhanced by combination of cyclodextrin and ion exchange resins.  

PubMed

Abstract Context: The bitter taste of drug is masked by the exchange of ionized drugs with counter ions of ion exchange resin, forming "resinate". Cyclodextrin reduces the unpleasant taste and enhances the drug solubility by encapsulating drug molecules into its central cavity. Objective: Oral disintegrating tablets (ODTs) using the combination of ion exchange resin and cyclodextrin was developed, to mask the bitter taste and enhance drug dissolution. Methods: Meloxicam (MX) was selected as a model drug. Formulations containing various forms of MX (free drug, MX-loaded resin or resinate, complexes of MX and 2-hydroxypropyl-?-cyclodextrin (HP?CD) or MX/HP?CD complexes, and a mixture of resinate and MX/HP?CD complexes) were made by direct compression. The ODTs were evaluated for weight variation, thickness, diameter, hardness, friability, disintegration time, wetting time, MX content, MX release, degree of bitter taste and stability. Results and discussion: The tablet hardness was ?3?kg/in(2), and the friability was <1%. Tablets formulated with resinate and the mixture of resinate and MX/HP?CD complexes disintegrated rapidly within 60?s, which is the acceptable limit for ODTs. These results were corresponded to the in vivo disintegration and wetting times. However, only tablets containing the mixture of resinate and MX/HP?CD complexes provided complete MX dissolution and successfully masked the bitter taste. In addition, this tablet was stable at least 6 months. Conclusions: The combination of ion exchange resin and cyclodextrin could be used in ODTs to mask the bitter taste and enhance the dissolution of drugs that are weakly soluble in water. PMID:24865111

Samprasit, Wipada; Akkaramongkolporn, Prasert; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Opanasopit, Praneet

2014-05-28

66

The effect of sucralfate tablets vs. suspension on oral doxycycline absorption in dogs.  

PubMed

The purpose of this study was to determine the effect of concurrent sucralfate (tablet or suspension) on doxycycline pharmacokinetics and to determine the effects of delaying sucralfate by 2 h on doxycycline absorption. Five dogs were included in a crossover study receiving: doxycycline alone; doxycycline concurrently with sucralfate tablet; doxycycline followed 2 h by sucralfate tablet; doxycycline concurrently with sucralfate suspension; and doxycycline followed 2 h by sucralfate suspension. Doxycycline plasma concentrations were evaluated with liquid chromatography with mass spectrometry. No interaction was seen when sucralfate was administered as a tablet. Sucralfate tablet fragments were frequently observed in some dogs' feces. The area under the curve (AUC) and maximum plasma concentration (CMAX ) were significantly lower (P < 0.001) in the concurrent sucralfate suspension group (AUC 7.2 h·?g/mL, CMAX 0.43 ?g/mL) than with doxycycline alone (AUC 36.0 h·?g/mL, CMAX 2.53 ?g/mL) resulting in a relative bioavailability of 20%. Delaying sucralfate suspension by 2 h after doxycycline administration resulted in no difference in doxycycline absorption as compared with doxycycline administration alone with a relative bioavailability of 74%. The lack of an interaction with sucralfate tablets suggests sucralfate should be administered as a suspension rather than tablet in dogs. PMID:25233871

KuKanich, K; KuKanich, B

2015-04-01

67

Preparation and characterisation of Kolliphor® P 188 and P 237 solid dispersion oral tablets containing the poorly water soluble drug disulfiram.  

PubMed

The oral route of administration is the most common and preferred route of drug delivery due to its ease of administration, cost-effectiveness and flexibility in design. However, limited aqueous solubility of the active pharmaceutical ingredient can result in poor bioavailability, which is a major issue for the pharmaceutical industry. Increasing numbers of new drugs are falling into class II of the Biopharmaceutical Classification System (BCS), where they have a low solubility and high tissue permeability, meaning that bioavailability is solubility dependent. Here we demonstrate the development and characterisation of solid dispersion oral tablets, containing the poorly water-soluble drug disulfiram, prepared using both the hot melt and solvent evaporation methods and manufactured from two different polymers, Kolliphor(®) P 188 and P 237, specifically designed for the manufacture of solid dispersions. This paper demonstrates that the disulfiram solid dispersions tablets have an enhanced release rate of disulfiram compared to the control tablets. The Kolliphor(®) P 188 polymer control tablets released approximately 48.8% of their disulfiram content over 8h, with the solvent evaporated tablets releasing approximately 65.8%, while the 60 and 80 °C hot melt tablets released approximately 73.2 and 100% of their disulfiram content respectively. A similar trend was seen with Kolliphor(®) P 237 as the control tablets released approximately 50.5% of their disulfiram content over 8h, while the solvent evaporated tablets released approximately 79.5% and the 60 and 80 °C hot melt tablets released 100.2 and 100.3% respectively. Depending on what method and polymer is used to manufacture the solid dispersions the disulfiram is either maintained completely or partially in its amorphous state and it is this which enhances its solubility and release rate from the tablets. The disulfiram in the Kolliphor(®) P 188 solvent evaporated and 60 °C hot melt tablets retained 50.5 and 44.1% of its crystallinity, while the disulfiram in the 80 °C hot melt tablets was completely amorphous. Whereas the disulfiram in the Kolliphor(®) P 237 solvent evaporated tablets retained 45.2% crystallinity, while the disulfiram in both of the hot melt tablets was completely in its amorphous form. PMID:25218186

Ramadhani, Nisrina; Shabir, Mehwish; McConville, Christopher

2014-11-20

68

[Pharmacokinetic study on peoniflorin, astilbin, rosmarinic acid, isofraxidin and liquiritin in rat blood after oral administration of shaolin xiaoyin tablets].  

PubMed

To establish a method for the determination of astilbin, peoniflorin, rasmarinci acid, isofraxidin and liquiritin contained in Shaolin Xiaoyin tablets, in order to lay a foundation for designing late-stage dosage forms and clinical medication schemes. In this paper, efforts were made to establish a method for the determination of the blood concentration of the five components and study the in vivo pharmacokinetics in rats. The blood concentration was determined by HPLC. Phenomenex C18 column (4.6 mm x 250 mm, 5 microm) was adopted and eluted with methanol-acetonitrile-0.05% formic acid, the flow rate was 0.8 mL x min(-1), and the wavelength was 275 nm. The samples were processed by the solid phase extraction method. After oral administration of Shaoling Xiaoyin tablets, the rat bloods were collected at different time points to determine the blood concentrations. The experimental results showed that the baseline separation could be adopted for the five components, and astilbin, peoniflorin, rasmarinci acid, isofraxidin and liquiritin showed good linear relations within ranges of 2.48-248, 0.213 6-21.36, 0.531-53.1, 0.704-70.4, 0.253-25.3 mg x L(-1). All the five components could be absorbed in blood and excreted quickly. The method established in this paper is rapid and accurate, and could be used for in vivo analysis on preparations containing similar components. The main components in Shaoling Xiaoyin tablets could be absorbed and excreted quickly, and thus suitable to be made into sustained release tablets. Common preparations are required to be taken for 4-6 times a day. PMID:25276982

Zhao, Rui-Zhi; Wang, Yin-Jie; Feng, Li-Min; Lu, Chuan-Jian

2014-07-01

69

21 CFR 520.1284 - Sodium liothyronine tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 false Sodium liothyronine tablets. 520.1284 Section 520.1284 Food...DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of tablets intended for oral...

2014-04-01

70

21 CFR 520.1284 - Sodium liothyronine tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 false Sodium liothyronine tablets. 520.1284 Section 520.1284 Food...DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of tablets intended for oral...

2011-04-01

71

21 CFR 520.1284 - Sodium liothyronine tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 false Sodium liothyronine tablets. 520.1284 Section 520.1284 Food...DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of tablets intended for oral...

2013-04-01

72

21 CFR 520.1284 - Sodium liothyronine tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 false Sodium liothyronine tablets. 520.1284 Section 520.1284 Food...DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of tablets intended for oral...

2012-04-01

73

Albizia procera gum as an excipient for oral controlled release matrix tablet.  

PubMed

The purpose of this research was to develop and evaluate controlled release matrix tablets of paracetamol based on natural gum exudates of Albizia procera. Procera gum was characterized of its properties like compressibility index, angle of repose, viscosity and moisture content. The interaction between the gum and paracetamol was also studied through differential scanning calorimetry (DSC) and FTIR spectroscopy. Matrix tablets were then prepared by wet granulation method with different concentrations of procera gum and hydroxypropyl methylcellulose (HPMC) and evaluated for their physical properties like weight variation, hardness, friability and content uniformity. Dissolution study was conducted to characterize release mechanism from the matrix system and data were fitted to various kinetic models. The mechanism of drug release from both types of matrix tablets was found to be anomalous type. Results from various evaluations suggested that A. procera gum could be used as drug release retardant in controlled release matrix systems. PMID:24751043

Pachuau, Lalduhsanga; Mazumder, Bhaskar

2012-09-01

74

The preparation of orally disintegrating tablets using a hydrophilic waxy binder.  

PubMed

The demand for rapidly disintegrating tablets (RDT) has been growing during the last decade especially for elderly and children who have swallowing difficulties. The problem of certain RDT is their low physical resistance and high friability. This work describes a new approach to prepare RDT with sufficient mechanical integrity, involving the use of a hydrophilic waxy binder (Superpolystate, PEG-6-stearate). Superpolystate is a waxy material with a melting point of 33-37 degrees C and an HLB value of 9. So it will not only act as a binder and increase the physical resistance of tablets but will also help the disintegration of the tablets as it melts in the mouth and solublises rapidly leaving no residues. The incorporation of Superpolystate in the formulation of RDT was realised by means of two different granulation methods: wet granulation by using an emulsion of this waxy binder as granulating liquid and melt granulation where the molten form of the binder was used. Granule size distributions of both wet and melt granules of crystallised Paracetamol and D-mannitol were compared using laser light diffractometer. Scanning electron microscopy (SEM) was used to examine their morphological characteristics. The potential of the intragranular addition of croscarmellose sodium as a disintegrating agent was also evaluated. The subsequent step encompassed the preparation and the evaluation of the tablets, including the effect of the extragranular introduction of croscarmellose sodium. An improvement in tablet hardness and friability was observed with both granulation methods where we were able to obtain RDT with a disintegration time of 40 +/- 2 s and a hardness of 47.9 +/- 2.5N. PMID:15196646

Abdelbary, G; Prinderre, P; Eouani, C; Joachim, J; Reynier, J P; Piccerelle, Ph

2004-07-01

75

Stability of extemporaneous pediatric oral liquids compounded from tablets and drug substance: case of propranolol and theophylline.  

PubMed

The stability of theophylline (T) and propranolol hydrochloride (P) in extemporaneously compounded oral suspensions (25 mg/mL or 50 mg/mL for T and 2 mg/mL or 5 mg/mL for P) were studied. Suspension with P and T were prepared with bulk substance or tablets using three different suspending vehicles: Ora-Sweet (M1), modified Ora-Sweet (M2) and simple syrup with glycerol and sorbitol (M3). Each suspension was stored for 35 days in a dark place at 25 degrees C and 4 degrees C. The results demonstrated that the prepared suspensions with P either from tablets or from a substance were stable in all three studied vehicles (more than 95% of initial concentration remaining). However, it is recommended that storage at 4 degrees C of suspensions prepared with M2 should be avoided because of crystallization of the buffer substances. Extemporaneous suspensions with T in an appropriate pediatric concentrations of the drug were not obtained because the problem of fast crystallization of T was not eliminated. PMID:23610969

Mu?ko, Monika; Sznitowska, Ma?gorzata

2013-01-01

76

Characterization, optimisation and process robustness of a co-processed mannitol for the development of orally disintegrating tablets.  

PubMed

This is a study to fully assess a commercially available co-processed mannitol for its usefulness as an off-the-shelf excipient for developing orally disintegrating tablets (ODTs) by direct compression on a pilot scale (up to 4 kg). This work encompassed material characterization, formulation optimisation and process robustness. Overall, this co-processed mannitol possessed favourable physical attributes including low hygroscopicity and compactibility. Two design-of-experiments (DoEs) were used to screen and optimise the placebo formulation. Xylitol and crospovidone concentrations were found to have the most significant impact on disintegration time (p < 0.05). Higher xylitol concentrations retarded disintegration. Avicel PH102 promoted faster disintegration than PH101, at higher levels of xylitol. Without xylitol, higher crospovidone concentrations yielded faster disintegration and reduced tablet friability. Lubrication sensitivity studies were later conducted at two fill loads, three levels for lubricant concentration and number of blend rotations. Even at 75% fill load, the design space plot showed that 1.5% lubricant and 300 blend revolutions were sufficient to manufacture ODTs with ? 0.1% friability and disintegrated within 15 s. This study also describes results using a modified disintegration method based on the texture analyzer as an alternative to the USP method. PMID:22582882

Soh, Josephine Lay Peng; Grachet, Maud; Whitlock, Mark; Lukas, Timothy

2013-02-01

77

Comparing the Therapeutic Effects of Garlic Tablet and Oral Metronidazole on Bacterial Vaginosis: A Randomized Controlled Clinical Trial  

PubMed Central

Background: Bacterial vaginosis (BV) is one of the most common gynecological infections during reproductive age. Although metronidazole is one of the most effective medications recommended as the first-line treatment, it has various side effects. Because of the side effects and contraindications of some chemical medicines, using herbs has been investigated in treating BV. Objectives: The aim of this study was to compare the effect of garlic tablet (Garsin) and oral metronidazole in clinical treatment of the BV in women referred to Resalat Health Center, affiliated with Mazandaran University of Medical Sciences, in 2013. Patients and Methods: This randomized clinical trial was conducted on 120 married women aged 18 to 44 years who were diagnosed with BV by Amsel’s clinical criteria and Gram staining. Enrolled women were randomly allocated to two groups of 60 patients and were treated with either garlic tablet or oral metronidazole for seven days. Amsel’s criteria and Gram stain were assessed seven to ten days after beginning the treatment period and side effects were registered. Results: Amsel’s criteria were significantly decreased after treatment with garlic or metronidazole (70% and 48.3%, respectively; P < 0.001). Therapeutic effects of garlic on BV were similar to that of metronidazole (63.3% and 48.3%, respectively; P = 0.141). There were significant differences between the two treatment groups in terms of side effects; metronidazole was associated with more complications (P = 0.032). Conclusions: This study reveals that garlic could be a suitable alternative for metronidazole in treatment of BV in those interested in herbal medicines or those affected by side effects of metronidazole. PMID:25237588

Mohammadzadeh, Farnaz; Dolatian, Mahrokh; Jorjani, Masoome; Alavi Majd, Hamid; Borumandnia, Nasrin

2014-01-01

78

Xanthan and galactomannan (from M. scabrella) matrix tablets for oral controlled delivery of theophylline.  

PubMed

Directly compressed theophylline tablets, containing commercial xanthan (X) (Keltrol) and a highly hydrophilic galactomannan (G) from the seeds of Mimosa scabrella (a brazilian leguminous tree called bracatinga) as release-controlling agents, were obtained. Gums were used at 4, 8, 12.5 and 25% (w/w), either alone or in mixture (X:G 1:1). During galactomannan extraction process, the biopolymer was dried in a scale up, by vacuum oven (VO) or spray dryer (SD). The in vitro drug release was evaluated at different time intervals during 8 h using apparatus 1 (USP 26) at 100 rpm. The pH of the dissolution medium (1.4) was changed to 4.0 and 6.8 after 2 and 3 h, respectively. Tablets containing G(SD) resulted in more uniform drug release than G(VO) ones, due to their smaller particle size. The drug release decreased with the increase of polymer concentration and all formulations at 25% w/w of gums showed excessive sustained release effect. The matrices made with alone X showed higher drug retention for all concentrations, compared with G matrices that released the drug too fast. The XG matrices were able to produce near zero-order drug release. The XG(SD) 8% tablets provided the required release rate (about 90% at the end of 8 h), with zero-order release kinetics. Tablets containing G(VO) in low concentration showed a complete erosion, while the others demonstrated fast hydration and swelling in contact with the dissolution medium. The release mechanism was a combination of diffusion and relaxation. The relative importance of these two processes varied with matrix composition. The XG(SD) 8% matrix showed higher contribution of polymer relaxation. PMID:15885450

Vendruscolo, C W; Andreazza, I F; Ganter, J L M S; Ferrero, C; Bresolin, T M B

2005-05-30

79

Safety of fluralaner chewable tablets (BravectoTM), a novel systemic antiparasitic drug, in dogs after oral administration  

PubMed Central

Background Fluralaner is a novel systemic insecticide and acaricide that provides long acting efficacy in dogs after a single oral treatment. This study investigated the safety of oral administration of fluralaner in chewable tablets to dogs at the highest recommended treatment dose and at multiples of this dose. Methods Thirty-two (16 male and 16 female) healthy 8-week old Beagle dogs weighing 2.0 - 3.6 kg at first administration were included in the study. Fluralaner was administered on three occasions at 8-week intervals at doses of up to 56, 168, and 280 mg fluralaner/kg body weight, equivalent to 1, 3, and 5 times the highest recommended treatment dose of fluralaner; sham dosed dogs served as controls. During the study, all dogs were clinically observed, and their health was carefully monitored including body weight development, food consumption and measurement of hematology, coagulation, clinical chemistry (including measurement of levels of ACTH and C-reactive protein) and urinalysis. Following euthanasia of the dogs, complete gross post mortem examination, including organ weight determination, and histopathological examination of multiple tissues were conducted. Results There were no clinical findings related to fluralaner treatment. Statistically significant differences between the treated groups and the control group were observed for some clinical pathology parameters and organ weights; none of these findings were considered to be of clinical relevance. Conclusions Oral administration of fluralaner at the highest recommended treatment dose (56 mg/kg) at 8-week intervals is well tolerated and has a safety margin of more than five in healthy dogs eight weeks of age or older and weighing at least 2 kg. PMID:24606886

2014-01-01

80

Formulation Optimization of Hydrodynamically Balanced Oral Controlled Release Bioadhesive Tablets of Tramadol Hydrochloride  

PubMed Central

The directly compressible floating-bioadhesive tablets of tramadol were formulated using varying amounts Carbopol 971P (CP) and hydroxy-propylmethyl cellulose (HPMC), along with other requisite excipients. In vitro drug release profile, floatational characteristics and ex vivo bioadhesive strength using texture analyzer were determined, and systematically optimized using a 32 central composite design (CCD). The studies indicated successful formulation of gastroretentive compressed matrices with excellent controlled release, mucoadhesion and hydrodynamic balance. Comparison of the dissolution profiles of the optimized formulation, with optimal composition of CP:HPMC :: 80.0:125.0, with that of the marketed controlled release formulation other indicated analogy of drug release performance with each other. Validation of optimization study using eight confirmatory experimental runs indicated very high degree of prognostic ability of CCD with mean ± SEM of ?0.06% ± 0.37. Further, the study successfully unravels the effect of the polymers on the selected response variables. PMID:21179349

Singh, Bhupinder; Rani, Ashu; Babita; Ahuja, Naveen; Kapil, Rishi

2010-01-01

81

Evaluation of the palatabilities in 10 different famotidine orally disintegrating tablets by combination of disintegration device and taste sensor.  

PubMed

Abstract The purpose of this study was to evaluate the palatabilities of the original and nine generic versions of famotidine orally disintegrating tablets (FODTs) by means of disintegration times and bitterness intensities determined using in combination disintegration device and taste sensor comparison of human gustatory sensation tests. The disintegration times were determined using a new disintegration testing equipment for ODTs, the OD-mate and bitterness intensities were determined using the SA501C taste-sensing system. The disintegration time and bitterness of each FODT was evaluated in gustatory sensation tests. There was a good correlation between the disintegration times of 10 FODTs estimated in human gustatory testing and those found using the OD-mate. The bitterness intensities of FODTs at 10, 20 and 30?s after starting the disintegration using the OD-mate and the values determined by the taste sensor were highly correlated with the bitterness intensities determined in gustatory sensation testing. A combination of the OD-mate and the SA501C was capable of predicting the palatabilities, disintegration properties and bitterness intensity of FODTs. PMID:25196898

Yoshida, Miyako; Hazekawa, Mai; Haraguchi, Tamami; Uchida, Takahiro

2014-09-01

82

Comparative Studies on the Dissolution Profiles of Oral Ibuprofen Suspension and Commercial Tablets using Biopharmaceutical Classification System Criteria.  

PubMed

In vitro dissolution studies for solid oral dosage forms have recently widened the scope to a variety of special dosage forms such as suspensions. For class II drugs, like Ibuprofen, it is very important to have discriminative methods for different formulations in physiological conditions of the gastrointestinal tract, which will identify different problems that compromise the drug bioavailability. In the present work, two agitation speeds have been performed in order to study ibuprofen suspension dissolution. The suspensions have been characterised relatively to particle size, density and solubility. The dissolution study was conducted using the following media: buffer pH 7.2, pH 6.8, 4.5 and 0.1 M HCl. For quantitative analysis, the UV/Vis spectrophotometry was used because this methodology had been adequately validated. The results show that 50 rpm was the adequate condition to discriminate the dissolution profile. The suspension kinetic release was found to be dependent on pH and was different compared to tablet release profile at the same experimental conditions. The ibuprofen release at pH 1.0 was the slowest. PMID:23626386

Rivera-Leyva, J C; García-Flores, M; Valladares-Méndez, A; Orozco-Castellanos, L M; Martínez-Alfaro, M

2012-07-01

83

Preliminary buprenorphine sublingual tablet pharmacokinetic data in plasma, oral fluid and sweat during treatment of opioid-dependent pregnant women  

PubMed Central

Background Buprenorphine is currently under investigation as a pharmacotherapy to treat pregnant women for opioid dependence. This research evaluates buprenorphine (BUP), norbuprenophine (NBUP), buprenorphine-glucuronide (BUP-Gluc) and norbuprenorphine-glucuronide (NBUP-Gluc) pharmacokinetics after high dose (14–20 mg) BUP sublingual tablet administration in three opioid-dependent pregnant women. Methods Oral fluid and sweat specimens were collected in addition to plasma specimens for 24 h during gestation weeks 28 or 29 and 34, and 2 months after delivery. Tmax was not affected by pregnancy; however, BUP and NBUP Cmax and AUC0–24h tended to be lower during pregnancy compared to postpartum levels. Results Statistically significant but weak positive correlations were found for BUP plasma and OF concentrations, and BUP/NBUP ratios in plasma and OF. Conclusion Statistically significant negative correlations were observed for times of specimen collection and BUP and NBUP OF/plasma ratios. BUP-Gluc and NBUP-Gluc were detected in only 5% of OF specimens. In sweat, BUP and NBUP were detected in only 4 of 25 (12 or 24 h) specimens in low concentrations (<2.4 ng/patch). These preliminary data describe BUP and metabolite pharmacokinetics in pregnant women and suggest that, like methadone, upward dose adjustments may be needed with advancing gestation. PMID:21860340

Concheiro, Marta; Jones, Hendreé E.; Johnson, Rolley E.; Choo, Robin; Huestis, Marilyn A.

2011-01-01

84

[Thermoplastic granulation as an alternative method for the preparation of hydrophilic-lipophilic oral matriix tablets].  

PubMed

The paper focuses on the formulation of HPMC K-matrix tablets by compression of granulates previously prepared by melt granulation. The model drug was theophylline monohydrate. Montanglycol wax was used as the solid lipid binder in a concentration of 10-20 %. With respect to the obtained results, thermoplastic granulation was found to ensure suitable porosity, flow, and particle size of the granulates. In both dissolution media (phosphate buffer pH 6.8 and artificial gastric juice pH 1.2), the release of the model drug is dependent on the HPMC viscosity grade used. The release rate can be modified by a change in the HPMC-to-montanglycol wax ratio. A decrease in this ratio increases the liberation of theophylline monohydrate. Due to different drug solubilities in the selected dissolution media, theophylline is released significantly faster in phosphate buffer pH 6.8 then in artificial gastric juice pH 1.2. The matrices of the same composition were prepared by direct compression; the comparison of dissolution profiles shows that the release of the active substance is not influenced by the employed method of manufacture. PMID:17867525

Dvorácková, K; Rabisková, M; Masteiková, R; Vocilková, L

2007-06-01

85

Novel Pullulan-Eudragit® S100 blend microparticles for oral delivery of risedronate: formulation, in vitro evaluation and tableting of blend microparticles.  

PubMed

Polymer blends have been considered a promising strategy to tailor drug release. In order to achieve gastroresistance and controlled release, Pullulan, a polysaccharide, and Eudragit® S100, an enteric polymer were selected to prepare microparticles for oral delivery of risedronate, an antiresorptive drug associated with GI tract injuries. Blend microparticles were prepared by spray-drying technique at 3 Pullulan and Eudragit® S100 ratios (MP2:1, MP1:1 and MP1:2) and were characterized in terms of yield, particle size, encapsulation efficiency, morphology, moisture content, flowability and in vitro drug release profiles. Microparticles presented yields between 31 and 42%, encapsulation efficiencies close to 100%, moisture contents lower than 11%, particle size ranging from 2.9 to 4.8 ?m and narrow distribution. In the gastric medium, MP1:2 showed the best gastroresistance profile. In the intestinal fluid, all samples were able to prolong drug release. MP1:2 was compressed into tablets with or without polyvinylpyrrolidone. Both tableted microparticles could be obtained with acceptable average weights, drug content close to 100%, sufficient hardness and low friability. In vitro studies showed that tablets maintained the gastroresistance observed for microparticles and were also able to prolong risedronate release. In conclusion, Pullulan/Eudragit® S100 microparticles are promising alternatives for the oral delivery of risedronate in the future. PMID:24656371

de Arce Velasquez, Aline; Ferreira, Luana Mota; Stangarlin, Mônica Fabiele Lorensi; da Silva, Cristiane de Bona; Rolim, Clarice Madalena Bueno; Cruz, Letícia

2014-05-01

86

[Involvement of zinc in taste disturbance occurring during treatment for malignant tumor in the chest and the effects of polaprezinc oral disintegrating tablets (a retrospective study)].  

PubMed

We analyzed the correlation between serum zinc levels and taste disturbance, and between patient backgrounds and serum zinc levels or taste disturbance, and evaluated the effects of polaprezinc oral disintegrating tablets on taste disturbance in 29 patients with lung cancer and one patient with malignant pleural mesothelioma who were receiving chemotherapy. Taste disturbance developed in 11 (36.7%) out of 30 patients. Serum zinc levels significantly correlated with taste disturbance (p=0.0227). Serum zinc levels were significantly lower (p=0.0235) and taste disturbance tended to be more frequent (p=0.0625) in males. Polaprezinc improved taste disturbance in 5 of 8 patients. PMID:18633224

Nakata, Yoko; Hirashima, Tomonori; Kondou, Yoko; Tokuoka, Yoshie; Imazato, Hitomi; Iwata, Kaori; Oomori, Yukari; Yamato, Akihiro; Shimizu, Saburou; Nagao, Sadako; Matsui, Kaoru; Abe, Noriko

2008-06-01

87

The effects of screw configuration and polymeric carriers on hot-melt extruded taste-masked formulations incorporated into orally disintegrating tablets.  

PubMed

The primary aim of this research was to produce successfully taste masked formulations of Sildenafil Citrate (SC) using hot-melt extrusion (HME) technology. Multiple screw configurations and polymeric carriers were evaluated for their effects on taste masking efficiency, which was assessed by both E-tongue analysis and in vitro dissolution in simulated salivary fluid (SSF, pH 6.8 artificial saliva). The screw configurations were further assessed for their effects on the morphology of the API using PXRD, FT-IR and mid-infrared chemical imaging. It was determined that the screw configuration had a profound effect on the taste masking efficiency of the formulations as a result of altering the physical state of the API. Selected extruded formulations using ethylcellulose (EC) with a pore former were further formulated into orally disintegrating tablets (ODTs), which were optimized by varying the grade and percentage of the superdisintegrant used. An optimized disintegration time of approximately 8 seconds was achieved. The final ODT formulation exhibited excellent taste masking properties with over 85% drug release in gastric media as well as physical tablet properties. Interestingly, friability, which tends to be a common concern when formulating ODTs, was well within the acceptable limits (<1%) for common tablets. PMID:25410968

Morott, Joseph T; Pimparade, Manjeet; Park, Jun-Bom; Worley, Chelsea P; Majumdar, Soumyajit; Lian, Zhuoyang; Pinto, Elanor; Bi, Yunxia; Durig, Thomas; Repka, Michael A

2015-01-01

88

Pharmacokinetic Comparative Study of Gastrodin and Rhynchophylline after Oral Administration of Different Prescriptions of Yizhi Tablets in Rats by an HPLC-ESI/MS Method  

PubMed Central

Pharmacokinetic characters of rhynchophylline (RIN), gastrodin (GAS), and gastrodigenin (p-hydroxybenzyl alcohol, HBA) were investigated after oral administration of different prescriptions of Yizhi: Yizhi tablets or effective parts of tianma (total saponins from Gastrodiae, EPT) and gouteng (rhynchophylla alkaloids, EPG). At different predetermined time points after administration, the concentrations of GAS, HBA, and RIN in rat plasma were determined by an HPLC-ESI/MS method, and the main pharmacokinetic parameters were investigated. The results showed that the pharmacokinetic parameters Cmax and AUC0–? (P < 0.05) were dramatically different after oral administration of different prescriptions of Yizhi. The data indicated that the pharmacokinetic processes of GAS, HBA, and RIN in rats would interact with each other or be affected by other components in Yizhi. The rationality of the compatibility of Uncaria and Gastrodia elata as a classic “herb pair” has been verified from the pharmacokinetic viewpoint. PMID:25610474

Ge, Zhaohui; Liang, Qionglin; Wang, Yiming; Luo, Guoan

2014-01-01

89

Rationale and design of the oral HEMe iron polypeptide Against Treatment with Oral Controlled Release Iron Tablets trial for the correction of anaemia in peritoneal dialysis patients (HEMATOCRIT trial)  

PubMed Central

Background The main hypothesis of this study is that oral heme iron polypeptide (HIP; Proferrin® ES) administration will more effectively augment iron stores in erythropoietic stimulatory agent (ESA)-treated peritoneal dialysis (PD) patients than conventional oral iron supplementation (Ferrogradumet®). Methods Inclusion criteria are peritoneal dialysis patients treated with darbepoietin alpha (DPO; Aranesp®, Amgen) for ? 1 month. Patients will be randomized 1:1 to receive either slow-release ferrous sulphate (1 tablet twice daily; control) or HIP (1 tablet twice daily) for a period of 6 months. The study will follow an open-label design but outcome assessors will be blinded to study treatment. During the 6-month study period, haemoglobin levels will be measured monthly and iron studies (including transferring saturation [TSAT] measurements) will be performed bi-monthly. The primary outcome measure will be the difference in TSAT levels between the 2 groups at the end of the 6 month study period, adjusted for baseline values using analysis of covariance (ANCOVA). Secondary outcome measures will include serum ferritin concentration, haemoglobin level, DPO dosage, Key's index (DPO dosage divided by haemoglobin concentration), and occurrence of adverse events (especially gastrointestinal adverse events). Discussion This investigator-initiated multicentre study has been designed to provide evidence to help nephrologists and their peritoneal dialysis patients determine whether HIP administration more effectively augments iron stores in ESP-treated PD patients than conventional oral iron supplementation. Trial Registration Australia New Zealand Clinical Trials Registry number ACTRN12609000432213. PMID:19635169

2009-01-01

90

Low-dose oral immunization with lyophilized tissue of herbicide-resistant lettuce expressing hepatitis B surface antigen for prototype plant-derived vaccine tablet formulation.  

PubMed

Efficient immunization against hepatitis B virus (HBV) and other pathogens with plant-based oral vaccines requires appropriate plant expressors and the optimization of vaccine compositions and administration protocols. Previous immunization studies were mainly based on a combination of the injection of a small surface antigen of HBV (S-HBsAg) and the feeding with raw tissue containing the antigen, supplemented with an adjuvant, and coming from plants conferring resistance to kanamycin. The objective of this study was to develop a prototype oral vaccine formula suitable for human immunization. Herbicide-resistant lettuce was engineered, stably expressing through progeny generation micrograms of S-HBsAg per g of fresh weight and formed into virus-like particles (VLPs). Lyophilized tissue containing a relatively low, 100-ng VLP-assembled antigen dose, administered only orally to mice with a long, 60-day interval between prime and boost immunizations and without exogenous adjuvant, elicited mucosal and systemic humoral anti-HBs responses at the nominally protective level. Lyophilized tissue was converted into tablets, which preserved S-HBsAg content for at least one year of room temperature storage. The results of the study provide indications on immunization methodology using a durable, efficacious, and convenient plant-derived prototype oral vaccine against hepatitis B. PMID:21107787

Pniewski, Tomasz; Kapusta, Józef; Boci?g, Piotr; Wojciechowicz, Jacek; Kostrzak, Anna; Gdula, Micha?; Fedorowicz-Stro?ska, Olga; Wójcik, Piotr; Otta, Halina; Samardakiewicz, S?awomir; Wolko, Bogdan; P?ucienniczak, Andrzej

2011-05-01

91

DEM simulation of continuous tablet coating: Effects of tablet shape and fill level on inter-tablet coating variability  

Microsoft Academic Search

Tablet coating is a common pharmaceutical technique of applying a thin polymer-based film to a tablet or a granule containing active pharmaceutical ingredients (APIs). Inter- and intra-tablet variability of film coating is a critical issue in the production of solid oral dosage forms. In fact, inhomogeneity in the coating thickness can lead to significant variations in the delivery rate of

Daniele Suzzi; Gregor Toschkoff; Stefan Radl; Daniel Machold; Simon D. Fraser; Benjamin J. Glasser; Johannes G. Khinast

92

Direct UPLC-MS-MS validated method for the quantification of 5-aminolevulinic acid: application to in-vitro assessment of colonic-targeted oral tablets.  

PubMed

A reliable, sensitive, specific, and rapid ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS-MS) method was developed for the determination of 5-aminolevulinic acid (5-ALA) in orally-administered colonic delivery system. The prepared system is a compression-coated tablet using granulated chitosan as the coat layer. L-Tyrosine (TYR) was used as an internal standard with no need for derivatization. The chromatographic system consisted of Acquity UPLC BEH C18 column and isocratic mobile phase composed of acetonitrile and 0.1% formic acid with a flow rate of 2.5 min. The assay was based on ESI+ mode in a multiple reaction monitoring (MRM) transitions at m/z 132.08 > 86.0 and m/z 132.08 > 114.0 and m/z 182.1 > 91.2 for 5-ALA and TYR, respectively. Limit of quantification was 5.0 ng/mL and the calibration curve was linear (r(2) = 0.994). Within-run precision and between-run repeatability were expressed as relative standard deviation and were lower than 2.5%. The recoveries from control samples were > 95%. The method was successfully applied for evaluation in assay and release profile of 5-ALA colon targeted tablets media containing suspended rat cecal contents pH 6.8 medium (colonic) for colonic delivery. PMID:21682991

Alsarra, Ibrahim A; Yassin, Alaa Eldeen B; Abdel-Hamid, Magdi; Alanazi, Fars K; Aljuffali, Ibrahim A

2011-01-01

93

A five way crossover human volunteer study to compare the pharmacokinetics of paracetamol following oral administration of two commercially available paracetamol tablets and three development tablets containing paracetamol in combination with sodium bicarbonate or calcium carbonate.  

PubMed

This report concerns a single dose randomized five way crossover study to compare the pharmacokinetics of paracetamol from two commercially available paracetamol (500 mg) tablets and three different development paracetamol (500 mg) tablet formulations containing either sodium bicarbonate (400 mg), sodium bicarbonate (630 mg) or calcium carbonate (375 mg). The results demonstrated that addition of sodium bicarbonate (630 mg) to paracetamol tablets, increased the rate of absorption of paracetamol relative to conventional paracetamol tablets and soluble paracetamol tablets. Addition of sodium bicarbonate (400 mg) to paracetamol tablets increased the absorption rate of paracetamol relative to conventional paracetamol tablets, but there was no difference in the rate of absorption compared to soluble paracetamol tablets. Inclusion of calcium carbonate (375 mg) to paracetamol tablets had no effect on absorption kinetics compared to the conventional paracetamol tablet. The faster absorption observed for the sodium bicarbonate formulations may be as a result of an increase in gastric emptying rate leading to faster transport of paracetamol to the small intestine where absorption takes place. PMID:10799813

Grattan, T; Hickman, R; Darby-Dowman, A; Hayward, M; Boyce, M; Warrington, S

2000-05-01

94

Synergistic affective analgesic interaction between delta-9-tetrahydrocannabinol and morphine  

Microsoft Academic Search

Evidence for an analgesic interaction between delta-9-tetrahydrocannabinol (?9-THC) and morphine was sought using an experimental pain model applied to normal volunteers. The study incorporated a double blinded, four treatment, four period, four sequence, crossover design. Subjects received ?9-THC 5 mg orally or placebo and 90 min later morphine 0.02 mg\\/kg intravenously or placebo. Fifteen minutes later subjects rated the pain

John D. Roberts; Chris Gennings; Margaret Shih

2006-01-01

95

The influence of morphine on the absorption of paracetamol from various formulations in subjects in the supine position, as assessed by TDx measurement of salivary paracetamol concentrations.  

PubMed

The aim of this study was to determine the influence of the type of paracetamol formulation on the rate of absorption when subjects are in the supine position, with or without taking concomitant morphine. Two groups of healthy volunteers were used, who were in the fasting state and remained in the supine position during the study. One group took 1,500 mg of paracetamol on three occasions as conventional tablets, dispersible tablets or a suspension in a randomized crossover design. Seventeen saliva samples per subject were obtained (time zero to 360 min post-dose), which were then centrifuged and kept at -20 degrees C prior to analysis. The second group repeated the study following four doses of morphine syrup (10 mg 4 hourly) in the 12 h preceding paracetamol ingestion. In this phase of the study, paracetamol absorption from suspension was not investigated. A TDx assay was used to determine salivary paracetamol concentrations. The tmax for conventional tablets when taken concomitantly with morphine was 160 (+/- 81) min compared to 51 (+/- 58) min for subjects not taking morphine. For dispersible tablets the tmax in the morphine group was 14 (+/- 9) min compared to 15 (+/- 12) min without morphine. The results suggest that patients who are confined to bed and taking morphine will have an unacceptably long delay between taking conventional paracetamol tablets and the paracetamol reaching therapeutic plasma concentrations. Conversely, there is little effect on the absorption of dispersible paracetamol under the same conditions. PMID:14607015

Kennedy, Julia M; Tyers, Nicola M; Davey, Andrew K

2003-10-01

96

The effect of perinatal lead exposure on dopamine receptor D2 expression in morphine dependent rats.  

PubMed

The aim of this study was to investigate the behavioral and molecular effects of pre- and postnatal lead (Pb) exposure on the expression of morphine withdrawal and tolerance in adult rats. Rats were orally treated with 0.1% (1000ppm) lead acetate from conception, through gestation, up to postnatal day (PND) 28. Subsequently, behavioral experiments were conducted on adult (PND 60) male rats. To assess behavioral effects of morphine dependence in Pb-exposed rats two experimental models were used: naloxone-precipitated withdrawal signs and the assessment of morphine tolerance to antinociceptive effect in the tail-immersion test. Morphine withdrawal and tolerance were more expressed in Pb-exposed morphine administered rats than in morphine administered rats. In the case of morphine withdrawal signs the analysis of protein (Western blotting) and mRNA (RT PCR) expression revealed significantly higher dopamine D2 receptor (D2R) expression in prefrontal cortex, but not in striatum and hippocampus, in Pb-exposed morphine administered rats than in morphine administered rats. Differently, in the case of morphine tolerance the significant upregulation of D2R protein and mRNA expression in hippocampus, but not in prefrontal cortex or striatum, was demonstrated in Pb-exposed and morphine administered rats in comparison with morphine administered. These findings suggest that in morphine withdrawal and tolerant rats the perinatal Pb-exposure can affect D2R expression in brain region-specific manner. Immunohistochemical assessment of D2R expression in hippocampus showed translocation of D2R from membrane-cytoplasm in control rats to nucleus in morphine administered rats. Perinatal Pb-exposure did not induce the changes in the localization of D2R irrespective of morphine effect. PMID:23702354

Listos, Joanna; Baranowska-Bosiacka, Irena; Talarek, Sylwia; Listos, Piotr; Orzelska, Jolanta; Fidecka, Sylwia; Gutowska, Izabela; Kolasa, Agnieszka; Rybicka, Marta; Chlubek, Dariusz

2013-08-01

97

Simultaneous determination by UPLC-MS/MS of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets: application to a pharmacokinetic study*  

PubMed Central

A rapid, reliable, and sensitive method was developed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with an electrospray ionization (ESI) source for determination of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets (GBTs). The method simultaneously detects bilobalide (BB), ginkgolide A (GA), ginkgolide B (GB), ginkgolide C (GC), quercetin (QCT), kaempferol (KMF), and isorhamnetin (ISR) for pharmacokinetic study. The analytes and internal standard (IS) were extracted from rat plasma by acetidin. An MS/MS detection was conducted using multiple reaction monitoring (MRM) and operating in the negative ionization mode. The calibration curve ranges were 5–500, 5–500, 2.5–250, 1–100, 1–100, 1–100, and 1–100 ng/ml for BB, GA, GB, GC, QCT, KMF, and ISR, respectively. The mean recovery of the analytes ranged from 68.11% to 84.42%. The intra- and inter-day precisions were in the range of 2.33%–9.86% and the accuracies were between 87.67% and 108.37%. The method was used successfully in a pharmacokinetic study of GBTs. The pharmacokinetic parameters of seven compounds were analyzed using a non-compartment model. Plasma concentrations of the seven compounds were determined up to 48 h after administration, and their pharmacokinetic parameters were in agreement with previous studies. PMID:25367786

Wang, Wen-ping; Liu, Na; Kang, Qian; Du, Pei-pei; Lan, Yi; Zhao, Bo-chen; Chen, Yan-yan; Zhang, Qing; Li, Hui; Zhang, Ye-wen; Wu, Qing

2014-01-01

98

Molecular Structure of Morphine  

NSDL National Science Digital Library

Morphine is a narcotic that is derived from opium. It was first obtained from unripe seed pods of the opium poppy (Papaver somniferum) by a German pharmacist, F. W. A. Sertuerner. Morphine was used as a pain-killer and as a cure for opium addiction. The mechanism of action of morphine occurs by binding to the mu-opioid receptor in the brain. It impairs mental and physical performance, relieves fear and anxiety, and produces euphoria. It also decreases hunger, inhibits the cough reflex, produces constipation, and usually reduces the sex drive; in women it may interfere with the menstrual cycle. Morphine is used medicinally for severe pain, cough suppression, and as an anesthetic.

2002-09-12

99

Propranolol and morphine.  

PubMed

The morphine blocking and anticonvulsant effects of propranolol were investigated in mice. Three different convulsant procedures (electroshock, pentylenetetrazol and thebaine) were used. In addition, LD50's of morphine after different doses of propranolol were done. Sotalol was used as a control drug to check which of the effects of propranolol could be regarded as due to beta blockade. Morphine LD50 in mice is not altered by pre-treatment with propranolol. The anticonvulsant characteristics of propranolol are different from those of sotalol, the former acting mainly on the tonic phase of the seizures. This study does not support the hypothesis that propranolol is a morphine antagonist but reinforces the idea that propranolol has definite central nervous system effects. PMID:189341

Navarro, G; Richardson, R; Zuban, A T

1976-12-21

100

Effect of hydrophilic natural gums in formulation of oral-controlled release matrix tablets of propranolol hydrochloride.  

PubMed

In order to develop a controlled delivery of highly water-soluble propranolol hydrochloride (PPHCl) using hydrophilic natural gums (xanthan gum [X] and locust bean gum [LBG]) as cost-effective, nontoxic, easily available. The granules of PPHCl were prepared by wet granulation method using a different ratios drug: gum ratios of X, LBG and XLBG(X and LBG in 1:1 ratios). To increase the flowability and compressibility of the granules, and to prevent its adhesion to punch and die, magnesium stearate and talc were added to the granules in 1:2 ratios before punching. The tablet was analysed to determine hardness, friability, % assay and invitro release study was carried out. The release of PPHCl from a gelatinous swollen mass, which controls the diffusion of drug molecules through the polymeric material into aqueous medium. The XLBG matrice shows precise controlled release than the X and LBG matrice because of burst effect and fast release in case of X and LBG matrice respectively and there was no chemical interaction between drug and polymer in XLBG formulation as confirmed by FTIR studies. First pass effect of PPHCl can be avoided by these formulations. Matrices with XLBG show zero-order release via swelling, diffusion and relaxation mechanism. The XLBG matrice leads to more precise result than X and LBG alone by the utilization of synergistic interaction between two biopolymers and uniformity in the hydration layer in dissolution media. However, according to the similarity factor (f(2)) XLBG3 were the most similar formulations to Lol-SR as the reference standard. PMID:19339235

Rajesh, K S; Venkataraju, M P; Gowda, D V

2009-04-01

101

Investigation and analysis of oncologists’ knowledge of morphine usage in cancer pain treatment  

PubMed Central

Purpose To examine oncologists’ knowledge of cancer pain and morphine’s clinical application in the People’s Republic of China. In addition, this study analyzes and discusses the negative factors that currently affect the clinical application of morphine. Patients and methods A questionnaire survey was given to a random sample of 150 oncologists from Tianjin Medical University Cancer Institute and Hospital. The statistical results were analyzed and processed using SPSS version 21.0 and Matlab version 2012a statistical software. Single-factor analysis of variance, Kruskal–Wallis nonparametric test, and independent samples t-test were adopted to analyze the difference in knowledge scores of morphine usage. The study also identified major impediment factors on clinical use of morphine. Results Among the 127 respondents, morphine controlled-release tablets were the most popular drug chosen to treat severe cancer pain (76 respondents, 35.8%). Participants who reported having received training in cancer pain management and drug use demonstrated a significantly higher mean score of basic knowledge compared with their untrained peers (11.51±2.60 versus 9.28±3.68, t=2.48, P=0.022). The top four barriers to widespread clinical use of morphine for cancer pain were 1) insufficient analgesia administration training for medical personnel, 2) poor patient compliance, 3) drug side effects, and 4) concerns surrounding drug addiction. Conclusion The oncologists in the People’s Republic of China simultaneously lack comprehensive knowledge and harbor misconceptions with regard to cancer pain treatment and morphine’s clinical application. Creating professional training initiatives for oncologists is necessary to enhance their awareness and expertise in morphine use for cancer pain treatment. PMID:24876783

Liu, Weiran; Xie, Shumin; Yue, Lin; Liu, Jiahao; Woo, Stephanie Mu-Lian; Liu, Weilin; Miller, Adam R; Zhang, Jing; Huang, Lijun; Zhang, Lei

2014-01-01

102

Tablet Weaving  

ERIC Educational Resources Information Center

Article described a weaving technique called tablet weaving, an ancient textile process that provides opportunity for making a variety of items, such as guitar straps, belts, and decorative bands. (Author/RK)

Kren, Margo

1976-01-01

103

Wuchereria bancrofti antigenemia clearance among Myanmar migrants after biannual mass treatments with diethylcarbamazine, 300 mg oral-dose FILADEC tablet, in Southern Thailand.  

PubMed

Using qualitative ICT Filariasis and quantitative Og4C3 ELISA, we assessed a long-term macrofilaricidal effect of two-year biannual mass treatments with a 300 mg oral-dose FILADEC tablet, a reformulation of 6 mg/kg diethylcarbamazine (DEC), on clearance of the Wuchereria bancrofti adult worm circulating filarial antigens (CFA) in Myanmar migrants, at risk of emergence of imported bancroftian filariasis in Southern Thailand. Of the 34 antigenemic Myanmar index cases of varying initial CFA levels, who were initially screened out with the ICT Filariasis, 13 index cases were follow-up treated and monitored at the DEC post treatments, 6, 12, and 18 months. At the 18-month post treatment, residual antigenemias (%) in 4 of 5 index cases (group 1) with high antigen titers (99.7-181.6 x 10(3) AU/ml) were 54.44%, 33.58%, 27.43%, and 9.97%. Significant decreases of the CFA levels in only 3 out of 5 index cases were affected by the response to DEC treatments (p < 0.007). The treatment effects on clearance of the CFA in 8 index cases (group II) with low antigen titers (15.4-37.2 x 10(3) AU/ml) were shown for at least 6 months post DEC treatment and hence had 100% efficacy in the first 6 months of the first year of year round treatment. Group I, was more likely to show an increase of the DEC efficacy after the first 6 months of the second year round treatment, but there was no statistically significant difference (p = 0.063). We reemphasized that, for use in the national program to eliminate lymphatic filariasis (PELF) in Thailand, such a DEC regimen had a macrofilaricidal effect on antigenemia clearance, and confirmed its value in evaluating response to the treatment and monitoring the long-term efficacy of the DEC regimen in W. bancrofti adult worm burden reductions in Myanmar migrants on a wide scale. PMID:15115084

Koyadun, Surachart; Bhumiratana, Adisak; Prikchu, Pathomporn

2003-12-01

104

Mucoadhesive tablets for controlled release of acyclovir.  

PubMed

Mucoadhesive chitosan (CS) and/or hydroxypropyl-methylcellulose (HPMC) tablets for gastric drug delivery of acyclovir (ACV) have been developed in order to improve the ACV oral bioavailability. Swelling, bioadhesive and dissolution studies were carried out in two acidic media (pH 1.5 and 4) in order to determine the tablets behaviour in both fed and fasted states. All the designed tablets showed good mucoadhesive properties on gastric mucosa due to the presence of CS and/or HPMC. In vitro dissolution of ACV from tablets was influenced by the swelling behaviour of each polymer. All data release of the studied tablets fitted to Hopfenberg model, which describes drug release from tablets displaying heterogeneous erosion. HPMC and CS/HPMC tablets revealed a sustained release for 24 h, but a complete dissolution of the tablets was not produced at this time. On the contrary, tablets which contained only CS as polymer were able to release the total amount of ACV for 4 h, due to the CS imbibition and erosion processes in pH 1.5 medium. These results allowed us to conclude that CS is the excipient to be chosen to obtain gastroretentive formulations, due to its demonstrated gastric compatibility. PMID:22863800

Ruiz-Caro, Roberto; Gago-Guillan, Manuel; Otero-Espinar, Francisco Javier; Veiga, María Dolores

2012-01-01

105

Relative bioavailability of the fentanyl effervescent buccal tablet (FEBT) 1080 pg versus Oral transmucosal fentanyl citrate 1600 pg and dose proportionality of FEBT 270 to 1300 ?g: A single-dose, randomized, open-label, three-period study in healthy adult volunteers  

Microsoft Academic Search

Background: The fentanyl effervescent buccal tablet (FEBT) was designed to enhance the rate and extent of absorption of fentanyl through the buccal mucosa. FEBT is being investigated for the management of breakthrough pain.Objectives: The primary objective of this study was to compare the relative bioavailability of FEBT 1080 ?g with that of oral transmucosal fentanyl citrate (OTFC®) 1600 ?g, and

Mona Darwish; Kenneth Tempero; Mary Kirby; Jeffrey Thompson

2006-01-01

106

Modelling concentration-analgesia relationships for morphine to evaluate experimental pain models.  

PubMed

The aim of this study was to develop population pharmacokinetic-pharmacodynamic models for morphine in experimental pain induced by skin heat and muscle pressure, and to evaluate the experimental pain models with regard to assessment of morphine pharmacodynamics. In a randomised, double-blind, placebo-controlled, crossover study, 39 healthy volunteers received an oral dose of 30mg morphine hydrochloride or placebo. Non-linear mixed effects modelling was used to describe the plasma concentrations of morphine and metabolites, and the analgesic effect of morphine on experimental pain in skin and muscle. Baseline pain metrics varied between individuals and occasions, and were described with interindividual and interoccasion variability. Placebo-response did not change with time. For both pain metrics, morphine effect was proportional to baseline pain and was described with a linear model with interindividual variability on drug effect slope and linked to an effect compartment for muscle pressure. The models indicate that a steady-state morphine concentration of 21ng/ml causes 33% and 0.84% increases in stimulus intensity from baseline for muscle pressure and skin heat, respectively. The population pharmacokinetic-pharmacodynamic models developed in this study indicate that mechanical stimulation of muscle is a more clinically relevant pain stimulus for the assessment of morphine pharmacodynamics than thermal stimulation of skin. PMID:25315409

Sverrisdóttir, Eva; Foster, David John Richard; Upton, Richard Neil; Olesen, Anne Estrup; Lund, Trine Meldgaard; Gabel-Jensen, Charlotte; Drewes, Asbjørn Mohr; Christrup, Lona Louring; Kreilgaard, Mads

2014-10-12

107

Role of various natural, synthetic and semi-synthetic polymers on drug release kinetics of losartan potassium oral controlled release tablets  

PubMed Central

Objective: The objective of the present work was to formulate and to characterize controlled release matrix tablets of losartan potassium in order to improve bioavailability and to minimize the frequency of administration and increase the patient compliance. Materials and Methods: Losartan potassium controlled release matrix tablets were prepared by direct compression technique by the use of different natural, synthetic and semisynthetic polymers such as gum copal, gum acacia, hydroxypropyl methyl cellulose K100 (HPMC K100), eudragit RL 100 and carboxy methyl ethyl cellulose (CMEC) individually and also in combination. Studies were carried out to study the influence of type of polymer on drug release rate. All the formulations were subjected to physiochemical characterization such as weight variation, hardness, thickness, friability, drug content, and swelling index. In vitro dissolution studies were carried out simulated gastric fluid (pH 1.2) for first 2 h and followed by simulated intestinal fluid (pH 6.8) up to 24 h, and obtained dissolution data were fitted to in vitro release kinetic equations in order to know the order of kinetics and mechanism of drug release. Results and Discussion: Results of physiochemical characterization of losartan potassium matrix tablets were within acceptable limits. Formulation containing HPMC K100 and CMEC achieved the desired drug release profile up to 24 h followed zero order kinetics, release pattern dominated by Korsmeyer — Peppas model and mechanism of drug release by nonfickian diffusion. The good correlation obtained from Hixson-Crowell model indicates that changes in surface area of the tablet also influences the drug release. Conclusion: Based on the results, losartan potassium controlled release matrix tablets prepared by employing HPMC K100 and CMEC can attain the desired drug release up to 24 h, which results in maintaining steady state concentration and improving bioavailability. PMID:25426439

Jayasree, J.; Sivaneswari, S.; Hemalatha, G.; Preethi, N.; Mounika, B.; Murthy, S. Vasudeva

2014-01-01

108

Intrathecal combination of ziconotide and morphine for refractory malignant pain: A rapidly acting and effective choice  

Microsoft Academic Search

Ziconotide is a nonopioid intrathecal analgesic drug used to manage moderate to severe chronic pain. The aim of this work is to assess the safety and efficacy of intrathecal (IT) combination of ziconotide and morphine in malignant pain refractory to high doses of oral opioids. Patients with malignant pain refractory to high oral opioids doses with a mean visual analogue

Ilaria Alicino; Mariateresa Giglio; Fabio Manca; Francesco Bruno; Filomena Puntillo

109

Population pharmacokinetics of azithromycin and chloroquine in healthy adults and paediatric malaria subjects following oral administration of fixed-dose azithromycin and chloroquine combination tablets  

PubMed Central

Background Population pharmacokinetics (PK) of azithromycin (AZ) and chloroquine (CQ) following administration of fixed-dose combination tablet formulations of AZ and CQ (AZCQ) was evaluated using data from two studies: 1) in children with symptomatic uncomplicated falciparum malaria in sub-Saharan Africa; and 2) in healthy adults in the United States. Methods Study 1 included paediatric subjects randomized to either AZCQ or artemether-lumefantrine treatment in Cohort 1 (age 5–12 years) and Cohort 2 (age 6–59 months). Dosing of AZCQ was approximately 30 mg/kg AZ and 10 mg/kg CQ once daily for 3 days (for ?20 kg weight: AZ/CQ 300/100 mg per tablet; 5 to <20 kg weight: AZ/CQ 150/50 mg per tablet). Study 2 included adults randomized to receive either two AZCQ tablets (AZ/CQ 250/155 mg per tablet) or individual commercial tablets of AZ 500 mg and CQ 300 mg. Serum AZ and plasma CQ concentrations from both studies were pooled. Population PK models were constructed using standard approaches to evaluate the concentration-time data for AZ and CQ and to identify any covariates predictive of PK behaviour. Results A three-compartment PK model with linear clearance and absorption adequately described AZ data, while a two-compartment model with linear clearance and absorption and an absorption lag adequately described CQ data. No overall bias or substantial model misspecification was evident using diagnostic plots and visual predictive checks. Body weight as an allometric function was the only covariate in the final AZ and CQ PK models. There were significantly lower AZ (0.488 vs 0.745 [mg•h/L]/[mg/kg], p?

2014-01-01

110

ADL 8-2698, a trans-3,4-dimethyl-4- (3-hydroxyphenyl) piperidine, prevents gastrointestinal effects of intravenous morphine without affecting analgesia  

Microsoft Academic Search

ADL-8-2698 is a novel peripherally restricted opioid antagonist that may selectively prevent opioid-induced gastrointestinal effects without reversing analgesia. Gastrointestinal transit time (lactulose hydrogen breath test) was measured in 14 volunteers with oral and intravenous placebo, oral placebo and intravenous morphine (0.05 mg · kg?1), and oral ADL 8-2698 (4 mg) and intravenous morphine (0.05 mg · kg?1) in a double

Spencer S. Liu; Peter S. Hodgson; Randall L. Carpenter; James R. Fricke

2001-01-01

111

A single-dose, randomized, open-label, two-period crossover bioequivalence study comparing a fixed-dose pediatric combination of lamivudine and stavudine tablet for oral suspension with individual liquid formulations in healthy adult male volunteers.  

PubMed

Lamivudine (CAS 134678-17-4) is a synthetic nucleoside analogue with activity against HIV-1 and HBV. Stavudine (CAS 3056-17-5) is a synthetic thymidine nucleoside analogue, active against the human immunodeficiency virus (HIV). Lamivudine and stavudine in combination with other antiretroviral (ARV) agents are indicated for the treatment of HIV infection. As there are no suitable pediatric ARVs, adult fixed-dose ARVs are commonly used in children. This practice poses concerns about dose inaccuracy, which may lead to resistance or toxicity. A new fixed-dose combination (FDC) tablet for oral suspension, containing lamivudine 40 mg and stavudine 10 mg has been developed. An open-label, balanced, randomised, two-treatment, two-period, two-sequence, single-dose, crossover bioequivalence study was conducted following administration of a fixed-dose combination of lamivudine and stavudine tablet for oral suspension (test formulation) and innovator products (reference formulations) in healthy, adult, male human subjects under fasting condition. Multiple blood samples were collected up to 36 h post dose. Plasma concentrations of lamivudine and stavudine were assayed using validated high-performance liquid chromatography with mass spectrometry analytical method. Pharmacokinetic parameters were calculated using non-compartmental analysis and bioequivalence was assessed using a mixed effect ANOVA model. The ratio of the least-square means (FDC to individual products) and 90% confidence intervals (CIs) of AUC(0-t), AUC(0-infinity) and C(max) for lamivudine and stavudine were all within 80.00-125.00%, suggesting a similar rate and extent of ARVs exposure in the bloodstream. The FDC and individual products were equally safe and well tolerated. The current FDC of lamivudine and stavudine is expected to provide a similar efficacy/safety profile as co-administration of the individual products, a better adherence to treatment, and considerable cost savings in the treatment of HIV in children. PMID:19338141

Monif, Tausif; Reyar, Simrit; Tiwari, Hari Krishan; Tippabhotla, Sudhakar Koundinya; Khuroo, Arshad; Thudi, Nageshwar Rao; Ahmed, Sarfaraz; Raghuvanshi, Rajeev

2009-01-01

112

An Investigation into the Influence of Experimental Conditions on In Vitro Drug Release from Immediate-Release Tablets of Levothyroxine Sodium and Its Relation to Oral Bioavailability  

Microsoft Academic Search

The aim of this study was to investigate the influence of experimental conditions on levothyroxine sodium release from two\\u000a immediate-release tablet formulations which narrowly passed the standard requirements for bioequivalence studies. The in vivo study was conducted as randomised, single-dose, two-way cross-over pharmacokinetic study in 24 healthy subjects. The in vitro study was performed using various dissolution media, and obtained

Ivana Kocic; Irena Homsek; Mirjana Dacevic; Jelena Parojcic; Branislava Miljkovic

113

Comparison of Echinacea alkylamide pharmacokinetics between liquid and tablet preparations  

Microsoft Academic Search

The relative oral bioavailability of alkylamides from two different Echinacea dosage forms (liquid and tablet) were compared in a small two-way crossover study in humans (n=3). The liquid preparation investigated contained a mixture of Echinacea purpurea root (300mg\\/ml) and Echinacea angustifolia root (200mg\\/ml) extracted in 60% ethanol. The tablet preparation investigated was also a mixture of E. purpurea root (675mg\\/tablet)

A. Matthias; R. S. Addison; L. L. Agnew; K. M. Bone; K. Watson; R. P. Lehmann

2007-01-01

114

Role of cyclodextrin complexation in felodipine-sustained release matrix tablets intended for oral transmucosal delivery: in vitro and ex vivo characterization.  

PubMed

The objective of the present research was two-fold: To characterize the produced inclusion complex of felodipine (FDP)-hydroxypropyl-?-cyclodextrin (HP?CD) utilizing lyophilization, and to develop and characterize a complexed sustained-release polymeric matrix tablets intended for buccal delivery. The phase-solubility diagram suggested an A(L) type system with 1:1 stoichiometry. Solid complexes prepared by physical mixing and lyophilization were characterized by thermal and non-thermal analytical techniques to corroborate the fact of complex formation. The sustained-release FDP tablets were produced by direct compression, and these drug or complex-loaded hydrophilic matrices were assessed for in vitro bioadhesion and release modulation, ex vivo permeation, and in vivo residence time. The in vitro drug release and ex vivo permeation across the porcine buccal membrane demonstrated that the matrix tablets containing FDP-HP?CD (FH5) solid complex exhibited a complete and sustained drug release pattern, and a significantly higher drug permeation (p?

Palem, Chinna Reddy; Kumar Battu, Sunil; Gannu, Ramesh; Yamsani, Vamshi Vishnu; Repka, Michael A; Yamsani, Madhusudan Rao

2012-01-01

115

Miconazole mucoadhesive tablet for oropharyngeal candidiasis  

PubMed Central

Oropharyngeal candidiasis is a commonly encountered problem in daily clinical practice. Topical therapies for oropharyngeal candidiasis are considered preferable to systemic therapies in most patient populations. However, traditional topical therapies have limitations including short contact time with the oral mucosa and the need for multiple doses each day. Miconazole mucoadhesive tablet has recently been approved in Europe (Loramyc®) and the USA (Oravig™) for the treatment of oropharyngeal candidiasis. This tablet adheres to the oral mucosa and provides sustained local release of miconazole over a period of several hours with just one daily application. This article reviews the pharmacology, safety and efficacy of this novel agent. PMID:21171872

Lalla, Rajesh V; Bensadoun, René-Jean

2011-01-01

116

21 CFR 520.763a - Dithiazanine iodide tablets.  

Code of Federal Regulations, 2014 CFR

...1) The tablets are administered orally to dogs immediately after feeding using the following dosage schedule for various parasite infestations: Milligrams per pound of body weight Length of treatment—days Large roundworms (Toxocara canis,...

2014-04-01

117

21 CFR 520.763a - Dithiazanine iodide tablets.  

Code of Federal Regulations, 2013 CFR

...1) The tablets are administered orally to dogs immediately after feeding using the following dosage schedule for various parasite infestations: Milligrams per pound of body weight Length of treatment—days Large roundworms (Toxocara canis,...

2013-04-01

118

21 CFR 520.763a - Dithiazanine iodide tablets.  

Code of Federal Regulations, 2011 CFR

...1) The tablets are administered orally to dogs immediately after feeding using the following dosage schedule for various parasite infestations: Milligrams per pound of body weight Length of treatment—days Large roundworms (Toxocara canis,...

2011-04-01

119

21 CFR 520.763a - Dithiazanine iodide tablets.  

Code of Federal Regulations, 2012 CFR

...1) The tablets are administered orally to dogs immediately after feeding using the following dosage schedule for various parasite infestations: Milligrams per pound of body weight Length of treatment—days Large roundworms (Toxocara canis,...

2012-04-01

120

21 CFR 520.903e - Febantel tablets.  

Code of Federal Regulations, 2012 CFR

...RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.903e Febantel tablets...Limitations. Do not use in pregnant animals. Consider alternative therapy or use with caution in animals with preexisting liver or kidney...

2012-04-01

121

[Examination of anti-emetic effect, safety and usefulness of single oral dose of ondansetron tablet in nausea and emesis induced by anti-cancer drugs--dose-finding study of ondansetron tablet in patients receiving non-platinum anti-cancer drugs].  

PubMed

Inhibitory effects on acute nausea and emesis, safety and usefulness of a single oral dose of Ondansetron tablet were evaluated in 3 different dose levels for comparison by telephone registration system, in patients receiving non-platinum anti-cancer drugs. A single dose of ondansetron at 4 mg, 8 mg or 12 mg was given orally at 2 hrs before the initial administration of anti-cancer drugs. The patients were observed for 24 hours after administration of anti-cancer drugs, for occurrence of nausea and emesis. Efficacy rates of inhibitory effects on nausea and emesis were 83.3% (10/12 cases) in 4 mg dose group, 78.6% (11/14 cases) in 8 mg dose group and 84.6% (11/13 cases) in 12 mg dose group, without statistically significant difference. Side effects were observed in 3 cases (headache, cold feeling and trembling in limbs, sleepiness) in 12 mg dose group, but these symptoms were not severe and disappeared after several hours or several days. No abnormality in clinical laboratory findings attributable to Ondansetron was observed. From the above, it was considered that Ondansetron was a clinically useful anti-emetic for nausea and emesis induced by non-platinum anti-cancer drugs and that 4 mg once daily was the optimal dose. PMID:1386976

Nukariya, N; Niitani, H; Taguchi, T; Furue, H; Ota, K; Tsukagoshi, S; Ariyoshi, Y; Ikeda, M; Akasaka, Y; Ohta, J

1992-08-01

122

MTN-001: Randomized Pharmacokinetic Cross-Over Study Comparing Tenofovir Vaginal Gel and Oral Tablets in Vaginal Tissue and Other Compartments  

PubMed Central

Background Oral and vaginal preparations of tenofovir as pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection have demonstrated variable efficacy in men and women prompting assessment of variation in drug concentration as an explanation. Knowledge of tenofovir concentration and its active form, tenofovir diphosphate, at the putative vaginal and rectal site of action and its relationship to concentrations at multiple other anatomic locations may provide key information for both interpreting PrEP study outcomes and planning future PrEP drug development. Objective MTN-001 was designed to directly compare oral to vaginal steady-state tenofovir pharmacokinetics in blood, vaginal tissue, and vaginal and rectal fluid in a paired cross-over design. Methods and Findings We enrolled 144 HIV-uninfected women at 4 US and 3 African clinical research sites in an open label, 3-period crossover study of three different daily tenofovir regimens, each for 6 weeks (oral 300 mg tenofovir disoproxil fumarate, vaginal 1% tenofovir gel [40 mg], or both). Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p<0.001). Vaginal tissue tenofovir diphosphate was quantifiable in ?90% of women with vaginal dosing and only 19% of women with oral dosing. Vaginal tissue tenofovir diphosphate was ?130-fold higher with vaginal compared to oral dosing (p<0.001). Rectal fluid tenofovir concentrations in vaginal dosing periods were higher than concentrations measured in the oral only dosing period (p<0.03). Conclusions Compared to oral dosing, vaginal dosing achieved much lower serum concentrations and much higher vaginal tissue concentrations. Even allowing for 100-fold concentration differences due to poor adherence or less frequent prescribed dosing, vaginal dosing of tenofovir should provide higher active site concentrations and theoretically greater PrEP efficacy than oral dosing; randomized topical dosing PrEP trials to the contrary indicates that factors beyond tenofovir’s antiviral effect substantially influence PrEP efficacy. Trial Registration ClinicalTrials.gov NCT00592124 PMID:23383037

Hendrix, Craig W.; Chen, Beatrice A.; Guddera, Vijayanand; Hoesley, Craig; Justman, Jessica; Nakabiito, Clemensia; Salata, Robert; Soto-Torres, Lydia; Patterson, Karen; Minnis, Alexandra M.; Gandham, Sharavi; Gomez, Kailazarid; Richardson, Barbra A.; Bumpus, Namandje N.

2013-01-01

123

Morphine, morphine-6-glucuronide and morphine-3-glucuronide pharmacokinetics in newborn infants receiving diamorphine infusions.  

PubMed

1. The pharmacokinetics of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) were studied in 19 ventilated newborn infants (24-41 weeks gestation) who were given a loading dose of 50 micrograms kg-1 or 200 micrograms kg-1 of diamorphine followed by an intravenous infusion of 15 micrograms kg-1 h-1 of diamorphine. Plasma concentrations of morphine, M3G and M6G were measured during the accrual to steady-state and at steady state of the diamorphine infusion. 2. Following both the 50 micrograms kg-1 or 200 micrograms kg-1 loading doses the mean steady-state plasma concentration (+/- s.d.) of morphine, M3G and M6G were 86 +/- 52 ng ml-1, 703 +/- 400 ng ml-1 and 48 +/- 28 ng ml-1 respectively and morphine clearance was found to be 4.6 +/- 3.2 ml min-1 kg-1. 3. M3G formation clearance was estimated to be 2.5 +/- 1.8 ml min-1 kg-1, and the formation clearance of M6G was estimated to be 0.46 +/- 0.32 ml min-1 kg-1. 4. M3G metabolite clearance was 0.46 +/- 0.60 ml min-1 kg-1, the elimination half-life was 11.1 +/- 11.3 h and the volume of distribution was 0.55 +/- 1.13 l kg-1. M6G metabolite clearance was 0.71 +/- 0.36 ml min-1 kg-1, the elimination half-life was 18.2 +/- 13.6 h and the volume of distribution was 1.03 +/- 0.88 l kg-1. 5. No significant effect of the loading dose (50 micrograms kg-1 or 200 micrograms kg-1) on the plasma morphine or metabolite concentrations or their derived pharmacokinetic parameters was found. 6. We were unable to identify correlations between gestational age of the infants and any of the determined pharmacokinetic parameters. 7. M3G: morphine and M6G: morphine steady-state plasma concentration ratios were 11.0 +/- 10.8 and 0.8 +/- 0.8, respectively. 8. The metabolism of morphine in neonates, in terms of the respective contributions of each glucuronide pathway, was similar to that in adults. PMID:8799518

Barrett, D A; Barker, D P; Rutter, N; Pawula, M; Shaw, P N

1996-06-01

124

Morphine, morphine-6-glucuronide and morphine-3-glucuronide pharmacokinetics in newborn infants receiving diamorphine infusions  

PubMed Central

1The pharmacokinetics of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) were studied in 19 ventilated newborn infants(24–41 weeks gestation) who were given a loading dose of 50??g?kg?1 or 200??g?kg?1 of diamorphine followed by an intravenous infusion of 15??g?kg?1?h?1 of diamorphine. Plasma concentrations of morphine, M3G and M6G were measured during the accrual to steady-state and at steady state of the diamorphine infusion. 2Following both the 50??g?kg?1 or 200??g?kg?1 loading doses the mean steady-state plasma concentration (±s.d.) of morphine, M3G and M6G were 86±52?ng?ml?1, 703±400?ng?ml?1 and 48±28?ng?ml?1 respectively and morphine clearance was found to be 4.6±3.2?ml min?1?kg?1. 3M3G formation clearance was estimated to be 2.5±1.8?ml min?1?kg?1, and the formation clearance of M6G was estimated to be 0.46±0.32?ml min?1?kg?1. 4M3G metabolite clearance was 0.46±0.60?ml min?1?kg?1, the elimination half-life was 11.1±11.3?h and the volume of distribution was 0.55±1.13?l?kg?1. M6G metabolite clearance was 0.71±0.36?ml min?1?kg?1, the elimination half-life was 18.2±13.6?h and the volume of distribution was 1.03±0.88?l?kg?1. 5No significant effect of the loading dose (50??g?kg?1 or 200??g?kg?1) on the plasma morphine or metabolite concentrations or their derived pharmacokinetic parameters was found. 6We were unable to identify correlations between gestational age of the infants and any of the determined pharmacokinetic parameters. 7M3G:morphine and M6G:morphine steady-state plasma concentration ratios were 11.0±10.8 and 0.8±0.8, respectively. 8The metabolism of morphine in neonates, in terms of the respective contributions of each glucuronide pathway, was similar to that in adults. PMID:8799518

BARRETT, D. A.; BARKER, D. P.; RUTTER, N.; PAWULA, M.; SHAW, P. N.

1996-01-01

125

Morphine Induces Splenocyte Trafficking into the CNS  

Microsoft Academic Search

Opioids significantly alter functional responses of lymphocytes following activation. The opiate Morphine, alters the Th1\\u000a to Th2 response and modulates functional responses such as cytolytic activity and T-cell proliferation. Although there has\\u000a been extensive research involving morphine’s effects on lymphocytes, little is known about the effects morphine has on lymphocyte\\u000a trafficking. The objective of the study was to use in

Michael Olin; Seunguk Oh; Sabita Roy; Phillip Peterson; Thomas Molitor

126

A clinical evaluation of amlexanox oral adhesive pellicles in the treatment of recurrent aphthous stomatitis and comparison with amlexanox oral tablets: a randomized, placebo controlled, blinded, multicenter clinical trial  

Microsoft Academic Search

BACKGROUND: Amlexanox has been developed as a 5 percent topical oral paste for the treatment of patients with recurrent aphthous stomatitis (RAS) in most European countries. However, it is not yet available in China and has not been generally accepted in clinical treatment. The aim of this study was to explore the effectiveness of amlexanox oral adhesive pellicles in the

Wenxia Meng; Yi Dong; Jie Liu; Zhi Wang; Xiaobo Zhong; Ruiyang Chen; Hongmei Zhou; Mei Lin; Lu Jiang; Feng Gao; Tao Xu; Qianming Chen; Xin Zeng

2009-01-01

127

Reduction of dyskinesia and induction of akinesia induced by morphine in two Parkinsonian patients with severe sciatica  

Microsoft Academic Search

Summary.   In two patients with Parkinson's disease and L-Dopa induced dyskinesia we administered morphine orally to alleviate lumboradicular\\u000a pain unresponsive to any other form of treatment. Besides an alleviation of the pain both patients showed a decrease in dyskinetic\\u000a movements at very low doses of morphine and an increase in akinesia at higher doses. This observation indicates a modulation\\u000a of

D. Berg; G. Becker; K. Reiners

1999-01-01

128

Neuraxial morphine and respiratory depression: finding the right balance.  

PubMed

Morphine is a drug commonly administered via the epidural or intrathecal route, and is regarded by many as the 'gold-standard' single-dose neuraxial opioid due to its postoperative analgesic efficacy and prolonged duration of action. However, respiratory depression is a recognized side effect of neuraxial morphine administered in the perioperative setting. We conducted an extensive review of articles published since 1945 that examine respiratory depression or failure associated with perioperative intrathecal or epidural morphine use. Respiratory depression was previously thought to result from the interaction of opioid in the cerebrospinal fluid with ventral medullary opioid receptors. More recently, the preBötzinger complex located in the medulla has been identified as the site responsible for the decrease in respiratory rate following systemic administration of opioids. Neurons in the preBötzinger complex expressing neurokinin-1 receptors are selectively inhibited by opioids, and therefore are the mediators of opioid-induced respiratory depression. Epidural, intrathecal and plasma pharmacokinetics of opioids are complex, vary between neuraxial compartments, and can even differ within the epidural space itself depending upon level of insertion. Caution should be exercised when prescribing systemic opioids (intravenous or oral) in addition to neuraxial morphine as this can compound the potential for early or delayed respiratory depression. There is a wide range of incidences for respiratory depression following neuraxial morphine in a perioperative setting. Disparity of definitions used for the diagnosis of respiratory depression in the literature precludes identification of the exact incidence of this rare event. The optimal neuraxial opioid dose is a balance between the conflicting demands of providing optimal analgesia while minimizing dose-related adverse effects. Dose-response studies show that neuraxial morphine appears to have an analgesic efficacy 'ceiling'. The optimal 'single-shot' intrathecal dose appears to be 0.075-0.15 mg and the ideal 'single-shot' epidural morphine dose is 2.5-3.75 mg. Analgesic efficacy studies have not been adequately powered to show differences in the incidence of clinically significant respiratory depression. Opioid antagonists such as naloxone to prevent or treat opioid-induced respiratory depression have a number of limitations. Researchers have recently focused on non-opioid drugs such as serotonin receptor agonists. Early evidence suggests that ampakine (?-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid [AMPA]) receptor modulators may be effective at reducing opioid-induced respiratory depression while maintaining analgesia. Sodium/proton exchanger type 3 (NHE3) inhibitors, which act centrally on respiratory pathways, also warrant further study. PMID:21942973

Sultan, Pervez; Gutierrez, Maria Cristina; Carvalho, Brendan

2011-10-01

129

[Modern polymers in matrix tablets technology].  

PubMed

Matrix tablets are the most popular method of oral drug administration, and polymeric materials have been used broadly in matrix formulations to modify and modulate drug release rate. The main goal of the system is to extend drug release profiles to maintain a constant in vivo plasma drug concentration and a consistent pharmacological effect. Polymeric matrix tablets offer a great potential as oral controlled drug delivery systems. Cellulose derivatives, like hydroxypropyl methylcellulose (HPMC) are often used as matrix formers. However, also other types of polymers can be used for this purpose including: Kollidon SR, acrylic acid polymers such as Eudragits and Carbopols. Nevertheless, polymers of natural origin like: carragens, chitosan and alginates widely used in the food and cosmetics industry are now coming to the fore of pharmaceutical research and are used in matrix tablets technology. Modern polymers allow to obtain matrix tablets by 3D printing, which enables to develop new formulation types. In this paper, the polymers used in matrix tablets technology and examples of their applications were described. PMID:25739125

Zimmer, ?ukasz; Kasperek, Regina; Poleszak, Ewa

2014-01-01

130

Gabapentin attenuates morphine tolerance through interleukin-10.  

PubMed

In this study, we examined the anti-inflammatory mechanism by which gabapentin attenuates morphine tolerance in rats. Gabapentin enhanced the antinociceptive effect of morphine and attenuated chronic morphine tolerance when administered intrathecally with morphine in naive rats. We found that a 7-day chronic intrathecal injection of morphine increased the expression of proinflammatory cytokines and decreased interleukin-10 (IL-10) levels in the rat spinal cord. These changes were minimized when gabapentin was combined with morphine. In addition, the effects of gabapentin were reversed by coadministration of the anti-IL-10 antibody. Our findings indicate that enhancement of the antinociceptive effect of morphine by gabapentin may occur through upregulation of the anti-inflammatory cytokine IL-10 and inhibition of proinflammatory cytokines in the rat spinal cord. PMID:24247277

Bao, Yu-Hua; Zhou, Quan-Hong; Chen, Rui; Xu, Hao; Zeng, Lulu; Zhang, Xin; Jiang, Wei; Du, Dongping

2014-01-22

131

Delayed-Release Oral Mesalamine at 4.8 g\\/day (800 mg tablet) for the Treatment of Moderately Active Ulcerative Colitis: The ASCEND II Trial  

Microsoft Academic Search

BACKGROUND AND AIMS:Preliminary data have shown that delayed release oral mesalamine (Asacol®) dosed at 4.8 g\\/day provided additional efficacy benefit compared to 1.6 g\\/day in patients with mildly to moderately active ulcerative colitis. Additionally, Asacol dosed at 2.4 g\\/day has been proved to be more effective than 1.6 g\\/day. Whether 4.8 g\\/day of mesalamine (dosed with an investigational 800 mg

Stephen B. Hanauer; William J. Sandborn; Asher Kornbluth; Seymour Katz; Michael Safdi; Scott Woogen; Gino Regalli; Chyon Yeh; Nancy Smith-Hall; Funmilay Ajayi

2005-01-01

132

Low-dose oral immunization with lyophilized tissue of herbicide-resistant lettuce expressing hepatitis B surface antigen for prototype plant-derived vaccine tablet formulation  

Microsoft Academic Search

Efficient immunization against hepatitis B virus (HBV) and other pathogens with plant-based oral vaccines requires appropriate plant expressors and the optimization of vaccine compositions and administration protocols. Previous immunization studies were mainly based on a combination of the injection of a small surface antigen of HBV (S-HBsAg) and the feeding with raw tissue contain- ing the antigen, supplemented with an

Tomasz Pniewski; Józef Kapusta; Piotr Boci?g; Jacek Wojciechowicz; Anna Kostrzak; Micha? Gdula; Olga Fedorowicz-Stro?ska; Piotr Wójcik; Halina Otta; S?awomir Samardakiewicz; Bogdan Wolko; Andrzej P?ucienniczak

2011-01-01

133

A paper-based lateral flow assay for morphine.  

PubMed

Morphine was used as a model analyte to examine the possibility of using cellulose, physically modified by papermaking and converting techniques, as a capillary matrix in a lateral flow type of diagnostic assay. This research was directed toward low-cost, disposable, and portable paper-based diagnostics, with the aim of addressing the analytical performance of paper as a substrate in the analysis for drugs of abuse. Antibody Fab fragments were used as sensing molecules, and gold nanoparticle detection was employed. Inkjet printing was used to pattern sensing biomolecules as detection zones on paper. To validate the usefulness of paper as a diagnostic platform, the principle of a direct sandwich assay, based on immunocomplex formation between morphine and the anti-morphine Fab fragment and detection of the formed immunocomplex by another Fab fragment, was implemented. Results were compared with that achieved by using nitrocellulose as a reference material. Possible interfering from the sample matrix on assay quality was investigated with spiked oral fluid samples. Under optimized conditions, a visually assessed limit of detection for the sandwich assay was 1 ng/mL, indicating that the paper-based test devices developed in this work can perform screening for drugs of abuse and can fulfill the requirement for a sensitive assay in diagnostically relevant ranges. PMID:25023970

Teerinen, Tuija; Lappalainen, Timo; Erho, Tomi

2014-09-01

134

Attenuation of morphine analgesic tolerance by rosuvastatin in naïve and morphine tolerance rats.  

PubMed

Recent studies suggested that statins have anti-inflammatory effects beyond their lipid-lowering properties. Since inflammation in the central nervous system was highly related to morphine tolerance, we sought to investigate whether statins could affect morphine tolerance by mediating glia-derived proinflammatory cytokines secretion. We have undertaken two separate studies: Firstly, we determined the effect of rosuvastatin on naïve rats during induction of morphine tolerance. Secondly, we investigated whether rosuvastation could attenuate the morphine analgesic tolerance in rats that the morphine tolerance established previously. Results demonstrated that peroral rosuvastatin not only delays, but also partially reverses the tolerance to morphine analgesia in rats. The administration of rosuvastatin during induction of morphine tolerance attenuated the activation of ERK and the release of proinflammatory cytokines in the lumbar spinal cord. Similar outcomes were observed in rats were morphine tolerance was established previously. Moreover, our study also found that repeated administration of morphine could activate the astrocytes in the spinal cord while rosuvastation succeeds in suppressing the activation of astrocytes. Our results support the idea that targeting glia-derived proinflammatory effects during morphine treatment is a novel and clinically promising method for enhancing analgesic effects of morphine. We identify a potential new application of statins in the treatment of morphine analgesic tolerance. PMID:25261133

Li, Yongle; Shu, Yinyin; Ji, Qing; Liu, Jian; He, Xiaoyun; Li, Weiyan

2015-02-01

135

Morphine, the Proteus of organic molecules.  

PubMed

This feature article encapsulates the senior author's longstanding interests in opiate chemistry and attempts to place it within an historical context and against the backdrop of related work by others who have viewed morphine as one of the pinnacles of natural product synthesis. Biomimetic and 'bioanalogous' routes to the morphine skeleton are discussed followed by approaches based on the elaboration of phenanthrene platforms. The latter include an asymmetric synthesis of ent-morphine developed in our laboratory. PMID:12109065

Blakemore, Paul R; White, James D

2002-06-01

136

Simultaneous determination of six hydrophilic components in rat plasma after oral administration of Jitai tablet by liquid chromatography-electrospray ionization-tandem mass spectrometry: application to a pharmacokinetic study.  

PubMed

A liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for the simultaneous determination of amygdalin (ADL), danshensu (DSS), ferulic acid (FA), hydroxysafflor yellow A (HSYA), salvianolic acid A (SAA) and salvianolic acid B (SAB) in rat plasma. Plasma samples were pretreated by protein precipitation with acetonitrile. LC separation was performed on a Zorbax Eclipse Plus C18 column (3.0mm×100mm I.D, 1.8?m) with gradient elution using a mobile phase consisting of acetonitrile-0.1% formic acid in water at a flow rate of 0.3mL/min. ESI-MS spectra was acquired in negative ion multiple reaction monitoring mode. The mass transition ion-pair was followed as m/z 456.0?323.1, m/z 197.3?178.8, m/z 193.0?133.9, m/z 611.1?325.2, m/z 493.0?295.0, and m/z 717.0?519.0 for ADL, DSS, FA, HSYA, SAA and SAB, respectively. All analytes showed good linearity over a wide concentration range (r>0.99). The lower limit of quantification was 7ng/mL, 2ng/mL, 4ng/mL, 1ng/mL, 2ng/mL, and 4ng/mL for ADL, DSS, FA, HSYA, SAA and SAB, respectively. The mean recovery of the analytes ranged from 86.29% to 93.16%. The intra- and inter-day precisions were in the range of 1.50-9.98% and the accuracies were between 91.17% and 99.46%. The validated method was successfully applied to a pharmacokinetic study of the six hydrophilic components in rat plasma after oral administration of Jitai tablet. PMID:23261824

Wang, Shu-Ping; Liu, Lei; Wang, Ling-Ling; Jiang, Peng; Xiang, Li; Zhang, Wei-Dong; Liu, Run-Hui

2013-01-01

137

Redesign of a Dioxygenase in Morphine Biosynthesis  

E-print Network

Opium poppy (Papaver somniferum) produces medicinally important benzylisoquinoline alkaloids, including the analgesics codeine and morphine, in the morphinan pathway. We aligned three dioxygenases that were recently ...

Runguphan, Weerawat

138

Novel approach of aceclofenac fast dissolving tablet.  

PubMed

Fast disintegrating tablets (FDTs) have received ever increasing demand during the last decade, and the ?eld has become a hastily growing area in the pharmaceutical industry. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. Aceclofenac, an NSAID, has been recommended orally for the treatment of bone and connective tissue disorder and thus the formulation of the same resulted in development of several FDT technologies. The present aim is to formulate a tablet which disintegrate and dissolve rapidly and give its rapid onset of action: analgesic, antipyretic and anti-inflammatory action. Besides, the conventional tablets also show poor patient compliance an attempt had been made to formulate for FDT of aceclofenac by using various super disintegrants like sodium starch glycolate, croscarmellose sodium and crosspovidone (polyplasdone XL) and PEG 6000 followed by novel technique. The tablets were evaluated for friability, hardness, weight variation, disintegration time, wetting time, in vitro dissolution studies and drug content studies. It was concluded that the batch which was prepared by using combination of crosspovidone and sodium starch glycolate as a super disintegrant shows excellent disintegration time, enhance dissolution rate, taste masking and hence lead to improve efficacy and bioavailability of drug. PMID:25553683

Dave, Vivek; Yadav, Sachdev; Sharma, Swapnil; Vishwakarma, Pushpendra; Ali, Nasir

2015-01-01

139

Delay of Morphine Tolerance by Palmitoylethanolamide  

PubMed Central

In spite of the potency and efficacy of morphine, its clinical application for chronic persistent pain is limited by the development of tolerance to the antinociceptive effect. The cellular and molecular mechanisms underlying morphine tolerance are complex and still unclear. Recently, the activation of glial cells and the release of glia-derived proinflammatory mediators have been suggested to play a role in the phenomenon. N-Palmitoylethanolamine (PEA) is an endogenous compound with antinociceptive effects able to reduce the glial activation. On this basis, 30?mg?kg?1 PEA was subcutaneously daily administered in morphine treated rats (10?mg?kg?1 intraperitoneally, daily). PEA treatment significantly attenuated the development of tolerance doubling the number of days of morphine antinociceptive efficacy in comparison to the vehicle + morphine group. PEA prevented both microglia and astrocyte cell number increase induced by morphine in the dorsal horn; on the contrary, the morphine-dependent increase of spinal TNF-? levels was not modified by PEA. Nevertheless, the immunohistochemical analysis revealed significantly higher TNF-? immunoreactivity in astrocytes of PEA-protected rats suggesting a PEA-mediated decrease of cytokine release from astrocyte. PEA intervenes in the nervous alterations that lead to the lack of morphine antinociceptive effects; a possible application of this endogenous compound in opioid-based therapies is suggested.

Di Cesare Mannelli, Lorenzo; Corti, Francesca; Micheli, Laura; Zanardelli, Matteo; Ghelardini, Carla

2015-01-01

140

Delay of morphine tolerance by palmitoylethanolamide.  

PubMed

In spite of the potency and efficacy of morphine, its clinical application for chronic persistent pain is limited by the development of tolerance to the antinociceptive effect. The cellular and molecular mechanisms underlying morphine tolerance are complex and still unclear. Recently, the activation of glial cells and the release of glia-derived proinflammatory mediators have been suggested to play a role in the phenomenon. N-Palmitoylethanolamine (PEA) is an endogenous compound with antinociceptive effects able to reduce the glial activation. On this basis, 30?mg?kg(-1) PEA was subcutaneously daily administered in morphine treated rats (10?mg?kg(-1) intraperitoneally, daily). PEA treatment significantly attenuated the development of tolerance doubling the number of days of morphine antinociceptive efficacy in comparison to the vehicle + morphine group. PEA prevented both microglia and astrocyte cell number increase induced by morphine in the dorsal horn; on the contrary, the morphine-dependent increase of spinal TNF-? levels was not modified by PEA. Nevertheless, the immunohistochemical analysis revealed significantly higher TNF-? immunoreactivity in astrocytes of PEA-protected rats suggesting a PEA-mediated decrease of cytokine release from astrocyte. PEA intervenes in the nervous alterations that lead to the lack of morphine antinociceptive effects; a possible application of this endogenous compound in opioid-based therapies is suggested. PMID:25874232

Di Cesare Mannelli, Lorenzo; Corti, Francesca; Micheli, Laura; Zanardelli, Matteo; Ghelardini, Carla

2015-01-01

141

Morphine Induces Desensitization of Insulin Receptor Signaling  

Microsoft Academic Search

between the MOR and the insulin receptor (IR) signaling cascades. We show that prolonged morphine exposure of cell lines expressing endogenous or transfected MOR, IR, and the insulin substrate 1 (IRS-1) protein specifically desensitizes IR signaling to Akt and ERK cascades. Morphine caused serine phosphory- lation of the IR and impaired the formation of the signaling complex among the IR,

Yu Li; Shoshana Eitan; Jiong Wu; Christopher J. Evans; Brigitte Kieffer; Xiaojian Sun; Roberto D. Polakiewicz

2003-01-01

142

Intravenous morphine pharmacokinetics in pediatric patients with sickle cell disease  

Microsoft Academic Search

To examine the pharmacokinetics of parenteral opioids, such as morphine, in patients with sickle cell disease, we determined the plasma morphine clearances in 18 patients (aged 6 to 19 years) who were receiving continuous intravenous infusions, and the pharmacokinetics of morphine in an additional six patients after single intravenous doses. Plasma morphine clearances ranged from 6.2 to 59.1 ml min-

Carlton D. Dampier; B. N. Y. Setty; Joann Logan; Jacqueline G. Ioli; Roger Dean

1995-01-01

143

Teaching with Tablet PC's  

Microsoft Academic Search

Tablet PC's are traditional notebook computers with the ability to process digital ink by writing with a stylus. They have recently attracted attention as a potential tool for educational use. This paper describes the author's experience using the Tablet PC to conduct a CS1 course and a software engineering (SWE) course. The SWE course consisted primarily of PowerPoint lectures while

Kenrick Mock

2004-01-01

144

Stable polymorph of morphine1  

PubMed Central

In the stable polymorph of the title compound, C17H19NO3 [systematic name: (5?,6?)-7,8-didehydro-4,5-ep­oxy-17-methyl­morphinan-3,6-diol], the mol­ecular conformation is in agreement with the characteristics of previously reported morphine forms. The molecule displays the typical T-shape and its piperidine ring adopts a slightly distorted chair conformation. Inter­molecular O—H?O hydrogen bonds link the mol­ecules into helical chains parallel to the b axis. Intra­molecular O—H?O hydrogen bonds are also observed. PMID:23476407

Gelbrich, Thomas; Braun, Doris E.; Griesser, Ulrich J.

2013-01-01

145

Photoaffinity labeling of opioid receptor with morphine-7,8-oxide (morphine epoxide)  

SciTech Connect

The opioid receptor mediating inhibitory action of morphine in the electrically stimulated guinea pig ileum was irreversibly photoinactivated by morphine epoxide (3 X 10(-6) M). Morphine epoxide (up to 3 X 10(-5) M) did not influence the responses of rat vas deferens (epsilon-receptor) or rabbit vas deferens (kappa-receptor) to electrical stimulation. Effective concentrations of morphine epoxide were much lower in the guinea pig ileum (mu-receptor) than in the mouse vas deference (delta-receptor). The inhibitory action of (Met)-enkephalin on the twitch responses of the rat vas deferens and mouse vas deferens to electrical stimulation were not influenced after irradiation in the presence of morphine epoxide (3 X 10(-6) M). Therefore, morphine epoxide is probably a useful probe for photoaffinity labeling of the mu-receptor in vitro.

Takayanagi, I.; Shibata, R.; Miyata, N.; Hirobe, M.

1982-05-01

146

Morphine effects on striatal transcriptome in mice  

PubMed Central

Background Chronic opiate use produces molecular and cellular adaptations in the nervous system that lead to tolerance, physical dependence, and addiction. Genome-wide comparison of morphine-induced changes in brain transcription of mouse strains with different opioid-related phenotypes provides an opportunity to discover the relationship between gene expression and behavioral response to the drug. Results Here, we analyzed the effects of single and repeated morphine administrations in selected inbred mouse strains (129P3/J, DBA/2J, C57BL/6J, and SWR/J). Using microarray-based gene expression profiling in striatum, we found 618 (false discovery rate < 1%) morphine-responsive transcripts. Through ontologic classification, we linked particular sets of genes to biologic functions, including metabolism, transmission of nerve impulse, and cell-cell signaling. We identified numerous novel morphine-regulated genes (for instance, Olig2 and Camk1g), and a number of transcripts with strain-specific changes in expression (for instance, Hspa1a and Fzd2). Moreover, transcriptional activation of a pattern of co-expressed genes (for instance, Tsc22d3 and Nfkbia) was identified as being mediated via the glucocorticoid receptor (GR). Further studies revealed that blockade of the GR altered morphine-induced locomotor activity and development of physical dependence. Conclusion Our results indicate that there are differences between strains in the magnitude of transcriptional response to acute morphine treatment and in the degree of tolerance in gene expression observed after chronic morphine treatment. Using whole-genome transcriptional analysis of morphine effects in the striatum, we were able to reveal multiple physiological factors that may influence opioid-related phenotypes and to relate particular gene networks to this complex trait. The results also suggest the possible involvement of GR-regulated genes in mediating behavioral response to morphine. PMID:17598886

Korostynski, Michal; Piechota, Marcin; Kaminska, Dorota; Solecki, Wojciech; Przewlocki, Ryszard

2007-01-01

147

Comparison of Echinacea alkylamide pharmacokinetics between liquid and tablet preparations.  

PubMed

The relative oral bioavailability of alkylamides from two different Echinacea dosage forms (liquid and tablet) were compared in a small two-way crossover study in humans (n=3). The liquid preparation investigated contained a mixture of Echinacea purpurea root (300 mg/ml) and Echinacea angustifolia root (200 mg/ml) extracted in 60% ethanol. The tablet preparation investigated was also a mixture of E. purpurea root (675 mg/tablet) and E. angustifolia root (600 mg/tablet), but was prepared from the dried 60% ethanolic extracts of these two Echinacea species. Alkylamides were found to be rapidly absorbed and measurable in plasma from both preparations. No significant differences in the tetraene alkylamide pharmacokinetic parameters for T(1/2), AUC(t-lin) and C(max) in the two different preparations were found. T(max) increased from 20 min for the liquid to 30 min for the tablet, which is not unexpected as the tablet required time for disintegration before absorption could occur. These results suggested that there was no significant difference in the bioavailability of alkylamides from the liquid and tablet Echinacea formulations. Furthermore, the results also indicated that the absorption site and any alkylamide loss due to digestive processes were similar in both preparations. PMID:17289362

Matthias, A; Addison, R S; Agnew, L L; Bone, K M; Watson, K; Lehmann, R P

2007-09-01

148

Fast disintegrating tablets: Opportunity in drug delivery system  

PubMed Central

Fast disintegrating tablets (FDTs) have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. Oral drug delivery remains the preferred route for administration of various drugs. Recent developments in the technology have prompted scientists to develop FDTs with improved patient compliance and convenience. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. The popularity and usefulness of the formulation resulted in development of several FDT technologies. FDTs are solid unit dosage forms, which disintegrate or dissolve rapidly in the mouth without chewing and water. FDTs or orally disintegrating tablets provide an advantage particularly for pediatric and geriatric populations who have difficulty in swallowing conventional tablets and capsules. This review describes various formulations and technologies developed to achieve fast dissolution/dispersion of tablets in the oral cavity. In particular, this review describes in detail FDT technologies based on lyophilization, molding, sublimation, and compaction, as well as approaches to enhancing the FDT properties, such as spray drying and use of disintegrants. In addition, taste-masking technologies, experimental measurements of disintegration times, and dissolution are also discussed. PMID:22247889

Parkash, Ved; Maan, Saurabh; Deepika; Yadav, Shiv Kumar; Hemlata; Jogpal, Vikas

2011-01-01

149

Calcification prevention tablets  

NASA Technical Reports Server (NTRS)

Citric acid tablets, which slowly release citric acid when flushed with water, are under development by the Navy for calcification prevention. The citric acid dissolves calcium carbonate deposits and chelates the calcium. For use in urinals, a dispenser is not required because the tablets are non-toxic and safe to handle. The tablets are placed in the bottom of the urinal, and are consumed in several hundred flushes (the release rate can be tailored by adjusting the formulation). All of the ingredients are environmentally biodegradable. Mass production of the tablets on commercial tableting machines was demonstrated. The tablets are inexpensive (about 75 cents apiece). Incidences of clogged pipes and urinals were greatly decreased in long term shipboard tests. The corrosion rate of sewage collection pipe (90/10 Cu/Ni) in citric acid solution in the laboratory is several mils per year at conditions typically found in traps under the urinals. The only shipboard corrosion seen to date is of the yellow brass urinal tail pieces. While this is acceptable, the search for a nontoxic corrosion inhibitor is underway. The shelf life of the tablets is at least one year if stored at 50 percent relative humidity, and longer if stored in sealed plastic buckets.

Lindsay, Geoffrey A.; Hasting, Michael A.; Gustavson, Michael A.

1991-01-01

150

[Afobazole influence on antinociceptive properties of morphine].  

PubMed

The effects of afobazole (1.0 and 10.0 mg/kg, i.p.) on the antinociceptive properties of morphine (3.0 mg/kg, i.p.) were studied in mice. It is shown that afobazole attenuates the analgesic action of morphine in the "hot plate" and "tail flick" tests. This effect was prevented by sigma 1 receptor antagonist haloperidol (2.0 mg/kg, i.p.). Data obtained suggested that a decrease in the morphine antinociceptive action by afobazole is related to its agonistic interaction with sigma 1 receptors at supraspinal and spinal levels. PMID:19334506

Kolik, L G; Zhukov, V N; Seredenin, S B

2009-01-01

151

Chronic morphine drinking establishes morphine tolerance, but not addiction in Wistar rats  

Microsoft Academic Search

Objective  Some animal models apply morphine in the drinking water to generate addiction, but related reports are not free of conflicting\\u000a results. Accordingly, this study aimed to figure out if chronic consumption of morphine in the drinking water can induce morphine\\u000a addiction in Wistar rats.\\u000a \\u000a \\u000a \\u000a Methods  For 3 weeks, the animals received a daily morphine dose of 35 mg\\/kg by offering a

Ralf Binsack; Ming-lan Zheng; Zhan-sai Zhang; Liu Yang; Yong-ping Zhu

2006-01-01

152

Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts.  

PubMed

This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest. PMID:23839029

Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

2013-09-01

153

Biopharmaceutical evaluation of new slow release tablets obtained by hot tableting of coated pellets with tramadol hydrochloride.  

PubMed

This study was aimed at a biopharmaceutical evaluation of a new oral dosage form of tramadol hydrochloride (TH)--slow release tablets obtained by hot tableting of coated pellets, 100 mg (TP), compared to the conventional slow release tablets, Tramal Retard, 100 mg (TR). Both TP and TR formulations showed a similar release profile of TH (f2 was 71) in in vitro release studies. The in vivo study was a two-treatment, two-period, two-sequence, single-oral dose 100 mg, crossover design using rabbit model with the phases separated by a washout period of 14 days. It was shown that the amount of TH absorbed into the systemic circulation is similar for TP and TR (the 90% confidence intervals for the AUC(0-1), AUC(0-infinity) and ratios were 85-122 and 92-107%, respectively). However, after administration of slow release tablets obtained by hot tableting of coated pellets, a prolonged absorption and elimination processes and a smoother and more extended plasma profile of TH were observed. It can be assumed that the use of a new oral dosage form of TH in patients affects the extension of analgesia after single administration of the drug, with its gradual absorption into the systemic circulation. PMID:25362810

Szkutnik-Fiedler, Danuta; Sawicki, Wies?aw; Balcerkiewicz, Monika; Mazgalski, Jaros?aw; Grabowski, Tomasz; Grze?kowiak, Edmund

2014-01-01

154

Oral calcitonin  

PubMed Central

Calcitonin is a hormone secreted by the C-cells of the thyroid gland in response to elevations of the plasma calcium level. It reduces bone resorption by inhibiting mature active osteoclasts and increases renal calcium excretion. It is used in the management of postmenopausal osteoporosis, Paget’s disease of bone, and malignancy-associated hypercalcemia. Synthetic and recombinant calcitonin preparations are available; both have similar pharmacokinetic and pharmacodynamic profiles. As calcitonin is a peptide, the traditional method of administration has been parenteral or intranasal. This hinders its clinical use: adherence with therapy is notoriously low, and withdrawal from clinical trials has been problematic. An oral formulation would be more attractive, practical, and convenient to patients. In addition to its effect on active osteoclasts and renal tubules, calcitonin has an analgesic action, possibly mediated through ?-endorphins and the central modulation of pain perception. It also exerts a protective action on cartilage and may be useful in the management of osteoarthritis and possibly rheumatoid arthritis. Oral formulations of calcitonin have been developed using different techniques. The most studied involves drug-delivery carriers such as Eligen® 8-(N-2hydroxy-5-chloro-benzoyl)-amino-caprylic acid (5-CNAC) (Emisphere Technologies, Cedar Knolls, NJ). Several factors affect the bioavailability and efficacy of orally administered calcitonin, including amount of water used to take the tablet, time of day the tablet is taken, and proximity to intake of a meal. Preliminary results looked promising. Unfortunately, in two Phase III studies, oral calcitonin (0.8 mg with 200 mg 5-CNAC, once a day for postmenopausal osteoporosis and twice a day for osteoarthritis) failed to meet key end points, and in December 2011, Novartis Pharma AG announced that it would not pursue further clinical development of oral calcitonin for postmenopausal osteoporosis or osteoarthritis. A unique feature of calcitonin is that it is able to uncouple bone turnover, reducing bone resorption without affecting bone formation and therefore increasing bone mass and improving bone quality. This effect, however, may be dose-dependent, with higher doses inhibiting both resorption and formation. Because so many factors affect the pharmacokinetics and pharmacodynamics of calcitonin, especially orally administered calcitonin, much work remains to be done to explore the full pharmacologic spectrum and potential of calcitonin and determine the optimum dose and timing of administration, as well as water and food intake. PMID:23071417

Hamdy, Ronald C; Daley, Dane N

2012-01-01

155

21 CFR 520.2150b - Stanozolol chewable tablets.  

Code of Federal Regulations, 2014 CFR

...b) Sponsor. No. 000009 in § 510.600(c) of this chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs. (2) Administered orally to small breeds of dogs, 1/2 to 1 tablet twice daily for...

2014-04-01

156

21 CFR 520.2150b - Stanozolol chewable tablets.  

Code of Federal Regulations, 2011 CFR

...b) Sponsor. No. 000009 in § 510.600(c) of this chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs. (2) Administered orally to small breeds of dogs, 1/2 to 1 tablet twice daily for...

2011-04-01

157

21 CFR 520.2150b - Stanozolol chewable tablets.  

Code of Federal Regulations, 2010 CFR

...b) Sponsor. No. 000009 in § 510.600(c) of this chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs. (2) Administered orally to small breeds of dogs, 1/2 to 1 tablet twice daily for...

2010-04-01

158

21 CFR 520.2150b - Stanozolol chewable tablets.  

Code of Federal Regulations, 2013 CFR

...b) Sponsor. No. 000009 in § 510.600(c) of this chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs. (2) Administered orally to small breeds of dogs, 1/2 to 1 tablet twice daily for...

2013-04-01

159

21 CFR 520.2150b - Stanozolol chewable tablets.  

Code of Federal Regulations, 2012 CFR

...b) Sponsor. No. 000009 in § 510.600(c) of this chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs. (2) Administered orally to small breeds of dogs, 1/2 to 1 tablet twice daily for...

2012-04-01

160

Morphine and codeine concentrations in human urine following controlled poppy seeds administration of known opiate content.  

PubMed

Opiates are an important component for drug testing due to their high abuse potential. Proper urine opiate interpretation includes ruling out poppy seed ingestion; however, detailed elimination studies after controlled poppy seed administration with known morphine and codeine doses are not available. Therefore, we investigated urine opiate pharmacokinetics after controlled oral administration of uncooked poppy seeds with known morphine and codeine content. Participants were administered two 45 g oral poppy seed doses 8 h apart, each containing 15.7 mg morphine and 3mg codeine. Urine was collected ad libitum up to 32 h after the first dose. Specimens were analyzed with the Roche Opiates II immunoassay at 2000 and 300 ?g/L cutoffs, and the ThermoFisher CEDIA(®) heroin metabolite (6-acetylmorphine, 6-AM) and Lin-Zhi 6-AM immunoassays with 10 ?g/L cutoffs to determine if poppy seed ingestion could produce positive results in these heroin marker assays. In addition, all specimens were quantified for morphine and codeine by GC/MS. Participants (N=22) provided 391 urine specimens over 32 h following dosing; 26.6% and 83.4% were positive for morphine at 2000 and 300 ?g/L GC/MS cutoffs, respectively. For the 19 subjects who completed the study, morphine concentrations ranged from <300 to 7522 ?g/L with a median peak concentration of 5239 ?g/L. The median first morphine-positive urine sample at 2000 ?g/L cutoff concentration occurred at 6.6 h (1.2-12.1), with the last positive from 2.6 to 18 h after the second dose. No specimens were positive for codeine at a cutoff concentration of 2000 ?g/L, but 20.2% exceeded 300 ?g/L, with peak concentrations of 658 ?g/L (284-1540). The Roche Opiates II immunoassay had efficiencies greater than 96% for the 2000 and 300 ?g/L cutoffs. The CEDIA 6-AM immunoassay had a specificity of 91%, while the Lin-Zhi assay had no false positive results. These data provide valuable information for interpreting urine opiate results. PMID:24887324

Smith, Michael L; Nichols, Daniel C; Underwood, Paula; Fuller, Zachary; Moser, Matthew A; LoDico, Charles; Gorelick, David A; Newmeyer, Matthew N; Concheiro, Marta; Huestis, Marilyn A

2014-08-01

161

Development of fixed dose combination tablets containing zidovudine and lamivudine for paediatric applications.  

PubMed

In view of the lack of suitable paediatric antiretroviral formulations on the market, a novel fixed dose combination (FDC) tablet containing 300mg zidovudine (AZT) and 160mg lamivudine (3TC) was developed to improve dosing accuracy and allow flexible drug dosing in function of the body weight of paediatric HIV patients as recommended by WHO. Rectangular tablets with multiple fraction bars were designed and each tablet can be broken into 8 subunits, each subunit containing a drug dose corresponding to a body weight of 5kg. These fast-disintegrating subunits can easily be administered to children after dispersion in a liquid or mixing with food. In vitro quality control of the FDC tablets was determined and a crossover bioavailability study using 18 adult volunteers was performed after oral administration of the novel FDC tablet and a Duovir tablet. The results of the study showed that the novel tablets as well as its subunits disintegrated fast (<20s). After 30min dissolution, AZT and 3TC released from Duovir and the novel tablets was above 95%, the similarity factors f2 were above 50 for both AZT and 3TC. A tablet breakability test showed low weight variability (125.1+/-5mg, R.S.D.=4.4%), with limited weight loss (0.3%). There was no significant difference in pharmacokinetic parameters (C(max), t(max) and AUC(0-12h) values) between Duovir and the novel tablets formulated for paediatric applications. PMID:19059324

Kayitare, E; Vervaet, C; Ntawukulilyayo, J D; Seminega, B; Bortel, Van; Remon, J P

2009-03-31

162

A morphine conjugate vaccine attenuates the behavioral effects of morphine in rats  

PubMed Central

Vaccines for opioid dependence may provide a treatment that would reduce or slow the distribution of the drug to brain, thus reducing the drug's reinforcing effects. We tested whether a conjugate vaccine against morphine (keyhole limpet hemocyanin-6-succinylmorphine; KLH-6-SM) administered to rats would produce antibodies and show specificity for morphine or other heroin metabolites. The functional effects of the vaccine were tested with antinociceptive and conditioned place preference (CPP) tests. Rats were either vaccinated with KLH-6-SM and received two boosts 3 and 16 weeks later or served as controls and received KLH alone. Anti-morphine antibodies were produced in vaccinated rats; levels increased and were sustained at moderate levels through 24 weeks. Antibody binding was inhibited by free morphine and other heroin metabolites as demonstrated by competitive inhibition ELISA. Vaccinated rats showed reduced morphine CPP, tested during weeks 4 to 6, and decreased antinociceptive responses to morphine, tested at week 7. Brain morphine levels, assessed using gas-chromatography coupled to mass spectrometry (GC–MS) on samples obtained at 26 weeks, were significantly lower in vaccinated rats. This suggests that morphine entry into the brain was reduced or slowed. These results provide support for KLH-6-SM as a candidate vaccine for opioid dependence. PMID:23739535

Kosten, Therese A.; Shen, Xiaoyun Y.; O'Malley, Patrick W.; Kinsey, Berma M.; Lykissa, Ernest D.; Orson, Frank M.; Kosten, Thomas R.

2013-01-01

163

Microstructural investigation of tablet compaction and tablet pharmacological properties  

E-print Network

In current tablet manufacturing processes, there is a knowledge gap concerning material transformation and the subsequent impact on tablet properties; this gap presents a barrier to rational formulation / process design. ...

Mao, Kangyi

2010-01-01

164

3D simulation of internal tablet strength during tableting.  

PubMed

This study presents a new approach to model powder compression during tableting. The purpose of this study is to introduce a new discrete element simulation model for particle-particle bond formation during tablet compression. This model served as the basis for calculating tablet strength distribution during a compression cycle. Simulated results were compared with real tablets compressed from microcrystalline cellulose/theophylline pellets with various compression forces. Simulated and experimental compression forces increased similarly. Tablet-breaking forces increased with the calculated strengths obtained from the simulations. The calculated bond strength distribution inside the tablets showed features similar to those of the density and pressure distributions in the literature. However, the bond strength distributions at the center of the tablets varied considerably between individual tablets. PMID:21541828

Siiriä, Simo Matti; Antikainen, Osmo; Heinämäki, Jyrki; Yliruusi, Jouko

2011-06-01

165

21 CFR 862.3640 - Morphine test system.  

Code of Federal Regulations, 2010 CFR

...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3640 Morphine test system. (a) Identification. A morphine...

2010-04-01

166

Preparation, characterization and tableting of cilnidipine solid dispersions.  

PubMed

Solid dispersion technique has been developed many years for improving solubility of water-insoluble drugs, aiming to achieve a better oral bioavailability. However, this technique exhibits many inconveniences when used for large-scale tableting procedures. The objective of current research work was to develop cilnidipine solid dispersions (SDs) to improve the dissolution behaviors of this water-insoluble drug. Moreover, an innovative granulation method was designed to simplify the traditional tableting technology used in solid dispersion technique. Three different kinds of polymers, polyethylene glycol (PEG), polyvinylpyrrolidone (PVP) and poloxamer, were used as carriers to prepare solid dispersions. The interactions in the solid state were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and FT-IR spectroscopy. The designed granulation method was employed to prepare solid dispersion tablets and the formulation was optimized through investigating the dissolution behaviors. The results indicated PEG solid dispersion showed the best effect both on physical characterizations and dissolution studies. Furthermore, all type of solid dispersions significantly improved the dissolution rates when compared to pure drug and its corresponding physical mixture (PM). The solid dispersion tablets prepared in simplified tableting method exhibited better operability, stability and dissolution behavior than the tablets prepared in traditional ways, which brought more opportunities to solid dispersion technique for industrial production. PMID:23625441

Hu, Liandong; Song, Weihua; Niu, Feng; Jiao, Kuiliang; Jia, Zheng

2013-05-01

167

Vindolanda Tablets Online  

NSDL National Science Digital Library

Written in ink on postcard-sized sheets of wood, the Vindolanda tablets constitute a fascinating record of life in Roman Britain in the area of northern England around Hadrian's Wall during the first and second centuries AD. The tablets and the accompanying visual and printed materials were brought online through the collaborative efforts of the Centre for the Study of Ancient Documents and the Academic Computing Development Team at Oxford University. Visitors unfamiliar with the world of Roman Britain would do well to go first to the Exhibition section which contains helpful areas devoted to the world of military life during this period, the tablets themselves, and the excavations at Vindolanda. The Reference section also provides a great deal of context to the commentaries contained on the tablets, providing information about the military units in the Roman army and important dates and events in early Roman Britain. The heart of the site is dedicated to the tablets themselves, which may be browsed by number or searched by such variables as title, author, English translation, or commentary.

168

Evidence for perceptual masking of the discriminative morphine stimulus  

Microsoft Academic Search

Morphine-amphetamine and morphine-naltrexone interactions were examined in three groups of White Carneaux pigeons (n=3), which were trained in a twochoice drug discrimination procedure under a FR-30 schedule of food reinforcement using 3.2 mg\\/kg morphine and saline as discriminative stimuli. Once stimulus control was acquired by these initial training stimuli, the training doses of morphine were gradually changed to 1.0 mg\\/kg

David V. Gauvin; Alice M. Young

1989-01-01

169

[Tablets and tablet production - with special reference to Icelandic conditions].  

PubMed

Modern tablet compression was instituted in England in 1844 by William Brockedon (1787-1854). The first tablets made according to Brockedon´s procedures contained watersoluble salts and were most likely compressed without expedients. In USA a watershed occurred around 1887 when starch (amylum maydis) was introduced to disperse tablets in aqueous milieu in order to corroborate bioavailability of drugs in the almentary canal. About the same time great advances in tablet production were introduced by the British firm Burroughs Wellcome and Co. In Denmark on the other hand tablet production remained on low scale until after 1920. As Icelandic pharmacies and drug firms modelled themselves mostly upon Danish firms tablet production was first instituted in Iceland around 1930. The first tablet machines in Iceland were hand-driven. More efficent machines came after 1945. Around 1960 three sizeable tablet producers were in Iceland; now there is only one. Numbers of individual tablet species (generic and proprietary) on the market rose from less than 10 in 1913 to 500 in 1965, with wide variations in numbers in between. Tablets have not wiped out other medicinal forms for peroral use but most new peroral drugs have been marketed in the form of tablets during the last decades. PMID:23695970

Skaftason, Jóhannes F; Jóhannesson, Thorkell

2013-04-01

170

Impact of cefpodoxime proxetil and amoxicillin on the normal oral and intestinal microflora  

Microsoft Academic Search

Ten healthy volunteers were given 200 mg cefpodoxime proxetil tablets every 12 h and ten volunteers received 500 mg amoxicillin tablets every 8 h for seven days and the impact of the agents on the oral and intestinal microflora was studied. In the oral microflora, only minor alterations were observed in both groups. In subjects receiving cefpodoxime proxetil, the numbers

B. Brismar; C. Edlund; C. E. Nord

1993-01-01

171

Tablet Process Simulator  

NSDL National Science Digital Library

The North Carolina Community College System BioNetwork's interactive eLearning tools (IETs) are reusable chunks of training that can be deployed in a variety of courses or training programs. IETs are designed to enhance, not replace hands-on training. Learners are able to enter a hands-on lab experience better prepared and more confident. This particular IET is a Tablet Process Simulator in which visitors set up and run a tablet press in a virtual 3D environment. The tool requires the program to be downloaded and installed, and gives helpful installation instructions. Users will start by downloading a zip file to their computer.

172

Morphine hydro­chloride anhydrate1  

PubMed Central

In the title mol­ecular salt [systematic name: (5?,6?)-7,8-didehydro-4,5-ep­oxy-17-methyl­morphinan-3,6-diol hydro­chloride], C17H20NO3 +·Cl?, the conformation of the morphinium ion is in agreement with the characteristics of the previously reported morphine forms [for example, Gylbert (1973 ?). Acta Cryst. B29, 1630–1635]. In the crystal, the cations and chloride anions are linked into a helical chain propagating parallel to the b-axis direction by N—H?Cl and O—H?Cl hydrogen bonds. The title salt and the morphine monohydrate [Bye (1976 ?) Acta Chem. Scand. 30, 549–554] display very similar one-dimensional packing modes of their morphine components. PMID:23476193

Gelbrich, Thomas; Braun, Doris E.; Griesser, Ulrich J.

2012-01-01

173

Redesign of a dioxygenase in morphine biosynthesis.  

PubMed

Opium poppy (Papaver somniferum) produces medicinally important benzylisoquinoline alkaloids, including the analgesics codeine and morphine, in the morphinan pathway. We aligned three dioxygenases that were recently discovered in P. somniferum and subsequently identified the nonconserved regions. Two of these enzymes, codeine O-demethylase (PsCODM) and thebaine O-demethylase (PsT6ODM), are known to facilitate regioselective O-demethylation in morphinan biosynthesis. We systematically swapped the residues that were nonconserved between the PsCODM and PsT6ODM sequences to generate 16 mutant PsCODM proteins that could be overexpressed in Escherichia coli. While wild-type PsCODM can demethylate both codeine and thebaine, one engineered PsCODM mutant selectively demethylates codeine. Use of this reengineered enzyme in the reconstitution of morphine biosynthesis could selectively disable a redundant pathway branch and therefore impact the yields of the downstream products codeine and morphine in subsequent metabolic engineering efforts. PMID:22726681

Runguphan, Weerawat; Glenn, Weslee S; O'Connor, Sarah E

2012-06-22

174

Intrathecal combination of ziconotide and morphine for refractory cancer pain: a rapidly acting and effective choice.  

PubMed

Ziconotide is a nonopioid intrathecal analgesic drug used to manage moderate to severe chronic pain. The aim of this work is to assess the safety and efficacy of intrathecal (IT) combination of ziconotide and morphine in malignant pain refractory to high doses of oral opioids. Patients with malignant pain refractory to high oral opioids doses with a mean visual analogue scale of pain intensity (VASPI) score of ? 70 mm were enrolled. An IT combination therapy was administered: Ziconotide was started at a dose of 2.4 ?g/day, followed by increases of 1.2 ?g/day at intervals of at least 7 days, and an initial IT daily dose of morphine was calculated based on its oral daily dose. Percentage change in VASPI scores from baseline was calculated at 2 days, at 7 days, and weekly until the first 28 days. The mean percentage change of VASPI score from baseline was used for efficacy assessment. Safety was monitored based on adverse events and routine laboratory values. Twenty patients were enrolled, with a mean daily VASPI score at rest of 90±7. All had a disseminated cancer with bone metastases involving the spine. The percentage changes in VASPI mean scores from baseline to 2 days, 7 days, and 28 days were 39±13% (95% confidence interval [CI]=13.61-64.49, P<.001), 51±12% (95% CI=27.56-74.56, P<.001), and 62±13% (95% CI=36.03-87.89%, P<.001), respectively. Four patients experienced mild adverse events related to the study drugs. In conclusion, an IT combination of low doses of ziconotide and morphine allows safe and rapid control of oral opioid-refractory malignant pain. PMID:22082570

Alicino, Ilaria; Giglio, Mariateresa; Manca, Fabio; Bruno, Francesco; Puntillo, Filomena

2012-01-01

175

Synthetic substances with morphine-like effect  

PubMed Central

A review of effects in man of morphine-like drugs which have been brought under international narcotics control is presented in the form of individual monographs. These are based on controlled observations with quantitative data and significant reports of results obtained in medical practice. In a summarizing section, the drugs are compared with respect to effectiveness, side-effects and addiction liability. Morphine-like drugs of natural and synthetic origin now cover a wide range of potency (analgesic, antitussive), not necessarily paralleled by incidence of side-effects or addiction liability. PMID:13511135

Eddy, Nathan B.; Halbach, H.; Braenden, Olav J.

1957-01-01

176

An open-label, randomized bioavailability study with alternative methods of administration of crushed ticagrelor tablets in healthy volunteers  

PubMed Central

Objective: To compare the bioavailability and safety profile of crushed ticagrelor tablets suspended in water and administered orally or via nasogastric tube, with that of whole tablets administered orally. Methods: In this single-center, open-label, randomized, three-treatment crossover study, 36 healthy volunteers were randomized to receive a single 90-mg dose of ticagrelor administered orally as a whole tablet or as crushed tablets suspended in water and given orally or via a nasogastric tube into the stomach, with a minimum 7-day wash-out between treatments. Plasma concentrations of ticagrelor and AR-C124910XX were assessed at 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-ticagrelor dose for pharmacokinetic analyses. Safety and tolerability was assessed throughout the study. Results: At 0.5 hours postdose, plasma concentrations of ticagrelor and AR-C124910XX were higher with crushed tablets administered orally (148.6 ng/mL and 13.0 ng/mL, respectively) or via nasogastric tube (264.6 ng/mL and 28.6 ng/mL, respectively) compared with whole-tablet administration (33.3 ng/mL and 5.2 ng/mL, respectively). A similar trend was observed at 1 hour postdose. Ticagrelor tmax was shorter following crushed vs. whole-tablet administration (1 vs. 2 hours, respectively). Geometric mean ratios between treatments for AUC and Cmax were contained within the bioequivalence limits of 80 – 125% for ticagrelor and AR-C124910XX. All treatments were generally well tolerated. Conclusions: Ticagrelor administered as a crushed tablet is bioequivalent to whole-tablet administration, independent of mode of administration (oral or via nasogastric tube), and resulted in increased plasma concentrations of ticagrelor and AR-C124910XX at early timepoints. PMID:25500486

Teng, Renli; Carlson, Glenn; Hsia, Judith

2015-01-01

177

CES 2011: Tablet Crazy  

ERIC Educational Resources Information Center

Ereaders are so last year. Tablets were the watchword at this year's annual Consumer Electronics Show (CES) in Las Vegas, January 6-9. This year, the show set new records, with some 2700 companies from around the world exhibiting at the multiple exhibition halls and 30,000 attendees gawking at the products. What did they see? There were still some…

Rapp, David

2011-01-01

178

Time Dependent Antinociceptive Effects of Morphine and Tramadol in the Hot Plate Test: Using Different Methods of Drug Administration in Female Rats  

PubMed Central

Morphine and tramadol which have analgesic effects can be administered acutely or chronically. This study tried to investigate the effect of these drugs at various times by using different methods of administration (intraperitoneal, oral, acute and chronic). Sixty adult female rats were divided into six groups. They received saline, morphine or tramadol (20 to 125 mg/Kg) daily for 15 days. A hot plate test was performed for the rats at the 1st, 8th and 15th days. After drug withdrawal, the hot plate test was repeated at the 17th, 19th, and 22nd days. There was a significant correlation between the day, drug, group, and their interaction (P<0.001). At 1st day (d1), both morphine, and tramadol caused an increase in the hot plate time comparing to the saline groups (P<0.001), while there was no correlation between drug administration methods of morphine and/or tramadol. At the 8th day (d8), morphine and tramadol led to the most powerful analgesic effect comparing to the other experimental days (P<0.001). At the 15th day (d15), their effects diminished comparing to the d8. After drug withdrawal, analgesic effect of morphine, and tramadol disappeared. It can be concluded that the analgesic effect of morphine and tramadol increases with the repeated use of them. Thereafter, it may gradually decrease and reach to a level compatible to d1. The present data also indicated that although the analgesic effect of morphine and tramadol is dose-and-time dependent, but chronic exposure to them may not lead to altered nociceptive responses later in life. PMID:25561936

Gholami, Morteza; Saboory, Ehsan; Mehraban, Sogol; Niakani, Afsaneh; Banihabib, Nafiseh; Azad, Mohamad-Reza; Fereidoni, Javid

2015-01-01

179

Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts  

PubMed Central

This double-blind, placebo-controlled study investigated effects of oral morphine (0, 45, 135 mg/70kg) and oral oxycodone (0, 15, 45 mg/70kg) in buprenorphine-maintained opioid addicts. Since a 3:1 morphine:oxycodone dose ratio had yielded equivalent subjective and physiological effects in non-dependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures, i.e. a drug vs. money and a drug vs. drug procedure, were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater compared to high-dose morphine. The study demonstrated that a 3:1 dose ratio of morphine:oxycodone was not equipotent in buprenorphine-dependent subjects. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest. PMID:23839029

Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

2014-01-01

180

Opiate dependence produced by ad libitum drinking of morphine in water, saline, and sucrose vehicles  

Microsoft Academic Search

Rats were given ad libitum morphine water, saline morphine, or sucrose morphine as their only source of liquid. Measures of liquid, food, caloric, and morphine intake along with body weight were taken daily, thereby monitoring the effects of morphine ingestion on these indices, and observing the course of dependence over time. To assess the degree of dependence the animals were

Khalil A. Khavari; Marc E. Risner

1973-01-01

181

Applications of poly(ethylene oxide) in controlled release tablet systems: a review.  

PubMed

To improve therapeutic effects and compatibility of patients, controlled release tablet systems based on polymers are of great interest for pharmaceutical technologies. Poly(ethylene oxide) (PEO) is a non-ionic linear hydrophilic and uncrosslinked polymer available in a number of molecular weights. It is synthesized by ethylene oxide and has many desirable properties for drug delivery applications. This review article aims to summary the recent developments on physicochemical properties of PEO and focus on the recent efforts and developments on PEO as oral controlled release matrix tablets, bioadhesive hydrophilic matrices and osmotic pump tablets. Commercial products employed PEO were also discussed. PMID:24001212

Ma, Lulu; Deng, Li; Chen, Jianming

2014-07-01

182

Solid self-microemulsifying dispersible tablets of celastrol: formulation development, charaterization and bioavailability evaluation.  

PubMed

The aims of this study were to choose a suitable adsorbent of self-microemulsion and to develop a fine solid self-microemulsifying dispersible tablets for promoting the dissolution and oral bioavailability of celastrol. Solubility test, self-emulsifying grading test, droplet size analysis and ternary phase diagrams test were performed to screen and optimize the composition of liquid celastrol self-microemulsifying drug delivery system (SMEDDS). Then microcrystalline cellulose KG 802 was added as a suitable adsorbent into the optimized liquid celastrol-SMEDDS formulation to prepare the dispersible tablets by wet granulation compression method. The optimized formulation of celastrol-SMEDDS dispersible tablets was finally determinated by the feasibility of the preparing process and redispersibility. The in vitro study showed that the dispersible tablets could disperse in the dispersion medium within 3 min with the average particle size of 25.32 ± 3.26 nm. In vivo pharmacokinetic experiments of rats, the relative bioavailability of celastrol SMEDDS and SMEDDS dispersible tablets compared to the 0.4% CMC-Na suspension was 569 ± 7.07% and 558 ± 6.77%, respectively, while there were no significant difference between the SMEDDS and SMEDDS dispersible tablets. The results suggest the potential use of SMEDDS dispersible tablets for the oral delivery of poorly water-soluble terpenes drugs, such as celastrol. PMID:24929011

Qi, Xiaole; Qin, Jiayi; Ma, Ning; Chou, Xiaohua; Wu, Zhenghong

2014-09-10

183

Influences of Gender on Postoperative Morphine Consumption  

PubMed Central

Background: Gender related differences on morphine consumption during postoperative period following abdominal surgeries. Materials and Methods: Four hundred and fifty ASA I & II patients of either sex (male =231, female = 219), between the age group of 18-65 y undergoing elective intra abdominal surgeries under general anaesthesia were included for the study. Patients with preexisting pain either acute or chronic preoperatively were excluded from the study. Anaesthesia and analgesia protocol during surgery was standardized. Postoperatively, a loading dose was given to achieve the visual analogue scale (VAS) of ?30 and subjects were connected to patient control analgesia (PCA) pump containing 0.4 mg/ml of morphine configured to deliver a bolus dose (1 mg) with a 5 min lock-out period. The total analgesic requirements along with VAS (visual analog scale) score were analysed between males and females in the first 24 h postoperatively. All demographic data and between group comparisons were analysed with student t-test. Within group comparisons were done by using one-way-ANOVA test and Tukey’s Honestly significant Difference test. Results: During the first 24 h, males consumed significantly higher amount of morphine (34.35 ± 6.68 mg) when compared to females (26.78 ± 7.14 mg), p < 0.001. Conclusion: We conclude that men require more morphine in the postoperative period than women. PMID:25653963

Poovathai, Raja; Pondiyadanar, Srinivasan

2014-01-01

184

21 CFR 520.312 - Carnidazole tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Carnidazole tablets. 520.312 Section 520.312 Food and...NEW ANIMAL DRUGS § 520.312 Carnidazole tablets. (a) Specifications. Each tablet contains 10 milligrams of carnidazole....

2014-04-01

185

21 CFR 520.1380 - Methocarbamol tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 false Methocarbamol tablets. 520.1380 Section 520.1380 ...ANIMAL DRUGS § 520.1380 Methocarbamol tablets. (a) Chemical name. 3-(O-Methoxyphenoxy...1-carbamate. (b) Specifications. Each tablet contains 500 milligrams of...

2013-04-01

186

21 CFR 520.1900 - Primidone tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Primidone tablets. 520.1900 Section 520.1900 Food and...NEW ANIMAL DRUGS § 520.1900 Primidone tablets. (a) Specifications. Each tablet contains 50 or 250 milligrams of...

2014-04-01

187

21 CFR 520.455 - Clomipramine tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Clomipramine tablets. 520.455 Section 520.455 Food and...NEW ANIMAL DRUGS § 520.455 Clomipramine tablets. (a) Specifications. Each tablet contains 5, 20, 40, or 80 milligrams...

2013-04-01

188

21 CFR 520.1451 - Moxidectin tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Moxidectin tablets. 520.1451 Section 520.1451 Food and...NEW ANIMAL DRUGS § 520.1451 Moxidectin tablets. (a) Specifications . Each tablet contains 30, 68, or 136 micrograms of...

2011-04-01

189

21 CFR 520.928 - Firocoxib tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Firocoxib tablets. 520.928 Section 520.928 Food...NEW ANIMAL DRUGS § 520.928 Firocoxib tablets. (a) Specifications . Each chewable tablet contains 57 or 227 milligrams (mg)...

2012-04-01

190

21 CFR 520.1900 - Primidone tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Primidone tablets. 520.1900 Section 520.1900 Food and...NEW ANIMAL DRUGS § 520.1900 Primidone tablets. (a) Specifications. Each tablet contains 50 or 250 milligrams of...

2010-04-01

191

21 CFR 520.928 - Firocoxib tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Firocoxib tablets. 520.928 Section 520.928 Food...NEW ANIMAL DRUGS § 520.928 Firocoxib tablets. (a) Specifications . Each chewable tablet contains 57 or 227 milligrams (mg)...

2013-04-01

192

21 CFR 520.581 - Dichlorophene tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Dichlorophene tablets. 520.581 Section 520.581 Food and...NEW ANIMAL DRUGS § 520.581 Dichlorophene tablets. (a) Specifications. Each tablet contains 1 gram of dichlorophene. (b)...

2012-04-01

193

21 CFR 520.1380 - Methocarbamol tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 false Methocarbamol tablets. 520.1380 Section 520.1380 ...ANIMAL DRUGS § 520.1380 Methocarbamol tablets. (a) Chemical name. 3-(O-Methoxyphenoxy...1-carbamate. (b) Specifications. Each tablet contains 500 milligrams of...

2014-04-01

194

21 CFR 520.2088 - Roxarsone tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Roxarsone tablets. 520.2088 Section 520.2088 Food...NEW ANIMAL DRUGS § 520.2088 Roxarsone tablets. (a)(1) Specifications. Each tablet contains 36 milligrams of roxarsone...

2013-04-01

195

21 CFR 520.1900 - Primidone tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Primidone tablets. 520.1900 Section 520.1900 Food and...NEW ANIMAL DRUGS § 520.1900 Primidone tablets. (a) Specifications. Each tablet contains 50 or 250 milligrams of...

2011-04-01

196

21 CFR 520.1451 - Moxidectin tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Moxidectin tablets. 520.1451 Section 520.1451 Food and...NEW ANIMAL DRUGS § 520.1451 Moxidectin tablets. (a) Specifications . Each tablet contains 30, 68, or 136 micrograms of...

2013-04-01

197

21 CFR 520.1380 - Methocarbamol tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 false Methocarbamol tablets. 520.1380 Section 520.1380 ...ANIMAL DRUGS § 520.1380 Methocarbamol tablets. (a) Chemical name. 3-(O-Methoxyphenoxy...1-carbamate. (b) Specifications. Each tablet contains 500 milligrams of...

2011-04-01

198

21 CFR 520.1870 - Praziquantel tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Praziquantel tablets. 520.1870 Section 520.1870 Food and...NEW ANIMAL DRUGS § 520.1870 Praziquantel tablets. (a) Specifications . Each tablet contains: (1) 34 milligrams (mg)...

2012-04-01

199

21 CFR 520.312 - Carnidazole tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Carnidazole tablets. 520.312 Section 520.312 Food and...NEW ANIMAL DRUGS § 520.312 Carnidazole tablets. (a) Specifications. Each tablet contains 10 milligrams of carnidazole....

2010-04-01

200

21 CFR 520.1451 - Moxidectin tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Moxidectin tablets. 520.1451 Section 520.1451 Food and...NEW ANIMAL DRUGS § 520.1451 Moxidectin tablets. (a) Specifications. Each tablet contains 30, 68, or 136 micrograms of...

2014-04-01

201

21 CFR 520.312 - Carnidazole tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Carnidazole tablets. 520.312 Section 520.312 Food and...NEW ANIMAL DRUGS § 520.312 Carnidazole tablets. (a) Specifications. Each tablet contains 10 milligrams of carnidazole....

2011-04-01

202

21 CFR 520.1451 - Moxidectin tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Moxidectin tablets. 520.1451 Section 520.1451 Food and...NEW ANIMAL DRUGS § 520.1451 Moxidectin tablets. (a) Specifications . Each tablet contains 30, 68, or 136 micrograms of...

2010-04-01

203

21 CFR 520.1870 - Praziquantel tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Praziquantel tablets. 520.1870 Section 520.1870 Food and...NEW ANIMAL DRUGS § 520.1870 Praziquantel tablets. (a) Specifications . Each tablet contains: (1) 34 milligrams (mg)...

2013-04-01

204

21 CFR 520.1870 - Praziquantel tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Praziquantel tablets. 520.1870 Section 520.1870 Food and...NEW ANIMAL DRUGS § 520.1870 Praziquantel tablets. (a) Specifications. Each tablet contains: (1) 34 milligrams (mg)...

2014-04-01

205

21 CFR 520.1900 - Primidone tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Primidone tablets. 520.1900 Section 520.1900 Food and...NEW ANIMAL DRUGS § 520.1900 Primidone tablets. (a) Specifications. Each tablet contains 50 or 250 milligrams of...

2013-04-01

206

21 CFR 520.1310 - Marbofloxacin tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Marbofloxacin tablets. 520.1310 Section 520.1310 Food and...ANIMAL DRUGS § 520.1310 Marbofloxacin tablets. (a) Specifications . Each tablet contains 25, 50, 100, or 200...

2012-04-01

207

21 CFR 520.1870 - Praziquantel tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Praziquantel tablets. 520.1870 Section 520.1870 Food and...NEW ANIMAL DRUGS § 520.1870 Praziquantel tablets. (a) Specifications . Each tablet contains: (1) 34 milligrams (mg)...

2011-04-01

208

21 CFR 520.581 - Dichlorophene tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Dichlorophene tablets. 520.581 Section 520.581 Food and...NEW ANIMAL DRUGS § 520.581 Dichlorophene tablets. (a) Specifications. Each tablet contains 1 gram of dichlorophene. (b)...

2014-04-01

209

21 CFR 520.581 - Dichlorophene tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Dichlorophene tablets. 520.581 Section 520.581 Food and...NEW ANIMAL DRUGS § 520.581 Dichlorophene tablets. (a) Specifications. Each tablet contains 1 gram of dichlorophene. (b)...

2011-04-01

210

21 CFR 520.1451 - Moxidectin tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Moxidectin tablets. 520.1451 Section 520.1451 Food and...NEW ANIMAL DRUGS § 520.1451 Moxidectin tablets. (a) Specifications . Each tablet contains 30, 68, or 136 micrograms of...

2012-04-01

211

21 CFR 520.312 - Carnidazole tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Carnidazole tablets. 520.312 Section 520.312 Food and...NEW ANIMAL DRUGS § 520.312 Carnidazole tablets. (a) Specifications. Each tablet contains 10 milligrams of carnidazole....

2012-04-01

212

21 CFR 520.455 - Clomipramine tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Clomipramine tablets. 520.455 Section 520.455 Food and...NEW ANIMAL DRUGS § 520.455 Clomipramine tablets. (a) Specifications. Each tablet contains 5, 20, 40, or 80 milligrams...

2014-04-01

213

21 CFR 520.928 - Firocoxib tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Firocoxib tablets. 520.928 Section 520.928 Food...NEW ANIMAL DRUGS § 520.928 Firocoxib tablets. (a) Specifications . Each chewable tablet contains 57 or 227 milligrams (mg)...

2010-04-01

214

21 CFR 520.1310 - Marbofloxacin tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Marbofloxacin tablets. 520.1310 Section 520.1310 Food and...ANIMAL DRUGS § 520.1310 Marbofloxacin tablets. (a) Specifications . Each tablet contains 25, 50, 100, or 200...

2010-04-01

215

21 CFR 520.1900 - Primidone tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Primidone tablets. 520.1900 Section 520.1900 Food and...NEW ANIMAL DRUGS § 520.1900 Primidone tablets. (a) Specifications. Each tablet contains 50 or 250 milligrams of...

2012-04-01

216

21 CFR 520.455 - Clomipramine tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Clomipramine tablets. 520.455 Section 520.455 Food and...NEW ANIMAL DRUGS § 520.455 Clomipramine tablets. (a) Specifications. Each tablet contains 5, 20, 40, or 80 milligrams...

2011-04-01

217

21 CFR 520.581 - Dichlorophene tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Dichlorophene tablets. 520.581 Section 520.581 Food and...NEW ANIMAL DRUGS § 520.581 Dichlorophene tablets. (a) Specifications. Each tablet contains 1 gram of dichlorophene. (b)...

2010-04-01

218

21 CFR 520.1310 - Marbofloxacin tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Marbofloxacin tablets. 520.1310 Section 520.1310 Food and...ANIMAL DRUGS § 520.1310 Marbofloxacin tablets. (a) Specifications . Each tablet contains 25, 50, 100, or 200...

2011-04-01

219

21 CFR 520.928 - Firocoxib tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Firocoxib tablets. 520.928 Section 520.928 Food...NEW ANIMAL DRUGS § 520.928 Firocoxib tablets. (a) Specifications. Each chewable tablet contains 57 or 227 milligrams (mg)...

2014-04-01

220

21 CFR 520.312 - Carnidazole tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Carnidazole tablets. 520.312 Section 520.312 Food and...NEW ANIMAL DRUGS § 520.312 Carnidazole tablets. (a) Specifications. Each tablet contains 10 milligrams of carnidazole....

2013-04-01

221

21 CFR 520.1380 - Methocarbamol tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 false Methocarbamol tablets. 520.1380 Section 520.1380 ...ANIMAL DRUGS § 520.1380 Methocarbamol tablets. (a) Chemical name. 3-(O-Methoxyphenoxy...1-carbamate. (b) Specifications. Each tablet contains 500 milligrams of...

2012-04-01

222

21 CFR 520.455 - Clomipramine tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Clomipramine tablets. 520.455 Section 520.455 Food and...NEW ANIMAL DRUGS § 520.455 Clomipramine tablets. (a) Specifications. Each tablet contains 5, 20, 40, or 80 milligrams...

2012-04-01

223

21 CFR 520.928 - Firocoxib tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Firocoxib tablets. 520.928 Section 520.928 Food...NEW ANIMAL DRUGS § 520.928 Firocoxib tablets. (a) Specifications . Each chewable tablet contains 57 or 227 milligrams (mg)...

2011-04-01

224

21 CFR 520.1310 - Marbofloxacin tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Marbofloxacin tablets. 520.1310 Section 520.1310 Food and...ANIMAL DRUGS § 520.1310 Marbofloxacin tablets. (a) Specifications. Each tablet contains 25, 50, 100, or 200...

2014-04-01

225

21 CFR 520.1870 - Praziquantel tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Praziquantel tablets. 520.1870 Section 520.1870 Food and...NEW ANIMAL DRUGS § 520.1870 Praziquantel tablets. (a) Specifications . Each tablet contains: (1) 34 milligrams (mg)...

2010-04-01

226

21 CFR 520.581 - Dichlorophene tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Dichlorophene tablets. 520.581 Section 520.581 Food and...NEW ANIMAL DRUGS § 520.581 Dichlorophene tablets. (a) Specifications. Each tablet contains 1 gram of dichlorophene. (b)...

2013-04-01

227

Primary microparticles and agglomerates of morphine for nasal insufflation.  

PubMed

The aim of this work was to study the characteristics of powders of morphine HCl suitable for nasal administration to be employed for pain treatment as alternative to injection. Primary microparticles of morphine were prepared by spray drying of aqueous drug solutions using sugars or sugar derivatives as drying protectors and particle shapers. The spray drying procedure modified morphine crystallinity making the substance amorphous and affecting its stability in dependence on the excipient employed. A tendency of the spray-dried powders to turn to varying degrees of yellow was observed. Tumbling the powder in a rotating pan allowed the agglomeration of the primary microparticles. Agglomerates were also obtained by tumbling a mixture of morphine crystals and spray-dried microparticles of excipients, with advantages for the stability of the preparation. A nasal device quantitatively insufflated all the morphine agglomerates. The in vitro transport of morphine through rabbit nasal mucosa was faster using nasal powders than with the saturated solution of morphine. Lactose was the most effective excipient for agglomerate manufacturing and delivery of spray-dried morphine. The agglomerates of morphine crystals mixed with mannitol/lecithin microparticles showed superior stability. However, the drug permeation through rabbit mucosa was slower than with spray-dried morphine microparticle agglomerates. PMID:16937333

Russo, Paola; Sacchetti, Cecilia; Pasquali, Irene; Bettini, Ruggero; Massimo, Gina; Colombo, Paolo; Rossi, Alessandra

2006-12-01

228

Attitudes of Polish physicians and medical students toward breaking bad news, euthanasia and morphine administration in cancer patients.  

PubMed

Medical students and physicians should possess basic knowledge concerning medical ethics and palliative care. The aim of the study was to explore the knowledge on the end-of-life ethics and palliative care in third-year medical students and physicians during internal medicine specialty training and their attitude towards breaking bad news and euthanasia. A voluntary and anonymous questionnaire survey with the participation of 401 students and 217 physicians filled after lectures concerning ethics for medical students and after palliative medicine course for physicians during internal medicine specialty training. A total of 28 % students and 24 % physicians (p = 0.282) were ready to reveal full information to advanced cancer patients. A total of 82 % of students and 90 % of physicians (p = 0.008) would not practice euthanasia; 67 % of students and 75 % of physicians (p = 0.039) were opponents of euthanasia legalisation. A total of 70 % doctors and 23 % students indicated oral as the most preferable route of morphine administration. A total of 74 % physicians and 43 % students stated that there is no maximal dose of morphine; 64 % of doctors and 6 % of students indicated constipation as a constant adverse effect of morphine. Breaking bad news is a significant difficulty for both students and physicians. There is a small percentage of those tending to practice euthanasia and bigger accepting its legalisation with fewer physicians than students. In contrast to medical students, the majority of physicians have knowledge concerning chronic morphine use in the treatment of cancer patients. PMID:24170311

Leppert, Wojciech; Majkowicz, Mikolaj; Forycka, Maria

2013-12-01

229

Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose.  

PubMed Central

1. The pharmacokinetics of ethylmorphine after administration of a single dose of the cough mixture Cosylan were investigated in 10 healthy subjects. 2. The median urinary recovery of ethylmorphine and measured metabolites was 77% over 48 h. The median tmax of unchanged ethylmorphine was 45 min, and the terminal elimination t1/2 was 2 h. Ethylmorphine-6-glucuronide was found to be the major metabolite. 3. Two subjects had significantly lower urinary recovery (0.48 h) of morphine and morphine-glucuronides than the remainder. Furthermore, these two had urinary metabolic ratios (MRO) and partial metabolic clearances (CLmO) for O-deethylation of ethylmorphine tentatively classifying them phenotypically as poor metabolisers of the debrisoquine/sparteine type. 4. Genotyping for cytochrome P450 (CYP) 2D6 alleles revealed five homozygote (wt/wt) and five heterozygote subjects. Two subjects phenotypically classified as poor metabolisers were genotypically CYP2D6A/wt and CYP2D6D/wt, respectively. 5. Serum and urine samples taken more than 8 and 24 h after administration of ethyl-morphine respectively, contained morphine and morphine-glucuronides, but no ethylmorphine, ethylmorphine-6-glucuronide or (serum only) norethylmorphine. Norethylmorphine could be detected after hydrolysis of urine samples in all subjects. The urinary recovery of the active metabolites morphine and morphine-6-glucuronide after administration of ethylmorphine varied by a factor of 9 between individuals. 6. The wide variation in recovery of morphine and morphine-glucuronides after oral administration of ethylmorphine could not be explained simply by a difference in CYP2D6 genotype. Constitutional variation in other enzymatic pathways involved in ethylmorphine metabolism is probably crucial. Ratios of morphine to parent drug cannot be used to distinguish the source of morphine after administration of ethylmorphine. Norethylmorphine should be included in urine assays for opiates in forensic toxicology, and no firm conclusions about the source of morphine are possible based on serum samples obtained more than 24 h after drug administration. PMID:7654478

Aasmundstad, T A; Xu, B Q; Johansson, I; Ripel, A; Bjørneboe, A; Christophersen, A S; Bodd, E; Mørland, J

1995-01-01

230

Aloe vera Aqueous Extract Effect on Morphine Withdrawal Syndrome in Morphine-Dependent Female Rats  

PubMed Central

Background: Aloe vera is a medicinal herb used as an anti-inflammatory and sedative agent. Objectives: The current study aimed to evaluate the effect of Aloe vera aqueous extract on morphine withdrawal symptoms in morphine-dependent female rats. Patients and Methods: The current research was performed on 40 female Wista-Albino rats which were made dependent on morphine using Houshyar protocol and were randomly divided into five groups (A, B, C, D, and E). Group A did not receive any agent in the period of handling but other groups (B, C, D and E) received 5, 10, 20 and 40 mg/kg of Aloe vera aqueous extract by gavage, three times daily for a week, respectively. Withdrawal symptoms, stool form, agitation, disparity, floppy eyelids, and body mass variations were checked for 10 days. The obtained data were analyzed using SPSS v.11 software, and Friedman, Kruskal-Wallis, and Mann-Whitney statistical tests. Statistical difference was considered significant (P < 0.05). Results: The results of the present study showed that agitation, disparity, and floppy eyelids in group E were significantly higher than those of others groups; however, these symptoms in group C were significantly lower than those of the other groups. Conclusions: The results of the present study revealed that the Aloe vera aqueous extract had various effects on morphine withdrawal syndrome in morphine-dependent female rats . PMID:25593890

Shahraki, Mohammad Reza; Mirshekari, Hamideh; Sabri, Azame

2014-01-01

231

The effects of proglumide on morphine induced motility changes  

Microsoft Academic Search

Proglumide (0.02 mg\\/kg), a cholecystokinin antagonist, was administered to rats either together with or without morphine (0, 5, 15, or 45 mg\\/kg). Whereas proglumide in the absence of morphine showed a trend towards enhanced behavioral activation, it potentiated the hy[okinesia induced by morphine. These results are consistent with the hypothesis that endogenous cholecystokinin tonically antagonizes opiate modulation of motility, irrespective

Nitsan Ben-Horin; Einat Ben-Horin; Hanan Frenk

1984-01-01

232

The role of morphine in regulation of cancer cell growth  

Microsoft Academic Search

Morphine is considered the “gold standard” for relieving pain and is currently one of the most effective drugs available clinically\\u000a for the management of severe pain associated with cancer. In addition to its use in the treatment of pain, morphine appears\\u000a to be important in the regulation of neoplastic tissue. Although morphine acts directly on the central nervous system to

Katarzyna Gach; Anna Wyr?bska; Jakub Fichna; Anna Janecka

233

Tablet PCs: The Write Approach  

ERIC Educational Resources Information Center

This article discusses the transforming effects of tablet PCs in the classroom. As 1-to-1 computing becomes the goal on K-12 campuses, school districts are turning to this newer, pen-based technology. Saint Mary's School's new Lenovo ThinkPad X41 tablet PCs had transformed the way Saint Mary's teachers did their jobs. Teachers created outlines for…

Milner, Jacob

2006-01-01

234

Morphine and tumor growth and metastasis  

Microsoft Academic Search

Morphine is an analgesic widely used to alleviate cancer pain. In addition, the perioperative management of pain in cancer\\u000a surgery patients most often includes opioids. However, there are reports that these drugs may alter cancer recurrence or metastasis.\\u000a Several mechanisms have been proposed, such as the modulation of the immune response or cellular pathways that control the\\u000a survival and migratory

Banafsheh Afsharimani; Peter Cabot; Marie-Odile Parat

2011-01-01

235

Tablet PC and Computing Curriculum Initiative Evaluation of Tablet PC Supported Pedagogy  

E-print Network

Tablet PC and Computing Curriculum Initiative 2006 Evaluation of Tablet PC Supported Pedagogy http://www.cs.washington.edu/education/dl/presenter/ University of Washington Richard Anderson 2. Students write answers on slides on their tablets and send them to show on public display for discussion Classroom Interaction with Tablet PCs Classroom Presenter Tablet

Anderson, Richard

236

Efficacy, safety and early response of paliperidone extended-release tablets (paliperidone ER): Results of a 6-week, randomized, placebo-controlled study  

Microsoft Academic Search

BackgroundPaliperidone extended-release tablet (paliperidone ER) is an oral psychotropic agent developed for schizophrenia treatment. Paliperidone (9-OH-risperidone, metabolite of risperidone), when used with OROS technology has a unique pharmacokinetic profile undergoing limited hepatic metabolism.

Michael Davidson; Robin Emsley; Michelle Kramer; Lisa Ford; Guohua Pan; Pilar Lim; Mariëlle Eerdekens

2007-01-01

237

Different effects of morphine and oxycodone in experimentally evoked hyperalgesia: a human translational study  

PubMed Central

AIM Similar analgesics may have different analgesic potencies especially in patients in whom the pain system is sensitized. The aim was to investigate different opioid effects on experimental pain after the sensitized pain system was mimicked evoking hyperalgesia in healthy volunteers. METHODS Twenty-four healthy volunteers were randomized to treatment with morphine (30 mg orally) and oxycodone (15 mg orally) or placebo in a double-blind crossover study. Hyperalgesia was induced by oesophageal perfusion with acid and capsaicin. Several exploratory endpoints were studied using skin heat, muscle pressure and oesophageal mechanical, heat and electrical stimulation. Effects on pain from deeper structures were considered most important. RESULTS Different analgesic potencies were found. Oxycodone had a greater analgesic effect than morphine attenuating pain from: (i) heat stimulation of skin (P= 0.016); difference between the means of 0.39°C, 95% CI 0.22, 2.09. (ii) muscle pressure (P < 0.001); difference between the means of 11.93kPa, 95% CI 5.4, 18.5. (iii) oesophageal heat stimulation (P < 0.001); difference between the means of 38.54 cm2, 95% CI 15.37, 61.71 and (iv) oesophageal electrical stimulation (P= 0.016); difference between the means of 6.69mA, 95% CI 1.23, 12.13. CONCLUSION After sensitization of the pain system different analgesic potencies of morphine and oxycodone were found in response to skin, muscle and oesophageal pain stimulation, in which oxycodone had a greater effect. As similar differential analgesic potencies of the two opioids have been found in patients with chronic pain, the experimental hyperalgesia model bridged findings from studies in healthy volunteers to patients. PMID:20653672

Olesen, Anne Estrup; Staahl, Camilla; Arendt-Nielsen, Lars; Drewes, Asbjørn Mohr

2010-01-01

238

Glucuronidation in the chimpanzee (Pan troglodytes): studies with acetaminophen, oestradiol and morphine.  

PubMed

The chimpanzee has recently been characterized as a surrogate for oxidative drug metabolism in humans and as a pharmacokinetic model for the selection of drug candidates. In the current study, the glucuronidation of acetaminophen, morphine and oestradiol was evaluated in the chimpanzee to extend the characterization of this important animal model. Following oral administration of acetaminophen (600 mg) to chimpanzees (n=2), pharmacokinetics were comparable with previously reported human values, namely mean oral clearance 0.91 vs. 0.62+/-0.05 l h-1 kg-1, apparent volume of distribution 2.29 vs. 1.65+/-0.25 l kg-1, and half-life 1.86 vs. 1.89+/-7h, for chimpanzee vs. human, respectively. Urinary excretions (percentage of dose) of acetaminophen, acetaminophen glucuronide and acetaminophen sulfate were also similar between chimpanzees and humans, namely 2.3 vs. 5.0, 63.1 vs. 54.7, and 25.0 vs. 32.3%, respectively. Acetaminophen, oestradiol and morphine glucuronide formation kinetics were investigated using chimpanzee (n=2) and pooled human liver microsomes (n=10). V(max) (app) and K(m)(app) (or S(50)(app)) for acetaminophen glucuronide, morphine 3- and 6-glucuronide, and oestradiol 3- and 17-glucuronide formation were comparable in both species. Eadie-Hofstee plots of oestradiol 3-glucuronide formation in chimpanzee microsomes were characteristic of autoactivation kinetics. Western immunoblot analysis of chimpanzee liver microsomes revealed a single immunoreactive band when probed with anti-human UGT1A1, anti-human UGT1A6, and anti-human UGT2B7. Taken collectively, these data demonstrate similar glucuronidation characteristics in chimpanzees and humans. PMID:17162465

Wong, H; Grace, J E; Wright, M R; Browning, M R; Grossman, S J; Bai, S A; Christ, D D

2006-12-01

239

21 CFR 520.1199 - Ivermectin, pyrantel, and praziquantel tablets.  

Code of Federal Regulations, 2012 CFR

... Ivermectin, pyrantel, and praziquantel tablets. 520.1199 Section 520.1199 Food... Ivermectin, pyrantel, and praziquantel tablets. (a) Specifications . Each chewable tablet contains: (1) 34 micrograms...

2012-04-01

240

21 CFR 520.1200 - Ivermectin, fenbendazole, and praziquantel tablets.  

Code of Federal Regulations, 2013 CFR

...Ivermectin, fenbendazole, and praziquantel tablets. 520.1200 Section 520.1200 Food...Ivermectin, fenbendazole, and praziquantel tablets. (a) Specifications . Each chewable tablet contains either: (1) 68...

2013-04-01

241

21 CFR 520.1200 - Ivermectin, fenbendazole, and praziquantel tablets.  

Code of Federal Regulations, 2011 CFR

...Ivermectin, fenbendazole, and praziquantel tablets. 520.1200 Section 520.1200 Food...Ivermectin, fenbendazole, and praziquantel tablets. (a) Specifications . Each chewable tablet contains either: (1) 68...

2011-04-01

242

21 CFR 520.1200 - Ivermectin, fenbendazole, and praziquantel tablets.  

Code of Federal Regulations, 2014 CFR

...Ivermectin, fenbendazole, and praziquantel tablets. 520.1200 Section 520.1200 Food...Ivermectin, fenbendazole, and praziquantel tablets. (a) Specifications. Each chewable tablet contains either: (1) 68...

2014-04-01

243

21 CFR 520.1200 - Ivermectin, fenbendazole, and praziquantel tablets.  

Code of Federal Regulations, 2012 CFR

...Ivermectin, fenbendazole, and praziquantel tablets. 520.1200 Section 520.1200 Food...Ivermectin, fenbendazole, and praziquantel tablets. (a) Specifications . Each chewable tablet contains either: (1) 68...

2012-04-01

244

21 CFR 520.1199 - Ivermectin, pyrantel, and praziquantel tablets.  

Code of Federal Regulations, 2013 CFR

... Ivermectin, pyrantel, and praziquantel tablets. 520.1199 Section 520.1199 Food... Ivermectin, pyrantel, and praziquantel tablets. (a) Specifications . Each chewable tablet contains: (1) 34 micrograms...

2013-04-01

245

21 CFR 520.1199 - Ivermectin, pyrantel, and praziquantel tablets.  

Code of Federal Regulations, 2014 CFR

... Ivermectin, pyrantel, and praziquantel tablets. 520.1199 Section 520.1199 Food... Ivermectin, pyrantel, and praziquantel tablets. (a) Specifications. Each chewable tablet contains: (1) 34 micrograms...

2014-04-01

246

21 CFR 520.1199 - Ivermectin, pyrantel, and praziquantel tablets.  

Code of Federal Regulations, 2011 CFR

... Ivermectin, pyrantel, and praziquantel tablets. 520.1199 Section 520.1199 Food... Ivermectin, pyrantel, and praziquantel tablets. (a) Specifications . Each chewable tablet contains: (1) 34 micrograms...

2011-04-01

247

Differential effects of oxycodone, hydrocodone, and morphine on the responses of D2/D3 dopamine receptors.  

PubMed

Oxycodone and hydrocodone are opioids which are widely used for pain management and are also commonly misused and abused. The exposure to opioid analgesics has been associated with altered responses of D2-like dopamine receptors (D2DRs). Our recent results suggest that various opioids will differentially modulate the responses of D2DRs. The D2DRs are known to be involved in the pathology of addiction and other mental illnesses, indicating the need to improve our understanding of the effects of opioid analgesics on the responses of the D2DRs. Thus, in this study, we first established equianalgesic oral doses of oxycodone, hydrocodone, and morphine using the tail withdrawal assay. Then, mice were orally administered (gavage) with the various opioids or saline once daily for 6 days. Twenty-four hours later, the mice were tested for their locomotor response to quinpirole, a D2/D3 dopamine receptor agonist. Mice pretreated with oxycodone showed significantly greater locomotor supersensitivity to quinpirole than did morphine-pretreated mice, while hydrocodone-pretreated mice showed sensitivity in between that of mice treated with morphine and oxycodone. This finding suggests that various opioids differentially modulate the responses of D2DRs. It provides further evidence supporting of the notion that various opioids carry differential risks to the dopamine reward system. PMID:25617530

Emery, Michael A; Bates, M L Shawn; Wellman, Paul J; Eitan, Shoshana

2015-05-01

248

Preparation and pharmacokinetics study on gastro-floating sustained-release tablets of troxipide.  

PubMed

Abstract The purpose of this research aimed at preparing gastro-floating sustained-release tablets of troxipide and a further study on in vitro release and in vivo bioavailability. Under the circumstances of direct powder compression, the floating tablets were successfully prepared with HPMC as main matrix material, Carbopol as assistant matrix material, octadecanol as floating agent and sodium bicarbonate as foaming agent to float by gas-forming. The floating time and accumulative release amount as evaluation indexes were utilized to perform pre-experiment screening and single-factor test, respectively, while central composite design response surface method was applied for formulation optimization, followed by in vivo pharmacokinetic study in beagles after oral administration for floating tablets and commercial tablets used as the control. The results indicated that the floating sustained-release tablets held a better capability for floating and drug release and more satisfactory pharmacokinetic parameters, such as a lower Cmax, a prolonged Tmax, but an equivalent bioavailability calculated by AUC0-24 compared to commercial tablets. So a conclusion was finally drawn that the floating sustained-release tablets possessing a good release property could be suitable for demands of design. PMID:25190152

Gao, Yunyun; Gao, Yang; Yin, Fei; Wang, Mi; Wang, Zhenhong; Ye, Tiantian; Yang, Yonggang; Pan, W S; Yang, Xinggang

2014-09-01

249

Novel receptor mechanisms for heroin and morphine-6?-glucuronide analgesia  

Microsoft Academic Search

The rapid metabolism of heroin to 6-acetylmorphine and its slower conversion to morphine has led many to believe that heroin and morphine act through the same receptors and that the differences between them are due to their pharmacokinetics. We now present evidence strongly implying that heroin and two potent mu drugs, fentanyl and etonitazine, act through a unique receptor mechanism

Grace C. Rossi; George P. Brown; Liza Leventhal; Ke Yang; Gavril W. Pasternak

1996-01-01

250

Interaction between alcohol deprivation and morphine withdrawal in mice.  

PubMed

Hybrid mice having had 12 weeks free access to flavored alcohol were deprived of it for 3 days. The increase in alcohol intake rate during first 1.5 h of renewal access as compared with its intake rate during the remaining 22.5 h (alcohol-deprivation effect, ADE) was used to select individuals having (HD) or lacking (LD) the ADE. The mice received morphine or placebo pellet implantation for 4 days followed by removal of alcohol and pellets. Cross-maze, acoustic startle response, and tail flick tests were conducted 1 day after morphine withdrawal and after 2 days of alcohol deprivation. Next day, during a second ADE test, placebo-treated HDs again showed ADE and LDs showed no ADE; the HDs during morphine withdrawal also still showed an ADE similar to those in placebo HDs, but LDs after morphine removal differed in showing an ADE. Significantly more hyperalgesia in HD than LD mice was observed during morphine withdrawal. Placebo HDs differed from placebo LDs in showing stereotyped behavior and kindling-like rise in acoustic startle response. Morphine withdrawal caused body weight loss, and converted the startle response curve in both LD and HD mice to a bell-shape curve. In HD mice the alcohol deprivation behavioral pattern was substituted by the corresponding morphine withdrawal pattern. The existence of distinct neural circuits responsible for the development of alcohol and morphine dependence is proposed. PMID:8174503

Salimov, R; Salimova, N; Klodt, P; Maisky, A

1993-12-01

251

Conditioned temperature effects using morphine as the unconditioned stimulus  

Microsoft Academic Search

The conditioning of body temperature changes using an injection of morphine sulphate as the conditioned stimulus was studied in 30 male Wistar rats. Three groups of animals received daily i.p. injections of either 5, 25, or an increasing dose to 200 mg\\/kg morphine; a fourth group received saline injections throughout. Rectal temperature was measured in three different environments five times

Roelof Eikelboom; Jane Stewart

1979-01-01

252

Tests for addiction (chronic intoxication) of morphine type  

PubMed Central

A survey is presented of laboratory and clinical methods for the determination of addiction liability of substances with morphine-like effects. Since physical dependence is the outstanding pharmacological criterion of addiction of morphine type, the procedures for its qualitative and quantitative assessment are described in detail. PMID:13952049

Halbach, H.; Eddy, Nathan B.

1963-01-01

253

Morphine and alternative opioids in cancer pain: the EAPC recommendations  

Microsoft Academic Search

An expert working group of the European Association for Palliative Care has revised and updated its guidelines on the use of morphine in the management of cancer pain. The revised recommendations presented here give guidance on the use of morphine and the alternative strong opioid analgesics which have been introduced in many parts of the world in recent years. Practical

G W Hanks; F de Conno; N Cherny; M Hanna; E Kalso; H J McQuay; S Mercadante; J Meynadier; P Poulain; C Ripamonti; L Radbruch; J Roca i Casas; J Sawe; R G Twycross; V Ventafridda

2001-01-01

254

Morphine Discriminative Control Is Mediated by the Mu Opioid Receptor  

Microsoft Academic Search

Morphine is an effective training drug in drug discrimination procedures. In subsequent generalization tests in which other opioids are administered, mu opioid agonists selectively substitute for the training drug. Given the relative selectivity of morphine for the mu receptor, such substitution patterns suggest that the mu opioid receptor is mediating the discriminative control of this compound. The present study assessed

Glenn W Stevenson; Fernando CAñadas; Xiaoyan Zhang; Kenner C Rice; Anthony L Riley

2000-01-01

255

Risedronate-loaded Eudragit S100 microparticles formulated into tablets.  

PubMed

Risedronate, an anti-osteoporotic drug, is associated with low patient compliance due to the upper gastrointestinal side-effects and stringent dosing regimes. This study aimed to prepare and characterize risedronate-loaded Eudragit® S100 microparticles and develop a final dosage form by the compression of microparticles using direct tableting excipients. Microparticles were prepared by spray-drying and presented yield of 54%, encapsulation efficiency higher than 90%, mean diameter of 3.3?µm, moisture content around 8% and exhibited spherical shape and poor flowability. At pH 1.2, 23% of risedronate was released from microparticles in 120?min, while at pH 6.8 the drug took 90?min to reach 99.5%. Microparticles were compressed into tablets using microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide and 2 polyvinylpyrrolidone concentrations (5% and 15%). Tablets presented low variations in weight, thickness and drug content. Besides, the formulations showed sufficient hardness, low friability and disintegrated in less than 15 min. In acid medium, no more than 16% of the drug was released in 120?min, while in intestinal medium the formulations prolonged the risedronate release for 240?min. Finally, the developed tableted microparticles can be considered a promising dosage form for oral risedronate administration. PMID:23506303

Velasquez, Aline A; Mattiazzi, Juliane; Ferreira, Luana M; Pohlmann, Lauren; Silva, Cristiane B; Rolim, Clarice M B; Cruz, Letícia

2014-05-01

256

Formulation, Characterization and Physicochemical Evaluation of Ranitidine Effervescent Tablets  

PubMed Central

Purpose: The aim of this study was to design, formulate and physicochemically evaluate effervescent ranitidine hydrochloride (HCl) tablets since they are easily administered while the elderly and children sometimes have difficulties in swallowing oral dosage forms. Methods: Effervescent ranitidine HCl tablets were prepared in a dosage of 300 mg by fusion and direct compression methods. The powder blend and granule mixture were evaluated for various pre-compression characteristics, such as angle of repose, compressibility index, mean particle size and Hausner's ratio. The tablets were evaluated for post-compression features including weight variation, hardness, friability, drug content, dissolution time, carbon dioxide content, effervescence time, pH, content uniformity and water content. Effervescent systems with appropriate pre and post-compression qualities dissolved rapidly in water were selected as the best formulations. Results: The results showed that the flowability of fusion method is more than that of direct compression and the F5 and F6 formulations of 300 mg tablets were selected as the best formulations because of their physicochemical characteristics. Conclusion: In this study, citric acid, sodium bicarbonate and sweeteners (including mannitol, sucrose and aspartame) were selected. Aspartame, mint and orange flavors were more effective for masking the bitter taste of ranitidine. The fusion method is the best alternative in terms of physicochemical and physical properties. PMID:24312854

Aslani, Abolfazl; Jahangiri, Hajar

2013-01-01

257

Long-Term Follow-Up of Orally Administered Diacetylmorphine Substitution Treatment  

Microsoft Academic Search

Background: To assess the long-term course of the feasibility and safety of orally administered heroin [diacetylmorphine (DAM)] tablets in substitution treatment of severely addicted opioid users. Design: Open-label, prospective cohort study with 2 non-randomly assigned treatment arms: DAM tablets only (n = 128) or DAM tablets combined with injected DAM and\\/or other opioids (n = 237). The average duration of

Ulrich Frick; Jürgen Rehm; Daniele Zullino; Manrique Fernando; Gerhard Wiesbeck; Jeannine Ammann; Ambros Uchtenhagen

2010-01-01

258

Solid dispersion tablets of breviscapine with polyvinylpyrrolidone K30 for improved dissolution and bioavailability to commercial breviscapine tablets in beagle dogs.  

PubMed

Breviscapine, one of cardiovascular drugs extracted from a Chinese herb Erigeron breviscapinus, has been frequently used to treat cardiovascular diseases such as hypertension, angina pectoris, coronary heart disease and stroke. However, its poor water solubility and low bioavailability in vivo severely restrict the clinical application. To overcome these drawbacks, breviscapine solid dispersion tablets consisting of breviscapine, polyvinylpyrrolidone K30 (PVP K30), microcrystalline cellulose and crospovidone were appropriately prepared. In vitro dissolution profiles showed that breviscapine released percentage of solid dispersion tablets reached 90 %, whereas it was only 40 % for commercial breviscapine tablets. Comparative pharmacokinetic study between solid dispersion tablets and commercial products was investigated on the normal beagle dogs after oral administration. Results showed that the bioavailability of breviscapine was greatly increased by 3.45-fold for solid dispersion tablets. The greatly improved dissolution rate and bioavailability might be attributed to intermolecular hydrogen bonding reactions between PVP K30 and scutellarin. These findings suggest that our solid dispersion tablets can greatly improve the bioavailability as well as the dissolution rate of breviscapine. PMID:24061692

Cong, Wenjuan; Shen, Lan; Xu, Desheng; Zhao, Lijie; Ruan, Kefeng; Feng, Yi

2014-09-01

259

Age adapted morphine titration produces equivalent analgesia and side effects in younger and older patients  

E-print Network

1 Age adapted morphine titration produces equivalent analgesia and side effects in younger: To determine efficacy and safety of postoperative titrated morphine in elderly patients when intravenous complaining of pain received morphine until adequate pain relief. Intravenous morphine was titrated as 3 mg

Boyer, Edmond

260

Is the Combination of Morphine with Ketamine Better than Morphine Alone for Postoperative Intravenous Patient-Controlled Analgesia?  

Microsoft Academic Search

BACKGROUND: The addition of ketamine to morphine for patient-controlled analgesia (PCA) is supported by previous basic and clinical research, but has been challenged by subsequent negative studies. Important limitations of previous studies are the low number of patients analyzed, the use of morphine-ketamine combinations that may not the optimal, and that not all the relevant outcomes have been analyzed. In

Gorazd Sveticic; Farzan Farzanegan; Patrick Zmoos; Sandra Zmoos; Urs Eichenberger; Michele Curatolo

2008-01-01

261

A history of morphine-induced taste aversion learning fails to affect morphine-induced place preference conditioning in rats.  

PubMed

Drugs of abuse have both rewarding and aversive effects, as indexed by the fact that they support place preferences and taste aversions, respectively. In the present study, we explored whether having a history with the aversive effects of morphine (via taste aversion conditioning) impacted the subsequent rewarding effects of morphine, as measured in the place preference design. In Experiment 1, rats were exposed to a taste aversion procedure in which saccharin was followed by morphine. Place preference conditioning was then initiated in which animals were injected with morphine and placed on one side of a two-chambered apparatus. Animals with a taste aversion history acquired place preferences to the same degree as controls without such a history, suggesting that morphine's affective properties condition multiple effects, dependent on the specific stimuli present during conditioning. To determine whether these results were a reflection of processes operating in traditional associative conditioning, in a modified blocking procedure, place preference conditioning was attempted in the presence of a taste previously associated with morphine (Exp. 2). Under these conditions, animals still acquired morphine-induced place preferences comparable to those of animals without a morphine or conditioning history. These results are consistent with the position that drugs of abuse have multiple stimulus effects (positive and negative) that are differentially associated with specific stimuli (environmental and taste) that drive different behavioral responses (approach and avoidance). PMID:23943541

King, Heather E; Riley, Anthony L

2013-12-01

262

Effects of morphine on the human sphincter of Oddi.  

PubMed Central

The effects of morphine on intraluminal pressures recorded from the sphincter of Oddi (SO) at endoscopic retrograde cholangiopancreatography in 19 patients who were without evidence of biliary or pancreatic disease were studied. Morphine was given in four successive doses of 2.5, 2.5, 5, and 10 micrograms/kg iv at five minute intervals. Morphine in subanalgesic doses increased the frequency of SO phasic pressure waves to a maximum of 10-12/min, caused the phasic waves to occur simultaneously along the sphincter segment, increased phasic wave amplitude from 72 (26) (SE) to 136 (31) mmHg, and increased SO basal pressure from 10 (1) to 29 (9) mmHg (p less than 0.05). The effects of morphine on the SO are mediated by more than one opioid receptor type, as naloxone competitively antagonised the increase in phasic wave frequency induced by morphine, but did not affect the increase in SO basal pressure elicited by morphine. When given after naloxone, morphine decreased phasic wave amplitude, an inhibitory effect that is normally masked by morphine's dominant naloxone sensitive excitatory effect. Mu receptors do not appear to be involved in control of spontaneous SO motor function, as naloxone alone did not affect SO motor activity. The excitatory effects of morphine on the SO are not mediated by cholinergic nerves, as they were not blocked by atropine. Cholinergic nerves, however, may have a role in regulating spontaneous SO motor function because atropine alone depressed phasic wave activity and basal pressure. Although morphine does cause 'spasm' of the human SO, its effects are more complex than is commonly believed. PMID:3197985

Helm, J F; Venu, R P; Geenen, J E; Hogan, W J; Dodds, W J; Toouli, J; Arndorfer, R C

1988-01-01

263

Effect of hydroxypropylmethylcellulose (HPMC) on the release profiles and bioavailability of a poorly water-soluble drug from tablets prepared using macrogol and HPMC.  

PubMed

The aim of the present study was to investigate the effect of hydroxypropylmethylcellulose (HPMC-2208), used as an excipient for controlled release of drug, on the release profiles and bioavailability of the poorly water-soluble nifedipine (NP) from a tablet prepared using macrogol 6000 (PEG) and HPMC. The crushing tolerance of the NP tablet prepared using PEG and HPMC (NP-PEG-HPMC tablet) was markedly increased with increasing compression force used during the preparation from 20 to 200 MPa. The values reached their maximal levels (approximately 13 kg for the NP-PEG-HPMC tablet and 8 kg for the PEG tablet) at the compression force of 100 MPa. Although NP is a poorly water-soluble drug, it was rapidly dissolved from the NP-PEG tablet (without HPMC) due to the improvement of its dissolution rate in the presence of PEG. NP dissolution was complete at the latest within 1 h. On the other hand, dissolution of NP from the NP-PEG-HPMC tablet was significantly delayed with an increase in the concentration of HPMC in the tablet. The dissolution of NP from the NP-PEG-HPMC tablet containing 50% HPMC-2208 was markedly delayed as the viscosity of HPMC also increased. Interestingly, the same peak plasma NP concentration (C(max)) and the area under the plasma NP concentration-time curve (AUC(0-10)) were observed for both the NP-PEG tablet and NP-PEG-HPMC tablets, however, the time to C(max) (t(max)) for the NP-PEG-HPMC tablet was significantly higher when the NP-PEG-HPMC tablet was orally administered to rabbits. We describe here a preparation method of a new sustained-release NP-PEG-HPMC tablet using a mixture of NP-PEG granules (prepared with PEG) and HPMC. PMID:10915941

Ishikawa, T; Watanabe, Y; Takayama, K; Endo, H; Matsumoto, M

2000-07-20

264

Tablet Splitting: A Risky Practice  

MedlinePLUS

... the medicine slowly. Splitting these tablets destroys the coating, which means you might absorb the medicine too ... Continuing Education Inspections/Compliance State & Local Officials Consumers Industry Health Professionals FDA Archive Links on this page:

265

Postoperative morphine requirements, nausea and vomiting following anaesthesia for tonsillectomy. Comparison of intravenous morphine and non-opioid analgesic techniques.  

PubMed

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be as effective as opioid analgesia following tonsillectomy in children. Opioids are still frequently used but tonsillectomy is associated with a high incidence of vomiting. This study has attempted to assess postoperative analgesic consumption and nausea and vomiting after general anaesthesia for tonsillectomy using either paracetamol premedication, paracetamol plus a NSAID or intravenous morphine to provide postoperative analgesia. Some children required a rescue dose of morphine in the recovery room, including some who had received intravenous morphine at induction. Least supplementary morphine was required by those who had received paracetamol plus ketorolac. Postoperative nausea and vomiting was significantly less in the two groups which were not given intraoperative morphine. The number of vomiting incidents was also much less. We conclude that the preoperative administration of paracetamol alone provides satisfactory analgesia in many children but that supplementary analgesia is still required for some. PMID:7489439

Mather, S J; Peutrell, J M

1995-01-01

266

21 CFR 520.82a - Aminopropazine fumarate tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 false Aminopropazine fumarate tablets. 520.82a Section 520.82a Food...DRUGS § 520.82a Aminopropazine fumarate tablets. (a) Specifications. The drug is in tablet form. Each tablet contains...

2012-04-01

267

21 CFR 520.82a - Aminopropazine fumarate tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 false Aminopropazine fumarate tablets. 520.82a Section 520.82a Food...DRUGS § 520.82a Aminopropazine fumarate tablets. (a) Specifications. The drug is in tablet form. Each tablet contains...

2013-04-01

268

21 CFR 520.82a - Aminopropazine fumarate tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 false Aminopropazine fumarate tablets. 520.82a Section 520.82a Food...DRUGS § 520.82a Aminopropazine fumarate tablets. (a) Specifications. The drug is in tablet form. Each tablet contains...

2014-04-01

269

21 CFR 520.82a - Aminopropazine fumarate tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 false Aminopropazine fumarate tablets. 520.82a Section 520.82a Food...DRUGS § 520.82a Aminopropazine fumarate tablets. (a) Specifications. The drug is in tablet form. Each tablet contains...

2011-04-01

270

Treatment of schizophrenia with paliperidone extended-release tablets: A 6-week placebo-controlled trial  

Microsoft Academic Search

BackgroundPaliperidone extended-release tablet (paliperidone ER) is an investigational oral psychotropic developed for schizophrenia treatment. It utilizes OROS® technology to provide a unique pharmacokinetic profile, eliminating the need for titration and potentially leading to improved tolerability. Furthermore, paliperidone undergoes limited hepatic metabolism.

J. Kane; F. Canas; M. Kramer; L. Ford; C. Gassmann-Mayer; P. Lim; M. Eerdekens

2007-01-01

271

Alkaloids; Strychnine, Codeine, Heroin, and Morphine  

NSDL National Science Digital Library

The featured molecules this month come from the article "The Conversion of Carboxylic Acids to Ketones: A Repeated Discovery" by John W. Nicholson and Alan D. Wilson. The authors describe the repeated discovery of this reaction and illustrate its central role in Woodward's total synthesis of strychnine. Strychnine is a member of a large class of nitrogen heterocycles known as alkaloids, a name derived from the fact that all produce basic solutions in water. Other well-known members of this class of compounds, all of which are pharmacologically active, are nicotine, atropine (deadly nightshade), quinine, lysergic acid, cocaine, and the three structurally similar compounds codeine, heroin, and morphine.

272

Synthetic substances with morphine-like effect*  

PubMed Central

As a basis for a series of studies on the pharmacological, therapeutic, and addictive properties of synthetic drugs with morphine-like effect, this paper deals with chemical aspects of the compounds of this type so far known. Four major groups, each with a fundamentally different chemical structure, are described: pethidine, methadone, morphinan, and dithienylbutenylamine. For each substance belonging to these groups, the formula, synonyms, and methods of synthesis are indicated. A description of pethidine according to the specifications of the Pharmacopoea Internationalis is annexed to the paper. PMID:13199662

Braenden, Olav J.; Wolff, P. O.

1954-01-01

273

Morphine tolerance offers protection from radiogenic performance deficits  

SciTech Connect

When rats are exposed to a sufficiently large dose of ionizing radiation they exhibit lethargy, hypokinesia, and deficits in performance. These and other behavioral changes parallel those often observed in this species after a large dose of morphine. Since the release of endogenous opiates has been implicated in some stress reactions, we sought to determine if they might play a part in radiogenic behavioral deficits. Rats were trained to criterion on a signaled avoidance task. Some subjects were then implanted with a pellet containing 75 mg of morphine. Other animals received placebo implants. Over a number of days, morphine tolerance was evaluated by measurement of body temperature changes. Prior to 2500 rad /sup 60/Co exposure or sham irradiation, morphine (or placebo) pellets were removed. Twenty-four hours later rats were retested to assess their performance on the avoidance task. Morphine-tolerant subjects performed significantly better than the irradiated placebo-implanted group and no differently than morphine-tolerant/sham-irradiated animals. Morphine tolerance seems to provide a degree of behavioral radiation resistance. These data are consistent with the hypothesis that endogenous opiate hyperexcretion may play some part in the behavioral deficits often observed after irradiation.

Mickley, G.A. (U.S. Air Force Acamemy, Co); Stevens, K.E.; Burrows, J.M.; White, G.A.; Gibbs, G.L.

1983-02-01

274

Endogenous Cholinergic Neurotransmission Contributes to Behavioral Sensitization to Morphine  

PubMed Central

Neuroplasticity in the mesolimbic dopaminergic system is critical for behavioral adaptations associated with opioid reward and addiction. These processes may be influenced by cholinergic transmission arising from the laterodorsal tegmental nucleus (LDTg), a main source of acetylcholine to mesolimbic dopaminergic neurons. To examine this possibility we asked if chronic systemic morphine administration affects expression of genes in ventral and ventrolateral periaqueductal gray at the level of the LDTg using rtPCR. Specifically, we examined gene expression changes in the area of interest using Neurotransmitters and Receptors PCR array between chronic morphine and saline control groups. Analysis suggested that chronic morphine administration led to changes in expression of genes associated, in part, with cholinergic neurotransmission. Furthermore, using a quantitative immunofluorescent technique, we found that chronic morphine treatment produced a significant increase in immunolabeling of the cholinergic marker (vesicular acetylcholine transporter) in neurons of the LDTg. Finally, systemic administration of the nonselective and noncompetitive neuronal nicotinic antagonist mecamylamine (0.5 or 2 mg/kg) dose-dependently blocked the expression, and to a lesser extent the development, of locomotor sensitization. The same treatment had no effect on acute morphine antinociception, antinociceptive tolerance or dependence to chronic morphine. Taken together, the results suggest that endogenous nicotinic cholinergic neurotransmission selectively contributes to behavioral sensitization to morphine and this process may, in part, involve cholinergic neurons within the LDTg. PMID:25647082

Bajic, Dusica; Soiza-Reilly, Mariano; Spalding, Allegra L.; Berde, Charles B.; Commons, Kathryn G.

2015-01-01

275

A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects  

PubMed Central

Background In type 2 diabetes mellitus, fixed-dose combination (FDC) can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD), pharmacokinetic (PK), and tolerability profiles of gemigliptin and extended-release metformin (metformin XR) between FDC and separate tablets. Methods A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1) and metformin XR (500 mg ×2) were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4) activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs) of FDC to separate tablet formulations and their 90% confidence intervals (CIs) were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study. Results The plasma DPP-4 activity–time curves of the FDC and the separate tablets almost overlapped, leading to a GMR (90% CI) of the FDC to separate tablets for the plasma DPP-4 activity and its maximum inhibition of 1.00 (0.97–1.04) and 0.92 (0.82–1.05), respectively. Likewise, all of the GMRs (90% CIs) of FDC to separate tablets for the area under the plasma concentration–time curve and maximum plasma concentration of gemigliptin and metformin fell entirely within the conventional bioequivalence range of 0.80–1.25. Both the FDC and separate tablets were well tolerated. Conclusion The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable. The FDC tablet of gemigliptin and metformin sustained release can be a convenient therapeutic option in patients with type 2 diabetes mellitus requiring a combination approach. PMID:25678778

Park, Sang-In; Lee, Howard; Oh, Jaeseong; Lim, Kyoung Soo; Jang, In-Jin; Kim, Jeong-Ae; Jung, Jong Hyuk; Yu, Kyung-Sang

2015-01-01

276

Morphine dependence and withdrawal induced changes in cholinergic signaling  

PubMed Central

Cholinergic signaling is thought to be involved in morphine dependence and withdrawal, but the specific mechanisms involved remain unclear. The current study aimed to identify alterations in the cholinergic system that may contribute to the development of morphine dependence and withdrawal. Acetylcholinesterase (AChE) activity and [3H]-epibatidine binding were evaluated in order to determine if morphine dependence and withdrawal induces alterations in cholinergic signaling or expression of high affinity nicotinic acetylcholine receptors (nAChRs) in the midbrain (MB), medial habenula (MHb) and interpeduncular nucleus (IPN). The effect of cholinergic signaling through nAChRs on morphine-withdrawal induced jumping behavior was then determined. Lastly, the contribution of ?4-containing nAChRs receptors in the MHb to morphine-withdrawal induced jumping behavior and neuronal activity as indicated by c-fos expression was assessed. Chronic morphine administration decreased AChE activity in MB and MHb, an effect that was no longer present following precipitated withdrawal. Morphine dependent mice showed increased nicotinic acetylcholine receptor (nAChR) levels in MB. Further, nicotine (0.4 mg/kg) and lobeline (3 mg/kg) decreased jumping behavior while mecamylamine (1 mg/kg) had no effect. Knock-down of ?4 subunit-containing nAChRs in the MHb attenuated c-fos activation, but did not decrease morphine withdrawal-induced jumping. Thus, morphine withdrawal induces cholinergic signaling in the MHb, but this does not appear to be responsible for the effects of cholinergic drugs on somatic signs of opiate withdrawal, as measured by jumping behavior. PMID:23651795

Neugebauer, Nichole M.; Einstein, Emily B.; Lopez, Maria B.; McClure-Begley, Tristan D.; Mineur, Yann S.; Picciotto, Marina R.

2013-01-01

277

2557 (1 2556) 1 1182 ACARBOSE 50 MG COMPRESSED TAB. FOIL ACARBOSE TABLET TABLET 3.32  

E-print Network

TABLET TABLET 3.32 2 735 ACETAR 1000 ML ACETATED RINGERS INJECTION 1000 ML 44.00 3 2338 ACETAZOLAMIDE 250 MG COMPRESSED TAB. ACETAZOLAMIDE TABLET TABLET 1.75 4 1553 ACETYLCYSTEINE 100 MG GRANULE VIAL 214.00 12 962 ACYCLOVIR 200 MG COMPRESSED TAB. FOIL ACYCLOVIR TABLET TABLET 1.80 13 108 ACYCLOVIR

Laksanacharoen, Sathaporn

278

Effects of morphine and naloxone on feline colonic transit  

SciTech Connect

The effects of endogenous and exogenous opioid substances on feline colonic transit were evaluated using colonic transit scintigraphy. Naloxone accelerated emptying of the cecum and ascending colon, and filling of the transverse colon. Endogenous opioid peptides thus appear to play a significant role in the regulation of colonic transit. At a moderate dose of morphine cecum and ascending colon transit was accelerated, while at a larger dose morphine had no effect. Since naloxone, a relatively nonspecific opioid antagonist, and morphine, a principally mu opioid receptor agonist, both accelerate proximal colonic transit, a decelerating role for at least one of the other opioid receptors is inferred.

Krevsky, B.; Libster, B.; Maurer, A.H.; Chase, B.J.; Fisher, R.S.

1989-01-01

279

Cholescintigraphy in acute cholecystitis: use of intravenous morphine  

SciTech Connect

Conventional cholescintigraphy (60 patients) and a modified protocol (59 patients) were compared in 74 females and 45 males with acute cholecystitis. In the modified protocol, intravenous morphine was administered whenever the gallbladder was not seen 40 minutes after injection of Tc-99m-pyroxylidene-glutamate. Accuracy was 98% with morphine, compared with 88% for the conventional protocol; specificity improved from 83% to 100% with no loss of sensitivity. Low doses of morphine are well tolerated and can result in a highly accurate diagnosis of acute cholecystitis without the need for delayed imaging.

Choy, D.; Shi, E.C.; McLean, R.G.; Hoschl, R.; Murray, I.P.C.; Ham, J.M.

1984-04-01

280

Recent Advances in the Synthesis of Morphine and Related Alkaloids  

NASA Astrophysics Data System (ADS)

Morphine, an alkaloid isolated from the opium poppy, has been widely used as an analgesic, and has been a fascinating synthetic target of organic chemists. After the first total synthesis reported in 1952, a number of synthetic studies toward morphine have been reported, and findings obtained in such studies have greatly contributed to the progress of synthetic organic chemistry as well as medicinal chemistry. This review provides an overview of recent studies toward the total synthesis of morphine and related alkaloids. Work reported in the literature since 2004 will be reviewed.

Chida, Noritaka

281

Stress antagonizes morphine-induced analgesia in rats  

NASA Technical Reports Server (NTRS)

Exposure to restraint stress resulted in antagonism of the analgesic effect of administered morphine in adult male rats. This antagonism of morphine-induced analgesia by restraint stress was not affected by adrenalectomy one day prior to testing, suggesting that stress-induced secretion of corticosteroids is not critical to this antagonism. In addition, parenteral administration of exogenous adrenocorticotropin (ACTH) mimicked the effect of stress in antagonizing morphine's analgesic efficacy. The hypothesis that ACTH is an endogenous opiate antagonist involved in modulating pain sensitivity is supported.

Vernikos, J.; Shannon, L.; Heybach, J. P.

1981-01-01

282

Morphine actions on supraoptic oxytocin neurones in anaesthetized rats: tolerance after i.c.v. morphine infusion.  

PubMed Central

1. The effects of acute i.v. administration of morphine on putative oxytocin neurones of the supraoptic nucleus were studied in urethane-anaesthetized female rats which had been exposed to i.c.v. infusion of morphine (up to 50 micrograms h-1) or vehicle for 5 days. 2. In vehicle-infused rats, i.v. morphine inhibited the spontaneous activity of six out of seven putative oxytocin neurones. Increasing doses of morphine were given, from 1 microgram kg-1 to 5 mg kg-1. The median cumulative threshold dose to produce significant inhibition was 20 micrograms kg-1 (seven cells in six rats); six out of seven cells were inhibited at 161 micrograms kg-1. The highest doses tested inhibited by approximately 90% (excluding one unaffected cell). Inhibition was fully reversed by i.v. naloxone without overshoot, indicating a lack of acute dependence. 3. Injection of morphine i.c.v. inhibited firing at doses that were ineffective by i.v. injection and the effects of i.c.v. morphine were reversed by i.v. naloxone. 4. Acute morphine (500 micrograms kg-1 i.v.) reduced the plasma concentration of oxytocin, measured after 15 min by specific radioimmunoassay, by 34% (n = 14). 5. In lactating rats i.c.v. injection of morphine (1-2 micrograms) inhibited the activity of supraoptic neurones identified as oxytocinergic by their responses to suckling. 6. In seventeen rats infused with i.c.v. morphine the initial firing rate of twenty-eight spontaneously active, non-phasic neurones was significantly less, by 24%, than thirty-four similar cells in control rats, indicating incomplete tolerance to i.c.v. morphine. Morphine (up to 161 micrograms kg-1 given i.v.) inhibited none of nine active non-phasic neurones (P less than 0.01 compared to control rats), but at higher doses inhibited four of nine cells; the overall median threshold cumulative dose (1660 micrograms kg-1) was significantly greater than in vehicle-infused controls, indicating tolerance to i.v. morphine. In contrast with control rats, some cells (5/9) were modestly excited by low doses of morphine. Naloxone (5 mg kg-1 i.v.) produced withdrawal excitation: the firing rate of putative oxytocin neurones increased to approximately 260% of the pre-i.v. morphine value, indicating dependence in mechanisms regulating the firing rate of these neurones. 7. In morphine-infused rats, the basal firing rate of nineteen phasically active, putative vasopressin supraoptic neurones was not different in nineteen phasic cells in controls (6.4 +/- 0.7 vs. 4.2 +/- 0.6 Hz). 8. Thus morphine potently inhibits the firing of magnocellular oxytocin neurones in the female rat, inhibiting oxytocin secretion. Morphine tolerance and dependence develop during i.c.v. infusion of morphine for 5 days. Similar tolerance to and dependence upon endogenous opioids during pregnancy may be important in the preparation of oxytocin neurones for parturition. PMID:1804971

Pumford, K M; Leng, G; Russell, J A

1991-01-01

283

CCL5 and cytokine expression in the rat brain: differential modulation by chronic morphine and morphine withdrawal  

PubMed Central

Opioids have been shown to influence the immune system and to promote the expression of pro-inflammatory cytokines in the central nervous system. However, recent data have shown that activation of opioid receptors increases the expression and release of the neuroprotective chemokine CCL5 from astrocytes in vitro. To further define the interaction between CCL5 and inflammation in response to opioids, we have examined the effect of chronic morphine and morphine withdrawal on the in vivo expression of CCL5 as well as of pro-inflammatory cytokines interleukin-1? (IL-1?) and tumor necrosis factor-? (TNF-?). Rats undergoing a chronic morphine paradigm (10 mg/kg increasing to 30 mg/kg, twice a day for 5 days) showed a two-fold increase of CCL5 protein and mRNA within the cortex and striatum. No changes were observed in the levels of IL-1? and TNF-?. Naltrexone blocked the effect of morphine. A chronic morphine paradigm with no escalating doses (10 mg/kg, twice a day) did not alter CCL5 levels compared to saline-treated animals. On the contrary, rats undergoing spontaneous morphine withdrawal exhibited lower levels of CCL5 within the cortex as well as increased levels of pro-inflammatory cytokines and Iba-1 positive cells than saline-treated rats. Overall, these data suggest that morphine withdrawal may promote cytokines and other inflammatory responses that have the potential of exacerbating neuronal damage. PMID:23968971

Campbell, Lee A.; Avdoshina, Valeriya; Rozzi, Summer; Mocchetti, Italo

2013-01-01

284

E-Books and the Tablet PC.  

ERIC Educational Resources Information Center

Highlights the emerging technologies of e-books, electronic versions of texts, and the Tablet PC, a new hybrid laptop computer and personal digital assistant that features a writing tablet and stylus-based input/navigation. (Author/VWL)

Goodwin-Jones, Bob

2003-01-01

285

Blockade of Toll-Like Receptor 4 Attenuates Morphine Tolerance and Facilitates the Pain Relieving Properties of Morphine  

PubMed Central

The ventrolateral periaqueductal gray (vlPAG) is an integral locus for morphine action. Although it is clear that glia contribute to the development of morphine tolerance, to date, the investigation of their role has been limited to spinal and medullary loci. Opioids induce a neuroinflammatory response that opposes acute and long-term analgesia, thereby limiting their efficacy as therapeutic agents. Recent data suggest that the innate immune receptor Toll-like receptor 4 (TLR4), along with its coreceptor myeloid differentiation factor-2 (MD-2), mediates these effects. To date, the brain loci through which TLR4 modulates morphine tolerance have not been identified. We have previously demonstrated that chronic subcutaneous morphine results in tolerance that is accompanied by increases in vlPAG glial cell activity. Using in vivo pharmacological manipulations of vlPAG glia and TLR4 in the adult male rat, we show that intra-vlPAG administration of the general glial cell metabolic inhibitor propentofylline or the astrocyte activity inhibitor fluorocitrate attenuate tolerance to morphine. Characterization of MD-2 expression within the PAG revealed dense MD-2 expression throughout the vlPAG. Further, antagonizing vlPAG TLR4 dose dependently prevented the development of morphine tolerance, and vlPAG microinjections of TLR4 agonists dose dependently produced a “naive” tolerance to subsequent challenge doses of morphine. Finally, using a model of persistent inflammatory pain and pharmacological manipulation of TLR4 we demonstrate that systemic antagonism of TLR4 potentiated acute morphine antihyperalgesia. These results, together, indicate that vlPAG glia regulate morphine tolerance development via TLR4 signaling, and implicate TLR4 as a potential therapeutic target for the treatment of pain. PMID:24089500

Eidson, Lori N.

2013-01-01

286

Detection of morphine-3-sulfate and morphine-6-sulfate in human urine and plasma, and formation in liver cytosol  

PubMed Central

Morphine is still the mainstay in treatment of severe pain and is metabolized in the liver mainly by glucuronidation, partly to the pharmacologically active morphine-6-glucuronide (M6G). The sulfation pathway has attracted much less attention but may also form active metabolites. The aim of the present study was to study two sulfate metabolites of morphine in humans. Urine and plasma from newborns, adult heroin addicts, and terminal cancer patients was analyzed for the presence of morphine-3-sulfate (M3S) and morphine-6-sulfate (M6S) by a new liquid chromatography – tandem mass spectrometry (LC-MS/MS) method. In addition, morphine sulfation was studied in vitro in human liver cytosol preparations. M3S was present in urine and plasma from all study groups although at lower concentrations than morphine-3-glucuronide (M3G). The plasma M3S/M3G ratio was 30 times higher in newborns than in adults indicating that the relative sulfation is more important at early stage of life. M6S was measurable in only one plasma sample from a newborn patient, and in one of the urine sample from the drug testing group. The incubation of morphine with liver cytosol extracts resulted in approximately equal rate of formation of both M3S and M6S. In conclusion, sulfation of morphine is catalyzed in human liver but this minor metabolic pathway probably lacks clinical significance. The M6S metabolite is formed at a low rate, making it undetectable in most individuals. PMID:25505615

Andersson, Maria; Björkhem-Bergman, Linda; Ekström, Lena; Bergqvist, Lena; Lagercrantz, Hugo; Rane, Anders; Beck, Olof

2014-01-01

287

Bioequivalence study of 400 and 100 mg imatinib film-coated tablets in healthy volunteers.  

PubMed

The aim of the study was to investigate the bioavailability of a generic product of 100 mg and 400 mg imatinib film-coated tablets (test) as compared to that of a branded product (reference) at the same strength to determine bioequivalence. The secondary objective of the study was to evaluate tolerability of both products. An open-label, randomized, crossover, two-period, single-dose, comparative study was conducted in 43 (Imatynib-Biofarm 100 mg film-coated tablet) and in 42 (Imatynib-Biofarm 400 mg film-coated tablet), brand name Imatenil, Caucasian healthy volunteers in fed conditions. A single oral dose administration of the test or reference product was separated by 14-day washout period. The imatinib and its metabolite N-desmethyl imatinib concentrations were determined using a validated LC MS/MS method. The results of the single-dose study in healthy volunteers indicated that the film-coated tablets of Imatynib-Biofarm 100 mg and 400 mg film-coated tablets manufactured by Biofarm Sp. z o.o. (test products) are bioequivalent to those of Glivec 100 mg and 400 mg film-coated tablets manufactured by Novartis Pharma GmbH (reference products). Both products in the two doses of imatinib were well tolerated. PMID:25362813

Ostrowicz, Andrzej; Miko?ajczak, Przemys?aw L; Wierzbicka, Marzena; Boguradzki, Piotr

2014-01-01

288

Self nano-emulsifying simvastatin based tablets: design and in vitro/in vivo evaluation.  

PubMed

The aim of this work is to improve the oral bioavailability of poorly water soluble drug, simvastatin (SV) through combining the advantages of self-nanoemulsifying systems (SNEs) and tablets. Ternary phase diagram was constructed using Labrafil, Tween 80 and Transcutol, in order to evaluate self-nanoemulsification domain. The particle size distribution and zeta potential of the prepared systems were evaluated using Malvern Zetasizer. Liquisolid powders were prepared using Aeroperl(®) as a coating material and Avicel(®) or Starch 1500 as carrier materials, the powder flow properties were then evaluated. Compressed SV SNE based tablets were evaluated regarding their physical characteristics, in-vitro release properties as well as in-vivo pharmacokinetic evaluation in six healthy human volunteers using a validated LC/MS/MS method. The in-vitro release results revealed that the developed SNE based tablets improved the release of SV significantly, compared to commercially available SV tablets (Zocor(®)). The optimal SV SNE tablet formulation was S3St10 (10% Labrafil, 60% Tween 80, and 30% Transcutol). The in-vivo evaluation of S3St10 revealed that rapid and enhanced absorption of SV could be obtained from the SNE based tablet, with a 1.5 fold increase in bioavailability than that obtained after administration of Zocor(®). Hence such an approach could be promising in improving the bioavailability of SV. PMID:22468935

Abdelbary, Ghada; Amin, Maha; Salah, Salwa

2013-01-01

289

Quantitative analysis of visible surface defect risk in tablets during film coating using terahertz pulsed imaging.  

PubMed

Tablets are the most common form of solid oral dosage produced by pharmaceutical industries. There are several challenges to successful and consistent tablet manufacturing. One well-known quality issue is visible surface defects, which generally occur due to insufficient physical strength, causing breakage or abrasion during processing, packaging, or shipping. Techniques that allow quantitative evaluation of surface strength and the risk of surface defect would greatly aid in quality control. Here terahertz pulsed imaging (TPI) was employed to evaluate the surface properties of core tablets with visible surface defects of varying severity after film coating. Other analytical methods, such as tensile strength measurements, friability testing, and scanning electron microscopy (SEM), were used to validate TPI results. Tensile strength and friability provided no information on visible surface defect risk, whereas the TPI-derived unique parameter terahertz electric field peak strength (TEFPS) provided spatial distribution of surface density/roughness information on core tablets, which helped in estimating tablet abrasion risk prior to film coating and predicting the location of the defects. TPI also revealed the relationship between surface strength and blending condition and is a nondestructive, quantitative approach to aid formulation development and quality control that can reduce visible surface defect risk in tablets. PMID:24300215

Niwa, Masahiro; Hiraishi, Yasuhiro

2014-01-30

290

Stability of an extemporaneously compounded levothyroxine sodium oral liquid.  

PubMed

The stability of levothyroxine sodium in oral liquid dosage forms compounded from commercially available tablets was studied. Levothyroxine sodium oral liquids (25 micrograms/mL) were prepared from tablets and from powder with and without methylparaben preservative and transferred to amber, high-density polyethylene bottles. Five bottles of each tablet-based formulation were stored at 2-8 degrees C, 23-27 degrees C, and 38-42 degrees C, and five bottles of each powder-based formulation were stored at 38-42 degrees C. On days 3, 8, 14, 22, 31, 61, and 90, samples were taken from each bottle and analyzed for drug concentration by stability-indicating high-performance liquid chromatography. There was significant degradation of levothyroxine sodium in all the formulations. However, the tablet-based formulation without preservative stored at 4 degrees C retained at least 90% of its initial concentration for eight days after compounding. Degradation occurred faster in the tablet-based formulation with preservative. None of the formulations retained > or = 90% initial potency by day 14. An extemporaneous oral liquid formulation of levothyroxine sodium 25 micrograms/mL compounded from crushed tablets was stable for eight days when stored in amber bottles at 4 degrees C. PMID:8734676

Boulton, D W; Fawcett, J P; Woods, D J

1996-05-15

291

Unleashed: Web tablet integration into the home  

Microsoft Academic Search

To understand how web access from a portable tablet appliance changes the way people use the Internet, MediaOne gave families pen-based tablet computers with a wireless connection to our high-speed data network. We used ethnographic and usability methods to understand how tablets would be integrated into household activities and to define user requirements for such devices. Participants viewed the tablet

Anne P. McClard; Patricia Somers

2000-01-01

292

Galileo's Telescopy and Jupiter's Tablet  

NASA Astrophysics Data System (ADS)

A previous paper (BAAS 33:4, 1363, 2001) reported on the dramatic scene in Shakespeare's Cymbeline that features the descent of the deity Jupiter. The paper suggested that the four ghosts circling the sleeping Posthumus denote the four Galilean moons of Jupiter. The god Jupiter commands the ghosts to lay a tablet upon the prone Posthumus, but says that its value should not be overestimated. When Posthumus wakens he notices the tablet, which he calls a "book." Not only has the deity's "tablet" become the earthling's "book," but it appears that the book has covers which Posthumus evidently recognizes because without even opening the book he ascribes two further properties to it: rarity, and the very property that Jupiter had earlier attributed, viz. that one must not read too much into it. The mystery deepens when the Jovian gift undergoes a second metamorphosis, to "label." With the help of the OED, the potentially disparate terms "tablet," "book," and "label," may be explained by terms appropriate either to supernatural or worldly beings. "Tablet" may recognize the Mosaic artifact, whereas "book" and "label" are probably mundane references to Galileo's Sidereus Nuncius which appeared shortly before Cymbeline. The message of the Olympian god indicates therefore that the book is unique even as its contents have limited value. The first property celebrates the fact that Galileo's book is the first of its kind, and the second advises that all results except the discovery of Jupiter's moons have been reported earlier, in Hamlet.

Usher, P. D.

2003-12-01

293

Novel gastroretentive sustained-release tablet of tacrolimus based on self-microemulsifying mixture: in vitro evaluation and in vivo bioavailability test  

PubMed Central

Aim: To develop a novel gastroretentive drug delivery system based on a self-microemulsifying (SME) lipid mixture for improving the oral absorption of the immunosuppressant tacrolimus. Methods: Liquid SME mixture, composed of Cremophor RH40 and monocaprylin glycerate, was blended with polyethylene oxide, chitosan, polyvinylpyrrolidone and mannitol, and then transformed into tablets via granulation, with ethanol as the wetting agent. The tablets were characterized in respect of swelling, bioadhesive and SME properties. In vitro dissolution was conducted using an HCl buffer at pH 1.2. Oral bioavailability of the tablets was examined in fasted beagle dogs. Results: The tablet could expand to 13.5 mm in diameter and 15 mm in thickness during the initial 20 min of contact with the HCl buffer at pH 1.2. The bioadhesive strength was as high as 0.98±0.06 N/cm2. The SME gastroretentive sustained-release tablets preserved the SME capability of the liquid SME formations under transmission electron microscope. The drug-release curve was fit to the zero-order release model, which was helpful in reducing fluctuations in blood concentration. Compared with the commercially available capsules of tacrolimus, the relative bioavailability of the SME gastroretentive sustained-release tablets was 553.4%±353.8%. Conclusion: SME gastroretentive sustained-release tablets can enhance the oral bioavailability of tacrolimus with poor solubility and a narrow absorption window. PMID:21927013

Wang, Yan-ping; Gan, Yong; Zhang, Xin-xin

2011-01-01

294

21 CFR 520.531 - Cythioate tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Cythioate tablets. 520.531 Section 520.531 Food...ANIMAL DRUGS § 520.531 Cythioate tablets. (a) [Reserved] (b) Sponsors...for use of 30- and 90-milligram (mg) tablets and see No. 053501 in §...

2014-04-01

295

21 CFR 520.1510 - Nitenpyram tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Nitenpyram tablets. 520.1510 Section 520.1510 Food and...NEW ANIMAL DRUGS § 520.1510 Nitenpyram tablets. (a) Specifications . Each tablet contains 11.4 or 57 milligrams (mg)...

2011-04-01

296

Touch Screen Tablets and Emergent Literacy  

ERIC Educational Resources Information Center

The use of touch screen tablets by young children is increasing in the home and in early childhood settings. The simple tactile interface and finger-based operating features of tablets may facilitate preschoolers' use of tablet application software and support their educational development in domains such as literacy. This article reviews…

Neumann, Michelle M.; Neumann, David L.

2014-01-01

297

21 CFR 520.816 - Epsiprantel tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Epsiprantel tablets. 520.816 Section 520.816 Food and...NEW ANIMAL DRUGS § 520.816 Epsiprantel tablets. (a) Specifications . Each tablet contains either 12.5, 25, 50, or 100...

2013-04-01

298

21 CFR 520.816 - Epsiprantel tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Epsiprantel tablets. 520.816 Section 520.816 Food and...NEW ANIMAL DRUGS § 520.816 Epsiprantel tablets. (a) Specifications . Each tablet contains either 12.5, 25, 50, or 100...

2010-04-01

299

21 CFR 520.531 - Cythioate tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Cythioate tablets. 520.531 Section 520.531 Food...ANIMAL DRUGS § 520.531 Cythioate tablets. (a) [Reserved] (b) Sponsors...for use of 30- and 90-milligram (mg) tablets and see No. 053501 in §...

2010-04-01

300

21 CFR 520.531 - Cythioate tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Cythioate tablets. 520.531 Section 520.531 Food...ANIMAL DRUGS § 520.531 Cythioate tablets. (a) [Reserved] (b) Sponsors...for use of 30- and 90-milligram (mg) tablets and see No. 053501 in §...

2011-04-01

301

21 CFR 520.1510 - Nitenpyram tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Nitenpyram tablets. 520.1510 Section 520.1510 Food and...NEW ANIMAL DRUGS § 520.1510 Nitenpyram tablets. (a) Specifications . Each tablet contains 11.4 or 57 milligrams (mg)...

2012-04-01

302

21 CFR 520.816 - Epsiprantel tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Epsiprantel tablets. 520.816 Section 520.816 Food and...NEW ANIMAL DRUGS § 520.816 Epsiprantel tablets. (a) Specifications . Each tablet contains either 12.5, 25, 50, or 100...

2011-04-01

303

Tablet PC Enhanced Curricula University of Washington  

E-print Network

Tablet PC Enhanced Curricula University of Washington Richard Anderson http://www.cs.washington.edu/education/dl/presenter/ 2. Students write answers on slides on their tablets and send them back to the instructor Classroom · Tablet PC based classroom interaction system · Supports inking on slides to integrate slide based content

Anderson, Richard

304

21 CFR 520.531 - Cythioate tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Cythioate tablets. 520.531 Section 520.531 Food...ANIMAL DRUGS § 520.531 Cythioate tablets. (a) [Reserved] (b) Sponsors...for use of 30- and 90-milligram (mg) tablets and see No. 053501 in §...

2013-04-01

305

21 CFR 520.1510 - Nitenpyram tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Nitenpyram tablets. 520.1510 Section 520.1510 Food and...NEW ANIMAL DRUGS § 520.1510 Nitenpyram tablets. (a) Specifications. Each tablet contains 11.4 or 57 milligrams (mg)...

2014-04-01

306

21 CFR 520.1510 - Nitenpyram tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Nitenpyram tablets. 520.1510 Section 520.1510 Food and...NEW ANIMAL DRUGS § 520.1510 Nitenpyram tablets. (a) Specifications . Each tablet contains 11.4 or 57 milligrams (mg)...

2010-04-01

307

21 CFR 520.812 - Enrofloxacin tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Enrofloxacin tablets. 520.812 Section 520.812 Food and...NEW ANIMAL DRUGS § 520.812 Enrofloxacin tablets. (a) Specifications. Each tablet contains either 22.7, 68.0, or...

2011-04-01

308

21 CFR 520.812 - Enrofloxacin tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Enrofloxacin tablets. 520.812 Section 520.812 Food and...NEW ANIMAL DRUGS § 520.812 Enrofloxacin tablets. (a) Specifications. Each tablet contains either 22.7, 68.0, or...

2012-04-01

309

Mathematics Instruction and the Tablet PC  

ERIC Educational Resources Information Center

The use of tablet PCs in teaching is a relatively new phenomenon. A cross between a notebook computer and a personal digital assistant (PDA), the tablet PC has all of the features of a notebook with the additional capability that the screen can also be used for input. Tablet PCs are usually equipped with a stylus that allows the user to write on…

Fister, K. Renee; McCarthy, Maeve L.

2008-01-01

310

21 CFR 520.816 - Epsiprantel tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Epsiprantel tablets. 520.816 Section 520.816 Food and...NEW ANIMAL DRUGS § 520.816 Epsiprantel tablets. (a) Specifications . Each tablet contains either 12.5, 25, 50, or 100...

2012-04-01

311

21 CFR 520.1510 - Nitenpyram tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Nitenpyram tablets. 520.1510 Section 520.1510 Food and...NEW ANIMAL DRUGS § 520.1510 Nitenpyram tablets. (a) Specifications . Each tablet contains 11.4 or 57 milligrams (mg)...

2013-04-01

312

21 CFR 520.812 - Enrofloxacin tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Enrofloxacin tablets. 520.812 Section 520.812 Food and...NEW ANIMAL DRUGS § 520.812 Enrofloxacin tablets. (a) Specifications. Each tablet contains either 22.7, 68.0, or...

2010-04-01

313

Scaffolding Equals Success in Teaching Tablet PCs  

ERIC Educational Resources Information Center

After many years of using the mouse and keyboard as the primary means of computer input, people are seeing a strong surge into a new generation of input technologies such as tablet PCs. As more professionals adopt tablet PCs for use in the workplace, there is a subsequent increased demand for tablet PC instruction in the classroom. Examples of…

Dickerson, Jeremy; Williams, Scott; Browning, J. B.

2009-01-01

314

21 CFR 520.812 - Enrofloxacin tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Enrofloxacin tablets. 520.812 Section 520.812 Food and...NEW ANIMAL DRUGS § 520.812 Enrofloxacin tablets. (a) Specifications. Each tablet contains either 22.7, 68.0, or...

2013-04-01

315

21 CFR 520.816 - Epsiprantel tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Epsiprantel tablets. 520.816 Section 520.816 Food and...NEW ANIMAL DRUGS § 520.816 Epsiprantel tablets. (a) Specifications. Each tablet contains either 12.5, 25, 50, or 100...

2014-04-01

316

21 CFR 520.1616 - Orbifloxacin tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Orbifloxacin tablets. 520.1616 Section 520.1616 Food and...NEW ANIMAL DRUGS § 520.1616 Orbifloxacin tablets. (a) Specifications. Each tablet contains 5.7, 22.7, or 68...

2014-04-01

317

21 CFR 520.531 - Cythioate tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Cythioate tablets. 520.531 Section 520.531 Food...ANIMAL DRUGS § 520.531 Cythioate tablets. (a) [Reserved] (b) Sponsors...for use of 30- and 90-milligram (mg) tablets and see No. 053501 in §...

2012-04-01

318

21 CFR 520.1616 - Orbifloxacin tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Orbifloxacin tablets. 520.1616 Section 520.1616 Food and...NEW ANIMAL DRUGS § 520.1616 Orbifloxacin tablets. (a) Specifications . Each tablet contains 5.7, 22.7, or 68...

2011-04-01

319

Fast Dissolving Tablets of Aloe Vera Gel  

Microsoft Academic Search

Purpose : The objective of this work was to prepare and evaluate fast dissolving tablets of the nutraceutical, freeze dried Aloe vera gel. Methods: Fast dissolving tablets of the nutraceutical, freeze-dried Aloe vera gel, were prepared by dry granulation method. The tablets were evaluated for crushing strength, disintegration time, wetting time, friability, drug content and drug release. A 3 2

Jyotsana Madan; AK Sharma; Ramnik Singh

320

Tablet - next generation sequence assembly visualization  

Microsoft Academic Search

Summary: Tablet is a lightweight, high-performance graphical viewer for next generation sequence assemblies and alignments. Supporting a range of input assembly formats, Tablet provides high- quality visualizations showing data in packed or stacked views, al- lowing instant access and navigation to any region of interest, and whole contig overviews and data summaries. Tablet is both multi- core aware and memory-efficient,

Iain Milne; Micha Bayer; Linda Cardle; Paul Shaw; Gordon Stephen; Frank Wright; David Marshall

2010-01-01

321

Toll-like receptor 4 mutant and null mice retain morphine-induced tolerance, hyperalgesia, and physical dependence  

E-print Network

low dose naltrexone attenuates chronic morphine-induced gliosis in rats. Mol Painlow doses of naltrexone on morphine antinociception and morphine tolerance in male and female rats of four strains. Pain

2014-01-01

322

Evaluation of some compression aids in tableting of roller compacted swellable core drug layer.  

PubMed

Swellable core technology (SCT) represents a broadly applicable oral osmotic drug delivery platform for the controlled release of drugs. SCT tablets control drug delivery by using osmosis to regulate the influx of water into the tablet's core. The tablet consists of two layers; drug layer and sweller layer, with a semi-permeable membrane coating and delivery port located in the drug layer side of the tablet. The key component of SCT formulations is polyethylene oxide (PEO), which is typically wet granulated with organic solvents to prevent rapid gel hydration observed during contact with aqueous environments. However, the use of organic solvents has their own environmental and cost considerations which make this form of processing undesirable. To overcome this issue, dry granulation can be employed. However, PEO is a very plastic material and problems may be encountered during the tableting process, when work hardening occurs upon double compression. The addition of compression aids to the drug layer will help to increase the roll force when generating ribbons - reducing fines and segregation potential - while also reducing work hardening effects which impact tablet friability. The five compression aids used in this study were microcrystalline cellulose (MCC), xylitol, di-calcium phosphate (anhydrous), lactose monohydrate and starch. The work undertaken here studies the compression properties of the drug layer blends with different levels of the five compression aids as part of the formulation. Roller compaction properties are also varied to provide granules with differing solid fractions. The results of this study indicate that addition of microcrystalline cellulose in the formulation in levels between 10% and 30% significantly improve the tablet hardness at lower tablet compression forces. Further work is required to investigate the impact on dissolution. PMID:23796839

Golchert, D; Bines, E; Carmody, A

2013-09-10

323

Life span extension in Drosophila melanogaster induced by morphine  

Microsoft Academic Search

The influence of morphine on the life span of Drosophila melanogaster fruit flies has been investigated. Morphine hydrochloride (MH) at concentrations of 0.01, 0.05 and 0.25 mg\\/ml was added to\\u000a a medium starting from day 5 or 54 of imaginal life. Supplementation with MH starting from day 5 of imaginal life has resulted\\u000a in significant increases in the mean life span of males

Tatyana A. Dubiley; Yury E. Rushkevich; Natalya M. Koshel; Vladimir P. Voitenko; Alexander M. Vaiserman

2011-01-01

324

Spinal morphine anesthesia and urinary retention.  

PubMed

Spinal anesthetic is a common form of surgical anesthetic used in foot and ankle surgery. Spinal morphine anesthetic is less common, but has the advantage of providing postoperative analgesia for 12 to 24 hr. A number of complications can occur with spinal anesthesia, including urinary retention that may be a source of severe and often prolonged discomfort and pain for the patient. Management of this problem may require repeated bladder catheterization, which may lead to urinary tract infections or impairment of urethrovesicular function. This study reviews the incidence of urinary retention in 80 patients (40 after general anesthesia and 40 after spinal anesthesia) who underwent foot and ankle surgery at Saint Joseph's Hospital, Philadelphia, PA. Twenty-five percent of the patients who had spinal anesthesia experienced urinary retention, while only 7 1/2% of the group who had general anesthesia had this complication. Predisposing factors, treatment regimen, and recommendations for the prevention and management of urinary retention are presented. PMID:8258772

Mahan, K T; Wang, J

1993-11-01

325

Endogenous morphine and its metabolites in mammals: history, synthesis, localization and perspectives.  

PubMed

Morphine derived from Papaver somniferum is commonly used as an analgesic compound for pain relief. It is now accepted that endogenous morphine, structurally identical to vegetal morphine-alkaloid, is synthesized by mammalian cells from dopamine. Morphine binds mu opioid receptor and induces antinociceptive effects. However, the exact role of these compounds is a matter of debate although different links with infection, sepsis, inflammation, as well as major neurological pathologies (Parkinson's disease, schizophrenia) have been proposed. The present review describes endogenous morphine and morphine derivative discovery, synthesis, localization and potential implications in physiological and pathological processes. PMID:23266549

Laux-Biehlmann, A; Mouheiche, J; Vérièpe, J; Goumon, Y

2013-03-13

326

Postmortem morphine concentrations following use of a continuous infusion pump.  

PubMed

We report a case involving unusually high postmortem morphine concentrations in a 44-year-old male with end-stage pancreatic cancer. He was receiving morphine for pain control via a single subclavian intravenous catheter. Allegations of foul play were made by family members at the time of death, so a full autopsy was performed. Comprehensive toxicology on autopsy samples indicated that morphine was the only drug present. Quantitative analysis of free and total morphine revealed extraordinarily high concentrations of the drug. Free morphine concentrations in heart blood, vitreous fluid, brain, liver, stomach contents, and urine were 96 mg/L, 52 mg/L, 26 mg/kg, 88 mg/kg, 82 mg/L, and 976 mg/L, respectively. Total morphine concentrations in heart blood, vitreous fluid, brain, liver, and stomach contents were 421 mg/L, 238 mg/L, 65 mg/kg, 256 mg/kg, and 325 mg/L, respectively. Records indicate that the infusion pump may have continued to deliver the drug for 15-45 min following death. Despite compelling toxicological data, the cause of death was determined to be complication of adenocarcinoma of the pancreas, and the manner was natural. This report highlights issues surrounding postmortem toxicological interpretation within the context of chronic pain management. PMID:15516310

Kerrigan, Sarah; Honey, Donna; Baker, Ginger

2004-09-01

327

Morphine activates neuroinflammation in a manner parallel to endotoxin  

PubMed Central

Opioids create a neuroinflammatory response within the CNS, compromising opioid-induced analgesia and contributing to various unwanted actions. How this occurs is unknown but has been assumed to be via classic opioid receptors. Herein, we provide direct evidence that morphine creates neuroinflammation via the activation of an innate immune receptor and not via classic opioid receptors. We demonstrate that morphine binds to an accessory protein of Toll-like receptor 4 (TLR4), myeloid differentiation protein 2 (MD-2), thereby inducing TLR4 oligomerization and triggering proinflammation. Small-molecule inhibitors, RNA interference, and genetic knockout validate the TLR4/MD-2 complex as a feasible target for beneficially modifying morphine actions. Disrupting TLR4/MD-2 protein–protein association potentiated morphine analgesia in vivo and abolished morphine-induced proinflammation in vitro, the latter demonstrating that morphine-induced proinflammation only depends on TLR4, despite the presence of opioid receptors. These results provide an exciting, nonconventional avenue to improving the clinical efficacy of opioids. PMID:22474354

Wang, Xiaohui; Loram, Lisa C.; Ramos, Khara; de Jesus, Armando J.; Thomas, Jacob; Cheng, Kui; Reddy, Anireddy; Somogyi, Andrew A.; Hutchinson, Mark R.; Watkins, Linda R.; Yin, Hang

2012-01-01

328

Mitragynine Attenuates Withdrawal Syndrome in Morphine-Withdrawn Zebrafish  

PubMed Central

A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway. PMID:22205946

Khor, Beng-Siang; Amar Jamil, Mohd Fadzly; Adenan, Mohamad Ilham; Chong Shu-Chien, Alexander

2011-01-01

329

Acute morphine alters GABAergic transmission in the central amygdala during naloxone-precipitated morphine withdrawal: role of cyclic AMP  

PubMed Central

The central amygdala (CeA) plays an important role in opioid addiction. Therefore, we examined the effects of naloxone-precipitated morphine withdrawal (WD) on GABAergic transmission in rat CeA neurons using whole-cell recordings with naloxone in the bath. The basal frequency of miniature inhibitory postsynaptic currents (mIPSCs) increased in CeA neurons from WD compared to placebo rats. Acute morphine (10 ? M) had mixed effects (?20% change from baseline) on mIPSCs in placebo and WD rats. In most CeA neurons (64%) from placebo rats, morphine significantly decreased mIPSC frequency and amplitude. In 32% of placebo neurons, morphine significantly increased mIPSC amplitudes but had no effect on mIPSC frequency. In WD rats, acute morphine significantly increased mIPSC frequency but had no effect on mIPSC amplitude in 41% of CeA neurons. In 45% of cells, acute morphine significantly decreased mIPSC frequency and amplitude. Pre-treatment with the cyclic AMP inhibitor (R)-adenosine, cyclic 3',5'-(hydrogenphosphorothioate) triethylammonium (RP), prevented acute morphine-induced potentiation of mIPSCs. Pre-treatment of slices with the Gi/o G-protein subunit inhibitor pertussis toxin (PTX) did not prevent the acute morphine-induced enhancement or inhibition of mIPSCs. PTX and RP decreased basal mIPSC frequencies and amplitudes only in WD rats. The results suggest that inhibition of GABAergic transmission in the CeA by acute morphine is mediated by PTX-insensitive mechanisms, although PTX-sensitive mechanisms cannot be ruled out for non-morphine responsive cells; by contrast, potentiation of GABAergic transmission is mediated by activated cAMP signaling that also mediates the increased basal GABAergic transmission in WD rats. Our data indicate that during the acute phase of WD, the CeA opioid and GABAergic systems undergo neuroadaptative changes conditioned by a previous chronic morphine exposure and dependence. PMID:24926240

Bajo, Michal; Madamba, Samuel G.; Roberto, Marisa; Siggins, George R.

2014-01-01

330

Metronidazole Oral  

MedlinePLUS

Metronidazole eliminates bacteria and other microorganisms that cause infections of the reproductive system, gastrointestinal tract, skin, vagina, ... Metronidazole comes as a tablet to take by mouth. It is usually taken two or three times ...

331

Echinacea alkamide disposition and pharmacokinetics in humans after tablet ingestion.  

PubMed

Echinacea is a widely used herbal remedy for the treatment of colds and other infections. However, almost nothing is known about the disposition and pharmacokinetics of any of its components, particularly the alkamides and caffeic acid conjugates which are thought to be the active phytochemicals. In this investigation, we have examined serial plasma samples from 9 healthy volunteers who ingested echinacea tablets manufactured from ethanolic liquid extracts of Echinacea angustifolia and Echinacea purpurea immediately after a standard high fat breakfast. Caffeic acid conjugates could not be identified in any plasma sample at any time after tablet ingestion. Alkamides were rapidly absorbed and were measurable in plasma 20 min after tablet ingestion and remained detectable for up to 12 h. Concentration-time curves for 2,4-diene and 2-ene alkamides were determined. The maximal concentrations for the sum of alkamides in human plasma were reached within 2.3 h post ingestion and averaged 336+/-131 ng eq/mL plasma. No obvious differences were observed in the pharmacokinetics of individual or total alkamides in 2 additional fasted subjects who took the same dose of the echinacea preparation. This single dose study provides evidence that alkamides are orally available and that their pharmacokinetics are in agreement with the one dose three times daily regimen already recommended for echinacea. PMID:15919096

Matthias, A; Addison, R S; Penman, K G; Dickinson, R G; Bone, K M; Lehmann, R P

2005-09-01

332

Preparation and evaluation of sublingual tablets of zolmitriptan  

PubMed Central

Aim: Zolmitriptan is a 5-HT receptor agonist (1B/1D). It is used in the acute treatment of migraine having low bioavailability about 40% orally due to hepatic first pass metabolism. The purpose of the present research was to formulate fast acting sublingual tablets of zolmitriptan. Materials and Methods: Sublingual tablets were prepared using ispaghula husk powder, gellan gum, sodium alginate as super disintegrating polymers and citric acid, tartaric acid and camphor as permeation enhancers by direct compressible technique and evaluated for weight variation, thickness, friability, content uniformity, hardness, disintegration time, wetting time, in-vitro drug release, in-vitro and ex-vivo permeation study. Stability study of optimized formulation was performed as per ICH (International Conference on Harmonisation) guideline. Results: The in-vitro disintegration time of the optimized formulation (D5) was 9 ± 2 s and all formulations showed 100% of dissolution within 6 ± 2 min. Formulation containing 4% of gellan gum (D5) showed highest disintegration and 2% of citric acid formulation (P3) showed highest permeation 88% within 30 min and ex-vivo permeation was 52% within 30 min. Optimized formulation was stable for 1 month during stability study as per ICH guideline. Conclusion: The sublingual tablet formulation gives better results using natural super disintegrant for fast onset of action. PMID:24678459

Prajapati, Shailesh T; Patel, Manoj V; Patel, Chhaganbhai N

2014-01-01

333

Acceptability of different oral formulations in infants and preschool children  

PubMed Central

Objective Liquid medicines are easy to swallow. However, they may have disadvantages, such as a bad taste or refrigerated storage conditions. These disadvantages may be avoided by the use of oral solid medicines, such as powders or tablets. The aim of this study was to investigate the acceptability of and preference among four oral formulations in domiciliary infants and preschool children in The Netherlands. Methods Parents administered four oral placebo dosage forms that were aimed at a neutral taste, at home, to their child (1–4?years of age) twice on one day following a randomised cross-over design: small (4 mm) tablet, powder, suspension and syrup. They were asked to report the child's acceptability by a score on a 10 cm visual analogue scale (VAS score) and by the result of the intake. At the end of the study, they were asked to report the preference of the child and themselves. Results 183 children were included and 148 children were evaluated. The data revealed a period/cross-over effect. The estimate of the mean VAS score was significantly higher for the tablet than for the suspension (tablet 9.39/9.01; powder 8.84/8.20, suspension 8.26/7.90, syrup 8.35/8.19; data day 1/all days). The estimate of the mean number of intakes fully swallowed was significantly higher for the tablet than for the other formulations (all p values <0.05). Children and parents preferred the tablet and syrup over the suspension and the suspension over the powder (all p values <0.05). Conclusions All formulations were well accepted. The tablets were the best accepted formulation; the tablets and syrup the most preferred. Trial Registration number ISRCTN63138435. PMID:23853004

van Riet-Nales, Diana A; de Neef, Barbara J; Schobben, Alfred F A M; Ferreira, José A; Egberts, Toine C G; Rademaker, Catharine M A

2013-01-01

334

Phosphoproteomics and Bioinformatics Analyses of Spinal Cord Proteins in Rats with Morphine Tolerance  

PubMed Central

Introduction Morphine is the most effective pain-relieving drug, but it can cause unwanted side effects. Direct neuraxial administration of morphine to spinal cord not only can provide effective, reliable pain relief but also can prevent the development of supraspinal side effects. However, repeated neuraxial administration of morphine may still lead to morphine tolerance. Methods To better understand the mechanism that causes morphine tolerance, we induced tolerance in rats at the spinal cord level by giving them twice-daily injections of morphine (20 µg/10 µL) for 4 days. We confirmed tolerance by measuring paw withdrawal latencies and maximal possible analgesic effect of morphine on day 5. We then carried out phosphoproteomic analysis to investigate the global phosphorylation of spinal proteins associated with morphine tolerance. Finally, pull-down assays were used to identify phosphorylated types and sites of 14-3-3 proteins, and bioinformatics was applied to predict biological networks impacted by the morphine-regulated proteins. Results Our proteomics data showed that repeated morphine treatment altered phosphorylation of 10 proteins in the spinal cord. Pull-down assays identified 2 serine/threonine phosphorylated sites in 14-3-3 proteins. Bioinformatics further revealed that morphine impacted on cytoskeletal reorganization, neuroplasticity, protein folding and modulation, signal transduction and biomolecular metabolism. Conclusions Repeated morphine administration may affect multiple biological networks by altering protein phosphorylation. These data may provide insight into the mechanism that underlies the development of morphine tolerance. PMID:24392096

Liaw, Wen-Jinn; Tsao, Cheng-Ming; Huang, Go-Shine; Wu, Chin-Chen; Ho, Shung-Tai; Wang, Jhi-Joung; Tao, Yuan-Xiang; Shui, Hao-Ai

2014-01-01

335

Trans-stilbene oxide administration increased hepatic glucuronidation of morphine but decreased biliary excretion of morphine glucuronide in rats  

SciTech Connect

The effect of the inducing agent trans-stilbene oxide (TSO) on the metabolism and biliary excretion of (/sup 14/C)morphine was studied in the isolated in situ perfused rat liver. After administration of morphine by intraportal injection or by the segmented retrograde intrabiliary injection technique, the TSO-treated group showed a marked decrease in the biliary recovery of morphine as its glucuronide conjugate (morphine-3-glucuronide (MG)). However, recovery of MG in the venous outflow of the single pass perfusate was greatly increased. These findings suggested that TSO treatment enhanced the formation of MG from morphine and changed the primary route of hepatic elimination of MG. TSO treatment also decreased the excretion of morphine (as MG) in the bile of anesthetized renal-ligated rats. This decreased biliary function required several days to develop and appeared closely associated with the inductive effect of TSO. After i.v. administration of (/sup 14/C)MG itself, biliary recovery was also markedly decreased in TSO-treated rats. It is postulated that the effect of the TSO treatment led to either a decrease in canalicular transport of MG into bile or an increase in the efficiency of transfer of MG to the blood at the sinusoidal side of the hepatocyte. Regardless of the mechanism, the results indicate the need to study compartmentalization of drug transport and metabolism functions.

Fuhrman-Lane, C.; Fujimoto, J.M.

1982-09-01

336

Combined morphine-bupivacaine caudals for reconstructive penile surgery in children: systemic absorption of morphine and postoperative analgesia.  

PubMed

We wished to determine if the addition of a small dose of morphine (0.05 mg.kg-1) to a caudal solution of 0.25% bupivacaine could extend the duration of analgesia after major reconstructive penile surgery and also to measure the systemic absorption of morphine after caudal injection. Thirty children undergoing reconstructive penile surgery received a caudal injection of 0.25% bupivacaine 0.75 ml.kg-1 with or without morphine 0.05 mg.kg-1. All patients awoke pain-free, but eight of the fifteen patients receiving bupivacaine alone required supplementary injections of opioid postoperatively, whereas none of the patients receiving the bupivacaine-morphine mixture required additional opioids. The incidence of side-effects was similar for the two groups. Morphine was absorbed rapidly after caudal injection to reach a peak plasma level of 21.2 (+/- 4.8) ng.ml-1 at ten minutes and then fell to 10.1 (+/- 3.8) ng.ml-1 at one hour and 4.1 (+/- 2.6) ng.ml-1 at three hours. These levels are low compared with plasma levels associated with systemic analgesia. We conclude that the extended duration of analgesia from morphine 0.05 mg/kg given caudally is due at least in part to specific spinal analgesia. PMID:2012289

Wolf, A R; Hughes, D; Hobbs, A J; Prys-Roberts, C

1991-02-01

337

Clinical utility of orally disintegrating olanzapine in Chinese patients with schizophrenia: a review of effectiveness, patient preference, adherence, and other properties  

PubMed Central

The primary objective of this systematic review was to examine the evidence for the efficacy, effectiveness, and safety of orally disintegrating olanzapine in Chinese populations. A systematic literature search was conducted using databases covering international and Chinese journals, ClinicalTrials.gov, and internal and external trial registries at Eli Lilly and Company using search terms related to target countries (People’s Republic of China, Hong Kong, and Taiwan) and orally disintegrating olanzapine treatment. A publication and one clinical study report were retrieved. The clinical study showed orally disintegrating olanzapine and the standard oral tablet to have similar efficacy and tolerability profiles. A bioequivalence study has shown that orally disintegrating olanzapine and the standard oral tablet have similar pharmacokinetic profiles. Orally disintegrating olanzapine and the standard oral tablet have similar efficacy and tolerability profiles. PMID:24600225

Zhao, Jingping; Ou, Jianjun; Xue, Haibo; Liu, Li; Montgomery, William; Treuer, Tamas

2014-01-01

338

Clinical utility of orally disintegrating olanzapine in Chinese patients with schizophrenia: a review of effectiveness, patient preference, adherence, and other properties.  

PubMed

The primary objective of this systematic review was to examine the evidence for the efficacy, effectiveness, and safety of orally disintegrating olanzapine in Chinese populations. A systematic literature search was conducted using databases covering international and Chinese journals, ClinicalTrials.gov, and internal and external trial registries at Eli Lilly and Company using search terms related to target countries (People's Republic of China, Hong Kong, and Taiwan) and orally disintegrating olanzapine treatment. A publication and one clinical study report were retrieved. The clinical study showed orally disintegrating olanzapine and the standard oral tablet to have similar efficacy and tolerability profiles. A bioequivalence study has shown that orally disintegrating olanzapine and the standard oral tablet have similar pharmacokinetic profiles. Orally disintegrating olanzapine and the standard oral tablet have similar efficacy and tolerability profiles. PMID:24600225

Zhao, Jingping; Ou, Jianjun; Xue, Haibo; Liu, Li; Montgomery, William; Treuer, Tamas

2014-01-01

339

Galileo's Telescopy and Jupiter's Tablet  

Microsoft Academic Search

A previous paper (BAAS 33:4, 1363, 2001) reported on the dramatic scene in Shakespeare's Cymbeline that features the descent of the deity Jupiter. The paper suggested that the four ghosts circling the sleeping Posthumus denote the four Galilean moons of Jupiter. The god Jupiter commands the ghosts to lay a tablet upon the prone Posthumus, but says that its value

P. D. Usher

2003-01-01

340

Oral myiasis.  

PubMed

Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability and history of epilepsy. PMID:25709196

Saravanan, Thalaimalai; Mohan, Mathan A; Thinakaran, Meera; Ahammed, Saneem

2015-01-01

341

Oral Myiasis  

PubMed Central

Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability and history of epilepsy. PMID:25709196

Saravanan, Thalaimalai; Mohan, Mathan A; Thinakaran, Meera; Ahammed, Saneem

2015-01-01

342

Social environment modulates morphine sensitivity: A partial role of vasopressin V1b receptor  

E-print Network

environment-induced alteration of morphine sensitivity. Interaction with drug-intoxicated cage-mates enhanced locomotor sensitivity in previously drug-naive males and altered their production of testosterone. Conversely, interaction of morphine experienced...

Hofford, Rebecca 1983-

2012-08-31

343

Seletos 1 COMPARING NATIVE AND CROSS-PLATFORM DEVELOPMENT TABLET  

E-print Network

Seletos 1 COMPARING NATIVE AND CROSS-PLATFORM DEVELOPMENT TABLET ENVIRONMENTS BASED Term 2012 #12;Seletos 2 ABSTRACT Software development on tablet devices is very important. The leading tablet devices on the market are Google's Android tablet and Apple's iPad tablet. We

Miles, Will

344

Alterations in rat intestinal transit by morphine promote bacterial translocation.  

PubMed

Translocation of enteric microorganisms from the intestinal tract to extraintestinal sites has been proposed as an early step in the development of gram-negative sepsis. This study examined the role of altered bowel transit in influencing intestinal bacteriostasis and bacterial translocation using morphine as a pharmacologic inhibitor of such transit. In the first experiment, either normal saline (N = 8) or morphine sulfate (20 mg/kg; N = 8) was injected subcutaneously. Two hours later, morphine (7.5 mg/kg) was infused subcutaneously for an additional 22 hr; control animals received saline alone. After completion of this regimen, a volume of 0.2 ml of 2.5 mM FITC dextrans (10,000 daltons) were injected intraduodenally in each group. The bowel was removed 25 min later, divided into 5-cm segments, and the content of dextrans measured. Small bowel propulsion was expressed as the geometric center of the distribution of dextrans throughout the intestine (in percentage length of small bowel). Gut propulsion was significantly reduced after morphine treatment as compared to controls (32.8 +/- 8.2% vs. 55.8 +/- 4.0%; P < 0.01). In 16 additional rats, saline or morphine was again administered as described. After 24 hr, samples were obtained from the mesenteric lymph node (MLN) complex, blood, spleen, liver, duodenum, jejunum, ileum, and cecum for standard bacteriology. The bacterial counts increased significantly in each intestinal segment following morphine treatment. Microorganisms translocated to the MLN complex in 5, and to distant sites in four of eight morphine-treated animals, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8344112

Runkel, N S; Moody, F G; Smith, G S; Rodriguez, L F; Chen, Y; Larocco, M T; Miller, T A

1993-08-01

345

Antinarcotic effects of the velvet antler water extract on morphine in mice  

Microsoft Academic Search

The present study was undertaken to investigate the antinarcotic effects of velvet antler water extract (VAWE) from Cervus elaphus on morphine. Morphine-induced analgesic action was measured by tail-flick method. Morphine-induced hyperactivity and reverse tolerance were evidenced by measuring the enhanced ambulatory activity using a tilting-type ambulometer. Dopamine (DA) receptor supersensitivity in mice displaying morphine-induced reverse tolerance was evidenced by the

Hack-Seang Kim; Hwa-Kyung Lim; Woo-Kyu Park

1999-01-01

346

? Opioid receptor knockout in mice: effects on ligand-induced analgesia and morphine lethality  

Microsoft Academic Search

The ? opioid receptor gene (MOR) was mutated in mice by a gene targeting procedure. In these MOR-knockout mice, the analgesic effects of morphine, its major metabolites, morphine-6-glucuronide (M-6-G) and morphine-6-ethereal sulfate (M-6-S), and endomorphin-2, as well as morphine-induced lethality, were drastically reduced, whereas the effects of DPDPE and U50488 remained unchanged. It is concluded that analgesic effects of ?-specific

Horace H Loh; Hsien-Ching Liu; Antonella Cavalli; Wanling Yang; Yuh-Fung Chen; Li-Na Wei

1998-01-01

347

Profiling of Ecstasy Tablets Seized in Iran  

PubMed Central

In this study 50 samples of ecstasy tablets seized in Iran during the period of 2007 through 2008 were examined and their physical characteristics (appearance, marking, scored/not scored, color, weight, diameter, thickness) were determined. In order to determine the chemical characteristics of these tablets, color tests (Marquis test, Simon’s test, Chen’s test and Gallic acid test), Thin Layer Chromatography (TLC), anion test, residual solvents, Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) were carried out on the tablets. The range of tablets weight was 96–308 mg and the range of 3,4-methylenedioxymethamphetamine (MDMA) hydrochloride content in these tablets was 60–180 mg. No good correlation was found between the tablets weight and their MDMA contents. All of the tablets containing MDMA had this compound in hydrochloride form. Ketamine, phenmetrazine and ephedrine (or pseudoephedrine) were found in some of the tablets along with MDMA. No MDMA was found in 20% of the tablets. Some of these tablets contained compounds such as caffeine or tramadol as their active ingredient. PMID:24250345

Khajeamiri, Ali Reza; Kobarfard, Farzad; Ahmadkhaniha, Reza; Mostashari, Gelareh

2011-01-01

348

Influence of low doses of naltrexone on morphine antinociception and morphine tolerance in male and female rats of four strains.  

PubMed

In a recently proposed bimodal opioid receptor model, the inhibitory actions of opioids on action potential duration in dorsal root ganglion neurons have been proposed to produce antinociception, and the excitatory actions of hyperalgesia. Recent studies indicate that selectively blocking these excitatory actions with low doses of opioid antagonists enhances opioid antinociception and attenuates the development of opioid tolerance. To determine if the excitatory actions of opioids contribute to sex as well as strain differences in opioid sensitivity, the effects of morphine alone and in combination with low doses of naltrexone were examined in male and female rats of four strains. The strains examined differed in their sensitivity to opioid antinociception and magnitude of sex differences in opioid sensitivity. All testing was conducted using a thermal tail-flick procedure with the nociceptive stimulus intensity adjusted so that baseline latencies were comparable across strains/sexes. In chronic studies, the morphine dosing regimen was adjusted in each strain/sex to produce comparable levels of tolerance. In each of the strains tested, morphine produced dose-dependent increases in antinociception, with differences in morphine potency observed across strains and sexes. In male and female Sprague-Dawley and Long-Evans rats, naltrexone enhanced morphine antinociception and attenuated the development of morphine tolerance. These effects were not observed in F344 and Lewis rats, even when tests were conducted across a range of morphine and naltrexone doses. These results suggest that the ability of low doses of naltrexone to enhance opioid antinociception does not contribute to sex or rat strain differences in opioid sensitivity. PMID:16527399

Terner, Jolan M; Barrett, Andrew C; Lomas, Lisa M; Negus, S Stevens; Picker, Mitchell J

2006-05-01

349

Role of P-glycoprotein in the intestinal absorption and clinical effects of morphine  

E-print Network

Role of P-glycoprotein in the intestinal absorption and clinical effects of morphine Introduction P-glycoprotein regulates brain access and intestinal absorption of numerous drugs. Morphine is a P-glycoprotein substrate in vitro, and P-glycoprotein affects morphine brain access and pharmacodynamics in animals

Steinbach, Joe Henry

350

BIOTRANSFORMATIONS OF MORPHINE ALKALOIDS BY FUNGI: N-DEMETHYLATIONS, OXIDATIONS, AND REDUCTIONS  

E-print Network

BIOTRANSFORMATIONS OF MORPHINE ALKALOIDS BY FUNGI: N-DEMETHYLATIONS, OXIDATIONS, AND REDUCTIONS on the occasion of his 85th birthday. Morphine alkaloids and some of its derivatives (morphine, codeine, thebaine. The alkaloids were transformed to a variety of products via biological oxidations, reductions, and oxidative

Hudlicky, Tomas

351

Ultra-low dose naltrexone attenuates chronic morphine-induced gliosis in rats  

Microsoft Academic Search

BACKGROUND: The development of analgesic tolerance following chronic morphine administration can be a significant clinical problem. Preclinical studies demonstrate that chronic morphine administration induces spinal gliosis and that inhibition of gliosis prevents the development of analgesic tolerance to opioids. Many studies have also demonstrated that ultra-low doses of naltrexone inhibit the development of spinal morphine antinociceptive tolerance and clinical studies

Theresa-Alexandra M Mattioli; Brian Milne; Catherine M Cahill

2010-01-01

352

Inhibition of tolerance to spinal morphine antinociception by low doses of opioid receptor antagonists  

Microsoft Academic Search

Ultra-low doses of opioid receptor antagonists inhibit development of chronic spinal morphine tolerance. As this phenomenon mechanistically resembles acute tolerance, the present study examined actions of opioid receptor antagonists on acute spinal morphine tolerance. In adult rats, administration of three intrathecal injections of morphine (15 ?g) at 90 min intervals produced a significant decline of the antinociceptive effect and loss of agonist

Benjamin McNaull; Tuan Trang; Maaja Sutak; Khem Jhamandas

2007-01-01

353

The glial activation inhibitor AV411 reduces morphine-induced nucleus accumbens dopamine release  

Microsoft Academic Search

Glial activation has recently been discovered to modulate several effects of morphine, including analgesia, tolerance, and dependence. The present studies extend this line of investigation by exploring whether glial activation may also affect extracellular levels of dopamine (DA) in the nucleus accumbens (NAc) shell, a neurochemical corollary of morphine-induced drug reward, during a challenge dose of morphine in experiments both

Sondra T. Bland; Mark R. Hutchinson; Steven F. Maier; Linda R. Watkins; Kirk W. Johnson

2009-01-01

354

Effect of morphine on sympathetic nerve activity in humans  

NASA Technical Reports Server (NTRS)

There are conflicting reports for the role of endogenous opioids on sympathetic and cardiovascular responses to exercise in humans. A number of studies have utilized naloxone (an opioid-receptor antagonist) to investigate the effect of opioids during exercise. In the present study, we examined the effect of morphine (an opioid-receptor agonist) on sympathetic and cardiovascular responses at rest and during isometric handgrip (IHG). Eleven subjects performed 2 min of IHG (30% maximum) followed by 2 min of postexercise muscle ischemia (PEMI) before and after systemic infusion of morphine (0.075 mg/kg loading dose + 1 mg/h maintenance) or placebo (saline) in double-blinded experiments on separate days. Morphine increased resting muscle sympathetic nerve activity (MSNA; 17 +/- 2 to 22 +/- 2 bursts/min; P < 0.01) and increased mean arterial pressure (MAP; 87 +/- 2 to 91 +/- 2 mmHg; P < 0.02), but it decreased heart rate (HR; 61 +/- 4 to 59 +/- 3; P < 0.01). However, IHG elicited similar increases for MSNA, MAP, and HR between the control and morphine trial (drug x exercise interaction = not significant). Moreover, responses to PEMI were not different. Placebo had no effect on resting, IHG, and PEMI responses. We conclude that morphine modulates cardiovascular and sympathetic responses at rest but not during isometric exercise.

Carter, Jason R.; Sauder, Charity L.; Ray, Chester A.

2002-01-01

355

Morphine enhances Tat-induced activation in murine microglia  

PubMed Central

There is increasing evidence that opiates accelerate the pathogenesis and progression of acquired immunodeficiency syndrome (AIDS), as well as the incidence of human immunodeficiency virus (HIV) encephalitis (HIVE), a condition characterized by inflammation, leukocyte infiltration, and microglial activation. The mechanisms, by which the HIV-1 transactivating protein Tat and opioids exacerbate microglial activation, however, are not fully understood. In the current study, we explored the effects of morphine and HIV-1 Tat1–72 on the activation of mouse BV-2 microglial cells and primary mouse microglia. Both morphine and Tat exposure caused up-regulation of the chemokine receptor CCR5, an effect blocked by the opioid receptor antagonist naltrexone. Morphine in combination with Tat also induced morphological changes in the BV-2 microglia from a quiescent to an activated morphology, with a dramatic increase in the expression of the microglial activation marker CD11b, as compared with cells exposed to either agent alone. In addition, the mRNA expression of inducible nitric oxide synthase (iNOS), CD40 ligand, Interferon-gamma-inducible protein 10 (IP-10), and the proinflammatory cytokines tumor necrosis factor alpha (TNF?), interleukin (IL)-1f?, and IL-6, which were elevated with Tat alone, were dramatically enhanced with Tat in the presence of morphine. In summary, these findings shed light on the cooperative effects of morphine and HIV-1 Tat on both microglial activation and HIV coreceptor up-regulation, effects that could result in exacerbated neuropathogenesis. PMID:19462331

Bokhari, Sirosh M; Yao, Honghong; Bethel-Brown, Crystal; Fuwang, Peng; Williams, Rachel; Dhillon, Navneet K; Hegde, Ramakrishna; Kumar, Anil; Buch, Shilpa J

2011-01-01

356

[Afobazole decreases severity of morphine withdrawal syndrome: experimental evidence].  

PubMed

Effect of afobazole upon morphine dependency has been studied in rats upon the administration of incremental doses of morphine (10-20 mg/kg, i.p.) for 5 days. The state of dependency was evaluated by monitoring sixteen specific behavioral indices of "spontaneous" (24 h after the last morphine injection) or naloxone-induced withdrawal syndrome. The effect of afobazole (a single dose of 5 mg/kg injected before the test or subchronically for 5 days) was estimated through its influence upon the total index of withdrawal syndrome, which was calculated using the set of behavioural signs. It is established that afobazole upon either single or subchronic injections significantly decreased the expression of spontaneous morphine withdrawal syndrome. The effect was also statistically significant but less pronounced in the case of naloxone-induced withdrawal syndrome. The obtained data suggest that afobazole can be considered as potential effective drug for the correction of various clinical symptoms of morphine withdrawal syndrome. PMID:22238980

Konstantinopol'ski?, M A; Cherniakova, I V

2011-01-01

357

Endogenous Morphine Levels Are Increased in Sepsis: A Partial Implication of Neutrophils  

PubMed Central

Background Mammalian cells synthesize morphine and the respective biosynthetic pathway has been elucidated. Human neutrophils release this alkaloid into the media after exposure to morphine precursors. However, the exact role of endogenous morphine in inflammatory processes remains unclear. We postulate that morphine is released during infection and can be determined in the serum of patients with severe infection such as sepsis. Methodology The presence and subcellular immunolocalization of endogenous morphine was investigated by ELISA, mass spectrometry analysis and laser confocal microscopy. Neutrophils were activated with Interleukin-8 (IL-8) or lipopolysaccharide (LPS). Morphine secretion was determined by a morphine-specific ELISA. ? opioid receptor expression was assessed with flow cytometry. Serum morphine concentrations of septic patients were determined with a morphine-specific ELISA and morphine identity was confirmed in human neutrophils and serum of septic patients by mass spectrometry analysis. The effects of the concentration of morphine found in serum of septic patients on LPS-induced release of IL-8 by human neutrophils were tested. Principal Findings We confirmed the presence of morphine in human neutrophil extracts and showed its colocalisation with lactoferrin within the secondary granules of neutrophils. Morphine secretion was quantified in the supernatant of activated human polymorphonuclear neutrophils in the presence and absence of Ca2+. LPS and IL-8 were able to induce a significant release of morphine only in presence of Ca2+. LPS treatment increased ? opioid receptor expression on neutrophils. Low concentration of morphine (8 nM) significantly inhibited the release of IL-8 from neutrophils when coincubated with LPS. This effect was reversed by naloxone. Patients with sepsis, severe sepsis and septic shock had significant higher circulating morphine levels compared to patients with systemic inflammatory response syndrome and healthy controls. Mass spectrometry analysis showed that endogenous morphine from serum of patient with sepsis was identical to poppy-derived morphine. Conclusions Our results indicate that morphine concentrations are increased significantly in the serum of patients with systemic infection and that morphine is, at least in part, secreted from neutrophils during sepsis. Morphine concentrations equivalent to those found in the serum of septic patients significantly inhibited LPS-induced IL-8 secretion in neutrophils. PMID:20098709

Lavaux, Thomas; Muller, Arnaud H.; Laux, Alexis; Zhang, Dan; Schmidt, Alexander R.; Delalande, François; Laventie, Benoît-Joseph; Dirrig-Grosch, Sylvie; Colin, Didier A.; Van Dorsselaer, Alain; Aunis, Dominique; Metz-Boutigue, Marie-Hélène; Schneider, Francis; Goumon, Yannick

2010-01-01

358

Development and evaluation of gastroretentive floating tablets of an antihypertensive drug using hydrogenated cottonseed oil.  

PubMed

The aim of the present work was to develop a gastroretentive floating tablet of Atenolol and investigate the effects of both hydrophilic and hydrophobic retardant on in vitro release. Atenolol is an antihypertensive drug with an oral bioavailability of only 50% because of its poor absorption from lower gastrointestinal tract. The floating tablets of Atenolol were prepared to increase the gastric retention, to extend the drug release, and to improve the bioavailability of the drug. The floating tablets were formulated using hydrophilic polymers as Hydroxy propyl methyl cellulose (HPMC K4M and HPMC K15M), hydrophobic retardant as a hydrogenated cottonseed oil (HCSO), and sodium bicarbonate as a gas generating agent to reduce floating lag time. The formulated tablets were evaluated for the quality control tests such as weight variation, hardness, friability, swelling index, floating lag time, and total floating time. The in vitro release study of the tablets was performed in 0.1?N HCl as a dissolution media. The results of the present study clearly indicates the promising potential of Atenolol floating system as an alternative to the conventional dosage and other sustained release formulations. The study also revealed the effectiveness of HCSO as retardant in combination with HPMC. PMID:24455312

Pawar, Harshal Ashok; Gharat, Pooja Ramchandra; Dhavale, Rachana Vivek; Joshi, Pooja Rasiklal; Rakshit, Pushpita Pankajkumar

2013-12-18

359

21 CFR 520.2123a - Spectinomycin tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Spectinomycin tablets. 520.2123a Section 520.2123a Food...ANIMAL DRUGS § 520.2123a Spectinomycin tablets. (a) Specifications . Each tablet contains spectinomycin dihydrochloride...

2013-04-01

360

21 CFR 520.784 - Doxylamine succinate tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 false Doxylamine succinate tablets. 520.784 Section 520.784 Food...DRUGS § 520.784 Doxylamine succinate tablets. (a) Specifications. The drug is in tablet form and contains doxylamine succinate...

2011-04-01

361

21 CFR 520.1720a - Phenylbutazone tablets and boluses.  

Code of Federal Regulations, 2011 CFR

... 2011-04-01 false Phenylbutazone tablets and boluses. 520.1720a Section 520...ANIMAL DRUGS § 520.1720a Phenylbutazone tablets and boluses. (a) Specifications . Each tablet contains 100, 200, or 400...

2011-04-01

362

21 CFR 520.623 - Diethylcarbamazine citrate, oxibendazole chewable tablets.  

Code of Federal Regulations, 2013 CFR

...Diethylcarbamazine citrate, oxibendazole chewable tablets. 520.623 Section 520.623 Food and...Diethylcarbamazine citrate, oxibendazole chewable tablets. (a) Specifications. Each tablet contains either 60, 120, or 180...

2013-04-01

363

21 CFR 520.1193 - Ivermectin tablets and chewables.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Ivermectin tablets and chewables. 520.1193 Section...ANIMAL DRUGS § 520.1193 Ivermectin tablets and chewables. (a) Specifications . (1) Each tablet or chewable contains 68, 136, or...

2011-04-01

364

21 CFR 520.2582 - Triflupromazine hydrochloride tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 false Triflupromazine hydrochloride tablets. 520.2582 Section 520.2582 Food and...520.2582 Triflupromazine hydrochloride tablets. (a) Specifications. Each tablet contains either 10 milligrams or 25...

2012-04-01

365

21 CFR 520.622c - Diethylcarbamazine citrate chewable tablets.  

Code of Federal Regulations, 2012 CFR

...false Diethylcarbamazine citrate chewable tablets. 520.622c Section 520.622c Food...622c Diethylcarbamazine citrate chewable tablets. (a) Specifications. Each chewable tablet contains 30, 45, 60, 120, 150, or...

2012-04-01

366

21 CFR 520.2041 - Pyrantel pamoate chewable tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 false Pyrantel pamoate chewable tablets. 520.2041 Section 520.2041 Food and...DRUGS § 520.2041 Pyrantel pamoate chewable tablets. (a) Specifications. Each tablet contains pyrantel pamoate equivalent to...

2011-04-01

367

21 CFR 520.246 - Butorphanol tartrate tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 false Butorphanol tartrate tablets. 520.246 Section 520.246 Food and...ANIMAL DRUGS § 520.246 Butorphanol tartrate tablets. (a) Specifications. Each tablet contains 1, 5, or 10 milligrams of...

2013-04-01

368

21 CFR 520.1720a - Phenylbutazone tablets and boluses.  

Code of Federal Regulations, 2013 CFR

... 2013-04-01 false Phenylbutazone tablets and boluses. 520.1720a Section 520...ANIMAL DRUGS § 520.1720a Phenylbutazone tablets and boluses. (a) Specifications . Each tablet contains 100, 200, or 400...

2013-04-01

369

21 CFR 520.2123a - Spectinomycin tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Spectinomycin tablets. 520.2123a Section 520.2123a Food...ANIMAL DRUGS § 520.2123a Spectinomycin tablets. (a) Specifications . Each tablet contains spectinomycin dihydrochloride...

2011-04-01

370

21 CFR 520.434 - Chlorphenesin carbamate tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 false Chlorphenesin carbamate tablets. 520.434 Section 520.434 Food and...DRUGS § 520.434 Chlorphenesin carbamate tablets. (a) Specifications. Each tablet contains 400 milligrams of chlorphenesin...

2011-04-01

371

21 CFR 520.1193 - Ivermectin tablets and chewables.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Ivermectin tablets and chewables. 520.1193 Section...ANIMAL DRUGS § 520.1193 Ivermectin tablets and chewables. (a) Specifications . (1) Each tablet or chewable contains 68, 136, or...

2013-04-01

372

21 CFR 520.2604 - Trimeprazine tartrate and prednisolone tablets.  

Code of Federal Regulations, 2012 CFR

...false Trimeprazine tartrate and prednisolone tablets. 520.2604 Section 520.2604 Food and...2604 Trimeprazine tartrate and prednisolone tablets. (a) Specifications. Each tablet contains: trimeprazine tartrate, 5...

2012-04-01

373

21 CFR 520.1242e - Levamisole hydrochloride effervescent tablets.  

Code of Federal Regulations, 2011 CFR

...false Levamisole hydrochloride effervescent tablets. 520.1242e Section 520.1242e Food...1242e Levamisole hydrochloride effervescent tablets. (a) Specifications. Each tablet contains 907 milligrams of levamisole...

2011-04-01

374

21 CFR 520.246 - Butorphanol tartrate tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 false Butorphanol tartrate tablets. 520.246 Section 520.246 Food and...ANIMAL DRUGS § 520.246 Butorphanol tartrate tablets. (a) Specifications. Each tablet contains 1, 5, or 10 milligrams of...

2011-04-01

375

21 CFR 520.2123a - Spectinomycin tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Spectinomycin tablets. 520.2123a Section 520.2123a Food...ANIMAL DRUGS § 520.2123a Spectinomycin tablets. (a) Specifications. Each tablet contains spectinomycin dihydrochloride...

2014-04-01

376

21 CFR 520.863 - Ethylisobutrazine hydrochloride tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 false Ethylisobutrazine hydrochloride tablets. 520.863 Section 520.863 Food and...520.863 Ethylisobutrazine hydrochloride tablets. (a) Specifications. Each tablet contains either 10 milligrams or 50...

2013-04-01

377

21 CFR 520.2041 - Pyrantel pamoate chewable tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 false Pyrantel pamoate chewable tablets. 520.2041 Section 520.2041 Food and...DRUGS § 520.2041 Pyrantel pamoate chewable tablets. (a) Specifications. Each tablet contains pyrantel pamoate equivalent to...

2013-04-01

378

21 CFR 520.784 - Doxylamine succinate tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 false Doxylamine succinate tablets. 520.784 Section 520.784 Food...DRUGS § 520.784 Doxylamine succinate tablets. (a) Specifications. The drug is in tablet form and contains doxylamine succinate...

2013-04-01

379

21 CFR 520.863 - Ethylisobutrazine hydrochloride tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 false Ethylisobutrazine hydrochloride tablets. 520.863 Section 520.863 Food and...520.863 Ethylisobutrazine hydrochloride tablets. (a) Specifications. Each tablet contains either 10 milligrams or 50...

2011-04-01

380

21 CFR 520.1720a - Phenylbutazone tablets and boluses.  

Code of Federal Regulations, 2014 CFR

... 2014-04-01 false Phenylbutazone tablets and boluses. 520.1720a Section 520...ANIMAL DRUGS § 520.1720a Phenylbutazone tablets and boluses. (a) Specifications. Each tablet contains 100, 200, or 400...

2014-04-01

381

21 CFR 520.2041 - Pyrantel pamoate chewable tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 false Pyrantel pamoate chewable tablets. 520.2041 Section 520.2041 Food and...DRUGS § 520.2041 Pyrantel pamoate chewable tablets. (a) Specifications. Each tablet contains pyrantel pamoate equivalent to...

2012-04-01

382

21 CFR 520.1193 - Ivermectin tablets and chewables.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Ivermectin tablets and chewables. 520.1193 Section...ANIMAL DRUGS § 520.1193 Ivermectin tablets and chewables. (a) Specifications. (1) Each tablet or chewable contains 68, 136, or...

2014-04-01

383

21 CFR 520.1157 - Iodinated casein tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 false Iodinated casein tablets. 520.1157 Section 520.1157 Food...ANIMAL DRUGS § 520.1157 Iodinated casein tablets. (a) Specifications. Each 1-gram tablet contains 25 milligrams of iodinated...

2011-04-01

384

21 CFR 520.2123a - Spectinomycin tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Spectinomycin tablets. 520.2123a Section 520.2123a Food...ANIMAL DRUGS § 520.2123a Spectinomycin tablets. (a) Specifications . Each tablet contains spectinomycin dihydrochloride...

2012-04-01

385

21 CFR 520.623 - Diethylcarbamazine citrate, oxibendazole chewable tablets.  

Code of Federal Regulations, 2012 CFR

...Diethylcarbamazine citrate, oxibendazole chewable tablets. 520.623 Section 520.623 Food and...Diethylcarbamazine citrate, oxibendazole chewable tablets. (a) Specifications. Each tablet contains either 60, 120, or 180...

2012-04-01

386

21 CFR 520.1157 - Iodinated casein tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 false Iodinated casein tablets. 520.1157 Section 520.1157 Food...ANIMAL DRUGS § 520.1157 Iodinated casein tablets. (a) Specifications. Each 1-gram tablet contains 25 milligrams of iodinated...

2013-04-01

387

21 CFR 520.622c - Diethylcarbamazine citrate chewable tablets.  

Code of Federal Regulations, 2014 CFR

...false Diethylcarbamazine citrate chewable tablets. 520.622c Section 520.622c Food...622c Diethylcarbamazine citrate chewable tablets. (a) Specifications. Each chewable tablet contains 30, 45, 60, 120, 150, or...

2014-04-01

388

21 CFR 520.623 - Diethylcarbamazine citrate, oxibendazole chewable tablets.  

Code of Federal Regulations, 2014 CFR

...Diethylcarbamazine citrate, oxibendazole chewable tablets. 520.623 Section 520.623 Food and...Diethylcarbamazine citrate, oxibendazole chewable tablets. (a) Specifications. Each tablet contains either 60, 120, or 180...

2014-04-01

389

21 CFR 520.863 - Ethylisobutrazine hydrochloride tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 false Ethylisobutrazine hydrochloride tablets. 520.863 Section 520.863 Food and...520.863 Ethylisobutrazine hydrochloride tablets. (a) Specifications. Each tablet contains either 10 milligrams or 50...

2014-04-01

390

21 CFR 520.434 - Chlorphenesin carbamate tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 false Chlorphenesin carbamate tablets. 520.434 Section 520.434 Food and...DRUGS § 520.434 Chlorphenesin carbamate tablets. (a) Specifications. Each tablet contains 400 milligrams of chlorphenesin...

2014-04-01

391

21 CFR 520.2098 - Selegiline hydrochloride tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 false Selegiline hydrochloride tablets. 520.2098 Section 520.2098 Food and...DRUGS § 520.2098 Selegiline hydrochloride tablets. (a) Specifications. Each tablet contains either 2, 5, 10, 15, or 30...

2014-04-01

392

21 CFR 520.784 - Doxylamine succinate tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 false Doxylamine succinate tablets. 520.784 Section 520.784 Food...DRUGS § 520.784 Doxylamine succinate tablets. (a) Specifications. The drug is in tablet form and contains doxylamine succinate...

2012-04-01

393

21 CFR 520.623 - Diethylcarbamazine citrate, oxibendazole chewable tablets.  

Code of Federal Regulations, 2011 CFR

...Diethylcarbamazine citrate, oxibendazole chewable tablets. 520.623 Section 520.623 Food and...Diethylcarbamazine citrate, oxibendazole chewable tablets. (a) Specifications. Each tablet contains either 60, 120, or 180...

2011-04-01

394

21 CFR 520.2610 - Trimethoprim and sulfadiazine tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 false Trimethoprim and sulfadiazine tablets. 520.2610 Section 520.2610 Food and...520.2610 Trimethoprim and sulfadiazine tablets. (a) Specifications. Each tablet contains 30 milligrams (5...

2011-04-01

395

21 CFR 520.2610 - Trimethoprim and sulfadiazine tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 false Trimethoprim and sulfadiazine tablets. 520.2610 Section 520.2610 Food and...520.2610 Trimethoprim and sulfadiazine tablets. (a) Specifications. Each tablet contains 30 milligrams (5...

2012-04-01

396

21 CFR 520.2123a - Spectinomycin tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Spectinomycin tablets. 520.2123a Section 520.2123a Food...ANIMAL DRUGS § 520.2123a Spectinomycin tablets. (a) Specifications . Each tablet contains spectinomycin dihydrochloride...

2010-04-01

397

21 CFR 520.2582 - Triflupromazine hydrochloride tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 false Triflupromazine hydrochloride tablets. 520.2582 Section 520.2582 Food and...520.2582 Triflupromazine hydrochloride tablets. (a) Specifications. Each tablet contains either 10 milligrams or 25...

2013-04-01

398

21 CFR 520.1157 - Iodinated casein tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 false Iodinated casein tablets. 520.1157 Section 520.1157 Food...ANIMAL DRUGS § 520.1157 Iodinated casein tablets. (a) Specifications. Each 1-gram tablet contains 25 milligrams of iodinated...

2014-04-01

399

21 CFR 529.400 - Chlorhexidine tablets and suspension.  

Code of Federal Regulations, 2011 CFR

... 2011-04-01 false Chlorhexidine tablets and suspension. 529.400 Section 529...ANIMAL DRUGS § 529.400 Chlorhexidine tablets and suspension. (a) Specification. Each tablet and each 28-milliliter syringe of...

2011-04-01

400

21 CFR 520.246 - Butorphanol tartrate tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 false Butorphanol tartrate tablets. 520.246 Section 520.246 Food and...ANIMAL DRUGS § 520.246 Butorphanol tartrate tablets. (a) Specifications. Each tablet contains 1, 5, or 10 milligrams of...

2012-04-01

401

21 CFR 520.2610 - Trimethoprim and sulfadiazine tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 false Trimethoprim and sulfadiazine tablets. 520.2610 Section 520.2610 Food and...520.2610 Trimethoprim and sulfadiazine tablets. (a) Specifications. Each tablet contains 30 milligrams (5...

2010-04-01

402

EXPERIENCE WITH TABLET PC VIDEO BASED HYBRID COURSEWORK IN  

E-print Network

EXPERIENCE WITH TABLET PC VIDEO BASED HYBRID COURSEWORK IN COMPUTER SCIENCE Jaspal Subhlok, Olin Keywords: Hybrid Learning, Online Learning, Video Lectures, Tablet PC Abstract Online learning, defined classroom interaction is detrimental to learning. Employing Tablet PCs with slide presentation

Subhlok, Jaspal

403

21 CFR 520.863 - Ethylisobutrazine hydrochloride tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 false Ethylisobutrazine hydrochloride tablets. 520.863 Section 520.863 Food and...520.863 Ethylisobutrazine hydrochloride tablets. (a) Specifications. Each tablet contains either 10 milligrams or 50...

2012-04-01

404

21 CFR 520.2041 - Pyrantel pamoate chewable tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 false Pyrantel pamoate chewable tablets. 520.2041 Section 520.2041 Food and...DRUGS § 520.2041 Pyrantel pamoate chewable tablets. (a) Specifications. Each tablet contains pyrantel pamoate equivalent to...

2014-04-01

405

21 CFR 520.784 - Doxylamine succinate tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 false Doxylamine succinate tablets. 520.784 Section 520.784 Food...DRUGS § 520.784 Doxylamine succinate tablets. (a) Specifications. The drug is in tablet form and contains doxylamine succinate...

2010-04-01

406

21 CFR 520.784 - Doxylamine succinate tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 false Doxylamine succinate tablets. 520.784 Section 520.784 Food...DRUGS § 520.784 Doxylamine succinate tablets. (a) Specifications. The drug is in tablet form and contains doxylamine succinate...

2014-04-01

407

21 CFR 520.2604 - Trimeprazine tartrate and prednisolone tablets.  

Code of Federal Regulations, 2013 CFR

...false Trimeprazine tartrate and prednisolone tablets. 520.2604 Section 520.2604 Food and...2604 Trimeprazine tartrate and prednisolone tablets. (a) Specifications. Each tablet contains: trimeprazine tartrate, 5...

2013-04-01

408

21 CFR 520.2604 - Trimeprazine tartrate and prednisolone tablets.  

Code of Federal Regulations, 2014 CFR

...false Trimeprazine tartrate and prednisolone tablets. 520.2604 Section 520.2604 Food and...2604 Trimeprazine tartrate and prednisolone tablets. (a) Specifications. Each tablet contains: trimeprazine tartrate, 5...

2014-04-01

409

21 CFR 520.434 - Chlorphenesin carbamate tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 false Chlorphenesin carbamate tablets. 520.434 Section 520.434 Food and...DRUGS § 520.434 Chlorphenesin carbamate tablets. (a) Specifications. Each tablet contains 400 milligrams of chlorphenesin...

2013-04-01

410

21 CFR 520.1446 - Milbemcyin oxime and lufenuron tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 false Milbemcyin oxime and lufenuron tablets. 520.1446 Section 520.1446 Food...520.1446 Milbemcyin oxime and lufenuron tablets. (a) Specifications —(1) Tablets containing: 2.3 milligrams (mg)...

2012-04-01

411

21 CFR 520.1157 - Iodinated casein tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 false Iodinated casein tablets. 520.1157 Section 520.1157 Food...ANIMAL DRUGS § 520.1157 Iodinated casein tablets. (a) Specifications. Each 1-gram tablet contains 25 milligrams of iodinated...

2012-04-01

412

21 CFR 520.434 - Chlorphenesin carbamate tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 false Chlorphenesin carbamate tablets. 520.434 Section 520.434 Food and...DRUGS § 520.434 Chlorphenesin carbamate tablets. (a) Specifications. Each tablet contains 400 milligrams of chlorphenesin...

2010-04-01

413

21 CFR 520.1242e - Levamisole hydrochloride effervescent tablets.  

Code of Federal Regulations, 2014 CFR

...false Levamisole hydrochloride effervescent tablets. 520.1242e Section 520.1242e Food...1242e Levamisole hydrochloride effervescent tablets. (a) Specifications. Each tablet contains 907 milligrams of levamisole...

2014-04-01

414

21 CFR 520.863 - Ethylisobutrazine hydrochloride tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 false Ethylisobutrazine hydrochloride tablets. 520.863 Section 520.863 Food and...520.863 Ethylisobutrazine hydrochloride tablets. (a) Specifications. Each tablet contains either 10 milligrams or 50...

2010-04-01

415

21 CFR 520.246 - Butorphanol tartrate tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 false Butorphanol tartrate tablets. 520.246 Section 520.246 Food and...ANIMAL DRUGS § 520.246 Butorphanol tartrate tablets. (a) Specifications. Each tablet contains 1, 5, or 10 milligrams of...

2014-04-01

416

21 CFR 520.622c - Diethylcarbamazine citrate chewable tablets.  

Code of Federal Regulations, 2013 CFR

...false Diethylcarbamazine citrate chewable tablets. 520.622c Section 520.622c Food...622c Diethylcarbamazine citrate chewable tablets. (a) Specifications. Each chewable tablet contains 30, 45, 60, 120, 150, or...

2013-04-01

417

21 CFR 529.400 - Chlorhexidine tablets and suspension.  

Code of Federal Regulations, 2012 CFR

... 2012-04-01 false Chlorhexidine tablets and suspension. 529.400 Section 529...ANIMAL DRUGS § 529.400 Chlorhexidine tablets and suspension. (a) Specification. Each tablet and each 28-milliliter syringe of...

2012-04-01

418

21 CFR 520.2582 - Triflupromazine hydrochloride tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 false Triflupromazine hydrochloride tablets. 520.2582 Section 520.2582 Food and...520.2582 Triflupromazine hydrochloride tablets. (a) Specifications. Each tablet contains either 10 milligrams or 25...

2014-04-01

419

21 CFR 529.400 - Chlorhexidine tablets and suspension.  

Code of Federal Regulations, 2010 CFR

... 2010-04-01 false Chlorhexidine tablets and suspension. 529.400 Section 529...ANIMAL DRUGS § 529.400 Chlorhexidine tablets and suspension. (a) Specification. Each tablet and each 28-milliliter syringe of...

2010-04-01

420

21 CFR 520.1720a - Phenylbutazone tablets and boluses.  

Code of Federal Regulations, 2010 CFR

... 2010-04-01 false Phenylbutazone tablets and boluses. 520.1720a Section 520...ANIMAL DRUGS § 520.1720a Phenylbutazone tablets and boluses. (a) Specifications . Each tablet contains 100, 200, or 400...

2010-04-01

421

Prototyping Hybrid Musical Interactions on Tablet Devices Henri Palleis  

E-print Network

Prototyping Hybrid Musical Interactions on Tablet Devices Henri Palleis Ludwig interactions on tablet devices that combine tangible, touch and gestural input. Existing low the rapid exploration of hybrid musical interaction concepts on tablet devices with capacitive touchscreens

422

21 CFR 520.1193 - Ivermectin tablets and chewables.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Ivermectin tablets and chewables. 520.1193 Section...ANIMAL DRUGS § 520.1193 Ivermectin tablets and chewables. (a) Specifications . (1) Each tablet or chewable contains 68, 136, or...

2010-04-01

423

21 CFR 529.400 - Chlorhexidine tablets and suspension.  

Code of Federal Regulations, 2014 CFR

... 2014-04-01 false Chlorhexidine tablets and suspension. 529.400 Section 529...ANIMAL DRUGS § 529.400 Chlorhexidine tablets and suspension. (a) Specification. Each tablet and each 28-milliliter syringe of...

2014-04-01

424

21 CFR 520.2610 - Trimethoprim and sulfadiazine tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 false Trimethoprim and sulfadiazine tablets. 520.2610 Section 520.2610 Food and...520.2610 Trimethoprim and sulfadiazine tablets. (a) Specifications. Each tablet contains 30 milligrams (5...

2014-04-01

425

21 CFR 520.434 - Chlorphenesin carbamate tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 false Chlorphenesin carbamate tablets. 520.434 Section 520.434 Food and...DRUGS § 520.434 Chlorphenesin carbamate tablets. (a) Specifications. Each tablet contains 400 milligrams of chlorphenesin...

2012-04-01

426

21 CFR 520.1720a - Phenylbutazone tablets and boluses.  

Code of Federal Regulations, 2012 CFR

... 2012-04-01 false Phenylbutazone tablets and boluses. 520.1720a Section 520...ANIMAL DRUGS § 520.1720a Phenylbutazone tablets and boluses. (a) Specifications . Each tablet contains 100, 200, or 400...

2012-04-01

427

21 CFR 520.1193 - Ivermectin tablets and chewables.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Ivermectin tablets and chewables. 520.1193 Section...ANIMAL DRUGS § 520.1193 Ivermectin tablets and chewables. (a) Specifications . (1) Each tablet or chewable contains 68, 136, or...

2012-04-01

428

21 CFR 520.2582 - Triflupromazine hydrochloride tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 false Triflupromazine hydrochloride tablets. 520.2582 Section 520.2582 Food and...520.2582 Triflupromazine hydrochloride tablets. (a) Specifications. Each tablet contains either 10 milligrams or 25...

2011-04-01

429

21 CFR 529.400 - Chlorhexidine tablets and suspension.  

Code of Federal Regulations, 2013 CFR

... 2013-04-01 false Chlorhexidine tablets and suspension. 529.400 Section 529...ANIMAL DRUGS § 529.400 Chlorhexidine tablets and suspension. (a) Specification. Each tablet and each 28-milliliter syringe of...

2013-04-01

430

21 CFR 520.1446 - Milbemcyin oxime and lufenuron tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 false Milbemcyin oxime and lufenuron tablets. 520.1446 Section 520.1446 Food...520.1446 Milbemcyin oxime and lufenuron tablets. (a) Specifications —(1) Tablets containing: 2.3 milligrams (mg)...

2011-04-01

431

21 CFR 520.1696d - Penicillin V potassium tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Penicillin V potassium tablets. 520.1696d...ANIMAL DRUGS § 520.1696d Penicillin V potassium tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to...

2012-04-01

432

21 CFR 520.1696d - Penicillin V tablets.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Penicillin V tablets. 520.1696d Section...NEW ANIMAL DRUGS § 520.1696d Penicillin V tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125...

2014-04-01

433

21 CFR 520.1696d - Penicillin V potassium tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Penicillin V potassium tablets. 520.1696d...ANIMAL DRUGS § 520.1696d Penicillin V potassium tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to...

2010-04-01

434

21 CFR 520.1696d - Penicillin V potassium tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Penicillin V potassium tablets. 520.1696d...ANIMAL DRUGS § 520.1696d Penicillin V potassium tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to...

2011-04-01

435

21 CFR 520.1696d - Penicillin V tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Penicillin V tablets. 520.1696d Section...NEW ANIMAL DRUGS § 520.1696d Penicillin V tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125...

2013-04-01

436

Polymers derived from Xanthomonas campesteris and Cyamopsis tetragonolobus used as retardant materials for the formulation of sustained release floating matrix tablet of atenolol.  

PubMed

The objective of the present study was to develop, optimize, in vitro, and in vivo evaluation of floating matrix tablet of atenolol using polymer blend derived from Xanthomonas campesteris and Cyamopsis tetragonolobus that are characterized by release requirements of sustained-release product and to improve the oral bioavailability of the drug. A 3(2) full factorial design was employed to optimize the tablets, where content of polymer blend (X1) and ratio of xanthan gum-to-guar gum (X2) were considered as independent variables. The effects of independent variables on dependent variables, i.e. floating time, diffusion exponent, and time to release 50% of atenolol were evaluated. The in vivo pharmacokinetic parameters of the optimized formulation were compared with the marketed sustained release formulation of atenolol (Aten(®)). The optimized formulation containing 20% (w/w) of polymer blend and 50:50 ratio of xanthan gum-to-guar gum was able to float more than 12h and showed the desired sustained drug release from the tablets. In vivo retention studies in rabbit stomach showed the gastric residence of tablet up to 6h. The in vivo study of optimized tablets illustrated significant improvement in the oral bioavailability of atenolol in rabbits. It can be concluded that floating matrix tablet of atenolol prepared by using xanthan gum and guar gum has potential for sustained release of the drug as well as improved oral bioavailability through enhanced gastric residence time of formulation in stomach. PMID:24472506

Dey, Sanjay; Mazumder, Bhaskar; Chattopadhyay, Sankha; Das, Malay Kanti; Sinha, Samarendu; Ganguly, Shantanu; De, Kakali; Mishra, Mridula

2014-04-01

437

Tablet Content Analysis Using Terahertz Transmission Spectroscopy  

Microsoft Academic Search

A group of pressed tablets with acetaminophen content between 60 mg and 120 mg were scanned in the terahertz spectral region\\u000a (2 cm?1–120 cm?1) in transmission mode. Tablet acetaminophen content was determined by a standard HPLC method. Despite the lack of discernible\\u000a spectral features and the tablets being opaque above 45 cm?1, a working partial least squares model could be constructed. The results show the

John A. Spencer; Everett H. Jefferson; Ajaz S. Hussain; David Newnham; Thomas Lo

2007-01-01

438

Evaluation of quick disintegrating calcium carbonate tablets  

Microsoft Academic Search

The purpose of this investigation was to develop a rapidly disintegrating calcium carbonate (CC) tablet by direct compression\\u000a and compare it with commercially available calcium tablets. CC tablets were formulated on a Carver press using 3 different\\u000a forms of CC direct compressed granules (Cal-Carb 4450®, Cal-Carb 4457®, and Cal-Carb 4462®). The breaking strength was measured using a Stokes-Monsanto hardness tester.

Hector Fausett; Charles Gayser Jr; Alekha K. Dash

2000-01-01

439

Quaternary naltrexone reverses radiogenic and morphine-induced locomotor hyperactivity  

SciTech Connect

The present study attempted to determine the relative role of the peripheral and central nervous system in the production of morphine-induced or radiation-induced locomotor hyperactivity of the mouse. Toward this end, we used a quaternary derivative of an opiate antagonist (naltrexone methobromide), which presumably does not cross the blood-brain barrier. Quaternary naltrexone was used to challenge the stereotypic locomotor response observed in these mice after either an i.p. injection of morphine or exposure to 1500 rads /sup 60/Co. The quaternary derivative of naltrexone reversed the locomotor hyperactivity normally observed in the C57BL/6J mouse after an injection of morphine. It also significantly attenuated radiation-induced locomotion. The data reported here support the hypothesis of endorphin involvement in radiation-induced and radiogenic behaviors. However, these conclusions are contingent upon further research which more fully evaluates naltrexone methobromide's capacity to cross the blood-brain barrier.

Mickley, G.A.; Stevens, K.E.; Galbraith, J.A.; White, G.A.; Gibbs, G.L.

1984-04-01

440

Morphine/prilocaine combination for intravenous regional anesthesia.  

PubMed

In this study we aimed to investigate clinically whether morphine acts on the peripheral nervous system directly. Twenty adult patients, who were scheduled for upper extremity surgery under tourniquet, had intravenous regional anesthesia. They were divided into two groups: one group was given 30 ml of 1% prilocaine plus 10 ml of 0.9% sodium chloride (P group) and the other group was given 30 ml of 1% prilocaine plus 6 mg morphine sulfate in 10 ml of 0.9% sodium chloride (P/M group). The onset of analgesia and anesthesia and recovery from anesthesia and analgesia were investigated in both groups. In the P/M group, the onset of analgesia and anesthesia was statistically faster and the recovery from anesthesia and analgesia was statistically slower than in the P group (P < 0.05). We conclude that morphine is clinically effective in the peripheral nervous system at this dosage range. PMID:7484046

Erciyes, N; Aktürk, G; Solak, M; Dohman, D

1995-08-01

441

Morphine hyperthermia in rats: role of neurochemical substances in brain.  

PubMed

Central neurochemical mechanism underlying the hyperthermic effect of morphine has been investigated in rats. 200 micrograms morphine hydrochloride, when administered through cerebroventricular route at different seasonal air temperature, caused a rise in rectal temperature of rats. This hyperthermia was not affected by prior administration of antiserotonergic (pCPA, 5.6-DHT) or anticatecholaminergic (PBZ, 6-OHDA) drugs, as well as by PGE synthetase inhibitor, indomethacin. Similarity, cholinergic muscarinic or nicotinic receptor blockers, such as atropine and pentolinium/ D-tubocurarine respectively, were ineffective to modify it. Whereas, the depletion of acetylcholine in brain by pretreating the animals with hemicholinium profoundly delayed the hyperthermia, suggesting a central cholinergic involvement in morphine induced hyperthermia in rats. PMID:7298148

Prakash, U; Dey, P K

1981-01-01

442

The stability of tetramine, morphine and meperidine in formalin solution.  

PubMed

The stability of tetramine, morphine and meperidine in formalin solution is an important factor for drug analysis in forensic investigation. In this paper, the tissues (liver, kidney, lung and heart) from poisoned rabbits were immersed in 50 ml 10% formalin solutions for 4 months before examination. We compared the levels of tetramine, morphine, meperidine and the main metabolite normeperidine, measured by GC/NPD or GC-MS, in frozen rabbit tissues, formalin-fixed rabbit tissues, and formalin solution. There was a decrease in the levels of tetramine, morphine, meperidine in formalin-preserved tissues compared with the levels of these drugs in the frozen tissues. It is suggested that the formalin-fixed tissues and formalin solution should be analyzed at the same time to assure the accurate results. PMID:11672971

Xiang, P; Shen, M; Bu, J; Huang, Z

2001-11-01

443

Interactions between 3,4-methylenedioxymethamphetamine, methamphetamine, ketamine, and caffeine in human intestinal Caco-2 cells and in oral administration to rats  

Microsoft Academic Search

Amphetamine-type stimulants (ATSs) are often abused orally in the form of tablets for recreational purposes. The ATS tablets contain one or more active ingredients such as 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine (MA), ketamine (KA), and caffeine (CF). The aim of this work is to determine whether such components in tablets interact with each other in intestinal absorption. The interactions between MDMA, MA,

Kenji Kuwayama; Hiroyuki Inoue; Tatsuyuki Kanamori; Kenji Tsujikawa; Hajime Miyaguchi; Yuko Iwata; Seiji Miyauchi; Naoki Kamo; Tohru Kishi

2007-01-01

444

The Venus Tablet and Refraction  

E-print Network

It is shown that the refraction near the horizon is introducing an additional bias into the Venus Tablet of Ammisaduqa, which is able to influence the interpretation of the data. We then discuss the attempts to link certain solar eclipses to the birth of Shamshi-Adad and conclude that a record of a single solar eclipse without description of details and/or unambiguous historical links, can hardly act as a reliable anchor.

Gurzadyan, V G

2003-01-01

445

Development of taste masked oral formulation of ornidazole.  

PubMed

Taste masked microspheres of ornidazole were prepared using amino alkyl methacrylate copolymers (Eudragit E-100) by solvent evaporation technique. Taste assessment of these microspheres was done by both spectrophotometric taste evaluation technique and panel testing. Compressed tablets of taste masked ornidazole microspheres which rapidly disintegrated in the oral cavity were prepared using microcrystalline cellulose as directly compressible filler and sodium starch glycolate as a super-disintegrant. These were subsequently evaluated for various pharmacopoeial tests, drug release, and disintegration time in the oral cavity. Sensory taste evaluation was carried by panel testing in 20 healthy human volunteers. Results indicate successful formulation of oral fast disintegrating tablets which disintegrated in the oral cavity in about 30 s and possessed good taste. PMID:20838525

Shishu; Kamalpreet; Kapoor, V R

2010-03-01

446

Ontogenesis of morphine-induced behavior in the cat.  

PubMed

We analyzed the behavioral responses to a single dose of morphine in kittens at postnatal (P) ages 7, 15, 30, 60, 90, and 120 days. Each kitten received 0.5 or 3.0 mg/kg i.p. of morphine sulphate or saline vehicle. An average of 6.5 kittens were studied at each dose and age. An ethogram was constructed, based on morphine effects in adult cats, to score appropriate behaviors from direct observation and video sampling. After injection behaviors were sampled for periods of 2 min every 15-30 min for a total of 4 h. The frequency of each selected behavior was scored at 2 s intervals during each of the 2 min periods and it was expressed as a percent of all time samples scored for the 4 h period. Statistical comparisons were made with control (saline) littermates. At P7-15 the drug's main effect was behavioral depression; i.e., kittens, away from the litter, laid sprawled as if with no muscle tonus; Nursing was suppressed and Vocalization was distressed. Mainly with the higher dose, at P30, morphine-specific behaviors appeared for the first time. With the kitten in a Sitting position, these included stereotypical Head and Paw Movements and body Torsion. At P60 other drug-elicited behaviors emerged, including Spinning, Retching, and Vomiting. By P90-120 the frequency of Head (16.0%) and Paw (16.9%) Movements doubled relative to P30-60. Morphine significantly changed frequencies of newly matured behaviors (in control kittens) including Sniffing and Licking (increased), and Grooming (decreased/blocked). Retching and Vomiting increased to adult levels. Morphine-induced hyperthermia was first detected at P60 and peaked by P90-P120. The early behavioral depression shifted to a pattern of increasing activity starting at P30 and peaking at P90-120, at which time Sleep was absent and Laying was reduced, while Walking and Sitting were increased. We concluded that the maturation of the stereotypical behavioral responses to morphine in cats begins at about P30 and is completed between P90 and 120. Results are discussed in terms of developmental parameters and putative brain sites of morphine's actions. PMID:17196189

Burgess, J Wesley; Villablanca, Jaime R

2007-02-23

447

A validated hybrid quadrupole linear ion-trap LC–MS method for the analysis of morphine and morphine glucuronides applied to opiate deaths  

Microsoft Academic Search

A hybrid quadrupole linear ion-trap mass spectrometer using an electrospray ionisation ion source coupled to a HPLC system has been used to develop a method which can accurately measure morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in plasma, whole blood and post-mortem blood following solid-phase extraction. The method can also qualitatively detect various other opioids and related compounds including: codeine, dihydrocodeine

Kerry Taylor; Simon Elliott

2009-01-01

448

Pharmacokinetics study of bio-adhesive tablet of Panax notoginseng saponins  

Microsoft Academic Search

Panax notoginseng saponin (PNS) is the main active gradient of Chinese traditional medicine Panax notoginseng. Although its\\u000a prominent therapeutic efficacy has been demonstrated by various researchers, the broader application is restricted by the\\u000a low bioavailability of PNS. This article aims to discuss PNS's plasma pharmacokinetics after oral administration of bio-adhesive\\u000a tablet of PNS to beagle dogs and improve its bioavailability

Hanzhou Feng; Wei Chen; Chunyan Zhu

2011-01-01

449

Morphine causes persistent induction of nitrated neurofilaments in cortex and subcortex even during abstinence.  

PubMed

Morphine has a profound role in neurofilament (NF) expression. However, there are very few studies on the fate of NFs during morphine abstinence coinciding with periods of relapse. Mice were treated chronically with morphine to render them tolerant to and dependent on morphine and sacrificed thereafter while another group, treated similarly, was left for 2months without morphine. A long-lasting alteration in the stoichiometric ratio of the three NFs was observed under both conditions in both the cortex and subcortex. Morphine abstinence caused significant alterations in the phosphorylated and nitrated forms of the three NF subunits. Nitrated neurofilament light polypeptide chain (NFL) was significantly increased during chronic morphine treatment which persisted even after 2months of morphine withdrawal. Mass spectrometric analysis following two-dimensional gel electrophoresis (2DE)-gel electrophoresis of cytoskeleton fractions of both cortex and subcortex regions identified enzymes associated with energy metabolism, cytoskeleton-associated proteins as well as NFs which showed sustained regulation even after abstinence of morphine for 2months. It is suggestive that alteration in the levels of some of these proteins may be instrumental in the increased nitration of NFL during morphine exposure. Such gross alteration in NF dynamics is indicative of a concerted biological process of neuroadaptation during morphine abstinence. PMID:25684749

Pal, A; Das, S

2015-04-16

450

Morphine promotes cancer stem cell properties, contributing to chemoresistance in breast cancer.  

PubMed

Morphine is an opioid analgesic drug commonly used for pain relief in cancer patients. Here, we report that morphine enhances the mammosphere forming capacity and increases the expression of stemness-related transcription factors Oct4, Sox2 and Nanog. Treatment with morphine leads to enrichment of a side population fraction in MCF-7 cells and the CD44+/CD24-/low population in BT549 cells. Consistently, morphine activates Wnt/?-catenin signaling to induce epithelial to mesenchymal transition and promotes metastasis. Moreover, morphine decreases the sensitivity of traditional anti-cancer drugs in breast cancer cells. Nalmefene, an antagonist of morphine, reverses morphine-induced cancer stem cell properties and chemoresistance in breast cancer. In addition, nalmefene abolishes morphine enhancing tumorigenesis in a NOD/SCID mouse model. In conclusion, our findings demonstrate that morphine contributes to chemoresistance via expanding the population of cancer stem cells and promotes tumor growth, thereby revealing a novel role of morphine and providing some new guides in clinical use of morphine. PMID:25686831

Niu, Dong-Ge; Peng, Fei; Zhang, Wei; Guan, Zhong; Zhao, Hai-Dong; Li, Jing-Lin; Wang, Kai-Li; Li, Ting-Ting; Zhang, Yan; Zheng, Fei-Meng; Xu, Fan; Han, Qian-Ni; Gao, Peng; Wen, Qing-Ping; Liu, Quentin

2015-02-28

451

The effects of morphine on basal neuronal activities in the lateral and medial pain pathways  

PubMed Central

Numerous studies indicate that morphine suppresses pain-evoked activities in both spinal and supraspinal regions. However, little is known about the effect of morphine on the basal brain activity in the absence of pain. The present study was designed to assess the effects of single-dose morphine on the spontaneous discharge of many simultaneously recorded single units, as well as their functional connections, in the lateral pain pathway, including the primary somatosensory cortex (SI) and ventral posterolateral thalamus (VPL), and medial pain pathway, including the anterior cingulate cortex (ACC) and medial dorsal thalamus (MD), in awake rats. Morphine (5mg/kg) was administered intraperitoneally before the recording. Naloxone plus morphine and normal saline injections were performed respectively as controls. The results showed that morphine administration produced significant changes in the spontaneous neuronal activity in more than one third of the total recorded neurons, with primary activation in the lateral pathway while both inhibition and activation in the medial pathway. Naloxone pretreatment completely blocked the effects induced by morphine. In addition, the correlated activities between and within both pain pathways was exclusively suppressed after morphine injection. These results suggest that morphine may play different roles in modulating neural activity in normal versus pain states. Taken together, this is the first study investigating the morphine modulation of spontaneous neuronal activity within parallel pain pathways. It can be helpful for revealing neuronal population coding for the morphine action in the absence of pain, and shed light on the supraspinal mechanisms for preemptive analgesia. PMID:22841696

Su, Yuan-Lin; Huang, Jin; Wang, Ning; Wang, Jin-Yan; Luo, Fei

2012-01-01

452

Alleviation of Morphine Withdrawal Signs but Not Tolerance by the Essential Oil of Kelussia odoratissima Mozaff.  

PubMed Central

The aim of the present study was to assess the effects of chronic and acute treatment of the essential oil (EO) of Kelussia odoratissima Mozaff. on the development of morphine tolerance and dependence in mice. Mice were rendered tolerant to and dependent on morphine by subcutaneous injection of morphine over a period of 5 days. Tolerance was assessed using the tail-pinch test and withdrawal signs of morphine were precipitated by injecting naloxone 2?h after the final morphine injection. Repeated injection of the EO of K. odoratissima (5 and 10?mg/kg) for 4 days significantly suppressed morphine-withdrawal jumps, a sign of the development of dependence to opiate as assessed by naloxone precipitation withdrawal on day 5 of testing. A single injection (25, 50, 100?mg/kg) of the EO on day 5, 1?h prior to morphine failed to produce any significant change in morphine withdrawal signs. Neither the acute nor the chronic administration of EO of the K. odoratissima did significantly influence the development of tolerance to the analgesic effect of morphine. Alleviation in morphine signs of withdrawal after chronic injection with K. odoratissima is indicative of reversal of neuronal adaptation that takes place during morphine presence in the brain. PMID:22829859

Rabbani, Mohammed; Sajjadi, Seyed Ebrahim; Izadi, Azadeh

2012-01-01

453

[Oral and formulated pharmaceutical preparations before the invention of tablets].  

PubMed

Author gave an overview of the main types of the fed and formated medicines used in times before invention of lozenges. Six main types of these pharmaceutical products are to be defined here: 1. conserva 2. electuaria or confectiones 3. morsuli 4. rotulae or tabulae made with sugar 5. trochsci or pastillae and 6. terrae sigillatae. Author defines the single forms, tells their short history and also presents the ways they were produced and the tools and machines needed for their fabrication. PMID:20481112

Bartók, Adrienn

2009-01-01

454

The effect of chitosan on the stability and morphological parameters of tablets with Epilobium parviflorum Schreb. extract.  

PubMed

The study is a continuation of research on manufacturing oral solid drug form containing extract from Epilobium parviflorum Schreb. This study aims at investigating the usefulness of selected high-molecular substances with particular consideration of chitosan (Ch), silicified microcrystalline cellulose (Prosolv) and croscarmellose sodium (Vivasol) as a carrier of E. parviflorum Schreb. extract in oral solid drug form in the process of direct tableting. In one series the alternative technological process (with initial granulation) was applied. The polymer carriers of extract were selected so as to obtain shorter disintegration time in relation to the earlier published studies and stability after longer time of storage. The effect of chitosan was estimated on selected morphological parameters of practical relevance during storage. The obtained results allow to state that the applied high-molecular adjuvant substances proved to be useful in adequate proportions in the production of tablets from dry extract from Epilobium parviflorum Schreb. through direct pressing of the tablet mass. The tablet properties in all series were in accordance with obligatory standards also after longer time of storage (12-month). The tablets formed from E. parviflorum Schreb. extract with chitosan can be included into preparations of sustained release time of the biologically active substances. PMID:18251200

Marczy?ski, Zbigniew; Bodek, Kazimiera Henryka

2007-01-01

455

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

PubMed Central

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

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

2012-01-01

456

Morphine with adjuvant ketamine versus higher dose of morphine alone for acute pain: a meta-analysis  

PubMed Central

Purpose: Ketamine is currently the N-methyl-D-aspartate receptor channel blocker in clinical use. Morphine in pain management is usually limited by adverse effect such as nausea and vomiting. Adjuvant treatment with ketamine may be value in giving better analgesia with fewer adverse effects. The purpose of this meta-analysis was to evaluate the differences when patients received morphine with adjuvant ketamine (MK) compared with higher dose of morphine (MO) for acute pain. Methods: The PubMed, EMBASE and the Cochrane Library databases were searched (Last search performed on July 1, 2014) by two reviewers independently. Data were extracted independently by the same two individuals who searched the studies. Results: A total of 7 trials involving 492 patients were included in the current analysis. We found pain scores were lower in the MK group compared to the MO group [MD 2.19, 95% CI (1.24, 3.13) P<0.00001]. And more patients in the MO required diclofenac [OR 1.97, 95% CI (1.06, 3.67) P=0.03]. Furthermore, morphine plus ketamine can reduced post-operative nausea and vomiting (PONV) [OR 3.71, 95% CI (2.37, 5.80) P<0.00001]. Importantly, the wakefulness scores for the MK group were consistently and significantly better than those for the MO group [MD -1.53, 95% CI (-2.67, -0.40) P=0.008]. Conclusion: The use of ketamine plus 1/4~2/3 the dose of morphine is better than higher dose of morphine alone in reducing pain scores, and rescuing analgesic requirement. It also improved PONV and wakefulness. PMID:25356103

Ding, Xibing; Jin, Shuqing; Niu, Xiaoyin; Wang, Tingting; Zhao, Xiang; Ren, Hao; Tong, Yao; Li, Quan

2014-01-01

457

Enhanced bioavailability of buspirone hydrochloride via cup and core buccal tablets: formulation and in vitro/in vivo evaluation.  

PubMed

This work aims to prepare sustained release buccal mucoadhesive tablets of buspirone hydrochloride (BH) to improve its systemic bioavailability. The tablets were prepared according to 5×3 factorial design where polymer type was set at five levels (carbopol, hydroxypropyl methylcellulose, sodium alginate, sodium carboxymethyl cellulose and guar gum), and polymer to drug ratio at three levels (1:1, 2:1 and 3:1). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h) and time for release of 50% BH (T(??%)) were chosen as dependent variables. Additional BH cup and core buccal tablets were prepared to optimize BH release profile and make it uni-directional along with the tablets mucoadhesion. Tablets were evaluated in terms of content uniformity, weight variation, thickness, diameter, hardness, friability, swelling index, surface pH, mucoadhesion strength and time and in vitro release. Cup and core formula (CA10) was able to adhere to the buccal mucosa for 8h, showed the highest Q8h (97.91%) and exhibited a zero order drug release profile. Pharmacokinetic study of formula CA10 in human volunteers revealed a 5.6 fold increase in BH bioavailability compared to the oral commercial Buspar® tablets. Conducting level A in vitro/in vivo correlation showed good correlation (r²=0.9805) between fractions dissolved in vitro and fractions absorbed in vivo. PMID:24412520

Kassem, Mohamed A A; Elmeshad, Aliaa N; Fares, Ahmed R

2014-03-10

458

Oral Medication  

MedlinePLUS

... doctor before starting anything new — even over-the-counter items. Explore: Oral Medication How Much Do Oral Medications Cost? Save money by finding the right type and dosage of medicine for your needs. In this section Treatment and ...

459

Tablet PCs: A Physical Educator's New Clipboard  

ERIC Educational Resources Information Center

Computers in education have come a long way from the abacus of 5,000 years ago to the desktop and laptop computers of today. Computers have transformed the educational environment, and with each new iteration of smaller and more powerful machines come additional advantages for teaching practices. The Tablet PC is one. Tablet PCs are fully…

Nye, Susan B.

2010-01-01

460

Enhancing Student Performance Using Tablet Computers  

ERIC Educational Resources Information Center

Tablet PCs have the potential to change the dynamics of classroom interaction through wireless communication coupled with pen-based computing technology that is suited for analyzing and solving engineering problems. This study focuses on how tablet PCs and wireless technology can be used during classroom instruction to create an Interactive…

Enriquez, Amelito G.

2010-01-01

461

Time to stop counting the tablets?  

Microsoft Academic Search

We attempted to assess compliance using both a pharmacologic indicator (low-dose phenobarbital) and a return tablet count in 225 patients who were taking part in three separate studies. There were 216 patients (96%) who kept a follow-up appointment after 28 days; 161 patients appeared to have good compliance (90% to 109%) by return tablet count. Of these 161 patients, 51

Thomas Pullar; Shubha Kumar; Hilary Tindall; Morgan Feely

1989-01-01

462

Putting Tablet PCs to the Test  

ERIC Educational Resources Information Center

Like many educators, the author and her colleagues (five faculty members and two IT techs) in the department of Media Communications and Technology at East Stroudsburg University in Pennsylvania were interested to find out the status of tablet PCs in education. Microsoft listed 10 manufacturers of tablet PCs following two forms: the slate and the…

Amirian, Susan

2004-01-01

463

Morphine-augmented cholescintigraphy in the diagnosis of acute cholecystitis  

SciTech Connect

Cholescintigraphy is a sensitive procedure for diagnosing or excluding acute cholecystitis. However, when rapid diagnosis is critical, the requirement for delayed images (4 hr or more after injection) to minimize the false-positive rate diminishes its utility. We prospectively evaluated 40 cholescintigraphic examinations that did not visualize the gallbladder 1 hr after injection of 99mTc diisopropyliminodiacetic acid. These examinations were then augmented by administration of IV morphine, followed by an additional 30 min of imaging. After the morphine, 18 of these examinations demonstrated visualization of the gallbladder; none subsequently required surgical exploration. Of the remaining 22, who demonstrated persistent nonvisualization of the gallbladder post-morphine, 11 were explored surgically and found to be abnormal. The 11 others were treated medically. Low-dose morphine administered when the gallbladder fails to visualize after 1 hr is a useful adjunct to conventional cholescintigraphy because it reduces the time required to obtain a diagnostic result and decreases the number of false-positive results.

Kim, E.E.; Pjura, G.; Lowry, P.; Nguyen, M.; Pollack, M.

1986-12-01

464

Use of morphine in cholescintigraphy for obstructive cholecystitis  

SciTech Connect

Non-visualization of the gallbladder (GB) during the first hour of cholescintigraphy is observed in cystic duct obstruction (e.g. in acute cholecystitis) but may also occur in chronic cholecystitis, hepatocellular disease, alcoholism and prolonged total parenteral nutrition. Low dose morphine is shown to improve the specificity of the diagnosis of acute cholecystitis (from 85% to 100%) with no loss in sensitivity (98%) at a small cost in terms of additional study time. The authors reviewed 27 selected cholescintigraphic examinations augmented by intravenous (IV) morphine (0.04 mg/Kg). Of the 16 cases with persistent nonvisualization of the GB, ultrasound revealed gallstones in 5 cases, sludge in 4, acalculous cholecystitis in 3, one distended GB, one contracted GB and 2 normal GB's. Of the 4 patients taken to surgery, one with gallstones and one with acalculous cholecystitis were confirmed to have acute cholecystitis while another with gallstones had chronic cholecystitis and the final patient, who was sonographically normal, presented a single common duct stone. The authors conclude that the use of IV morphine is an effective adjunct to cholescintigraphy in the evaluation of gallbladder disease, especially when visualization post morphine rules out acute cholecystitis.

Kim, E.E.; Nguyen, M.; Pjura, G.; Pollack, M.; Gobuty, A.

1985-05-01

465

Exposure of consumers to morphine from poppy seeds in Hungary.  

PubMed

Poppy seed-containing foods are popular dishes in Hungary and some other Central European countries. The alkaloids of poppy are used in the production of medicines. Poppy seeds used as food may also contain considerable amounts of alkaloids, which raises the question of food safety. Morphine, codeine, thebaine and noscapine concentrations of poppy seed samples from the period 2001-2010 and consumption data from two Hungarian surveys, carried out in 2003 and 2009, were evaluated. Exposure calculations were made for morphine intake by both point estimate and probabilistic methods, and the uncertainty of the calculated values was estimated. The point estimate for the acute consumer exposure, calculated using the 97.5th percentiles of morphine concentration and of poppy seed consumption and taking into account the reduction of morphine content by processing, was 78.64?µg (kg?bw)?¹?day?¹ for adults, and 116.90?µg (kg?bw)?¹?day?¹ for children. Based on probabilistic estimations, the 97.5th and 99th percentile exposures ranged between 18.3-25.4 and 25.6-47.4?µg (kg?bw)?¹?day?¹ for adults, and between 32.9 and 66.4?µg (kg?bw)?¹?day?¹ for children, respectively. As a no observed effect level (NOEL) had not been established, the significance of exposure could not be assessed. PMID:22165856

Zentai, A; Sali, J; Szeitzné-Szabó, M; Szabó, I J; Ambrus, Á

2012-01-01

466

Conditioning of morphine-induced taste aversion and analgesia  

Microsoft Academic Search

The process of selective associations is evident in the aversive conditioning literature, where it has been shown that external cues are readily associated with peripheral pain, whereas taste cues are more easily associated with effects of drug administration. Within this framework, it is of interest that the failures to obtain a conditioned analgesic response to a morphine-associated CS have used

James S. Miller; Kimberly S. Kelly; Janet L. Neisewander; D. F. McCoy; Michael T. Bardo

1990-01-01

467

Narcotic tapering in pregnancy using long-acting morphine  

PubMed Central

Abstract Objective To document the management of and outcomes for patients receiving narcotic replacement and tapering with long-acting morphine preparations during pregnancy. Design A prospective cohort study over 18 months. Setting Northwestern Ontario. Participants All 600 births at Meno Ya Win Health Centre in Sioux Lookout, Ont, from January 1, 2012, to June 30, 2013, including 166 narcotic-exposed pregnancies. Intervention Narcotic replacement and tapering of narcotic use with long-acting morphine preparations. Main outcome measures Prenatal management of maternal narcotic use, incidence of neonatal abstinence syndrome, and other neonatal outcomes. Results The incidence of neonatal abstinence syndrome fell significantly to 18.1% of pregnancies exposed to narcotics (from 29.5% in a previous 2010 study, P = .003) among patients using narcotic replacement and tapering with long-acting morphine preparations. Neonatal outcomes were otherwise equivalent to those of the nonexposed pregnancies. Conclusion In many patients, long-acting morphine preparations can be safely used and tapered in pregnancy, with a subsequent decrease in observed neonatal withdrawal symptoms.

Dooley, Roisin; Dooley, Joe; Antone, Irwin; Guilfoyle, John; Gerber-Finn, Lianne; Kakekagumick, Kara; Cromarty, Helen; Hopman, Wilma; Muileboom, Jill; Brunton, Nicole; Kelly, Len

2015-01-01

468

Monoamine mediation of the morphine-induced activation of mice  

PubMed Central

1. The dose-response relationship for hyperactivity in grouped mice following the injection of morphine sulphate has been established. 2. The activation response can be modified by drugs which affect either catecholamines or indoleamines. 3. The monoamine precursors L-DOPA and 5-hydroxytryptophan potentiate the response. 4. The monoamine synthesis inhibitors ?-methyl-p-tyrosine and p-chlorophenylalanine reduce the response. 5. Inhibition of monoamine oxidase activity by pargyline caused a great increase in the response. The simultaneous administration of reserpine resulted in a further potentiation. 6. Reserpine blocked the response whenever it was given alone, either before, with or after the injection of morphine. 7. Blockade of ?-adrenoceptors with phentolamine or phenoxybenzamine reduced the response. 8. Blockade of tryptaminergic receptors with methysergide or cinanserin also antagonized the response. 9. The major tranquillizers haloperidol and chlorpromazine reduced the response. Haloperidol was especially effective in this regard. 10. The tricyclic antidepressant drug imipramine potentiated the response. 11. The morphine antagonist nalorphine completely prevented the response. 12. The anticholinergic agent atropine and the antihistaminic drug mepyramine did not affect the response. 13. We conclude that dopamine, noradrenaline and 5-hydroxytryptamine are all involved in the normal activation response of grouped mice to morphine, with dopaminergic mechanisms being of primary importance. PMID:4263794

Carroll, Bernard J.; Sharp, Peter T.

1972-01-01

469

Gastric emptying of enteric-coated tablets  

SciTech Connect

To evaluate the gastric emptying time of pharmaceutical dosage forms in a clinical setting, a relatively simple dual-radionuclide technique was developed. Placebo tablets of six different combinations of shape and size were labeled with indium-111 DTPA and enteric coated. Six volunteers participated in a single-blind and crossover study. Tablets were given in the morning of a fasting stomach with 6 oz of water containing /sup 99m/Tc pertechnetate and continuously observed with a gamma camera. A scintigraph was obtained each minute. The results suggested that the size, shape, or volume of the tablet used in this study had no significant effect in the rate of gastric emptying. The tablets emptied erratically and unpredictably, depending upon their time of arrival in the stomach in relation to the occurrence of interdigestive myoelectric contractions. The method described is a relatively simple and accurate technique to allow one to follow the gastric emptying of tablets.

Park, H.M.; Chernish, S.M.; Rosenek, B.D.; Brunelle, R.L.; Hargrove, B.; Wellman, H.N.

1984-03-01

470

Smartphones and tablets: Reshaping radiation oncologists’ lives  

PubMed Central

Background Smartphones and tablets are new handheld devices always connected to an information source and capable of providing instant updates, they allow doctors to access the most updated information and provide decision support at the point of care. Aim The practice of radiation oncology has always been a discipline that relies on advanced technology. Smartphones provide substantial processing power, incorporating innovative user interfaces and applications. Materials and methods The most popular smartphone and tablet app stores were searched for “radiation oncology” and “oncology” related apps. A web search was also performed searching for smartphones, tablets, oncology, radiology and radiation oncology. Results Smartphones and tablets allow rapid access to information in the form of podcasts, apps, protocols, reference texts, recent research and more. Conclusion With the rapidly changing advances in radiation oncology, the trend toward accessing resources via smartphones and tablets will only increase, future will show if this technology will improve clinical care. PMID:24669308

Gomez-Iturriaga, Alfonso; Bilbao, Pedro; Casquero, Francisco; Cacicedo, Jon; Crook, Juanita

2012-01-01

471

Oral Cancer  

MedlinePLUS

Oral Cancer Are You at Risk? What Are the Signs & Symptoms? Should You Have an Oral Cancer Exam? U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES ... Health Early Detection It is important to find oral cancer as early as possible when it can be ...

472

Investigation of morphine and morphine glucuronide levels and cytochrome P450 isoenzyme 2D6 genotype in codeine-related deaths.  

PubMed

Compared to morphine and morphine-6-glucuronide (M6G), codeine and its other major metabolites codeine-6-glucuronide and norcodeine have weak affinity to opioid ?-receptors. Analgesic effects of codeine are thus largely dependent on metabolic conversion to morphine by the polymorphic cytochrome P450 isoenzyme 2D6 (CYP2D6). How this relates to toxicity and post-mortem whole blood levels is not known. This paper presents a case series of codeine-related deaths where concentrations of morphine, M6G and morphine-3-glucuronide (M3G), as well as CYP2D6 genotype, are taken into account. Post-mortem toxicological specimens from a total of 1444 consecutive forensic autopsy cases in Central Norway were analyzed. Among these, 111 cases with detectable amounts of codeine in femoral blood were identified, of which 34 had femoral blood concentrations exceeding the TIAFT toxicity threshold of 0.3mg/L. Autopsy records of these 34 cases were retrieved and reviewed. In the 34 reviewed cases, there was a large variability in individual morphine to codeine concentration ratios (M/C ratios), and morphine levels could not be predicted from codeine concentrations, even when CYP2D6 genotype was known. 13 cases had codeine concentrations exceeding the TIAFT threshold for possibly lethal serum concentrations (1.6 mg/L). Among these, 8 individuals had morphine concentrations below the toxic threshold according to TIAFT (0.15 mg/L). In one