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Control of severe pain with sustained-release morphine tablets v. oral morphine solution.  

PubMed Central

Recently a sustained-release morphine sulfate tablet (MS Contin [MSC]) was introduced in Canada. In a randomized double-blind crossover trial we compared MSC given every 12 hours with a morphine sulfate solution (MSS) given every 4 hours to 17 patients suffering from chronic severe pain. After titration of the morphine dosage to optimize the analgesic effect, each patient received 10 days of therapy with either MSC or MSS, then 10 days of therapy with an equal daily dose of the other formulation. Both preparations provided effective pain control, with minimal side effects. There was no significant difference between MSC and MSS in pain scores on a visual analogue scale (VAS), severity scores for tiredness and nausea, amount of supplemental morphine needed for break-through pain or patient preference. The plasma morphine concentrations tended to be greater during treatment with MSC. The study had an 89% probability of detecting a clinically significant difference in VAS pain scores. We conclude that an individualized, twice-daily regimen of MSC is as effective as MSS given every 4 hours for control of severe pain. The twice-daily regimen has several advantages: it provides for an uninterrupted night's sleep, it is substantially more convenient than the six doses per day required with MSS, and it should help reduce both medication errors and noncompliance.

Arkinstall, W W; Goughnour, B R; White, J A; Stewart, J H



Ondansetron, orally disintegrating tablets versus intravenous injection for prevention of intrathecal morphine-induced nausea, vomiting, and pruritus in young males.  


In this study we compared the efficacy of orally disintegrating tablets (ODT) and IV ondansetron for preventing spinal morphine-induced pruritus and postoperative nausea and vomiting (PONV) in healthy young male patients. Patients who received bupivacaine with 0.20 mg morphine for spinal anesthesia were randomly assigned to the ODT group (ODT ondansetron 8 mg, n = 50), the IV group (4 mg ondansetron IV, n = 50), or the placebo group (n = 50). Each individual was assessed for pruritus, postoperative nausea and vomiting, and pain at 0, 2, 6, 12, 18, and 24 h after surgery using three distinct visual analog scales. The frequencies of postoperative nausea and vomiting and frequencies of requirement for rescue antiemetic and antipruritic were recorded. There were no significant differences among the three groups with respect to incidence or severity of PONV or postoperative pain visual analog scale scores. The incidences of pruritus in the ODT (56%) and IV (66%) groups were significantly different from that in the placebo group (86%) (P < 0.02 for both). Only the ODT group had significantly lower mean pruritus visual analog scale scores at 0, 2, 6, and 12 h postsurgery than the placebo group (P < 0.023 for all). The frequency of requirement for rescue antipruritic was significantly less in the ODT group than the placebo group (P = 0.013). Both ODT ondansetron 8 mg and IV ondansetron 4 mg are more effective than placebo for preventing spinal morphine-induced pruritus, but neither form of this agent reduces spinal morphine-induced postoperative nausea and vomiting in this patient group. PMID:16243989

Pirat, Arash; Tuncay, Senay F; Torgay, Adnan; Candan, Selim; Arslan, Gulnaz



Guidance for Industry Orally Disintegrating Tablets.  

National Technical Information Service (NTIS)

This guidance provides pharmaceutical manufacturers of new and generic drug products with an Agency perspective on the definition of an orally disintegrating tablet (ODT)which is a different dosage form than, for example, a chewable tablet or a tablet tha...



Oral morphine in cancer pain: influences on morphine and metabolite concentration  

Microsoft Academic Search

One hundred fifty-one patients with chronic cancer pain were studied during chronic treatment with oral morphine. Plasma concentrations of morphine and metabolites (M3G and M6G) were measured. The ratio of plasma morphine to metabolites was not affected by dose. Generalized linear interactive modeling analysis using morphine dose, age, sex, renal and hepatic dysfunction, and concomitant medication as explanatory variables accounted

Henry J McQuay; Dawn Carroll; Clara C Faura; David J Gavaghan; Christopher W Hand; R Andrew Moore; Henry J McQuay DM



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.

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



Morphine and morphine-glucuronide concentrations in plasma and CSF during long-term administration of oral morphine.  

PubMed Central

Concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were measured by h.p.l.c. in plasma and cerebrospinal fluid (CSF) samples from 16 patients with cancer receiving oral (controlled-release) morphine. There was a close correlation between plasma and CSF morphine concentrations (r = 0.94, P = 0.0001) and both correlated with drug dosage (r = 0.61, P = 0.013 and r = 0.74, P = 0.0001, respectively). M3G and M6G in plasma and CSF were correlated (r = 0.81 and r = 0.82, both P = 0.0001). No relationship was apparent between M plus M6G concentrations in the CSF and pain scores.

van Dongen, R T; Crul, B J; Koopman-Kimenai, P M; Vree, T B



Pharmacokinetics of oral morphine sulfate in dogs: a comparison of sustained release and conventional formulations.  

PubMed Central

The pharmacokinetics and bioavailability (F) of single dose sustained release morphine sulfate (OSRMS) and nonsustained release morphine sulfate (NSRMS) were compared to each other and to a bolus injection of morphine sulfate (MS) intravenously (i.v.) in dogs. Beagles (n = 6) were randomly assigned to 3 treatment groups: namely, OSRMS 15 mg orally, NSRMS 15 mg orally, and 15 mg i.v. Serum samples were drawn at intervals up to 480 min following oral and 420 min following i.v. administration. Serum was analysed for morphine concentration using a radioimmunoassay. Data were analysed using non-compartmental pharmacokinetics. The only statistically significant difference between OSRMS and NSRMS was maximum serum concentration (Cmax). There were trends toward longer time to maximum serum concentration (Tmax) and longer mean absorption time (MAT) for OSRMS when compared to NSRMS, but the differences were not statistically significant (P < 0.05). Pharmacokinetic parameters for both oral formulations exhibited large variability in the rate of absorption of MS from the gastrointestinal tract. Bioavailability of both OSRMS and NSRMS was low (15%-17%). As expected, the area under the concentration vs time curve (AUC) and Cmax for the i.v. data was significantly greater than for both oral groups, and Tmax and mean residence time (MRT) were significantly less following i.v. administration. There were no statistically significant differences among the 3 treatment groups for apparent volume of distribution at steady state (Vdss) or elimination parameters. The OSRMS formulation used in this study provided equivalent bioavailability to NSRMS in dogs, accompanied by large individual variability in drug absorption. It also did not appear that the sustained release formulation provided sufficiently prolonged release of morphine sulfate from the tablet matrix in dogs to allow prolonged dosing intervals compared to NSRMS.

Dohoo, S E; Tasker, R A



Formulation and in vitro-in vivo evaluation of buccoadhesive morphine sulfate tablets.  


Buccoadhesive controlled-release systems for the delivery of morphine sulfate were prepared by compression of hydroxypropyl methylcellulose (HPMC) with carbomer (CP), which served as the bioactive adhesive compound. The release behavior of systems containing 30 mg of morphine sulfate and various amounts of the two polymers was found to be non-Fickian. The adhesion force was significantly affected by the mixing ratio of HPMC and CP in the tablet, and the weakest adhesion force was observed at a ratio of 1:1 (HPMC:CP). Interpolymer complex formation was confirmed between HPMC and CP in acidic medium by turbidity, viscosity, and FT-IR measurements. The amount absorbed (percentage of the drug loaded) of the controlled-release buccoadhesive tablets in six healthy volunteers and was 30 +/- 5%. PMID:8165181

Anlar, S; Capan, Y; Güven, O; Gö?ü?, A; Dalkara, T; Hincal, A A



Influence of oral buprenorphine, oral naltrexone or morphine on the effects of laparotomy in the rat  

Microsoft Academic Search

Summary The effects of oral administration of buprenorphine ('buprenorphine jello'), a partial ~t opioid agonist, oral naltrexone, a ~t antagonist and morphine, a J.1agonist, were investigated in rats following laparotomy. Food and water consumption and body weight were reduced in rats that underwent surgery. Rats undergoing anaesthesia alone showed only a small reduction in water consumption. Administration of oral buprenorphine

J. H. Liles; P. A. Flecknell; J. Roughan; I. Cruz-Madorran



Dissolution testing of orally disintegrating tablets.  


For industrially manufactured pharmaceutical dosage forms, product quality tests and performance tests are required to ascertain the quality of the final product. Current compendial requirements specify a disintegration and/or a dissolution test to check the quality of oral solid dosage forms. These requirements led to a number of compendial monographs for individual products and, at times, the results obtained may not be reflective of the dosage form performance. Although a general product performance test is desirable for orally disintegrating tablets (ODTs), the complexity of the release controlling mechanisms and short time-frame of release make such tests difficult to establish. For conventional oral solid dosage forms (COSDFs), disintegration is often considered to be the prerequisite for subsequent dissolution. Hence, disintegration testing is usually insufficient to judge product performance of COSDFs. Given the very fast disintegration of ODTs, the relationship between disintegration and dissolution is worthy of closer scrutiny. This article reviews the current status of dissolution testing of ODTs to establish the product quality standards. Based on experimental results, it appears that it may be feasible to rely on the dissolution test without a need for disintegration studies for selected ODTs on the market. PMID:22686339

Kraemer, Johannes; Gajendran, Jayachandar; Guillot, Alexis; Schichtel, Julian; Tuereli, Akif



Active ingredient: Risperidone Form/Route: Tablet/Oral ...  

Center for Biologics Evaluation and Research (CBER)

Text VersionPage 1. Contains Nonbinding Recommendations Draft Guidance on Risperidone ... Active ingredient: Risperidone Form/Route: Tablet/Oral ... More results from


Active ingredient: Meloxicam Form/Route: Tablets/Oral ...  

Center for Biologics Evaluation and Research (CBER)

Text VersionPage 1. Contains Nonbinding Recommendations Guidance on Meloxicam ... Active ingredient: Meloxicam Form/Route: Tablets/Oral ... More results from


Active ingredient: Trandolapril Form/Route: Tablet/Oral ...  

Center for Drug Evaluation (CDER)

Text VersionPage 1. Contains Nonbinding Recommendations Guidance on Trandolapril ... Active ingredient: Trandolapril Form/Route: Tablet/Oral ... More results from


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



[Quantitative determinations of glycyrrhizic acid, glycyrrhetinic acid, morphine and sodium benzoate in compound liquorice tablets by capillary zone electrophoresis].  


Capillary zone electrophoresis (CZE) was used to quantitatively determine the contents of glycyrrhizic acid, glycyrrhetinic acid, morphine and sodium benzoate in compound liquorice tablets. The detection wavelength was 228 nm and the applied voltage was 14 kV. Borax solution of 50 mmol/L was used as the background electrolyte and hydrochlorothiazide as the internal standard. There were all good linear relationships between the concentrations and the relative areas of glycyrrhizic acid, glycyrrhetinic acid, morphine and sodium benzoate. Their average recoveries were 98.2%, 97.3%, 97.1% and 97.5%, respectively. The method is simple, rapid and accurate. PMID:12541626

Sun, Guo-xiang; Wang, Yu; Sun, Yu-qing



Plasma concentrations of codeine and its metabolite, morphine, after single and repeated oral administration  

Microsoft Academic Search

Plasma concentrations of codeine and its demethylated metabolite, morphine, were determined after single and repeated oral administration of codeine. Twelve healthy volunteers received two doses of codeine 60 mg, 2.8 h apart. In order to achieve steady-state conditions codeine 60 mg was then taken every 8 h for a further five doses. The plasma concentrations of codeine and morphine after

H. Quiding; P. Anderson; U. Bondesson; L. O. Boréus; P.-Å. Hynning



The Quantitative Determinations of Glycyrrhizic Acid, Glycyrrhetinic Acid, Morphine, and Sodium Benzoate in Compound Liquorice Tablets by HPCE  

Microsoft Academic Search

Capillary zone electrophoresis (CZE) was used to quantitatively determine the contents of glycyrrhizic acid, glycyrrhetinic acid, morphine, and sodium benzoate in compound liquorice tablets. The detection wavelength was 228 nm and 14 kV voltage was applied, and the 50 mM sodium borate was used as the background electrolyte, in which hydrochlorothiazide served as an internal standard and the temperature was 24–25°C. There were

Guoxiang Sun; Yu Wang; Yuqing Sun



[Determination of morphine in compound liquorice tablets by high performance liquid chromatography with SEP-PAK C18 cartridge pretreatment].  


An efficient method combining SEP-PAK C18 cartridge solid phase extraction (SPE) with reversed-phase high performance liquid chromatography for the quantitation of morphine in the Compound Liquorice Tablet is presented. The tablets have been used for making expectoration easy and relieving cough for years. The tablet powder (approximately 1 tablet) was added into a stoppered centrifuge tube, and vertically extracted with 5 mL of 0.5% HAc for 5 min. After centrifugation the supernatant was transferred to a beaker and the extraction was repeated twice with 4 mL and then 3 mL of 0.5% HAc. Five millilitres of carbonate buffer (pH 8.9) was added to the combined extracts. A SEP-PAK C18 cartridge was pretreated by passing methanol and distilled water, using a glass syringe. The mixture was applied on it and allowed to flow through. The cartridge was washed first with 5 mL of 10% methanol solution and then the morphine was eluted with 4 mL of 70% methanol solution into a 5 mL volumetric flask and was finally diluted to volume with 70% methanol solution. Analysis was performed on a mu-Bondapak C18 column(300 mm x 4.6 mm i.d., 10 microns) with 0.1 mol/L NaH2PO4-methanol(5:1) as the mobile phase and detection at 286 nm. The average recovery of morphine was (101.2 +/- 1.5)% and RSD was 1.5%. The method is simple, rapid, accurate, and reproducible, and can be used in drug control. PMID:11327001

Wang, Y; Zeng, J



Mucoadhesive tablet releasing iodine for treating oral infections.  


Iodine complexes with ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) were prepared by immersing polymer powder in aqueous solutions of iodine. These complexes were incorporated in a mucoadhesive tablet for potential use as antimicrobial agent for treating oral infections. The release profile of iodine from the adhesive tablets was determined and the antimicrobial activity was assessed by diffusion assays using Candida albicans and Porphyromonas gingivalis cultures. Iodine was readily absorbed up to 35%w/w in the polymers. A differential scanning colorimeter (DSC) scan revealed a correlation between the endotherm peak of the complexes and the iodine content in the polymer complex. The tablets exhibited marked antifungal and antibacterial activities against the fungal/bacterial strains tested. PMID:17724656

Mizrahi, Boaz; Domb, Abraham J



Influence of oral buprenorphine, oral naltrexone or morphine on the effects of laparotomy in the rat.  


The effects of oral administration of buprenorphine ('buprenorphine jello'), a partial mu opioid agonist, oral naltrexone, a mu antagonist and morphine, a mu agonist, were investigated in rats following laparotomy. Food and water consumption and body weight were reduced in rats that underwent surgery. Rats undergoing anaesthesia alone showed only a small reduction in water consumption. Administration of oral buprenorphine (0.5 mg/kg in flavoured gelatin) decreased the effects of surgery on body weight and water intake when compared to untreated (vehicle alone) controls. The magnitude of this beneficial effect was similar to that seen in previous studies using subcutaneous administration of buprenorphine. The fall in body weight and food and water intake following surgery was similar in the groups which received morphine and the control group which received vehicle (jelly). Neither the magnitude of the fall in body weight, and food and water intake, nor the behavioural scores differed between naltrexone and control (vehicle alone) rats following surgery. This suggests that the beneficial effects of partial agonist analgesics are mediated by a reduction in pain rather than by antagonism of endogenous opioids. Both anaesthesia and surgery caused changes in behaviour, but the major effects of buprenorphine in normal (unoperated) rats severely limited the value of behavioural parameters as a means of assessing possible beneficial effects of analgesic administration. PMID:9587897

Liles, J H; Flecknell, P A; Roughan, J; Cruz-Madorran, I



Subjective, psychomotor, and analgesic effects of oral codeine and morphine in healthy volunteers  

Microsoft Academic Search

The subjective, psychomotor, and physiological effects of analgesic doses of oral codeine and morphine were examined in 12\\u000a healthy volunteers. Subjects ingested placebo, morphine 20 or 40?mg, or codeine 60 or 120?mg in a randomized, double-blind,\\u000a crossover design. The smaller and larger doses of each drug were putatively equianalgesic, and the cold-pressor test was included\\u000a to test this assumption. Codeine

D. J. Walker; James P. Zacny



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

Microsoft Academic Search

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

I. Stoltenberg; J. Breitkreutz



Oral pharmacokinetic comparison of different genistein tablets in beagle dogs.  


An accurate and sensitive analytical method has been developed for the quantification of genistein in dog plasma using high-performance liquid chromatography/tandem mass spectrometry. Genistein and diclofenac (internal standard) were extracted from the plasma sample using methyl tert-butyl ether and then separated on an Agilent Zorbax C18 column using a gradient mobile phase. The detector was a Q-trap mass spectrometer with an electrospray ionization interface operating in the multiple reaction monitoring mode. The assay was linear over the concentration range of 0.10-500 ng/mL with a lower limit of quantification of 0.10 ng/mL. The method was shown to be reproducible and reliable, with inter-day and intra-day accuracy and precision within ±15%. The method was successfully applied to a pharmacokinetic comparison of immediate and extended release tablets in beagle dogs after oral administration. Immediate release tablets showed rapid genistein absorption, with mean peak concentration of 726 ± 199 ng/mL reached at 0.2 ± 0.0 h. However, the absorption of genistein was considerably slower and more sustainable for extended release tablets. The relative bioavailability of the extended release tablet over the immediate release formulation was estimated to be 134 ± 47% based on the AUCInf values from non-compartmental analysis. PMID:22964950

Feng, Duiping; Qiu, Feng; Tong, Zhanqi; Xie, Chunming



Olanzapine orally disintegrating tablet: a review of efficacy and compliance.  


Medication nonadherence, especially in psychiatric disorders, has been associated with treatment failure and other negative outcomes. Orally disintegrating formulations have been developed as an alternative to improve medication adherence. This report reviews the properties, efficacy, and safety profile of olanzapine as an orally disintegrating tablet, and explores their association with medication compliance compared with standard oral formulation. Medical literature, published on orally disintegrating formulation of olanzapine identified using Pubmed and EMBASE, was used. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug. Studies evaluating the biostability, biodisposability, pharmacokinetics, efficacy, and safety of orally disintegrating olanzapine as treatment of patients with psychiatric disorders were reviewed. Measurement tools included the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions-Severity (CGI-S), Simpson-Angus Scale (SAS), Abnormal Involuntary Movement Scale, and Nursing Assessment of Medication Acceptance (NAMA). Orally disintegrating olanzapine, an effective atypical antipsychotic with an acceptable safety profile, can facilitate the burden of treatment on patients and caregivers due to its ease of administration. This is especially important in diseases such as schizophrenia and bipolar disorder, which can be chronic and require long-term treatment. PMID:18801113

San, Luis; Casillas, Marta; Ciudad, Antonio; Gilaberte, Inmaculada



The Brompton mixture versus morphine solution given orally: effects on pain.  

PubMed Central

The Brompton mixture is widely used as an effective method for controlling pain in cancer patients. In a double-blind crossover trial a standard Brompton mixture containing morphine, cocaine, ethyl alcohol, syrup BP and chloroform water was compared with morphine alone in a flavoured aqueous solution; both were administered orally. Pain was measured by means of the pain intensity index of the McGill Pain Questionnaire. Ratings of confusion, nausea and drowsiness were obtained from both the patients and their nurses and relatives. The data showed that there was no significant difference between the Brompton mixture and morphine administered orally for any of the variables. Both relieved pain effectively in about 85% of the patients.

Melzack, R.; Mount, B. M.; Gordon, J. M.



Further improvement of orally disintegrating tablets using micronized ethylcellulose.  


The aim of this study is to design a new orally disintegrating tablet (ODT) containing micronized ethylcellulose (MEC). The new ODT was prepared by physical mixing of rapidly disintegrating granules (RDGs) with MEC. To obtain RDGs, mannitol was spray-coated with a suspension of corn starch and crospovidone (9:1, w/w ratio) using a fluidized-bed granulator (suspension spray-coating method). The new ODTs were evaluated for their hardness, friability, thickness, internal structure (X-ray-CT scanning), in vivo disintegration time, and water absorption rate. Since MEC increases tablet hardness by increasing the contact frequency between the granules, the new ODTs could obtain high hardness (>50 N) and low friability (<0.5 %) with relatively low compression force. In addition, fine capillary channels formed in ODTs facilitated the wicking action and enabled rapid disintegration in vivo (<30 s). On the other hand, since MEC has low hygroscopicity, the tablet hardness of ODTs containing MEC remained high for 1 month in high-humidity conditions. In conclusion, the new ODTs containing MEC developed in this study possessed superior properties for clinical use and are expected to be applied for a wide range of functionally released drugs for bitter taste masking, sustained release, and controlled release (pH-dependent film coating, matrix, and microcapsule). PMID:22138608

Okuda, Yutaka; Irisawa, Yosuke; Okimoto, Kazuto; Osawa, Takashi; Yamashita, Shinji



Development of sildenafil-loaded orally disintegrating tablet with new lactate salt.  


To develop a sildenafil lactate-loaded orally disintegrating tablet with a faster drug effect onset and immediate action of erection, the orally disintegrating tablets were prepared with various amounts of menthol and colloidal silica using the direct compression technique followed by vacuum drying. Their tablet properties such as friability, hardness, wetting time and disintegration time were investigated. The oral bioavailability of sildenafil in the orally disintegrating tablet was then compared with the sildenafil citrate-loaded commercial tablet (Viagra(®)) in rabbits. Sildenafil lactate was a new salt form with more improved solubility and alleviated bitterness compared with commercial salt, sildenafil citrate. As the amount of menthol in the orally disintegrating tablet increased, the friability increased and hardness decreased, resulting in a shorter wetting time and disintegration time. Colloidal silica did the opposite. The sildenafil lactate-loaded orally disintegrating tablet prepared with 45 mg/tab of menthol and 1.5 mg/tab of colloidal silica gave a hardness of 3-4 KP, friability less than 0.5% and disintegration time less than 30 s, suggesting that it was a practical and commercial product with good tablet property and excellent efficacy. Furthermore, it gave higher AUC and C(max), and shorter T(max) values than did the commercial tablet, indicating that it improved the oral bioavailability of sildenafil in rabbits compared with the commercial tablet. Thus, the sildenafil lactate-loaded orally disintegrating tablet might induce a fast onset of action and immediate erection compared with the sildenafil citrate-loaded commercial tablet. PMID:22010981

Jung, Si-Young; Kim, Dong-Wuk; Seo, Youn Gee; Woo, Jong Soo; Yong, Chul Soon; Choi, Han-Gon



Morphine Stimulates Cell Migration of Oral Epithelial Cells by Delta-Opioid Receptor Activation  

PubMed Central

Oral mucositis is one of the most common side effects of chemoradiation regimens and manifestation can be dose-limiting for the therapy, can impair the patient's nutritional condition and quality of life due to severe pain. The therapeutic options are limited; often only an alleviation of the symptoms such as pain reduction by using systemic opioids is possible. Stimulating opioid receptors on peripheral neurons and dermal tissue, potent analgesic effects are induced e.g. in skin grafted patients. Advantageous effects on the cell migration and, thus, on the wound healing process are described, too. In this study, we investigated whether opioid receptors are also expressed on oral epithelial cells and if morphine can modulate their cell migration behavior. The expression of the opioid receptors MOR, DOR and KOR on primary human oral epithelial cells was verified. Furthermore, a significantly accelerated cell migration was observed following incubation with morphine. The effect even slightly exceeded the cell migration stimulating effect of TGF-ß: After 14 h of morphine treatment about 86% of the wound area was closed, whereas TGF-ß application resulted in a closed wound area of 80%. With respect to morphine stimulated cell migration we demonstrate that DOR plays a key role and we show the involvement of the MAPK members Erk 1/2 and p38 using Western blot analysis. Further studies in more complex systems in vitro and in vivo are required. Nevertheless, these findings might open up a new therapeutic option for the treatment of oral mucositis.

Charbaji, Nada; Schafer-Korting, Monika; Kuchler, Sarah



Morphine Withdrawal Lowers Host Defense to Enteric Bacteria: Spontaneous Sepsis and Increased Sensitivity to Oral Salmonella enterica Serovar Typhimurium Infection  

Microsoft Academic Search

Understanding the consequences of drug withdrawal on immune function and host defense to infection is important. We, and others, previously demonstrated that morphine withdrawal results in immunosuppression and sensitizes to lipopolysaccharide-induced septic shock. In the present study, the effect of morphine with- drawal on spontaneous sepsis and on oral infection with Salmonella enterica serovar Typhimurium was examined. Mice were chronically

Pu Feng; Allan L. Truant; Joseph J. Meissler; J. P. Gaughan; M. W. Adler; T. K. Eisenstein



A comparison of regularly dosed oral morphine and on-demand intramuscular morphine in the treatment of postsurgical pain  

Microsoft Academic Search

A randomized, placebo-controlled, double-blind clinical trial was conducted to compare the use of regularly dosed po morphine\\u000a and on-demand im morphine in 47 patients undergoing total hip arthroplasty. Patients were randomized to receive either 20\\u000a mg (initial dose) of regularly dosed morphine (every four hours po) plus breakthrough pain medication on-demand consisting\\u000a of both 10 mg morphine po and placebo

James P. McCormack; C. Brian Warriner; Marc Levine; Ned Glick



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



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

Microsoft Academic Search

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

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



Oral malodor reduction by a palatal mucoadhesive tablet containing herbal formulation  

Microsoft Academic Search

ObjectiveThe 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.

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



Engineering and Other Health Hazard Controls in Oral Contraceptive Tablet-Making Operations.  

National Technical Information Service (NTIS)

A survey of health hazard controls in oral contraceptive tablet making (SIC-2834) operations was conducted. Four facilities were included in the survey. Engineering controls included using hoods while weighing pure steroids, local and general ventilation,...

M. Y. Anastas



Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain  

PubMed Central

Objectives To compare patients' preference for transdermal fentanyl or sustained release oral morphine, their level of pain control, and their quality of life after treatment. Design Randomised, multicentre, international, open label, crossover trial. Setting 35 centres in Belgium, Canada, Denmark, Finland, the United Kingdom, the Netherlands, and South Africa. Participants 256 patients (aged 26-82 years) with chronic non-cancer pain who had been treated with opioids. Main outcome measures Patients' preference for transdermal fentanyl or sustained release oral morphine, pain control, quality of life, and safety assessments. Results Of 212 patients, 138 (65%) preferred transdermal fentanyl, whereas 59 (28%) preferred sustained release oral morphine and 15 (7%) expressed no preference. Better pain relief was the main reason for preference for fentanyl given by 35% of patients. More patients considered pain control as being “good” or “very good” with fentanyl than with morphine (35% v 23%, P=0.002). These results were reflected in both patients' and investigators' opinions on the global efficacy of transdermal fentanyl. Patients receiving fentanyl had on average higher quality of life scores than those receiving morphine. The incidence of adverse events was similar in both treatment groups; however, more patients experienced constipation with morphine than with fentanyl (48% v 29%, P<0.001). Overall, 41% of patients experienced mild or moderate cutaneous problems associated with wearing the transdermal fentanyl patch, and more patients withdrew because of adverse events during treatment with fentanyl than with morphine (10% v 5%). However, within the subgroup of patients naive to both fentanyl and morphine, similar numbers of patients withdrew owing to adverse effects (11% v 10%, respectively). Conclusion Transdermal fentanyl was preferred to sustained release oral morphine by patients with chronic non-cancer pain previously treated with opioids. The main reason for preference was better pain relief, achieved with less constipation and an enhanced quality of life. What is already known on this topicThe clinical use of potent opioids in the treatment of chronic non-cancer pain is supported by retrospective, survey data and small randomised controlled trials showing efficacy and safetyStudies with transdermal fentanyl have shown efficacy and preference over sustained release oral morphine in the treatment of cancer painWhat this study addsThis is the first study to provide comparative data supporting treatment options with potent opioids for chronic non-cancer painBoth transdermal fentanyl and sustained release oral morphine provided effective and well tolerated pain reliefDuring fentanyl treatment patients experienced superior pain relief, higher quality of life, and less constipation; fentanyl was preferred to morphine by 65% of patients

Allan, Laurie; Hays, Helen; Jensen, Niels-Henrik; de Waroux, Bernard Le Polain; Bolt, Michiel; Donald, Royden; Kalso, Eija



A phase I pharmacokinetic and safety evaluation of oral pazopanib dosing administered as crushed tablet or oral suspension in patients with advanced solid tumors  

Microsoft Academic Search

Summary  Because cancer patients may have difficulty swallowing whole tablets, crushing tablets or ingesting an oral suspension is\\u000a a practical alternative. This open-label, 2-part, randomized crossover, phase I study evaluated the pharmacokinetics and tolerability\\u000a of pazopanib administered as a crushed tablet or an oral suspension relative to whole tablet in patients with advanced cancer\\u000a (Part 1). Patients completing Part 1 were

Elisabeth I. Heath; Karen Forman; Lisa Malburg; Shelby Gainer; A. Benjamin Suttle; Laurel Adams; Howard Ball; Patricia LoRusso


A new formulation for orally disintegrating tablets using a suspension spray-coating method.  


The aim of this study was to design a new orally disintegrating tablet (ODT) that has high tablet hardness and a fast oral disintegration rate using a new preparation method. To obtain rapid disintegration granules (RDGs), a saccharide, such as trehalose, mannitol, or lactose, was spray-coated with a suspension of corn starch using a fluidized-bed granulator (suspension method). As an additional disintegrant, crospovidone, light anhydrous silicic acid, or hydroxypropyl starch was also included in the suspension. The RDGs obtained possessed extremely large surface areas, narrow particle size distribution, and numerous micro-pores. When tabletting these RDGs, it was found that the RDGs increased tablet hardness by decreasing plastic deformation and increasing the contact frequency between granules. In all tablets, a linear relationship was observed between tablet hardness and oral disintegration time. From each linear correlation line, a slope (D/H value) and an intercept (D/H(0) value) were calculated. Tablets with small D/H and D/H(0) values could disintegrate immediately in the oral cavity regardless of the tablet hardness and were considered to be appropriate for ODTs. Therefore, these values were used as key parameters to select better ODTs. Of all the RDGs prepared in this study, mannitol spray-coated with a suspension of corn starch and crospovidone (2.5:1 w/w ratio) showed most appropriate properties for ODTs; fast in vivo oral disintegration time, and high tablet hardness. In conclusion, this simple method to prepare superior formulations for new ODTs was established by spray-coating mannitol with a suspension of appropriate disintegrants. PMID:19686825

Okuda, Y; Irisawa, Y; Okimoto, K; Osawa, T; Yamashita, S



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


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



[Preparation of orally disintegrating tablets for masking of unpleasant taste: comparison with corrective-adding methods].  


Many orally disintegrating tablets have recently been developed to improve oral ingestion and usability and are widely administered clinically, resulting in improved quality of life for patients. Since orally disintegrating tablets rapidly disintegrate in the mouth, the masking of unpleasant taste is important. We investigated the masking of the taste of furosemide (FU) as a model drug with correctives and prepared orally disintegrating tablets. Using maltitol (MA) as a corrective, granules were prepared employing mixing, coating, and mixing/coating methods using a desktop granulator. Each preparation was subjected to tasting. The taste was masked well when granules were prepared by the mixing and mixing/coating methods. Tablets were prepared from these granules with mannitol and crystalline cellulose added as fillers. Tablets made from granules prepared by the mixing and mixing/coating methods showed appropriate strength and disintegrated rapidly. When the amount of MA was increased in the mixing method, the disintegration time was prolonged, and thus the amount should be determined considering both taste masking and disintegration property. The results showed that orally disintegrating tablets of insoluble drugs with an unpleasant taste such as FU should be prepared with the taste masked employing the methods used in this study. PMID:20046069

Kawano, Yayoi; Ito, Akihiko; Sasatsu, Masanaho; Machida, Yoshiharu



Effects of Oral Morphine on the Larvae, Pupae and Imago Development in Drosophila Melanogaster  

PubMed Central

Objective: Previous studies, focusing on the effects of abused drugs, have used mice or rats as the main animal models; the present study tries to introduce a simple animal model. For this propose, we investigated the effects of oral morphine consumption by parents on the development of larvae, pupae and imago in Drosophila Melanogaster (D. Melanogaster). Materials and Methods: In this experimental study, twenty male and 20 female D. Melanogaster pupae were housed in test tubes with banana (5 pupae /tube).). Male and female groups each were divided into three experimental group and one control group, which were maintained at 25?. Morphine (0.2, 0.02, 0.002 mg/ml) was added into the test tubes of the experimental groups. The control group maintained at morphine-free test tube. The male and female groups with the same treatment were coupled and then female fertilization, egg deposit, larval, pupae and imago stages were studied macro and microscopically. The SPSS software (version 9.01) was used for statistical evaluations. Results: In the experimental groups, in the larvae stage, both increase and decrease of length and surface area in the pupae stage were observed. The number of larvae pupae, and imago was reduced in the experimental groups. Conclusion: The study showed that oral morphine consumption by parents may affect the development of larvae, pupation and imago stages in D. Melanogaster. The results also showed that D. Melanogaster may be a reliable animal model to study on the concerns about abused drugs especially those with opioids.

Tekieh, Elaheh; Kazemi, Masoomeh; Dehghani, Leila; Bahramyian, Sina; Sadogi, Mehrangiz; Zardooz, Homeira; Fakhanik-Babaei, Javad; Sahraei, Hedayat



A Pharmacokinetic and Tolerability Evaluation of Two Continuous Subcutaneous Infusion Systems Compared to an Oral Controlled-Release Morphine  

Microsoft Academic Search

The pharmacokinetic profiles, safety, and tolerability of continuous subcutaneous infusion with a novel drug deliver system (the MEDIPAD system) was compared to a standard infusion pump (the CADD-Micro) and to controlled-release tablets (MS Contin) for the administration of morphine sulfate. This was a single-center, open-label, three-treatment study conducted in 24 male and female healthy volunteers. The mean age was 40.6

Pia Mikkelsen Lynch; Jackie Butler; Deanne Huerta; Izrail Tsals; Diana Davidson; Sharon Hamm



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.

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



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


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



Control Technology Assessment of Unit Operations Employed in Oral Contraceptive Tablet Making Operations at Mead Johnson and Company, Evansville, Indiana: In-Depth Survey Report.  

National Technical Information Service (NTIS)

Control technologies employed at Mead Johnson and Company (SIC-2834) oral contraceptive tablet manufacturing facility in Evansville, Indiana, were evaluated on February 7 to 11, 1983. Processing and tableting of oral contraceptives were performed in the s...

M. Anastas



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


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



Levetiracetam: relative bioavailability and bioequivalence of a 10% oral solution (750 mg) and 750-mg tablets.  


Levetiracetam, an antiepileptic drug, is used worldwide as an adjunctive treatment for partial-onset seizures. The availability of a new oral solution formulation would provide an additional treatment option for patients who have difficulty swallowing tablets. A phase I single-center, randomized, open-label, two-way crossover, single-dose study was conducted to confirm that a 10% oral solution of levetiracetam was bioequivalent to the 750-mg oral tablet and to characterize its pharmacokinetics. Each of 24 healthy subjects received a single oral 750-mg dose of the randomized levetiracetam formulation (7.5 mL of 10% solution or 750-mg tablet) on day 1 and a single oral dose of the alternate formulation on day 8. Serial blood samples were collected from 0 to 36 hours after each dose administration for determination of plasma levetiracetam concentrations. Pharmacokinetic parameters were calculated, and bioequivalence of the two formulations was evaluated. The mean levetiracetam plasma concentration-time curves and pharmacokinetic parameters essentially were identical for the oral 10% solution and tablet and consistent with previously reported levetiracetam pharmacokinetics. The 90% confidence limits of the geometric mean ratio of the two formulations for area under the plasma concentration-time curve from time 0 to infinity, area under the plasma concentration-time curve from time 0 to last measurable time point, and maximum plasma concentration were within the 80% to 125% range, demonstrating bioequivalence of the two formulations. Both levetiracetam formulations were well tolerated. The levetiracetam 10% oral solution is a bioequivalent, well-tolerated alternative to the tablet formulation in patients who have difficulty swallowing. PMID:14615473

Coupez, René; Straetemans, Roel; Sehgal, Geeta; Stockis, Armel; Lu, Zhihong Sarah



Microsphere-based once-daily modified release matrix tablets for oral administration in angina pectoris.  


The objective of this research was to develop microsphere-based once-daily modified release tablet formulations of diltiazem hydrochloride (DH), a potent calcium channel blocker used in angina pectoris. For this purpose, DH-loaded microspheres were prepared by the solvent evaporation technique using Eudragit RS 100. The effect of variation in the drug/polymer ratio on the physical and release characteristics of the microspheres was investigated. After the selection of the suitable microspheres, tablets were compressed using Compritol 888 ATO, Ludipress and Cellactose 80 as different direct tableting agents and excipients. As a result, modified release tablet formulations of DH-loaded microspheres were designed successfully for oral administration once rather than two or three times a day in angina pectoris. PMID:18465309

Sengel-Türk, Ceyda T; Hasçicek, Canan; Gönül, Nur?in



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



Design and evaluation of taste masked dextromethorphan hydrobromide oral disintegrating tablets.  


The present study is aimed to develop dextromethorphan hydrobromide (DXM) oral disintegrating tablets (ODT) with acceptable palatability to help patients of all age groups. The bitter taste of the drug was masked by binding the drug to ion exchange resin. The effect of the particle size of resin on drug loading was studied. In vitro and in vivo disintegration time and in vitro drug release studies were performed. Drug loading increased significantly with a decrease in the particle size of the resin. DSC and XRPD studies reveal that the molecular state of the drug changed from crystalline to amorphous form. The dissolution efficiency calculated for optimized ODT and conventional directly compressed tablet were almost comparable, indicating free dissociation of the drug from the resinate. The bitter taste of DXM can be masked by binding with ion exchange resin and the resinate can be successfully formulated into oral disintegrating tablets. PMID:21134862

Malladi, Madhusudhan; Jukanti, Raju; Nair, Rashmi; Wagh, Sanjay; Padakanti, Hari Shanker; Mateti, Ashok



Morphine Oral  


... difficulty urinating or pain when urinating Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately: blue or purple color to the skin fast or slow heartbeat seizures fainting chest pain hives ...


Amorphous to crystalline transformation in maltose: Implications for orally disintegrating tablets  

Microsoft Academic Search

The purpose of the present study was to determine how environmental factors affected the crystallization of amorphous maltose, determine how those factors affected the post compaction hardening of oral fast dissolve tablets containing amorphous maltose, and to determine the crystallization kinetics and activation energy of amorphous maltose crystallization and separate out the activation energy of nucleation of amorphous maltose. The

Scott Eric Hostetler



Sugar end-capped poly-D,L-lactides as excipients in oral sustained release tablets.  


Sugar end-capped poly-D,L-lactide (SPDLA) polymers were investigated as a potential release controlling excipient in oral sustained release matrix tablets. The SPDLA polymers were obtained by a catalytic ring-opening polymerization technique using methyl alpha-D-gluco-pyranoside as a multifunctional initiator in the polymerization. Polymers of different molecular weights were synthesized by varying molar ratios of monomer/catalyst. The matrix tablets were prepared by direct compression technique from the binary mixtures of SPDLA and microcrystalline cellulose, and theophylline was used as a model drug. The tablet matrices showed in vitro reproducible drug release profiles with a zero-order or diffusion-based kinetic depending on the SPDLA polymer grade used. Further release from the tablet matrices was dependent on the molecular weight of the SPDLA polymer applied. The drug release was the fastest with the lowest molecular weight SPDLA grade, and the drug release followed zero-order rate. With the higher molecular weight SPDLAs, more prolonged dissolution profiles for the matrix tablets (up to 8-10 h) were obtained. Furthermore, the prolonged drug release was independent of the pH of the dissolution media. In conclusion, SPDLAs are a novel type of drug carrier polymers applicable in oral controlled drug delivery systems. PMID:19430908

Vuorinen, Sirpa; Heinämäki, Jyrki; Antikainen, Osmo; Lahcini, Mohammed; Repo, Timo; Yliruusi, Jouko



[Hydrophilic gel matrix tablets for oral administration of drugs].  


Matrix tablets with a dispersed active ingredient are the simplest concept in the design of dosage forms with modified drug release. If they contain a swelling polymer as an auxiliary substance, the release from these systems, after initial liberation of a portion of the active ingredient from the surface, takes place by diffusion, erosion, or a combination of both mechanisms in dependence on the solubility of the contained active ingredient. Although hydrophilic matrix tablets have become a well-tried and widely used dosage form with retarded effects, their research continues and new auxiliary substances and their combinations are being tested. The present paper reviews the knowledge published in this field in recent years. PMID:14619697

Rabisková, M; Vostalová, L; Medvecká, G; Horácková, D



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


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



Design and evaluation of microwave-treated orally disintegrating tablets containing polymeric disintegrant and mannitol.  


Microwave (MW) treatment was used to develop a formulation process for the preparation of wet molded orally disintegrating tablets (ODTs) consisting of mannitol and polymeric disintegrant with improved hardness and disintegration properties. The wet molded tablets were prepared in accordance with the conventional methods and subsequently heated by MW irradiation to induce the swelling of the tablet. Croscarmellose sodium, crospovidone, and low-substituted hydroxypropylcellulose (L-HPC) were evaluated for their use with this technology. NBD-020, which is a grade of L-HPC, provided the better hardness and disintegration results. In addition, the crystalline forms of mannitol impacted on hardness and disintegration properties of the ODT upon MW irradiation. The effects of the disintegrant ratio, ? and ? crystalline mannitol ratio, amount of water, and compression force on the ODT properties were evaluated using the design of experiment method. MW-induced swelling was enhanced by an increase in the disintegrant ratio. Although the hardness of the tablet increased following MW treatment, the disintegration time became less than that of the MW-untreated tablets as the ?-mannitol ratios increased. Taken together, the results indicated that the polymeric disintegrant greatly improved the properties of the molded tablets in combination with MW treatment. PMID:23524122

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



Pharmacokinetics of olanzapine after single-dose oral administration of standard tablet versus normal and sublingual administration of an orally disintegrating tablet in normal volunteers.  


Olanzapine (OLZ) is a second-generation antipsychotic agent available in 2 solid oral dosage forms, a standard oral tablet (SOT) and an orally disintegrating tablet (ODT). This study assessed the absorption of each by different routes of administration. Secondarily, the influence of P-glycoprotein (P-gp) genotype was assessed. It was hypothesized that more rapid absorption of the OLZ ODT would occur when administered sublingually versus standard oral administration. A randomized, 3-way crossover study assessed the 5-mg OLZ formulations in healthy volunteers (n = 10). Blood was collected (0-8 hours) to assess OLZ pharmacokinetics using liquid chromatography/mass spectrometry. Both routes of ODT administration resulted in more measurable early concentrations relative to SOT. However, there were no statistically significant differences observed between any of the OLZ exposures for observed pharmacokinetic parameters (C(max), T(max), AUC(0-8h)). The homozygous TT genotype for P-gp resulted in an increased AUC of OLZ for SOT administration but not for either condition where sublingual absorption could occur. PMID:16432268

Markowitz, John S; DeVane, C Lindsay; Malcolm, Robert J; Gefroh, Holly A; Wang, Jun-Sheng; Zhu, Hao-Jie; Donovan, Jennifer L



The Role of Oral Controlled Release Matrix Tablets in Drug Delivery Systems  

PubMed Central

Formulations that are able to control the release of drug have become an integral part of the pharmaceutical industry. In particular oral drug delivery has been the focus of pharmaceutical research for many years. This type of drug delivery has been at the centre of research due to its many benefits over conventional dosage. The focus of this review is on matrix tablets due to their widely use and simplicity of the formulation. This includes the discussion of various types of matrix tablets and factors affecting the drug release from these formulations. The mechanism of drug release from HPMC matrices is also discussed.

Nokhodchi, Ali; Raja, Shaista; Patel, Pryia; Asare-Addo, Kofi



Comparison of an orally disintegrating ondansetron tablet with the conventional ondansetron tablet for cyclophosphamide-induced emesis in cancer patients: A multicenter, double-masked study  

Microsoft Academic Search

A total of 427 cancer patients receiving cyclophosphamide chemotherapy participated in this multicenter, double-masked, double-dummy, parallel-group, randomized study comparing the antiemetic efficacy and safety of an 8-mg conventional ondansetron tablet (OT, n = 212) taken twice daily with an 8-mg orally disintegrating ondansetron tablet (ODT, n = 215) taken twice daily for 3 days. In the primary efficacy analysis, complete

Neville Davidson; Bernardo Rapoport; Bjorn Erikstein; Bernard L'Esperance; Paul Ruff; Walter Paska; Irene Miller; Paula Curtis



Evaluation of Chlorpheniramine Maleate microparticles in orally disintegrating film and orally disintegrating tablet for pediatrics.  


Abstract Objective: To mask the bitterness of Chlorpheniramine Maleate via encapsulating drug into Eudragit EPO microparticles, and then incorporate these microparticles into orally disintegrating films (ODF) and orally disintegrating tablets (ODT) for pediatric uses. Methods: Spray drying of water-in-oil emulsion was utilized to encapsulate Chlorpheniramine Maleate into Eudragit EPO microparticles. Based on an orthogonal experimental design L9 (3(3)), polynomial regression models were developed to evaluate correlation between microparticle properties (encapsulation efficiency and drug release) and variables (X1: weight ratio of polymer to drug, X2: volume ratio of oil to water and X3: Q-flow of spray dryer). ODF and ODT formulations were evaluated including weight variation, content uniformity, tensile strength, disintegration time, friability and dissolution profiles. The bitterness taste test was evaluated in 10 adult volunteers. Results and discussion: From polynomial regression analysis, the best values of variables leading to the optimized microparticles were X1?=?10, X2?=?3 and X3?=?45. The optimized microparticles were incorporated into ODF and ODT with satisfactory weight and drug content uniformity, and acceptable physical strength. Both dosage forms disintegrated immediately (less than 40?s) in simulated saliva solutions. The outcome of taste-masking test indicated that microparticles alleviated drug bitterness significantly; bitterness was not discernible with microparticles incorporated in ODT, whereas only slight bitterness was detected from microparticles incorporated into ODF. Conclusion: Both ODF and ODT are shown to be suitable vehicles for taste masked Chlorpheniramine Maleate microparticles with potential for pediatric uses. PMID:23621768

Lou, Hao; Liu, Min; Qu, Wen; Hu, Zheyi; Brunson, Ed; Johnson, James; Almoazen, Hassan



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



A Bioequivalence Study of Two Oral Desmopressin Tablet Formulations  

Microsoft Academic Search

The present study was carried out to test bioequivalence between two different oral desmopressin formulations. Sixty healthy volunteers were enrolled in the study and were randomly assigned to receive the test (T) and reference (R) drug in a two-period two-sequence, crossover, analyst-blinded study design. Subjects received an oral dose of 400 ?g of desmopressin acetate separated by a wash-out period

Stefan T. Kaehler; Ilka M. Steiner; Robert Sauermann; Helmut Scheidl; Markus Mueller; Christian Joukhadar



Assessment of the relative potency of fentanyl buccal tablet to intravenous morphine in healthy volunteers using a thermally induced hyperalgesia pain model.  


This exploratory randomized, double-blind, placebo-controlled, 5-treatment, 5-period crossover study was conducted using a thermally induced hyperalgesia pain model in 51 healthy volunteers (33 evaluable) to characterize the relative potency of fentanyl buccal tablet (FBT) versus intravenous morphine. Relative potency was assessed using the sum of pain intensity differences over 60 minutes after the application of a 43°C, 46°C, and 49°C painful stimulus following thermally induced hyperalgesia. Relative potency was also assessed by pupil diameter and responses to subjective questionnaires. The relative potency of FBT was 46.2 times that of intravenous morphine (95% confidence interval [CI], 17.6-575.3) based on the 49°C stimulus. The relative potency of FBT based on opiate-induced miosis was 44.6 (95% CI, 29.7-77.0) at 60 minutes. These results are an initial relative potency assessment and should not be considered guidance for dose-equivalent switching between agents in clinical practice. PMID:21646442

Saunders, David L; Messina, John; Darwish, Mona; Xie, Fang; Leary, Kevin J; Cantilena, Louis R



Tableting lipid-based formulations for oral drug delivery: a case study with silica nanoparticle-lipid-mannitol hybrid microparticles.  


Silica-lipid-mannitol hybrid (SLMH) microparticles have been developed that were compressible into high quality tablets suitable for oral dosing and delivery of poorly soluble drugs. SLMH tablets enable high lipid-loading levels (>40%) and retain the immediate release, enhanced lipase digestion and drug solubilisation performance. Specifically, we report formulation optimisation of SLMH microparticles and tablets using coumarin 102 (log P = 4.09) as a model Biopharmaceutics Classification System class II drug. SLMH tablets were acceptable according to standard British Pharmacopoeia friability, hardness and disintegration tests; this is not the case for conventional dry emulsions. Furthermore, in vitro dissolution and pancreatic-lipase-induced lipolysis studies under simulated intestinal conditions have demonstrated enzymatic-digestion-mediated drug solubilisation. SLMH microparticles and tablets are suitable as liquid lipid containing solid dosage forms for enhancing and controlling oral absorption of poorly soluble drugs. PMID:23242712

Bremmell, Kristen E; Tan, Angel; Martin, Amanda; Prestidge, Clive A



Meloxicam taste-masked oral disintegrating tablet with dissolution enhanced by ion exchange resins and cyclodextrin.  


The purpose of this study was to develop taste-masked oral disintegrating tablets (ODTs) using the combination of ion exchange resin and cyclodextrin, to mask the bitter taste and enhance drug dissolution. Meloxicam (MX) was selected as a model drug with poor water solubility and a bitter taste. 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 and tablets were prepared 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. The results showed that thickness, diameter, weight, and friability did not differ significantly for all of these formulations. The tablet hardness was approximately 3 kg/in.(2), and the friability was less than 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 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 of MX. In addition, this tablet was stable at least 6 months. The results from this study suggest that the appropriate combination of ion exchange resin and cyclodextrin could be used in ODTs to mask the bitter taste of drug and enhance the dissolution of drugs that are weakly soluble in water. PMID:23835739

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



Miconazole nitrate oral disintegrating tablets: in vivo performance and stability study.  


The interest in and need for formulating miconazole nitrate (MN), a broad-spectrum antifungal, as an oral disintegrating tablet for treatment of some forms of candidiasis have increased. Formulation of MN in this dosage form will be more advantageous, producing dual effect: local in the buccal cavity and systemic with rapid absorption. Four formulations were prepared utilizing the foam granulation technique. The prepared tablets were characterized by measuring the weight uniformity, thickness, tensile strength, friability, and drug content. In addition, tablet disintegration time, in vitro dissolution, and in vivo disintegration time were also evaluated. Stability testing for the prepared tablets under stress and accelerated conditions in two different packs were investigated. Each pack was incubated at two different elevated temperature and relative humidity (RH), namely 40 ± 2°C/75 ± 5% RH and 50 ± 2°C/75 ± 5% RH. The purpose of the study is to monitor any degradation reactions which will help to predict the shelf life of the product under the defined storage conditions. Finally, in vivo study was performed on the most stable formula to determine its pharmacokinetic parameters. The results revealed that all the prepared tablets showed acceptable tablet characteristics and were stable under the tested conditions. The most stable formula was that containing magnesium stearate as lubricant, hydrophobic Aerosil R972 as glidant, low urea content, mannitol/microcrystalline cellulose ratio 2:1, and 9% Plasdone XL100 as superdisintegrant. The in vivo results revealed that the tested formula showed rapid absorption compared to the physical blend (t (max) were 1 and 4 h, respectively), while the extent of absorption was almost the same. PMID:22585373

Ahmed, Tarek A; El-Say, Khalid M; Mahmoud, Maged F; Samy, Ahmed M; Badawi, Alia A



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.

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



Slow-release oral morphine for opioid maintenance treatment: a systematic review  

PubMed Central

This review article summarizes the results of all available clinical trials considering the use of slow-release oral morphine (SROM) for opioid maintenance treatment (OMT). All studies published up to October 2010 and assessing SROM for OMT in adult patients are included. Three independent reviewers assessed the selected articles using a standardized checklist. Study design, study length and number of subjects included were recorded. Data about retention rate (proportion of participants remaining under maintenance treatment at the end of the study), quality of life, withdrawal symptoms, craving, additional drug consumption, driving capacity and adverse events were collected. We identified 13 articles corresponding to nine clinical trials considering the use of SROM for OMT. Among them, only one was a randomized trial and one was a controlled not randomized trial. All other studies were uncontrolled. Retention rates were good (from 80.6 to 95%) with SROM maintenance, but similar retention rates were obtained with methadone. Most of the studies showed that quality of life, withdrawal symptoms, craving and additional drug consumption improved with SROM. However, there was no comparison with other maintenance drugs. As most of the studies assessing SROM efficacy were uncontrolled, there is no definite evidence that SROM is an effective alternative to methadone for OMT.

Jegu, Jeremie; Gallini, Adeline; Soler, Pauline; Montastruc, Jean-Louis; Lapeyre-Mestre, Maryse



Effects of maternal oral morphine consumption on neural tube development in Wistar rats  

Microsoft Academic Search

Opiate abuse during pregnancy may result in abnormal nervous system function. In order to evaluate the effects of morphine on the development of the nervous system, the present study focused on the effects of maternal morphine consumption on neural tube development in Wistar rats.Female Wistar rats (250–300 g) were crossed with male rats and coupling time was recorded (embryonic day

Shiva Nasiraei-Moghadam; Hedayat Sahraei; Hossein Bahadoran; Mehrangiz Sadooghi; Seyed Hossein Salimi; Gholam Reza Kaka; Hossein Imani; Hossein Mahdavi-Nasab; Hossein Dashtnavard



Formulation and evaluation of taste-masked levocetirizine dihydrochloride orally disintegrating tablets.  


Orally disintegrating tablets of levocetirizine dihydrochloride were formulated with different superdisintegrants (sodium starch glycollate, croscarmellose sodium, and crospovidone) using mannitol as a diluent. Tulsion-335, Indion-204, and poly kyron T-134 cation exchange resins were used as taste-masking agents. The drug and resin complex was prepared by the kneading method. Ten formulations were prepared with varying combinations of superdisintegrants and ion-exchange resins by the wet granulation technique, using polyvinylpyrrolidone K-30 as the binder. The prepared tablets were evaluated for degree of taste masking, weight variation, hardness, friability, in vitro and in vivo disintegration time, content uniformity, and water absorption ratio. Dissolution studies were performed in two dissolution media: 0.1N HCl and distilled water. The corresponding dissolution rates were compared with the marketed formulation. Differential scanning calorimetry studies were carried out on the drug-resin complexes. Prepared tablets were good in appearance and showed acceptable results for hardness and friability. In vitro and in vivo disintegration times for the optimum formulation (F-1) were found to be 22 and 55 s, respectively. Relatively acceptable taste was achieved with both Indion-204 and Tulsion-335. Rapid disintegration time was achieved in tablets containing crosspovidone as the superdisintegrant. Dissolution studies indicated the formation of the complex of drug and resin. Differential scanning calorimetry studies indicated the formation of drug-resin complex. PMID:20169858

Devireddy, Srinivas Reddy; Gonugunta, Chandra Sekhara Rao; Veerareddy, Prabhakar Reddy


Pharmacokinetics and adverse effects of oral meloxicam tablets in healthy adult horses.  


The objective of this study was to assess the pharmacokinetic profile and determine whether any adverse effects would occur in seven healthy adult horses following oral meloxicam tablet administration once daily for 14 days at a dose of 0.6 mg/kg·bwt. Horses were evaluated for health using physical examination, complete blood count, serum chemistry, urinalysis, and gastroscopy at the beginning and end of the study. Blood was collected for the quantification of meloxicam concentrations with liquid chromatography and mass spectrometry. The mean terminal half-life was 4.99 ± 1.11 h. There was no significant difference between the mean Cmax , 1.58 ± 0.71 ng/mL at Tmax 3.48 ± 3.30 h on day 1, 2.07 ± 0.94 ng/mL at Tmax 1.24 ± 1.24 h on day 7, and 1.81 ± 0.76 ng/mL at 1.93 ± 1.30 h on day 14 (P = 0.30). There was a statistically significant difference between the Tmax on the sample days (P = 0.04). No statistically significant increase in gastric ulcer score or laboratory analytes was noted. Oral meloxicam tablets were absorbed in adult horses, and adverse effects were not statistically significant in this study. Further studies should evaluate the adverse effects and efficacy of meloxicam tablets in a larger population of horses before routine use can be recommended. PMID:23067209

Vander Werf, K A; Davis, E G; Kukanich, B



A phase I pharmacokinetic and safety evaluation of oral pazopanib dosing administered as crushed tablet or oral suspension in patients with advanced solid tumors.  


Because cancer patients may have difficulty swallowing whole tablets, crushing tablets or ingesting an oral suspension is a practical alternative. This open-label, 2-part, randomized crossover, phase I study evaluated the pharmacokinetics and tolerability of pazopanib administered as a crushed tablet or an oral suspension relative to whole tablet in patients with advanced cancer (Part 1). Patients completing Part 1 were eligible for continuous daily pazopanib 800 mg (Part 2). Administration of a single pazopanib 400 mg crushed tablet increased the area under the curve from 0 to 72 h (AUC((0-72)); 46%) and maximum observed plasma concentration (C(max); ~2-fold), and decreased time to achieve maximum plasma concentration (T(max); ~2 h), indicating increased rate and extent of oral absorption relative to whole-tablet administration. Similarly, a single dose of pazopanib 400 mg suspension increased AUC((0-72)) (33%) and C(max) (29%), and decreased T(max) (1 h). These changes in pharmacokinetic parameters were not associated with increases in the magnitude or duration of short-term (ie, up to 72 h) blood pressure elevation compared with whole-tablet administration. PMID:21811833

Heath, Elisabeth I; Forman, Karen; Malburg, Lisa; Gainer, Shelby; Suttle, A Benjamin; Adams, Laurel; Ball, Howard; LoRusso, Patricia



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



A multinational, multicentre, non-blinded, randomized study of moxifloxacin oral tablets compared with co-amoxiclav oral tablets in the treatment of acute exacerbation of chronic bronchitis.  


The aim of this study was to compare the efficacy and safety of once daily dosing with moxifloxacin (BAY 12-8039) with that of coamoxiclav given three times daily for the treatment of acute exacerbation of chronic bronchitis (AECB). Moxifloxacin (one 400 mg tablet daily) was administered orally for 5 days and co-amoxiclav (three 625 mg tablets daily) was given orally for 7 days. The study was randomized, non-blinded, multinational (12 countries) and multicentre (68 centres). A total of 575 patients, all with clear signs of AECB, were treated, 292 with moxifloxacin and 283 with co-amoxiclav. Of these, 512 patients were evaluable for efficacy (261 in the moxifloxacin group and 251 in the co-amoxiclav group). The primary efficacy parameter was clinical response at 14 days in the evaluable population. A clinical success was classified as resolution or improvement of symptoms. Variables used to assess clinical response included wheeze, cough, dyspnoea, sputum volume, rales and rhonchi. The success rate for moxifloxacin in the evaluable patients was 96.2% and that for co-amoxiclav was 91.6%. The 95% confidence intervals for this difference (0.4%; 8.7%) indicate equivalence in the treatments. Sputum samples were taken from patients and 140 of these contained a pathogen, Haemophilus influenzae being the most frequently isolated. Moraxella catarrhalis and Streptococcus pneumoniae were also commonly isolated pathogens. The eradication rate at 14 days in the evaluable patients was 87.7% in the moxifloxacin group and 89.6% in the coamoxiclav group. Both drugs were well tolerated with no significant differences in the numbers of drug-related adverse events or the numbers of patients withdrawing because of an adverse event. These results and the broad spectrum of antibacterial activity make moxifloxacin a promising and safe alternative to conventional therapy for the empirical treatment of AECB. PMID:11675905

Schaberg, T; Ballin, I; Huchon, G; Bassaris, H; Hampel, B; Reimnitz, P


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.

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



Effects of orally administered lactoferrin and lactoperoxidase-containing tablets on clinical and bacteriological profiles in chronic periodontitis patients.  


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



Three-layer guar gum matrix tablet formulations for oral controlled delivery of highly soluble trimetazidine dihydrochloride  

Microsoft Academic Search

The present study is carried out to design oral controlled drug delivery systems for highly water-soluble drugs using guar gum as a carrier in the form of three-layer matrix tablets. Trimetazidine dihydrochloride was chosen as a model drug because of its high water solubility. Matrix tablet granules containing 30% (M1), 40% (M2) or 50% (M3) of guar gum were prepared

Y. S. R. Krishnaiah; R. S. Karthikeyan; V. Gouri Sankar; V. Satyanarayana



Fabrication and evaluation of taste masked resinate of risperidone and its orally disintegrating tablets.  


The present investigation was undertaken to design a simple, rapid, cost effective and highly efficient process to fabricate a tasteless complex of risperidone using ion exchange resin (IER), evaluate the molecular properties of the resinate and finally incorporate it into orally disintegrating tablets (ODT). The resinate formation using Amberlite IRP64, was confirmed using the characterization methods: Fourier transform-infrared (FT-IR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The maximum loading efficiency achieved was 99.72+/-0.16% in 1 : 4 (drug : resin weight) ratio at pH 6.0, temperature at 22 degrees C in a period of 1.5 h using ethanol : water (1 : 1, v/v) as the complexation medium. The complex was compressed into orally disintegrating tablet. The drug release from the complex was about 2.5% in 120 s in 5 ml of pH 6.8 phosphate buffer which has been used to mimic the salivary fluid volume and pH. Dissolution studies using 500 ml of 0.1 N HCl at 50 rpm in USP Apparatus II released 92% in 5 min, indicating complete drug release from the complex in the stomach. Resinate was tasteless while the fabricated ODTs were pleasantly tasting without any bitterness of drug as confirmed by the taste panel. PMID:19336927

Shukla, Dali; Chakraborty, Subhashis; Singh, Sanjay; Mishra, Brahmeshwar



Effect of food on the oral bioavailability of isosorbide-5-mononitrate administered as an extended-release tablet.  


We evaluated the effect of a high-fat breakfast and gastric emptying rate on the oral bioavailability of a isosoribide-5-mononitrate (5-ISMN) controlled-release tablet formulation (IMDUR 60-mg tablets, Astra Hässle AB, Mölndal, Sweden) relative to an oral solution in 18 healthy men. Gastric emptying was monitored by radiotelemetry using the Heidelberg capsule technique. After administration of the 5-ISMN 60-mg solution, absorption was rapid with mean peak plasma 5-ISMN concentrations of 1533 ng/mL achieved in less than 1 hour. In contrast, after administration of IMDUR 60-mg tablets, the drug was more slowly absorbed, reaching mean peak plasma concentrations of 541 ng/mL in 3 to 4 hours. The bioavailability of 5-ISMN from IMDUR tablets under fasted conditions was approximately 78% relative to the solution; and, in the presence of food, the bioavailability was slightly increased to 86% (P = .057). The mean gastric residence time of IMDUR tablets under fasted conditions was 68 minutes, and in the presence of food was increased to 478 minutes, with 9 of the 18 subjects having gastric emptying delayed for at least 600 minutes. We conclude that in the presence of food, gastric emptying time is considerably increased causing a delay in drug absorption and a slight increase in the bioavailability of 5-ISMN from this controlled-release tablet formulation, however this effect is not clinically relevant. PMID:7751425

Kosoglou, T; Kazierad, D J; Schentag, J J; Patrick, J E; Heimark, L; Radwanski, E; Christopher, D; Flannery, B E; Affrime, M B



Absolute and relative bioavailability of fentanyl buccal tablet and oral transmucosal fentanyl citrate.  


This study assessed the absolute and relative bioavailabilities and transmucosal and gastrointestinal absorbency of fentanyl buccal tablet (FBT) and oral transmucosal fentanyl citrate (OTFC). In a randomized crossover design, 26 healthy subjects received FBT 400 microg (transmucosal), FBT 800 microg (oral), OTFC 800 microg (transmucosal), and fentanyl 400 microg (intravenous). The transmucosal FBT had the highest absolute bioavailability (0.65) compared with the oral FBT (0.31) or transmucosal OTFC (0.47). More fentanyl was absorbed transmucosally from FBT than OTFC (48% vs 22%). Median t(max) values were shorter following the transmucosal FBT (47 minutes) than the oral FBT (90 minutes) or the transmucosal OTFC (91 minutes). Transmucosal administration of FBT compared with dose-normalized OTFC resulted in higher total systemic fentanyl exposure, higher early systemic exposure, and higher C(max). The rate and extent of fentanyl absorption were greater following administration of FBT compared to OTFC. An approximately 30% smaller dose of FBT achieved systemic exposures comparable to OTFC. PMID:17322146

Darwish, Mona; Kirby, Mary; Robertson, Philmore; Tracewell, William; Jiang, John G



Determination of cetirizine dihydrochloride, related impurities and preservatives in oral solution and tablet dosage forms using HPLC  

Microsoft Academic Search

An HPLC method was developed and validated for the determination of cetirizine dihydrochloride (CZ) as well as its related impurities in commercial oral solution and tablet formulations. Furthermore, two preservatives associated with the drug formulations, namely, propyl (PP) and butylparabens (BP) were successfully determined by this method. The chromatographic system used was equipped with a Hypersil BDS C18, 5?m column

A. M. Y. Jaber; H. A. Al Sherife; M. M. Al Omari; A. A. Badwan



Comparison of an orally disintegrating ondansetron tablet with the conventional ondansetron tablet for cyclophosphamide-induced emesis in cancer patients: a multicenter, double-masked study. Ondansetron Orally Disintegrating Tablet Emesis Study Group.  


A total of 427 cancer patients receiving cyclophosphamide chemotherapy participated in this multicenter, double-masked, double-dummy, parallel-group, randomized study comparing the antiemetic efficacy and safety of an 8-mg conventional ondansetron tablet (OT, n = 212) taken twice daily with an 8-mg orally disintegrating ondansetron tablet (ODT, n = 215) taken twice daily for 3 days. In the primary efficacy analysis, complete or major control of emesis (0 to 2 emetic episodes) between days 1 and 3 was seen in 80% of OT and 78% of ODT patients. The 90% confidence interval for the differences between treatments was -8.6% to 4.4% (defined interval of equivalence, +/-15%), showing that the formulations were equivalent. In the secondary efficacy analysis, no significant differences were observed in the rates of complete control of emesis (no episodes of emesis) over 3 days (63% and 64% of the respective groups) and on day 1 (84% and 81%, respectively) and in the complete control of nausea over 3 days (37% and 43%, respectively) and on day 1 (59% and 61% of patients, respectively). The taste of ODT was acceptable to the majority of patients (89%) who received it. OT and ODT were both well tolerated. Thus 8 mg ODT twice daily represents a palatable, well-tolerated, and effective antiemetic treatment for the control of cyclophosphamide-induced emesis and nausea and provides equivalent treatment to OT 8 mg twice daily. PMID:10321418

Davidson, N; Rapoport, B; Erikstein, B; L'Esperance, B; Ruff, P; Paska, W; Miller, I; Curtis, P



In vitro and in vivo evaluation of guar gum matrix tablets for oral controlled release of water-soluble diltiazem hydrochloride.  


The objective of the study was to develop guar gum matrix tablets for oral controlled release of water-soluble diltiazem hydrochloride. Matrix tablets of diltiazem hydrochloride, using various viscosity grades of guar gum in 2 proportions, were prepared by wet granulation method and subjected to in vitro drug release studies. Diltiazem hydrochloride matrix tablets containing either 30% wt/wt low-viscosity (LM1), 40% wt/wt medium-viscosity (MM2), or 50% wt/wt high-viscosity (HM2) guar gum showed controlled release. The drug release from all guar gum matrix tablets followed first-order kinetics via Fickian-diffusion. Further, the results of in vitro drug release studies in simulated gastrointestinal and colonic fluids showed that HM2 tablets provided controlled release comparable with marketed sustained release diltiazem hydrochloride tablets (D-SR tablets). Guar gum matrix tablets HM2 showed no change in physical appearance, drug content, or in dissolution pattern after storage at 40 degrees C/relative humidity 75% for 6 months. When subjected to in vivo pharmacokinetic evaluation in healthy volunteers, the HM2 tablets provided a slow and prolonged drug release when compared with D-SR tablets. Based on the results of in vitro and in vivo studies it was concluded that that guar gum matrix tablets provided oral controlled release of water-soluble diltiazem hydrochloride. PMID:16353958

Al-Saidan, Saleh M; Krishnaiah, Yellela S R; Patro, Srinivas S; Satyanaryana, Vemulapalli



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


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



Preparation of orally disintegrating tablets with taste-masking function: masking effect in granules prepared with correctives using the dry granulation method and evaluation of tablets prepared using the taste-masked granules.  


We investigated several methods of taste masking in the preparation of orally disintegrating tablets (ODTs), using furosemide (FU) as a model drug. Four types of FU preparations were prepared: granules with maltitol (MA), granules with yogurt powder (YO), a physical mixture of FU and MA, and a physical mixture of FU and YO. All taste-masking granules were prepared using the dry granulation method. The taste of each type of preparation was evaluated. All four preparations markedly improved the taste of the FU tablets, but the mixing ratios of the correctives did not affect the masking effect. No difference in masking effect was found between MA and YO in the physical mixtures, but the masking effect in the granules with YO was superior to that of the granules with MA. Taste-masked FU tablets were prepared using the direct compression method; crystalline cellulose (Avicel PH-302) and mannitol were added as excipients at the mixing ratio of 1/1. All four types of tablets displayed sufficient hardness, but MA-containing tablets were harder than YO-containing tablets. The hardness of the tablets prepared from YO granules increased as the YO content increased. The most rapidly disintegrating tablets were those of YO granules prepared at a mixing ratio of FU/YO=1/1, which disintegrated within 20 s, followed by the tablets of MA granules prepared at a mixing ratio of FU/MA=1/1. The disintegration times of the tablets made from physical mixtures, in contrast, were longer than 200 s. Disintegration time lengthened as the mixing ratio of YO or MA increased. The hardness and disintegration time of these tablets could be controlled by varying the compression pressure. We found that YO is more useful than MA in masking unpleasant tastes and confirmed that orally disintegrating tablets with taste-masking function can be prepared using granules of YO prepared using the dry granulation method as a new corrective. PMID:20046070

Kawano, Yayoi; Ito, Akihiko; Sasatsu, Masanaho; Machida, Yoshiharu



Oral liquid L-thyroxine (L-t4) may be better absorbed compared to L-T4 tablets following bariatric surgery.  


Drug malabsorption is a potential concern after bariatric surgery. We present four case reports of hypothyroid patients who were well replaced with thyroxine tablets to euthyroid thyrotropin (TSH) levels prior to Roux-en-Y gastric bypass surgery. These patients developed elevated TSH levels after the surgery, the TSH responded reversibly to switching from treatment with oral tablets to a liquid formulation. PMID:23824980

Pirola, Ilenia; Formenti, Anna M; Gandossi, Elena; Mittempergher, Francesco; Casella, Claudio; Agosti, Barbara; Cappelli, Carlo



Expanding the application of the tablet processing workstation to support the sample preparation of oral suspensions.  


Sample preparation is the most time-consuming part of the analytical method for powder for oral suspension (POS) assay, purity, and preservative analysis, as this involves multiple dilution and filtration steps. The Tablet Processing Workstation (TPW) was used to automate the sample preparation of a POS formulation. Although the TPW is typically used to automate the preparation of solid oral dosage forms and powders, it contains all of the necessary components to perform POS sample preparation. The TPW exhibited acceptable repeatability in testing 3 lots using 10 replicate preparations per lot. Acceptable linearity of the drug and preservative in the presence of excipients was demonstrated over the range corresponding to 50-150% of intent. Accuracy showed suitable recoveries for all points evaluated. TPW results were shown to correlate to results obtained with the manual method. The TPW method was used to prepare samples in support of manufacturing scale-up efforts. With the efficiencies gained using the TPW, it was possible to analyze a large number of samples generated during process development activities for the POS formulation with minimal human intervention. The extensive data enabled trending of the manufacturing development runs and helped to identify optimization strategies for the process. PMID:21609706

Opio, Alex Manuel; Nickerson, Beverly; Xue, Gang; Warzeka, John; Norris, Ken



[Preparation and evaluation of taste masked orally disintegrating tablets with granules made by the wet granulation method].  


Using furosemide (FU) as a model drug, we examined the wet granulation method as a way to improve the taste masking and physical characteristics of orally disintegrating tablets (ODTs). In the wet granulation method, yogurt powder (YO) was used as a corrective and maltitol (MA) was used as a binding agent. The taste masked FU tablets were prepared using the direct compression method. Microcrystalline cellulose (Avicel® PH-302) and mannitol were added as excipients at a mixing ratio of 1/1 by weight. Based on the results of sensory test on taste, the prepared granules markedly improved the taste of FU, and a sufficient masking effect was obtained at the YO/FU ratio of 1 or more. Furthermore, it was found that the masking effect achieved by YO granules made with the wet granulation method was similar to or better than that produced by the granules made with dry granulation method. All types of tablets displayed sufficient hardness (over 3.5×10(-2) kN), and rapidly disintegrating tablets were obtained with YO granules produced at a mixing ratio of FU/YO=1/1, which disintegrated within 20 s. Disintegration time lengthened as the mixing ratio of YO to FU increased. In the mixing ratio of FU/YO=1/1, the hardness of tablets with granules made by the wet granulation method exceeded that of tablets with granules made by the dry granulation method, with minimal differences in disintegration time. The hardness and disintegration time of the tablets with granules made by the wet granulation method could be controlled by varying the compression force. In conclusion, YO was found to be a useful additive for masking unpleasant tastes. FU ODTs with improved taste, rapid disintegration and greater hardness could be prepared with YO-containing granules made by the wet granulation method using MA as a binding agent. PMID:21139401

Kawano, Yayoi; Ito, Akihiko; Sasatsu, Masanaho; Machida, Yoshiharu; Onishi, Hiraku



Morphine Rectal  


Rectal morphine is used to relieve moderate to severe pain. Morphine is in a class of medications called opiate ( ... Rectal morphine comes as a suppository to insert in the rectum. It is usually inserted every 4 hours. Use ...


Morphine Sulfate  

Center for Drug Evaluation (CDER)

Text Version... Contains Nonbinding Recommendations Draft Guidance on Morphine Sulfate This ... Drugs. Active ingredient: Morphine Sulfate ... More results from


Influence of non-water-soluble placebo pellets of different sizes on the characteristics of orally disintegrating tablets manufactured by freeze-drying.  


The present study describes the development of an orally disintegrating tablet containing a non-water-soluble drug delivery system. A model system was applied to evaluate the effect of different-sized particles on tablet characteristics. Cellets were incorporated into tablets prepared by freeze-drying from a 100 mg/mL mannitol or sucrose solution. Particle size distributions were 200-355 µm for Cellets 200 (C200) and 500-710 µm for Cellets 500 (C500). An examination of the tablets revealed that the particles could not be sufficiently embedded in mannitol because of its crystalline nature. The tablet hardness was also inadequate. In contrast, the hardness of sucrose tablets was increased by the addition of Cellets 500. Therefore, the sucrose-based formulation was studied further. Binders [hydroxyethylstarch, sodium alginate, methylcellulose (MC), and gelatin] were added in different concentrations, and tablets were made either with or without placebo pellets. A positive effect of the Cellets on the hardness of tablets was identified. Furthermore, disintegration time could be clearly reduced by Cellets for tablets made from 100 mg/mL sucrose with addition of 10 mg/mL MC, 20 or 40 mg/mL gelatin. The freeze-dried tablet index revealed that the formulations of sucrose with 50 mg/mL hydroxyethylstarch or 20 mg/mL gelatin were particularly advantageous. PMID:23568590

Stange, Ulrike; Führling, Christian; Gieseler, Henning



The efficacy of postoperative ondansetron (Zofran) orally disintegrating tablets for preventing nausea and vomiting after acoustic neuroma surgery.  


Postoperative nausea and vomiting is a frequent complication of craniotomy. We evaluated the ability of intraoperative IV ondansetron followed by postoperative ondansetron in an orally disintegrating tablet formulation to reduce the frequency and severity of postoperative nausea and vomiting in a prospective, randomized, placebo-controlled double-blind trial of 60 patients undergoing acoustic neuroma resection. Each patient received intraoperative ondansetron (4 mg IV) or placebo 30 min before case end. Postoperatively, patients received ondansetron in an orally disintegrating tablet formulation (8 mg BID) or placebo twice a day for up to 72 h. Metoclopramide was available as rescue therapy for both groups. Severity of nausea (as measured on a 10-cm visual scale), number of emetic episodes, and requirement for rescue therapy were recorded. In the immediate postoperative period, nausea severity was less in patients treated with ondansetron than placebo (3.3 +/- 4.1 versus 7.3 +/- 4.2; P < 0.001) and fewer patients experienced vomiting (3 of 28 versus 11 of 32; chi2 P < 0.01). More patients required some form of rescue treatment in the placebo group on the first postoperative day (26 of 32 versus 16 of 28; chi2 P < 0.01). We conclude that after acoustic neuroma surgery IV ondansetron treatment prevents immediate postoperative nausea and vomiting. Postoperative treatment with ondansetron in an orally disintegrating tablet formulation was associated with less frequent rescue therapy as compared with placebo on the first postoperative day. PMID:16244017

Hartsell, Theresa; Long, Donlin; Kirsch, Jeffrey R



A randomised crossover trial of patient controlled intranasal fentanyl and oral morphine for procedural wound care in adult patients with burns  

Microsoft Academic Search

This study sought to compare the analgesic efficacy and safety of patient controlled intra-nasal (PCIN) fentanyl with oral morphine for procedural wound care in burns patients. A randomised double-blind placebo controlled, two period, two-treatment crossover trial was conducted within the Burns Unit of a major teaching hospital in Perth, Western Australia. Patients requiring identical wound care procedures on two consecutive

Judith Finn; Jan Wright; Joy Fong; Eileen Mackenzie; Fiona Wood; Gavin Leslie; Anna Gelavis



Ondansetron oral disintegrating tablets for the prevention of postoperative vomiting in children undergoing strabismus surgery  

PubMed Central

Strabismus surgery in pediatric patients is associated with a high incidence of postoperative nausea and vomiting (PONV). Ondansetron disintegrating tablets (ODT), an oral freeze-dried formulation of the 5-HT3 antagonist, are well-tolerated and have been shown to reduce chemotherapy-induced vomiting. The purpose of this study was to assess the efficacy of the ODT in preventing postoperative vomiting (POV) in children undergoing strabismus repair. Healthy children aged 4–12 years of age were administered a 4 mg ODT 30 minutes prior to the induction of general anesthesia. Induction and maintenance of anesthesia were standardized; each child received acetaminophen and ketorolac pre-emptively for analgesia. This study group was compared with a historical control group who received a placebo in previously conducted identical trials of POV. The 35 children included in this study were compared with 31 controls. The incidence and severity of POV and use of rescue antiemetics were significantly lower in children who received ODT compared with placebo (p ? 0.001). The acute complete response (ie, no emesis and no rescue antiemetics in 24 hours) was 76% in the ODT group compared with 16% in the controls (p ? 0.001). Results suggest that ODT given preoperatively reduces the incidence and severity of POV in children undergoing strabismus surgery.

Wagner, Deborah S; Gauger, Virginia; Chiravuri, Devi; Faust, Kristin



Orally disintegrating vardenafil tablets for the treatment of erectile dysfunction: efficacy, safety, and patient acceptability  

PubMed Central

Background: Erectile dysfunction (ED) is a well-documented medical condition that is expected to increase significantly over the next several decades, especially as men live longer and the prevalence of diabetes and cardiovascular diseases increase. Pharmacology agents are often the first line treatment approach. Newer solid dosage forms, known as orally disintegrating tablets (ODT), are now available as one treatment option. Objectives: To review the drug delivery mechanisms of ODTs in general and to review safety and efficacy of vardenafil ODT (a PDE-5 inhibitor) as a treatment option for management of ED. Method: Literature reviews were performed of pharmaceutical dosage forms and the POTENT I (n = 358 subjects) and POTENT II (n = 337 subjects) studies that investigated vardenafil ODT. Results: Vardenafil ODT has been successfully used in multiple age groups and in multiple settings with men from various ethnic backgrounds. Efficacy of vardenafil ODT, as measured using the International Index of Erectile Function (IIEF-EF) and from the Sexual Encounter Profile (SEP) was significantly greater than placebo (P < 0.0001) at 12 weeks. Safety profiles were similar to film-coated dosage forms with no patient deaths reported. Conclusion: Vardenafil ODT offers a convenient, ready-to-use approach for combating ED. Safety concerns are similar to other PDE-5 inhibitors and practitioners should counsel patients accordingly.

Green, Roger; Hicks, Rodney W



Ondansetron oral disintegrating tablets for the prevention of postoperative vomiting in children undergoing strabismus surgery.  


Strabismus surgery in pediatric patients is associated with a high incidence of postoperative nausea and vomiting (PONV). Ondansetron disintegrating tablets (ODT), an oral freeze-dried formulation of the 5-HT(3) antagonist, are well-tolerated and have been shown to reduce chemotherapy-induced vomiting. The purpose of this study was to assess the efficacy of the ODT in preventing postoperative vomiting (POV) in children undergoing strabismus repair. Healthy children aged 4-12 years of age were administered a 4 mg ODT 30 minutes prior to the induction of general anesthesia. Induction and maintenance of anesthesia were standardized; each child received acetaminophen and ketorolac pre-emptively for analgesia. This study group was compared with a historical control group who received a placebo in previously conducted identical trials of POV. The 35 children included in this study were compared with 31 controls. The incidence and severity of POV and use of rescue antiemetics were significantly lower in children who received ODT compared with placebo (p

Wagner, Deborah S; Gauger, Virginia; Chiravuri, Devi; Faust, Kristin



Fast and pH-dependent release of domperidone from orally disintegrating tablets.  


There has been growing interest in orally disintegrating tablets (ODTs) during the last decade due to their better patient acceptance and compliance. Further, drug dissolution and absorption may be significantly improved. This work describes the preparation of fast and pH-dependent release ODTs for domperidone by direct compression using crospovidone as superdisintegrant. Solid dispersions of domperidone and Eudragit L100-55, at different weight ratios, were prepared and characterized by DSC, TGA, X-ray diffraction, and FTIR, which indicated the presence of drug-polymer interaction. Disintegration time, friability, and hardness of ODTs were evaluated. In vitro drug release in 0.1N HCl and in phosphate buffer (pH 5.8 and 6.8) was investigated. All domperidone ODTs had fast disintegration times (6 KP) and acceptable friability (<1%). Drug release from fast release ODTs was highly improved; reaching 97% after 10 min in 0.1N HCl, compared to the dissolution of the free drug. Drug release from solid dispersions was pH dependent; showing higher release rates at pH 6.8 than at lower pH values. The controlled-release ODT resulted in 47% drug release in 0.1N HCl, with the rest of drug released at pH 6.8. Domperidone ODTs were considered suitable for ODT formulation. PMID:22304659

Assaf, Shereen M; Qandil, Amjad M; Al-Ani, Enas A



RP-HPLC analytical method development and optimization for quantification of donepezil hydrochloride in orally disintegrating tablet.  


An easy, fast and validated RV-HPLC method was invented to quantify donepezil hydrochloride in drug solution and orally disintegrating tablet. The separation was carried out using reversed phase C-18 column (Agilent Eclipse Plus C-18) with UV detection at 268 nm. Method optimization was tested using various composition of organic solvent. The mobile phase comprised of phosphate buffer (0.01M), methanol and acetonitrile (50:30:20, v/v) adjusted to pH 2.7 with phosphoric acid (80%) was found as the optimum mobile phase. The method showed intraday precision and accuracy in the range of 0.24% to -1.83% and -1.83% to 1.99% respectively, while interday precision and accuracy ranged between 1.41% to 1.81% and 0.11% to 1.90% respectively. The standard calibration curve was linear from 0.125 ?g/mL to 16 ?g/mL, with correlation coefficient of 0.9997±0.00016. The drug solution was stable under room temperature at least for 6 hours. System suitability studies were done. The average plate count was > 2000, tailing factor <1, and capacity factor of 3.30. The retention time was 5.6 min. The HPLC method was used to assay donepezil hydrochloride in tablet and dissolution study of in-house manufactured donepezil orally disintegrating tablet and original Aricept. PMID:24035953

Liew, Kai Bin; Peh, Kok Khiang; Fung-Tan, Yvonne Tze



Design and In vitro Evaluation of Oral Floating Matrix Tablets of Aceclofenac  

Microsoft Academic Search

The purpose of this research was to prepare floating matrix drug delivery system of aceclofenac.Floating matrix tablets of aceclofenac were developed to prolong gastric residence time and increase its bioavailability. Rapid gastrointestinal transit could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy of the administered dose. Floating matrix tablets containing

Ravi Kumar; Swati Patil; M. B. Patil; Sachin R. Patil; Mahesh S. Paschapur


Studies on the response of nitroglycerin oral spray compared with sublingual tablets for angina pectoris patients with dry mouth. A multicenter trial.  


Nitroglycerin (glyceryl trinitrate, CAS 55-63-0, NTG) administered with an oral spray may be more effective in relieving anginal pain than sublingual tablets especially when the patient's mouth is dry. In this study, the effect of a NTG oral spray (Myocor Spray) on exercise-induced angina was compared with that of a sublingual tablet in relation to the oral dryness. In 17 patients with effort angina, graded bicycle exercise was performed twice at an interval of one week. Exercise was discontinued upon the onset of moderate anginal pain. Immediately after exercise, the oral dryness was evaluated by touching the tip of the tongue with a blotting paper for a moment. Then, 0.3 mg of NTG was administered by either a squirt of spray or a sublingual tablet in a randomized crossover fashion. Exercise results were reproducible between two exercise tests. According to the extent of the wet area of the blotting paper, the subjects were divided into two groups. In 7 patients of the wet group, the remission times of chest pain and ST segment depression were not significantly different by the formulation of NTG. In 10 patients of the dry group, however, both chest pain and ST depression more rapidly recovered with use of the oral spray (p < 0.05 and p < 0.05, respectively). These results strongly suggest that the NTG oral spray is superior to the sublingual tablet in relieving anginal attacks, when the oral wetness is decreased. PMID:9079231

Sato, H; Koretsune, Y; Taniguchi, T; Fukui, S; Shimazu, T; Sugii, M; Matsuyama, T; Karita, M; Hori, M



Single-dose phase I study to evaluate the pharmacokinetics of posaconazole in new tablet and capsule formulations relative to oral suspension.  


Posaconazole oral suspension, a marketed extended-spectrum triazole with proven efficacy as antifungal treatment and prophylaxis, should be taken with food to maximize absorption. New tablet and capsule formulations have been developed in an attempt to optimize absorption and bioavailability. The aims of this exploratory open-label, partially randomized, 2-part, 4-way, single-dose crossover study in 16 healthy adults were to characterize pharmacokinetics for posaconazole tablet and capsule formulations relative to those for posaconazole oral suspension under fasted and fed conditions and to assess safety and tolerability. Under fasted conditions, posaconazole exposures (area under the curve [AUC]) for the tablet and capsule formulations were similar (mean AUC from time zero to infinity [AUC(0-?)], tablet A, 11,700 ng · h/ml [coefficient of variation {CV}, 26%]; tablet B, 11,300 ng · h/ml [CV, 22%]; capsule, 11,000 ng · h/ml [CV, 25%]) and were substantially higher than the exposure for the oral suspension (mean AUC(0-?), 3,420 ng · h/ml [CV, 44%]). Tablets and capsule showed less variability in exposure than the oral suspension. In fed subjects, tablets and capsule resulted in similar AUC values (mean AUC(0-?), tablet A, 11,900 ng · h/ml [23%]; tablet B, 12,400 ng · h/ml [CV, 25%]; capsule, 12,300 ng · h/ml [CV, 28%]) and slightly higher exposure than the oral suspension (mean AUC(0-?), 8,750 [CV, 24%]). Median times to the maximum concentration of drug in plasma were 4 to 5 h (fasted conditions) and 6 to 8 h (fed conditions). Mean half-lives values were similar for all formulations under fed and fasted conditions (23.1 to 29.2 h). Consistent with previous data, exposure for the oral suspension increased 2.5- to 3-fold when it was given with a high-fat meal. Conversely, exposures for tablets and capsule were not markedly affected by food. All formulations of posaconazole at 100 mg were safe and well tolerated. PMID:22615291

Krishna, Gopal; Ma, Lei; Martinho, Monika; O'Mara, Edward



Formulation, Release Characteristics and Bioavailability Study of Oral Monolithic Matrix Tablets Containing Carbamazepine  

PubMed Central

This study examined the release of carbamazepine (CBZ) from hydrophobic (Compritol® 888 ATO) and hydrophilic-hydrophobic matrix combination (Compritol® 888 ATO-hydroxpropyl methylcellulose, HPMC). Hydrophobic matrix tablets were prepared by hot fusion technique, while hydrophilic-hydrophobic matrix tablets were prepared by wet granulation technique. The properties of the compressed matrix tablets were determined according to the US Pharmacopoeia. Both matrix formulations displayed a controlled-release profile when compared to the reference formulation (Tegretol® CR 200). The bioavailability of CBZ formulations and Tegretol® CR 200 were evaluated in beagle dogs. Carbamazepine presented a significant higher bioavailability from matrix tablets containing hydrophilic polymer (HPMC) than that obtained from Tegretol® CR200. The average inter-subject plasma concentration variability CV% was the least with tablet containing hydrophilic polymer (HPMC) and was the highest with Tegretol® CR 200 (33.8 and 54.1, respectively). Analysis of variance applied to log \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\text{AUC}}_{0 - \\alpha } $$\\end{document} and log C max showed statistical significant differences among the three formulations (P?tablets examined.

Elbagory, Ibrahim M.; Almurshedi, Alanood S.



Within-subject comparison of the psychopharmacological profiles of oral oxycodone and oral morphine in non-drug-abusing volunteers  

Microsoft Academic Search

Rationale  Nonmedical use and abuse of prescription opioids is a significant problem in the USA. Little attention has been paid to assessing\\u000a the relative psychopharmacological profile (including abuse liability-related effects) of specific prescription opioids.\\u000a \\u000a \\u000a \\u000a Objectives  The aim of this study is to directly compare the psychopharmacological profile of two oral opioids within the same subject.\\u000a \\u000a \\u000a \\u000a Methods  A randomized, placebo-controlled, crossover study was done

James P. Zacny; Stephanie A. Lichtor



The MERITO Study: a multicentre trial of the analgesic effect and tolerability of normal-release oral morphine during 'titration phase' in patients with cancer pain.  


Adequate and rapid pain control is one of the main goals of cancer pain treatment. The objective of this study was to assess the effect and tolerability of oral normal-release morphine during the initial phase of treatment in patients with moderate-to-severe cancer pain. Consecutive patients naïve to strong opioids received normal-release morphine 5 or 10 mg every 4 h during the titration phase (first 5 days), depending on previous analgesic therapy. Pain intensity was assessed using an 11-point Numerical Rating Scale (0-10), and data were recorded in a patient-compiled diary. The primary endpoint was the proportion of time with pain control (a reduction of at least 50% with respect to the baseline pain score) during the titration phase. A total of 159 consecutive patients (102 men; mean age 65 years) with cancer-related pain were enrolled. Pain control was observed for 75% (95% CI 70-80) of the follow-up period in the intent-to-treat population. Overall, 50% and 75% of patients achieved pain control within 8 and 24 h after starting normal-release morphine therapy respectively. The mean pain score was 7.63 points at baseline, and decreased to 2.43 and 1.67 points (both P<0.001) at days 3 and 5 respectively. The most commonly reported adverse events were somnolence (24% of patients), constipation (22%), vomiting (13%), nausea (10%) and confusion (7%). Normal-release morphine results in rapid and satisfactory pain control, and is well tolerated, during the strong-opioid titration phase in patients with moderate-to-severe cancer pain. PMID:18477715

De Conno, F; Ripamonti, C; Fagnoni, E; Brunelli, C; Luzzani, M; Maltoni, M; Arcuri, E; Bertetto, O



Development and in vitro evaluation of an oral floating matrix tablet formulation of diltiazem hydrochloride.  


The purpose of this research was to prepare a floating drug delivery system of diltiazem hydrochloride (DTZ). Floating matrix tablets of DTZ were developed to prolong gastric residence time and increase its bioavailability. Rapid gastrointestinal transit could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy of the administered dose. The tablets were prepared by direct compression technique, using polymers such as hydroxypropylmethylcellulose (HPMC, Methocel K100M CR), Compritol 888 ATO, alone or in combination and other standard excipients. Sodium bicarbonate was incorporated as a gas-generating agent. The effects of sodium bicarbonate and succinic acid on drug release profile and floating properties were investigated. A 3(2) factorial design was applied to systematically optimize the drug release profile. The amounts of Methocel K100M CR (X1) and Compritol 888 ATO (X2) were selected as independent variables. The time required for 50% (t50) and 85% (t85) drug dissolution were selected as dependent variables. The results of factorial design indicated that a high level of both Methocel K100M CR (X1) and Compritol 888 ATO (X2) favors the preparation of floating controlled release of DTZ tablets. Comparable release profiles between the commercial product and the designed system were obtained. The linear regression analysis and model fitting showed that all these formulations followed Korsmeyer and Peppas model, which had a higher value of correlation coefficient (r). While tablet hardness had little or no effect on the release kinetics and was found to be a determining factor with regards to the buoyancy of the tablets. PMID:17915823

Gambhire, Manoj N; Ambade, Kshitij W; Kurmi, Sushma D; Kadam, Vilasrao J; Jadhav, Kisan R



The Effects of Oral Ondansetron Disintegrating Tablets for Prevention of At-Home Emesis in Pediatric Patients After Ear-Nose-Throat Surgery  

Microsoft Academic Search

BACKGROUND: Tonsillectomy and adenoidectomy are associated with a frequent incidence of vomiting, both in the hospital and at home. We evaluated the effects of oral ondansetron disintegrating tablets (ODT) on the incidence of at-home emesis in children undergoing tonsillectomy with and without adenoidectomy and with and without bilateral myringotomy and tube insertion. METHODS: All patients underwent inhaled mask induction with

Peter J. Davis; Kathleen M. Fertal; Karen R. Boretsky; Gina M. Fedel; Michael D. Ingram; Susan K. Woelfel; Paul C. Hoffmann; Harshad Gurnaney; Michael C. Young



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


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



Bioavailability of two oral-tablet and two oral-suspension formulations of naproxen sodium\\/paracetamol (acetaminophen): Single-dose, randomized, open-label, two-period crossover comparisons in healthy Mexican adult subjects  

Microsoft Academic Search

Background: Naproxen sodium\\/paracetamol (acetaminophen) is a combination for the treatment of symptomatic pain and fever marketed both as a prescription and an over-the-counter product in Mexico.Objective: The aim of these 2 studies was to compare the bioavailability and to determine the bioequivalence of 2 test formulations (an oral-tablet formulation containing the combination of naproxen sodium\\/paracetamol 275\\/300 mg and an oral-suspension

Jose Antonio Palma-Aguirre; Jorge Villalpando-Hernández; Germán Novoa-Heckel; Iván Oliva; Lizbeth Cariño; Ericka López-Bojórquez; Victoria Burke-Fraga; Salvador Namur; Mario González-de la Parra



Confirmation of a Major QTL Influencing Oral Morphine Intake in C57 and DBA Mice Using Reciprocal Congenic Strains  

Microsoft Academic Search

C57BL\\/6 (B6) and DBA\\/2 (D2) mice exhibit disparate behavior when tested for voluntary morphine intake in a two-bottle choice drinking paradigm with B6 mice consuming 10 times more drug than D2 mice. Previous genetic mapping studies identified a locus, Mop2, on the proximal part of chromosome 10 that explained over half of the genetic variance in this mouse model of

Thomas N Ferraro; Gregory T Golden; George G Smith; James F Martin; Candice L Schwebel; Glenn A Doyle; Russell J Buono; Wade H Berrettini



Effect of Food on the Multiple-Peak Behavior After a Single Oral Dose of Diclofenac Sodium Slow-Release Tablet in Humans.  


This study evaluated the effect of a standard meal on the multiple-peak behavior of diclofenac sodium following oral administration of a 100-mg slow-release (SR) wax-matrix tablet. The study was a randomized, 3 × 3 Latin-square trial balanced for residual effects, in which 18 subjects were randomly assigned to treatment sequences consisting of three treatments: (A) one 100-mg SR tablet, fasted; (B) one 100-mg SR tablet, fed; and (C) 100-mg diclofenac sodium buffered aqueous solution, fasted. Blood samples were obtained over a 24-h period for Treatments A and B, and over an 8-h period for Treatment C. Food did not significantly affect the extent of absorption but generally delayed the onset of absorption from the SR tablet. The plasma concentration-time profile for the SR tablet under fasted conditions was characterized by multiple-peak behavior. Under fed conditions, the SR tablet showed a more consistent absorption pattern, with a single peak occurring usually between 5 and 6 h. The concentration-time profile of the buffered aqueous solution showed a very rapid absorption phase followed by a rapid decline and a terminal elimination half-life of approximately 1.8 h. A single peak was observed following the buffered aqueous solution. This observation, in conjunction with evidence from other studies, leads to the conclusion that gastrointestinal pH may be responsible for the multiple-peak behavior observed following diclofenac sodium dosing. As compared to the solution, the was-matrix tablet under both fasted and fed conditions showed slow-release, characteristics. PMID:11850655

Riad, Lillian E.; Sawchuk, Ronald J.; McAlary, Margaret M.; Chan, Keith K.H.



In-Depth Survey Report: Control Technology Assessment of Unit Operations Employed in Oral Contraceptive Tablet Making Operations at Ortho Pharmaceutical Corporation, Raritan, New Jersey, June 13-17, 1983,  

National Technical Information Service (NTIS)

An on site visit was made to the Ortho Pharmaceutical Corporation (OPC), Raritan, New Jersey to evaluate methods of controlling exposure to hazardous materials during the manufacturing of medications. OPC produced oral contraceptive tablets containing nor...

M. Y. Anastas P. E. Caplan P. A. Froehlich



Activation of ERM-family proteins via RhoA-ROCK signaling increases intestinal P-gp expression and leads to attenuation of oral morphine analgesia.  


Previously, we reported that repeated oral treatment with etoposide (ETP) causes attenuation of oral morphine analgesia through upregulation of ileal P-glycoprotein (P-gp) mediated by Ras homolog gene family, member A (RhoA) activation. However, the detailed mechanism of the increase in ileal P-gp via RhoA activation remains unknown. Recently, it has been reported that ezrin-radixin-moesin (ERM) proteins, linking several plasma-membrane proteins to the actin cytoskeleton, are involved in the membrane localization and functional activity of P-gp. Moreover, the cross-linking activities of ERM are known to be regulated by RhoA and Rho-associated coiled-coil containing kinase (ROCK). Here, we examined the involvement of ERM in the changes in expression of P-gp via RhoA and ROCK in ileal membrane induced by ETP. Repeated oral treatment with ETP significantly increased the ileal membrane localization of ERM and phosphorylated ERM (p-ERM) in association with upregulation of P-gp and activation of RhoA and ROCK. Interestingly, coadministration of rosuvastatin (inhibitor of RhoA activation) and fasudil (ROCK inhibitor) prevented increments in the activation and phosphorylation of ERM, respectively. In conclusion, upregulation of ileal membrane localization of ERM and p-ERM via activation of RhoA/ROCK induced by ETP treatment may be involved in the regulation of ileal membrane localization of P-gp. PMID:23303573

Kobori, Takuro; Harada, Shinichi; Nakamoto, Kazuo; Tokuyama, Shogo



Patient-Controlled Analgesia versus Oral Controlled-Release Oxycodone – Are They Interchangeable for Acute Postoperative Pain after Laparoscopic Colorectal Surgeries?  

Microsoft Academic Search

Background: Standard therapy for postoperative pain after laparoscopic colorectal surgeries at the Tan Tock Seng Hospital consists of intravenous morphine via patient-controlled analgesia (PCA) for the first 24–48 h, followed by oral analgesics. We compared the efficacy and safety of oral controlled-release (CR) oxycodone hydrochloride (OxyContin® tablets) and PCA after laparoscopic colorectal surgeries. Methods: Between March and August 2006 (phase

Hwee Shih Ho



Cefuroxime Axetil tablet  

Center for Drug Evaluation (CDER)

Text Version... Contains Nonbinding Recommendations Draft Guidance on Cefuroxime Axetil ... Active ingredient: Cefuroxime Axetil Form/Route: Tablet/Oral ... More results from


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

Microsoft Academic Search

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

K Nohno; T Yamaga; N Kaneko; H Miyazaki



[Method for the evaluation of the stability and usability after opening packages of orally disintegrating tablets: case of amlodipine besilate products].  


Orally disintegrating (OD) tablets are widely used in clinical practice. However, drug information on the choice and dispensing based on their stability after opening packages and usability in patients and dispensaries is not sufficient. The aim of this study was to investigate possible evaluation methods of the stability and usability of amlodipine OD tablets. Additives of the brand were changed in April 2009, and therefore the previous and current forms and two generics, current and newly marketed (in November 2009) products of different firms, were used. OD tablets were stored at 25 degrees C and 75% relative humidity for 3 months after opening the packages, and their physicochemical properties were evaluated. Their weight, diameter, thickness, and color difference increased slightly from the initial state. The extent of the change in their hardness, disintegration time, and friability was different among products. These physicochemical changes were acceptable in dispensary practice. Storage after opening the packages did not affect their dissolution rate. The dissolution rate at the initial state of the current brand was slower than that of the previous one. All products used were able to be dispensed by an automatic tablet-packing machine and applied to the so-called simple suspension method for intubational administration. Sensory evaluation tests revealed no major difference in the oral disintegration time, taste, impression, and preference among products. In conclusion, the stability and usability of amlodipine OD tablets used in this study were examined using several methods, and they can be used equivalently from the stability and usability viewpoints. PMID:20686207

Hori, Katsuhito; Yoshida, Naoko; Okumura, Tomonori; Okamura, Yasufumi; Kawakami, Junichi



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


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



Preparation and optimization of mouth/orally dissolving tablets using a combination of glycine, carboxymethyl cellulose and sodium alginate: a comparison with superdisintegrants.  


The purpose of the research was to prepare metoclopramide HCl mouth/orally dissolving tablets (MDTs) using glycine, carboxy methyl cellulose and sodium alginate with sufficient mechanical integrity and disintegration time comparable to superdisintegrants. Application of Plackett-Burman design revealed that concentration of glycine (X(1)), concentration of carboxy methyl cellulose (X(2)) and tablet crushing strength (X(4)) were found to actively influence the dependent variables (disintegration time in oral cavity (DT), wetting time (WT), porosity (P(0)) and water absorption ratio (WA). Additional MDTs were prepared utilizing central composite design for estimating extended effect in a spherical domain. The regression statistics (performed using Statistica(R)-7.0) of quadratic model revealed that DT, WT, P(0) were 97% correlated with active factors (X(1), X(2) or X(4)). The results revealed that optimized MDTs were capable of simulating DT comparable to MDTs containing croscarmellose sodium or crospovidone. Further, it can be envisaged that optimized MDTs were found to be superior to MDTs containing croscarmellose sodium or crospovidone in terms of friability and tablet crushing strength. PMID:18484492

Vora, Nishant; Rana, Vikas



Emerging oral treatments in multiple sclerosis - clinical utility of cladribine tablets  

PubMed Central

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS) that represents one of the first causes of neurological disability in young adults. Although the pathogenesis of MS is still unclear, an autoimmune mechanism has been demonstrated. According to this evidence in the last 15 years different treatments acting on the immune system have been developed. Current disease-modifying drugs (DMDs) for MS require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Moreover the clinical efficacy of these disease-modifying drugs is suboptimal. Thus, there is an important need for the development of new therapeutic strategies. Several oral therapies (fingolimod, fumaric acid, teriflunomide, laquinimod) are in development; Among these cladribine is the only therapy with the potential for short-course dosing. Cladribine is an immunosuppressant that offers sustained regulation of the immune system through a preferential lymphocyte depleting action. Cladribine has a well-characterized and well-known safety profile, derived from more than 15 years of use of the parenteral formulation both in the oncology field and in MS. This paper reviews the new oral emerging treatments and presents the available data about the use of cladribine in MS and the future perspective of its clinical use.

Gasperini, Claudio; Ruggieri, Serena; Pozzilli, Carlo



Emerging oral treatments in multiple sclerosis - clinical utility of cladribine tablets.  


Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS) that represents one of the first causes of neurological disability in young adults. Although the pathogenesis of MS is still unclear, an autoimmune mechanism has been demonstrated. According to this evidence in the last 15 years different treatments acting on the immune system have been developed. Current disease-modifying drugs (DMDs) for MS require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Moreover the clinical efficacy of these disease-modifying drugs is suboptimal. Thus, there is an important need for the development of new therapeutic strategies. Several oral therapies (fingolimod, fumaric acid, teriflunomide, laquinimod) are in development; Among these cladribine is the only therapy with the potential for short-course dosing. Cladribine is an immunosuppressant that offers sustained regulation of the immune system through a preferential lymphocyte depleting action. Cladribine has a well-characterized and well-known safety profile, derived from more than 15 years of use of the parenteral formulation both in the oncology field and in MS. This paper reviews the new oral emerging treatments and presents the available data about the use of cladribine in MS and the future perspective of its clinical use. PMID:20856685

Gasperini, Claudio; Ruggieri, Serena; Pozzilli, Carlo



Efficacy of an ondansetron orally disintegrating tablet: a novel oral formulation of this 5-HT(3) receptor antagonist in the treatment of fractionated radiotherapy-induced nausea and emesis. Emesis Study Group for the Ondansetron Orally Disintegrating Tablet in Radiotherapy Treatment.  


A significant number of patients who are receiving radiotherapy experience the distressing side effects of emesis and nausea. Although prophylactic antiemetics are often given to patients who are receiving single-fraction, high-dose radiotherapy to the abdomen, a survey has revealed that antiemetic prophylaxis is not routinely offered to those receiving fractionated radiotherapy. Hence there is a need for an effective treatment of emesis for use in this group of patients. Ondansetron is an effective and well-tolerated antiemetic, which is used for the prevention of both chemotherapy and radiotherapy-induced emesis and nausea. This agent has been developed as a novel freeze-dried oral formulation. Ondansetron orally disintegrating tablets (ondODT) disperse rapidly when placed on the tongue. As the tablet does not need to be swallowed with water, it is a particularly useful formulation for patients who have difficulty with swallowing or who do not feel able to drink. This study was undertaken to investigate the efficacy of ondODT in the treatment of established emesis and nausea induced by radiotherapy. Two doses of ondODT, 8 mg and 16 mg, were compared with placebo in patients who developed emesis and/or moderate/severe nausea after receiving fractionated radiotherapy to sites located between the thorax and the pelvis. The study showed that ondODT was clinically superior to placebo in treating emesis and nausea successfully over a 12-hour period after taking the medication. There were no statistically significant differences between the two doses of ondODT. In the 2 hours after taking the study medication, patients who received ondODT (8 mg and 16 mg) had significantly fewer emetic episodes compared with those who received placebo. They also experienced significantly less nausea. In conclusion, ondODT 8 mg is effective in the treatment of radiotherapy-induced emesis and nausea and provides an effective alternative to the conventional ondansetron tablet. PMID:10591823

LeBourgeois, J P; McKenna, C J; Coster, B; Feyer, P; Franzén, L; Goedhals, L; Marzecki, Z; Souhami, L; Stewart, A; Tønnessen, F; Haigh, C; Mitchell, T; Wilkinson, J R; Graham, E



A double-blind, single-dose comparison of the analgesic efficacy of tramadol\\/acetaminophen combination tablets, hydrocodone\\/acetaminophen combination tablets, and placebo after oral surgery  

Microsoft Academic Search

Background: Improved clinical outcomes have been documented with combinations of oral analgesic agents, particularly those with complementary activities. However, because not all combinations or dose ratios lead to enhanced analgesia or reduced adverse events (AEs), each combination and dose ratio must be evaluated individually in carefully designed preclinical and clinical trials.Objective: The goal of the study was to compare the

James R. Fricke; Rezaul Karim; Donna Jordan; Norman Rosenthal



Double-Layered Mucoadhesive Tablets Containing Nystatin  

Microsoft Academic Search

The objective of this work was to design a mucoadhesive tablet with a potential use in the treatment of oral candidosis. A 2-layered tablet containing nystatin was formulated. Lactose CD (direct compression), carbomer (CB), and hydroxypropylmethylcellulose (HPMC) were used as excipients. Tablets were obtained through direct compression. Properties such as in vitro mucoadhesion, water uptake, front movements, and drug release

Juan Manuel Llabot; Ruben Hilario Manzo; Alberto allemandi



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.



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


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



In-depth survey report: control technology assessment of unit operations employed in oral-contraceptive tablet-making operations at Ortho Pharmaceutical Corporation, Raritan, New Jersey, June 13-17, 1983  

Microsoft Academic Search

An on-site visit was made to the Ortho Pharmaceutical Corporation (OPC), Raritan, New Jersey to evaluate methods of controlling exposure to hazardous materials during the manufacturing of medications. OPC produced oral-contraceptive tablets containing norethindrone (NOR), mestranol, and ethynylestradiol (EE). Ventilation was an important engineering control at this site. Other engineering controls included the isolation of work procedures and automation of

M. Y. Anastas; P. E. Caplan; P. A. Froehlich



Endothelin receptor antagonists restore morphine analgesia in morphine tolerant rats  

Microsoft Academic Search

Several neurotransmitter mechanisms have been proposed to play a role in the development of morphine tolerance. The present study provides evidence for the first time that endothelin (ET) antagonists can restore morphine analgesia in morphine tolerant rats. Tolerance to morphine was induced by subcutaneous implantation of six morphine pellets during a 7-day period. The degree of tolerance to morphine was

Shaifali Bhalla; George Matwyshyn; Anil Gulati



Morphine and oxycodone hydrochloride in the management of cancer pain  

Microsoft Academic Search

In a double-blind crossover study, morphine and oxycodone hydrochloride were administered to 20 patients who were experiencing severe cancer pain. The peroral doses were determined on the basis of patient-controlled intravenous titration. The assumed oral bioavailability ratios were 44% (group 1, first 10 patients) and 33% (group 2, last 10 patients) for morphine and 66% (group 1) and 50% (group

Eija Kalso; Anneli Vainio



Central effects of morphine on GI motility in conscious dogs.  


It has been suggested that morphine has dual effects; emetic effects and anti-emetic effects. The chemoreceptor trigger zone, which is outside the BBB, mediates the emetic effect. In contrast, the vomiting center mediates the anti-emetic effect of opioids. Thus, naloxone methiodide, which does not cross the BBB, antagonizes emetic effects of opioids. We studied whether naloxone methiodide alters abnormal motility pattern induced by morphine in gastrointestinal (GI) tract. Strain gauge force transducers were sutured on the serosal surface of upper GI tract to record the circular muscle contractions in eight dogs. The ventricular access system was implanted to inject morphine intracerebroventricularly (icv). Effects of icv-injection of morphine (0.3-3.0 mug/kg, bolus) on GI motility were studied during intravenous infusion of naloxone hydrochloride or naloxone methiodide. Icv-injection of morphine (3.0 mug/kg) induced retching and vomiting in all dogs tested. Phasic contractions of the jejunum were observed after icv-injection of morphine. These contractions in the jejunum migrated orally to the antrum (retrograde peristaltic contractions; RPCs). Both naloxone hydrochloride and naloxone methiodide treatment virtually abolished the emetic effects of morphine. Naloxone hydrochloride completely abolished morphine-induced RPCs in all dogs, whereas naloxone methiodide converted morphine-induced RPCs to anterograde peristaltic contractions (APCs) in 6 of 8 dogs. Our current study suggests that central opioids may induce APCs and prevent emesis in conscious dogs. Naloxone methiodide may be useful to prevent the undesired side effects of morphine. PMID:17669372

Takahashi, Toku; Tsuchida, Daisuke; Pappas, Theodore N



Double-blind evaluation of transdermal nitroglycerine as adjuvant to oral morphine for cancer pain management 1 1 Sponsored by a financial grant from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo). Marcelo V Perez received a monthly grant from FAPESP during the realization of this paper  

Microsoft Academic Search

Study Objectives: To examine analgesia and adverse effects following transdermal application of nitroglycerine (a nitric oxide generator) combined with oral morphine, in cancer pain patients.Design: Randomized, double-blind study.Setting: Teaching hospital.Patients: 36 patients suffering from cancer pain.Interventions: Patients were divided into two groups (n = 18). All patients were regularly taking oral amitriptyline 50 mg at bedtime. Pain was evaluated using

Gabriela R Lauretti; Marcelo V Perez; Marlene P Reis; Newton L Pereira



21 CFR 520.62 - Aminopentamide hydrogen sulphate tablets.  

Code of Federal Regulations, 2013 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS...Dosage is administered by oral tablet every 8 to 12 hours...times the suggested dosage. Oral administration of...



Single- and multiple-dose pharmacokinetics of a novel tetramethylpyrazine reservoir-type transdermal patch versus tetramethylpyrazine phosphate oral tablets in healthy normal volunteers, and in vitro/in vivo correlation.  


A novel reservoir-type transdermal system of 2,3,5,6-tetramethylpyrazine (TMP) was developed containing eucalyptus oil as a penetration enhancer. The single and multiple-dose pharmacokinetic profiles of TMP administrated by TMP transdermal patch were characterized in healthy volunteers using an in vivo, randomized, open-label, two-way crossover design. 2,3,5,6-Tetramethylpyrazine phosphate (TMPP) oral tablets were chosen as reference. Following single/multiple oral administration of 200/100 mg TMPP tablets, a TMP C(max) of 1284/613.5 ng/mL was observed within 0.75 h. Single/multiple applications of the TMP patch yielded mean C(max) of 309/325 ng/mL at a median T(max) of 5/4 h, with steady state achieved at second application. The mean C(min) of the patch was 131±30.38 ng/mL, contrasting to nearly zero for the tablet. Multiple applications of patch produced an accumulative effect over single application. At steady state 250 mg/20 cm(2) TMP patch given daily provided comparable exposure to 100 mg TMPP tablets three times daily (3753.91 versus 3563.67 ng·h/mL). TMP tablets and patch yielded similar steady-state plasma concentrations: C(av) (148.48±51.27, 156.41±40.31 ng/mL). The results demonstrated that TMP patch can achieve a therapeutic effect that is comparable to oral administration, exhibited prolonged and sustained plasma levels, fewer drug fluctuations, lower adverse effects, more convenience, and improved patient compliance. In-vitro permeation through human skin demonstrated zero-order kinetics with the flux of 364 µg/cm(2)/h. The predicted C(av) (163.9 ng/mL) was in agreement with the observed C(av) (156.4 ng/mL). PMID:23514701

Shen, Teng; Xu, Huinan; Weng, Weiyu; Zhang, Jianfang



Double-layered mucoadhesive tablets containing nystatin  

Microsoft Academic Search

The objective of this work was to design a mucoadhesive tablet with a potential use in the treatment of oral candidosis. A\\u000a 2-layered tablet containing nystain was formulated. Lactose CD (direct compression), carbomer (CB), and hydroxypropylmethylcellulose\\u000a (HPMC) were used as excipients. Tablets were obtained through direct compression. Properties such as in vitro mucoadhesion,\\u000a water uptake, front movements, and drug release

Juan Manuel Llabot; Ruben Hilario Manzo; Alberto allemandi



Zolmitriptan Oral  


... with other symptoms such as upset stomach and sensitivity to sound and light). Zolmitriptan is in a ... To take the orally disintegrating tablet, use dry hands to peel back the foil packaging. Immediately take ...


Urinary excretion and metabolism of arbutin after oral administration of Arctostaphylos uvae ursi extract as film-coated tablets and aqueous solution in healthy humans.  


Bearberry leaves and preparations made from them are traditionally used for urinary tract infections. The urinary excretion of arbutin metabolites was examined in a randomized crossover design in 16 healthy volunteers after the application of a single oral dose of bearberry leaves dry extract (BLDE). There were two groups of application using either film-coated tablets (FCT) or aqueous solution (AS). The urine sample analysis was performed by a validated HPLC coolarray method (hydroquinone) and a validated capillary electrophoresis method (hydroquinone-glucuronide, hydroquinone-sulfate). The total amounts of hydroquinone equivalents excreted in the urine from BLDE were similar in both groups. With FCT, 64.8% of the arbutin dose administered was excreted; with AS, 66.7% was excreted (p = 0.61). The maximum mean urinary concentration of hydroquinone equivalents was a little higher and peaked earlier in the AS group versus the FCT group, although this did not reach statistical significance (Cur max = 1.6893 micromol/ml vs. 1.1250 micromol/ml, p = 0.13; tmax (t midpoint) = 3.60 h vs. 4.40 h, p = 0.38). The relative bioavailability of FCT compared to AS was 103.3% for total hydroquinone equivalents. There was substantial intersubject variability. No significant differences between the two groups were found in the metabolite patterns detected (hydroquinone, hydroquinone-glucuronide, and hydroquinone-sulfate). PMID:12162475

Schindler, Gernot; Patzak, Ulrich; Brinkhaus, Benno; von Niecieck, Alexander; Wittig, Jörg; Krähmer, Nils; Glöckl, Ingmar; Veit, Markus



Efficacy and safety of desmopressin orally disintegrating tablet in patients with central diabetes insipidus: results of a multicenter open-label dose-titration study.  


Central diabetes insipidus (CDI) is associated with arginine vasopressin (AVP) deficiency with resultant polyuria and polydipsia. Intranasal desmopressin provides physiological replacement but oral formulations are preferred for their ease of administration. This study aimed to demonstrate the efficacy and safety of desmopressin orally disintegrating tablet (ODT) in the treatment of Japanese patients with CDI, and confirm that antidiuresis is maintained on switching from intranasal desmopressin to desmopressin ODT. A total of 20 patients aged 6-75 years with CDI were included in this 4-week multicenter, open-label study. Following observation, patients switched from intranasal desmopressin to desmopressin ODT with titration to optimal dose over ?5 days at the study site. Following three consecutive doses with stable patient fluid balance, patients were discharged with visits at Weeks 2 and 4. Following titration from intranasal desmopressin to ODT, the mean 24-hour urine volume was unchanged, indicating similar antidiuresis with both formulations. The proportion of patients with endpoint measurements (urine osmolality, 24-hour urine volume, hourly diuresis rate and urine-specific gravity) within normal range at Days 1-2 (intranasal desmopressin) and Week 4 (desmopressin ODT) was similar. The mean daily dose ratio of intranasal desmopressin to desmopressin ODT (Week 4) was 1:24 but a wide range was observed across individuals to maintain adequate antidiuretic effect. Hyponatraemia was generally mild and managed by dose titration. Desmopressin ODT achieved sufficient antidiuretic control compared to intranasal therapy and was well tolerated over long-term treatment. The wide range of intranasal:ODT dose ratios underline the importance of individual titration. PMID:23811987

Arima, Hiroshi; Oiso, Yutaka; Juul, Kristian Vinter; Nørgaard, Jens Peter



A prospective randomized trial of the antiemetic efficacy and cost-effectiveness of intravenous and orally disintegrating tablet of ondansetron in children with cancer.  


Orally disintegrating tablet (ODT) of ondansetron is a new formulation, which instantaneously disintegrates and disperses in the saliva without need for ingestion of a liquid. This makes the formulation suitable for administration in children. The objective of this study was to compare the relative efficacy and cost of ODT and intravenous (IV) formulation of ondansetron in controlling nausea and vomiting in children receiving chemotherapy regimens without cisplatin. This prospective randomized trial was performed in a single institution to compare ODT and IV formulation of ondansetron for the prevention of acute emesis in a group of 22 children. Study agents were administered 30 min before chemotherapy and 12 hourly after chemotherapy (5 mg/m2 IV or 4-8 mg oral according to body surface area in 56 and 39 courses, respectively). After randomization, IV formulation was administered to some children instead of ODT due to unavailability of this formulation. Complete and major control of emesis was obtained in 92% of patients in the IV group and 93% of patients in the ODT group. In 56 courses with grade III-IV emetogenicity, complete response rates were not different between the two treatment arms. In the courses without corticosteroids complete response rates were not also different between the two arms. The mean costs per successfully controlled courses were 121.3 USD for the IV formulation whereas 63.2 USD for the ODT formulation. The results of this study confirmed that ODT formulation of ondansetron is a safe, well-tolerated, and cost-effective antiemetic for children during non-cisplatin-containing moderately and highly emetogenic chemotherapy. PMID:15804995

Corapçioglu, Funda; Sarper, Nazan



Morphine Sulfate Injection  


Your doctor has ordered morphine, a strong analgesic (painkiller), to relieve your pain. The drug will be either injected into a large muscle (such as ... or under your skin.You probably will receive morphine continuously for around-the-clock pain relief. Your ...


21 CFR 520.804 - Enalapril tablets.  

Code of Federal Regulations, 2013 CFR

...HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.804 Enalapril tablets...maleate is administered as conjunctive therapy with furosemide and digoxin in...



21 CFR 520.1380 - Methocarbamol tablets.  

Code of Federal Regulations, 2013 CFR

...HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1380 Methocarbamol tablets...administered to dogs and cats as an adjunct to therapy for acute inflammatory and...



21 CFR 520.812 - Enrofloxacin tablets.  

Code of Federal Regulations, 2013 CFR

...CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.812 Enrofloxacin tablets... Dogs and cats for management of diseases associated with bacteria susceptible to enrofloxacin. (3) Limitations...



Sucrose esters with various hydrophilic-lipophilic properties: novel controlled release agents for oral drug delivery matrix tablets prepared by direct compaction.  


Sucrose esters (SE) are esters of sucrose and fatty acids with various hydrophilic-lipophilic properties which have attracted interest from being used in pharmaceutical applications. This study aimed to gain insight into the use of SE as controlled release agents for direct compacted matrix tablets. The study focused on the effect of hydrophilic-lipophilic properties on tableting properties and drug release. Sucrose stearate with hydrophilic-lipophilic balance (HLB) values ranging from 0 to 16 was systematically tested. Tablet formulations contained SE, metoprolol tartrate as a highly soluble model drug and dibasic calcium phosphate dihydrate as a tablet formulation filler in the ratio 1:1:2. The compaction behaviour of matrix tablets was compared with the compacts of individual starting materials as reference. SE incorporation improved the plasticity, compressibility and lubricating property of powder mixtures. The hydrophilic-lipophilic properties of SE affected tableting properties, drug release rate and release mechanism. Increasing hydrophilicity corresponding to the increased monoesters in SE composition increased the relative porosity, elastic recovery and tensile strength of the tablets due to the increased hydrogen bonding between the monoesters. This also facilitated the swelling behaviour of SE, which sustained the drug release rate. A sustained release effect prevailed in tablets containing SE with HLB values of 3-16. The ability to improve the tableting properties as well as sustain the drug release rate of the highly soluble model drug via gelation of SE highlights SE as promising controlled release regulators for direct compacted matrix tablets comprising drugs with various solubilities according to the Biopharmaceutics Classification System. PMID:20132913

Chansanroj, K; Betz, G



Controlled-release oxycodone and morphine in cancer related pain  

Microsoft Academic Search

Controlled-release (CR) formulations of oxycodone and morphine were compared in 45 patients with chronic cancer pain. The study was started with an open-label, randomised titration phase to achieve stable pain control for at least 48 h, followed by a double-blind, randomised, crossover phase in two periods, 3–6 days each. To blind the study using available tablet strengths, the dose ratio

Tarja Heiskanen; Eija Kalso



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


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



Morphine Sleep in Pregnancy.  


Objectives To determine the incidence of admission in labor after morphine sleep (therapeutic rest), patient characteristics associated with labor, and adverse outcomes associated with treatment.Methods We reviewed medical records of women treated with morphine sleep from December 2005 to December 2009. Variables evaluated included medications used for treatment, cervical examination, maternal demographic characteristics and obstetric history, fetal heart rate patterns, and maternal/neonatal outcomes. These characteristics were compared between those admitted in labor after morphine sleep versus those discharged.Results Fifty-eight women received morphine sleep: 36 (62%) were admitted in labor, 17 (29%) were discharged, and 5 (9%) were admitted secondary to category II fetal heart rate tracings. All fetuses had category I fetal heart rate tracings prior to treatment. Median dose of morphine sulfate was 20 mg. Those with effacement > 50% (p < 0.01) and carrying term gestations (p < 0.01) were more likely to be admitted in labor after treatment. There were no adverse maternal outcomes. There were no significant differences in neonatal outcomes.Conclusion Sixty-two percent of women were admitted in labor after morphine sleep. Admission effacement > 50% and term gestational age were associated with admission in labor. There were no significant differences in maternal or neonatal morbidity in those admitted versus discharged home after treatment with morphine sleep. PMID:23471604

Mackeen, A Dhanya; Fehnel, Eric; Berghella, Vincenzo; Klein, Thomas



Self-intoxication with morphine obtained from an infusion pump.  


A 36-year-old Caucasian male was found unresponsive by his wife. He had white foam around his mouth and was pronounced dead shortly thereafter. He had a history of back pain and was treated with intrathecal morphine because of his previous addiction to oral opiate medications. Because of crimping of the pump catheter, it was replaced 4 days before his death. Toxicological findings included urine screen positive for amitriptyline, nortriptyline, opiates, hydrocodone metabolites, ibuprofen, acetaminophen, caffeine, nicotine, and metabolite. Drug concentrations were as follows: blood, 0.260 mg/L amitriptyline, 0.160 mg/L nortriptyline, 0.460 mg/L unconjugated morphine, and 0.624 mg/L total morphine; vitreous humor, 0.034 mg/L unconjugated morphine and 0.080 mg/L total morphine; and cerebrospinal fluid, 0.099 mg/L unconjugated morphine and 0.095 mg/L total morphine. Shortly after death, the volume of the residual pump reservoir was only 8 mL instead of the expected 17 mL. Testing by the FDA showed that the pump was functional. The residual content of the pump accounted for only 230 mg instead of the expected 488 mg. The high blood-morphine concentrations did not correlate with the intrathecal infusion dose. The symptoms were consistent with opiate overdose, possibly by injection of morphine withdrawn from the pump reservoir. The cause of death was determined to be fatal morphine self-intoxication, and the manner of death was accidental. This case is intended to alert regulatory agencies, pain management health professionals, pathologists, and toxicologists to the abuse potential of one of the newer analgesic-delivery systems. PMID:10192419

Gock, S B; Wong, S H; Stormo, K A; Jentzen, J M


The pharmacokinetics of morphine and morphine glucuronides in kidney failure.  


The pharmacokinetics of morphine and its glucuronide metabolites were investigated in three groups of patients with kidney failure (nondialyzed, receiving dialysis, and transplantation) and compared with a group of normal healthy volunteers. Patients in all three renal groups were undergoing surgical procedures (nondialyzed group undergoing arteriovenous fistula formation, dialysis group undergoing placement of a peritoneal dialysis catheter, and the transplant group undergoing live donor kidney transplant). A sensitive, specific high-performance liquid chromatographic assay was used to quantitate morphine, morphine-3-glucuronide, and morphine-6-glucuronide. Patients with kidney failure had a significantly increased morphine area under the curve (AUC) compared with control subjects. There was also an increase in the metabolites morphine-3-glucuronide and morphine-6-glucuronide that was severalfold greater than the increase in morphine AUC. This metabolite accumulation was reversed by kidney transplantation, providing an elegant confirmation on the role of the kidney in morphine pharmacology. PMID:8354025

Osborne, R; Joel, S; Grebenik, K; Trew, D; Slevin, M



21 CFR 520.2604 - Trimeprazine tartrate and prednisolone tablets.  

Code of Federal Regulations, 2010 CFR

...AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520...administered orally at an initial dosage level of 1/2 tablet twice...weighing 21 to 40 pounds, and three tablets twice daily to dogs...pounds. After 4 days, the dosage is reduced to...



Formal synthesis of (±)-morphine.  


The pain ends here: A novel synthetic strategy for the construction of (±)-morphine rings?B and E was developed, in which SmI2 -promoted reductive coupling/desulfurization and tandem alcoholysis/oxa-Michael addition featured as the key steps for the assembly of the C9-C14 and C5-O bonds, respectively. Asymmetric tandem alcoholysis/oxa-Michael addition was also feasible for the enantiocontrolled synthesis of morphine. PMID:23509056

Li, Jing; Liu, Guo-Liang; Zhao, Xian-He; Du, Ji-Yuan; Qu, Hu; Chu, Wen-Dao; Ding, Ming; Jin, Cong-Yang; Wei, Meng-Xue; Fan, Chun-An



Protective Effect of Bacoside-A against Morphine-Induced Oxidative Stress in Rats.  


In the present study, we investigated the protective effect of bacoside-A the active principle isolated from the plant Bacopa monniera against oxidative damage induced by morphine in rat brain. Morphine intoxicated rats received 10-160 mg/kg b.w. of morphine hydrochloride intraperitoneally for 21 days. Bacoside-A pretreated rats were administered with bacoside-A (10 mg/kg b.w/day) orally, 2 h before the injection of morphine for 21 days. Pretreatment with bacoside-A has shown to possess a significant protective role against morphine induced brain oxidative damage in the antioxidant status (total reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase and lipid peroxidation) and membrane bound ATP-ases(Na(+)/K(+)ATPase. Ca(2+) and Mg(2+) ATPases) activities in rat. The results of the present study indicate that bacoside-A protects the brain from oxidative stress induced by morphine. PMID:22707825

Sumathi, T; Nathiya, V C; Sakthikumar, M



Relative oral bioavailability of morphine and naltrexone derived from crushed morphine sulfate and naltrexone hydrochloride extended-release capsules versus intact product and versus naltrexone solution: A single-dose, randomized-sequence, open-label, three-way crossover trial in healthy volunteers  

Microsoft Academic Search

Background: Morphine sulfate\\/sequestered naltrexone hydrochloride (HCl) (MS-sNT) extended-release fixed-dose combination capsules, approved by the US Food and Drug Administration (FDA) in August 2009 for chronic moderate to severe pain, contain extended-release morphine pellets with a sequestered core of the opioid antagonist naltrexone. MS-sNT was designed so that if the product is tampered with by crushing, the naltrexone becomes bioavailable to

Franklin K. Johnson; Jeffrey G. Stark; Frederick A. Bieberdorf; Joe Stauffer



In-depth survey report: control technology assessment of unit operations employed in oral-contraceptive tablet-making operations at Ortho Pharmaceutical Corporation, Raritan, New Jersey, June 13-17, 1983  

SciTech Connect

An on-site visit was made to the Ortho Pharmaceutical Corporation (OPC), Raritan, New Jersey to evaluate methods of controlling exposure to hazardous materials during the manufacturing of medications. OPC produced oral-contraceptive tablets containing norethindrone (NOR), mestranol, and ethynylestradiol (EE). Ventilation was an important engineering control at this site. Other engineering controls included the isolation of work procedures and automation of work practices for weighing ingredients, granulation of substances, tableting, and packaging. Area samples were taken for air monitoring of steroid concentration levels in each manufacturing area. Access to the work areas was only through the locker rooms. Samples taken in the locker rooms revealed no detectable contaminant levels. Workers performing high risk activities wore air supplied vinyl suits and disposable rubber gloves. The vinyl suits had overshoes attached. For moderate risk activities the workers wore a disposable suit, rubber gloves and shoe covers. Appropriate respirators were provided. Workers in low risk activities wore disposable rubber gloves and appropriate respirators. Sampling indicated that processing workers experienced breathing-zone levels outside their vinyl suits of 16.40 and 0.36 micrograms/cubic meter of NOR and EE, respectively.

Anastas, M.Y.; Caplan, P.E.; Froehlich, P.A.



A simple gas chromatographic method for the simultaneous determination and pharmacokinetic study of tetramethylpyrazine phosphate and borneol in mouse plasma and brain tissue after oral administration of the fufang tetramethylpyrazine phosphate tablets.  


A rapid, sensitive, and simple gas chromatographic method with flame ionization detection is developed for the simultaneous determination of tetramethylpyrazine phosphate (TMPP) and borneol in mouse plasma and brain tissue. Sample preparations are carried out by deproteinization with an internal standard solution in methanol. The analytes and internal standard (dimethyl sulfoxide) are well-separated on an HP-5 MS capillary column. The analytical curves are linear over a wide concentration range of 0.02-40 microg/mL for both TMPP and borneol in plasma and brain tissue, with the intra- and inter-day precision (the relative standard deviation values) at less than 15%. TMPP and borneol are both stable under different conditions. The method described is successfully applied to the pharmacokinetic study of mouse plasma and brain tissue after oral administration of the Fufang TMPP and TMPP tablets to mice. PMID:18492348

Yan-Yu, Xiao; Qi-neng, Ping; Zhi-peng, Chen


Comparative efficacy of a spot-on formulation containing emodepside and praziquantel (Profender ®, Bayer) and praziquantel and pyrantel oral tablets (Drontal ® for Cats) against experimental Ancylostoma ceylanicum infections in cats.  


Ancylostoma ceylanicum is a common zoonotic hookworm of dogs and cats throughout Asia and has also been reported to occur within the Australasian region. The aim of this study to was to determine the efficacy of a spot-on formulation containing emodepside and praziquantel (Profender(®), Bayer) and praziquantel and pyrantel oral tablets (Drontal(®) for Cats, Bayer) against experimental A. ceylanicum infections in cats. Twenty-four kittens were each subcutaneously injected with 100 infective third-stage larvae of A. ceylanicum. Kittens were stratified by egg count and randomly allocated equally into control and two treatment groups. The first group were treated with emodepside 2.1%/praziquantel 8.6% (Profender®, Bayer) at the recommended label dose. The second group was treated with 80 mg pyrantel and 20mg praziquantel (Drontal(®) for Cats, Bayer) at the recommended label dose. The kittens in the control group were not treated. Egg counts were performed daily until the end of the study period and compared for the treated and control groups. No eggs were detected in the treated group of kittens within 4 days of treatment and faecal samples from this group remained negative throughout the rest of the study, resulting in a treatment efficacy (egg reduction) of 100% (P<0.0001). The egg counts remained high (993 ± 666 epg) in the untreated control group for the rest of the study period. This study demonstrated that both combination products containing topical emodepside/praziquantel (Profender(®), Bayer) and praziquantel/pyrantel oral tablets (Drontal(®) for Cats, Bayer) given at the recommended dose is highly effective against infection with A. ceylanicum in cats. PMID:23026558

Taweethavonsawat, Piyanan; Chungpivat, Sudchit; Watanapongchati, Supoj; Traub, Rebecca J; Schaper, Roland



The efficacy and side effects of continuous infusion intravenous morphine (CIVM) for pain and symptoms due to advanced cancer  

Microsoft Academic Search

Morphine is the strong opioid of choice in the management of moderate-to-severe chronic cancer pain. The preferred route of administration is oral, in individually titrated doses, regularly scheduled around the clock. We conducted a retrospective study of continuous intravenous morphine (CIVM) in a palliative medicine program in 107 consecutive patients. The results suggest CIVM is an effective, safe, and versatile

Paul Glare; Declan Walsh; Eileen Groh; Kristine A. Nelson



Hydrocortisone Oral  


... will decrease your dose gradually to allow your body to adjust before stopping the drug completely. Watch for these side effects if you are gradually decreasing your dose and after you stop taking the tablets or oral liquid, even if you switch to an inhalation. If ...


Triamcinolone Oral  


... will decrease your dose gradually to allow your body to adjust before stopping the drug completely. Watch for these side effects if you are gradually decreasing your dose and after you stop taking the tablets or oral liquid, even if you switch to an inhalation. If ...


Dexamethasone Oral  


... will decrease your dose gradually to allow your body to adjust before stopping the drug completely. Watch for these side effects if you are gradually decreasing your dose and after you stop taking the tablets or oral liquid, even if you switch to an inhalation corticosteroid ...


EDX-Element Analysis of the In Vitro Effect of Fluoride Oral Hygiene Tablets on Artificial Caries Lesion Formation and Remineralization in Human Enamel  

PubMed Central

Aim of this in-vitro-study was to assess the remineralization potential of a tooth cleaning tablet with different fluoride content quantitatively using EDX analysis. Twenty three caries free impacted third molars were examined; enamel surfaces were wax coated leaving two 3x4mm windows for exposure to demineralization/remineralization cycles. The teeth were randomly assigned to 4 groups of 5 control and 6 experimental teeth each. Demineralization by standardized HEC-gel, pH 4.7 at 37°C for 72h, was alternated by rinsing in remineralization solution, pH 7.0 at 37°C for 72h, total challenge time 432h. The negative control group N was treated during remineralization cycles with saline; positive control group P was treated with remineralization solution; experimental group D1 was exposed to remineralization solution containing Denttabs®-tablets with 1450 ppm F; experimental group D2 was exposed to remineralization solution and Denttabs®-tablets with 4350 ppm F. Each tooth was cut into serial sections and analyzed by scanning electron microscopy with EDX element analysis for assessment of the different zones of the lesions in 3 representative sections. Statistical analysis was based on the AVOVA test for repeated measurements and post hoc Bonferroni adjustment. The results showed a significantly higher Ca and P content in the body of the lesion in both fluoride treated groups compared to the controls. It can be concluded that higher concentrations of NaF may be more effective in remineralization of early advanced caries lesions.

Eggerath, J; Kremniczky, T; Gaengler, P; Arnold, W.H



21 CFR 520.903e - Febantel tablets.  

Code of Federal Regulations, 2010 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...



21 CFR 520.903e - Febantel tablets.  

Code of Federal Regulations, 2013 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...



21 CFR 520.2362 - Thenium closylate tablets.  

Code of Federal Regulations, 2013 CFR

...1) The tablets are administered orally to dogs as a single day treatment of canine ancylostomiasis by the removal from the intestines of the adult forms of the species Ancylostoma caninum and Uncinaria stenocephala (hookworms). Dogs weighing...



Evaluation of NK and LAK cell activities in neoplastic patients during treatment with morphine.  


The cytotoxic activity of Natural Killer (NK) and Lymphokine Activated Killer (LAK) cells in neoplastic patients with or without antalgic treatment was studied. NK cell activity was found reduced in untreated neoplastic patients when compared to healthy subjects. The atalgic treatment with morphine (orally or intrathecally administered) was able to significantly reduce the mean values of NK cell activity found in cancer patients. In three patients the cytotoxicity of NK cells significantly decreased during transfer from oral to intrathecal administration of morphine. In contrast to the NK cell function, the development of LAK cell activity significantly increased in neoplastic patients when compared to healthy controls. Further increments were obtained during treatment with morphine. The oral treatment with morphine was able to determine a higher induction of LAK cells than the intrathecal administration of the drug. Besides providing new knowledge on the effect of morphine on immune system our findings suggest that, in order to include neoplastic patients in clinical trials of adoptive immunotherapy with LAK cells and interleukin-2 (IL-2), the antalgic therapy with oral administration of morphine may represent a better solution than the intrathecal administration of the drug. PMID:1774133

Provinciali, M; Di Stefano, G; Raffaeli, W; Pari, G; Desiderio, F; Fabris, N



Plasma concentration profiles and antihypertensive effect of conventional and extended-release felodipine tablets.  

PubMed Central

1. The rate and extent of felodipine absorption from an oral solution, conventional and extended-release tablets were investigated in two groups of healthy volunteers (n = 18 + 15). 2. The antihypertensive effect of felodipine conventional tablets twice daily (n = 71) and extended-release tablets once daily (n = 76) were compared in a parallel-group study in hypertensive patients. 3. As from a solution, felodipine was completely absorbed from the two solid dosage forms. The rate of absorption increased in the order extended-release tablets, conventional tablets, solution. 4. The extended-release tablet gave more sustained plasma concentrations than the conventional tablet. 5. The extended-release tablet given once daily gave similar blood pressure control to the conventional tablet given twice daily.

Blychert, E; Wingstrand, K; Edgar, B; Lidman, K



Use of tablet-based kiosks in the emergency department to guide patient HIV self-testing with a point-of-care oral fluid test.  


Despite successes in efforts to integrate HIV testing into routine care in emergency departments, challenges remain. Kiosk-facilitated, directed HIV self-testing offers one novel approach to address logistical challenges. Emergency department patients, 18-64 years, were recruited to evaluate use of tablet-based-kiosks to guide patients to conduct their own point-of-care HIV tests followed by standard-of-care HIV tests by healthcare workers. Both tests were OraQuick Advance tests. Of 955 patients approached, 473 (49.5%) consented; 467 completed the test, and 100% had concordant results with healthcare workers. Median age was 41 years, 59.6% were female, 74.8% were African-American, and 19.6% were White. In all, 99.8% of patients believed the self-test was "definitely" or "probably" correct; 91.7% of patients "trusted their results very much"; 99.8% reported "overall" self-testing was "easy or somewhat easy" to perform. Further, 96.9% indicated they would "probably" or "definitely" test themselves at home were the HIV test available for purchase; 25.9% preferred self-testing versus 34.4% who preferred healthcare professional testing (p?>?0.05). Tablet-based kiosk testing proved to be highly feasible, acceptable, and an accurate method of conducting rapid HIV self-testing in this study; however, rates of engagement were moderate. More research will be required to ascertain barriers to increased engagement for self-testing. PMID:23970610

Gaydos, Charlotte A; Solis, Melissa; Hsieh, Yu-Hsiang; Jett-Goheen, Mary; Nour, Samah; Rothman, Richard E



Nebulized versus subcutaneous morphine for patients with cancer dyspnea: a preliminary study.  


This study compared the effects of nebulized versus subcutaneous morphine on the intensity of dyspnea in cancer patients. Patients with a resting dyspnea intensity > or =3 on a 0-10 scale (0=no dyspnea, 10=worst possible dyspnea) who received regular oral or parenteral opioids were included. On day 1, patients received either subcutaneous (SC) morphine plus nebulized placebo or nebulized morphine plus SC placebo. On day 2, a crossover was made. Dyspnea intensity, side effects, and blinded preference of treatment were assessed. Eleven patients completed the study. Dyspnea decreased from a median of 5 (range, 3-8) to 3 (range, 0-7) after SC morphine (P=0.025) and from 4 (range, 3-9) to 2 (range, 0-9) after nebulized morphine (P=0.007). There was no significant difference in dyspnea intensity between nebulized and subcutaneous morphine at 60 minutes. Unfortunately, due to limited sample size, there was insufficient power to rule out a significant difference between both routes of administration. Nebulized morphine offered dyspnea relief similar to that of SC morphine. Larger randomized controlled trials in patients with both continuous dyspnea and earlier stages of dyspnea are justified. PMID:15963870

Bruera, Eduardo; Sala, Raul; Spruyt, Odette; Palmer, J Lynn; Zhang, Tao; Willey, Jie



Speed of kill efficacy and efficacy of flavored spinosad tablets administered orally to cats in a simulated home environment for the treatment and prevention of cat flea (Ctenocephalides felis) infestations.  


The efficacy of spinosad against adult fleas (Ctenocephalides felis) on cats was evaluated in two separate controlled, blinded studies-one to determine flea knockdown and speed of flea kill (SOFK) on experimentally infested cats, another to assess the ability of spinosad to prevent flea infestations in a simulated home environment (SHE) study design. In each study, pre-treatment live flea counts were used as a blocking factor to randomize cats to treatment, and treated in the fed state, with flavored tablets containing either no active ingredient (control) or spinosad (50-100mg/kg in the SOFK study; 50-75mg/kg body weight in the SHE study). In the SOFK study, 6 cats per group were infested with unfed adult fleas on Day -1. Groups 1-5 received control tablets; groups 6-10 received spinosad tablets. Flea counts were conducted at 0.5, 2, 4, 8 and 24h post-dosing. In the SHE study, 12 flea-free cats per group, treated on Days 0, 30 and 60, were maintained in solid-sided cages with solid carpeted floors. Each cat was infested on Days 1, 7 and 14 with 100 unfed adult fleas. Individual flea comb counts were performed on Days 3, 9, 16, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84, 91 and 95. After each count, except Day 95, up to 300 live fleas were replaced on each cat. To augment flea challenge, the carpeted area in each cage was sprinkled weekly with larval flea growth media (dried blood, yeast). In the SOFK study, reductions in mean flea counts in the spinosad groups were observed at all post-treatment assessments, beginning at 0.5h post-infestation with significant differences (p<0.0001) from vehicle-treated cats from 2h post-treatment when efficacy was >90%, through the final flea counts 24h post-infestation when no fleas were found on spinosad treated cats. In the SHE study, GM post-treatment flea counts in the control group ranged between 38.9 and 107.0 (arithmetic means 58.8-118.1); no live fleas were combed from spinosad-treated cats (100% effectiveness) at any time point post-treatment. No adverse events that were attributable to the treatments were observed in either study. These studies demonstrated that spinosad administered orally to cats is safe and effective, providing >90% efficacy from 2h post-dosing and 100% knockdown at 24h, and preventing infestations over a 95 day study period from a flea-contaminated simulated home environment. PMID:23522900

Snyder, Daniel E; Meyer, Katherine A; Wiseman, Scott; Trout, Candace M; Young, David R



Protective role of Bacopa monniera on morphine-induced brain mitochondrial enzyme activity in rats  

Microsoft Academic Search

Alcoholic extract of Bacopa monniera was tested for its protective role on morphine-induced brain mitochondrial enzyme status in rats. The level of the brain mitochondrial enzymes was significantly lower in the morphine-treated group when compared with control animals. These enzymes were maintained at normal level when Bacopa extract was administered orally at a dose of 40 mg\\/kg, 2 h before

T. Sumathy; S. Govindasamy; K. Balakrishna; G. Veluchamy



Systemic Exposure to Morphine and the Risk of Acute Chest Syndrome in Sickle Cell Disease  

Microsoft Academic Search

Background: The etiology of acute chest syndrome, the most severe complication of the sickle cell crisis, is unknown.Objective: Our objective was to assess exposure to morphine as an etiologic factor for acute chest syndrome in sickle cell disease.Methods: A post hoc analysis of a randomized controlled trial comparing oral with continuous infusion of morphine was performed. Children (aged 5-17 years)

Ernest A. Kopecky; Sheila Jacobson; Prashant Joshi; Gideon Koren



Fast dispersible\\/slow releasing ibuprofen tablets  

Microsoft Academic Search

Eight formulations were developed containing ibuprofen in the form of orally disintegrating tablets. To prevent bitter taste and side effects of the drug, the drug was associated with Phospholipon 80H, a saturated lecithin, by wet granulation. The granules were then coated using different film forming agents (Kollicoat SR 30, Amprac 01, Kollidon 90F, Eudragit RD 100) obtaining four lots 1–4.

Adamo Fini; Valentina Bergamante; Gian Carlo Ceschel; Celestino Ronchi; Carlos Alberto Fonseca de Moraes



High-Dose Tramadol in Comparison to Low-Dose Morphine for Cancer Pain Relief  

Microsoft Academic Search

Cancer pain treatment following the World Health Organization guidelines is effective and feasible. However, the evidence supporting the use of opioids for mild to moderate pain on the second step of the analgesic ladder is widely discussed. The present evaluation compares the efficacy and safety of high doses of oral tramadol (?300 mg\\/d) with low doses of oral morphine (?60

Stefan Grond; Lukas Radbruch; Thomas Meuser; Georg Loick; Rainer Sabatowski; Klaus A. Lehmann



Initial pharmacokinetic, safety and efficacy evaluation of nasal morphine gluconate for breakthrough pain in cancer patients  

Microsoft Academic Search

Patients with controlled background pain associated with cancer frequently also experience episodes of moderate to severe intensity breakthrough pain. Opioid pharmacotherapy, particularly with oral morphine, remains the cornerstone for the management of cancer pain. Nasal administration of opioids provides a mechanism for more rapid drug absorption and more rapid onset of pain relief compared with oral dosing. This non-randomized, open-label,

Dermot Fitzgibbon; Donna Morgan; Deanna Dockter; Chris Barry; Evan D. Kharasch



Use of tablet-based kiosks in the emergency department to guide patient HIV self-testing with a point-of-care oral fluid test  

PubMed Central

Objective Despite successes in efforts to integrate HIV testing into routine care in emergency departments, challenges remain. Kiosk-facilitated, directed HIV self-testing offers one novel approach to address logistical challenges. Methods Emergency department patients, 18–64 years, were recruited to evaluate use of tablet-based-kiosks to guide patients to conduct their own point-of-care HIV tests followed by standard-of-care HIV tests by healthcare workers. Both tests were OraQuick Advance tests. Results Of 955 patients approached, 473 (49.5%) consented; 467 completed the test, and 100% had concordant results with healthcare workers. Median age was 41 years, 59.6% were female, 74.8% were African-American, and 19.6% were White. In all, 99.8% of patients believed the self-test was “definitely” or “probably” correct; 91.7% of patients “trusted their results very much”; 99.8% reported “overall” self-testing was “easy or somewhat easy” to perform. Further, 96.9% indicated they would “probably” or “definitely” test themselves at home were the HIV test available for purchase; 25.9% preferred self-testing versus 34.4% who preferred healthcare professional testing (p > 0.05). Conclusion Tablet-based kiosk testing proved to be highly feasible, acceptable, and an accurate method of conducting rapid HIV self-testing in this study; however, rates of engagement were moderate. More research will be required to ascertain barriers to increased engagement for self-testing.

Gaydos, Charlotte A; Solis, Melissa; Hsieh, Yu-Hsiang; Jett-Goheen, Mary; Nour, Samah; Rothman, Richard E



Controlled-release oxycodone compared with controlled-release morphine in the treatment of cancer pain: a randomized, double-blind, parallel-group study  

Microsoft Academic Search

Controlled-release oral formulations of oxycodone and morphine are both suitable analgesics for moderate to severe pain. They were compared in cancer-pain patients randomized to double-blind treatment with controlled-release oxycodone (n = 48) or controlled-release morphine (n = 52) every 12 h for up to 12 days. Stable analgesia was achieved by 83% of controlled-release oxycodone and 81% of controlled-release morphine

Patricia Mucci-LoRusso; Barry S. Berman; Peter T. Silberstein; Marc L. Citron; Linda Bressler; Sharon M. Weinstein; Robert F. Kaiko; Barbara J. Buckley; Robert F. Reder



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)  

Microsoft Academic Search

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

Katherine A Barraclough; Euan Noble; Diana Leary; Fiona Brown; Carmel M Hawley; Scott B Campbell; Nicole M Isbel; David W Mudge; Carolyn L van Eps; Joanna M Sturtevant; David W Johnson



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



Active ingredient: Loratadine Form/Route: Orally ...  

Center for Biologics Evaluation and Research (CBER)

Text VersionContains Nonbinding Recommendations Guidance on Loratadine ... Active ingredient: Loratadine Form/Route: Orally Disintegrating Tablets/Oral ... More results from


Effects of processed Aconiti tuber and its ingredient alkaloids on the development of antinociceptive tolerance to morphine.  


Processed Aconiti tuber (PAT) is a herbal medicine that has been widely used as an analgesic since ancient times. We investigated effects of subanalgesic doses of PAT on morphine tolerance in mice. Mice received subcutaneous morphine (10 mg/kg) and oral PAT at subanalgesic doses (0.1 or 0.3 g/kg), once a day for 7 days. Mechanical nociceptive thresholds were measured using the tail pressure test, at 60 min after the daily s.c. morphine injections. In the placebo-treated group, repeated administration of s.c. morphine resulted in development of analgesic tolerance. In the PAT-treated groups, oral PAT attenuated morphine tolerance, dose-dependently. The main ingredient alkaloid of PAT causing its tolerance-attenuating activity was mesaconitine, but other ingredient alkaloids, such as aconitine and hypaconitine, also contributed to this activity. In addition, repeated treatment with PAT could reverse already-developed morphine tolerance. Subanalgesic doses of oral PAT thus can attenuate and reverse morphine tolerance in mice. PMID:16169697

Shu, Haihua; Arita, Hideko; Hayashida, Masakazu; Sekiyama, Hiroshi; Hanaoka, Kazuo



A new transmucosal drug delivery system for patients with breakthrough cancer pain: the fentanyl effervescent buccal tablet  

PubMed Central

Breakthrough pain, a transitory severe pain with the background of otherwise controlled persistent pain has a prevalence between 52% and 67% in outpatients with cancer. Medications for such sudden-onset pain require non-invasive delivery of a potent and short-acting opioid for rapid pain relief. Although oral transmucosal delivery of fentanyl citrate (OTFC) has been shown to provide better pain relief than a typical oral opioid administration such as morphine sulfate immediate release (MSIR) in the management of breakthrough pain in patients with cancer-related pain, newer delivery systems offer a potential for further enhancement of pain relief. The fentanyl effervescent buccal tablet (FBT) formulation employs a novel drug delivery system that relies on an effervescence reaction to improve buccal fentanyl absorption. Using the effervescence reaction results in the production and dissipation of carbon dioxide with a dynamic shift in pH as the tablet dissolves. The induced low pH favors dissolution of fentanyl citrate in saliva (higher water solubility). The subsequent increase in pH thereafter favors the buccal absorption of non-ionized fentanyl across the buccal mucosa. Such a pH “pumping” mechanism increases the permeation of fentanyl into and through the buccal to the vascular system from where the agent is transported to the specific opioid receptor sites in the CNS. Compared with OTFC, data in healthy volunteers show that the effervescence reaction employed in FBT increases the total amount and the speed of absorption of fentanyl being absorbed. Compared with OTFC there is an increase in peak fentanyl blood concentrations, and an enhancement of the amount of buccal delivery of fentanyl. Such favorable data are underlined by the results of clinical studies where the FBT technology was studied in patients with breakthrough pain in chronic malignant pathologies.

Freye, Enno



Analgesic responses to intrathecal morphine in relation to CSF concentrations of morphine-3,?-glucuronide and morphine-6,?-glucuronide  

Microsoft Academic Search

This study was performed to determine whether variations in analgesic responses to intrathecal morphine could be explained by cerebrospinal fluid (CSF) concentrations of morphine metabolites. Twenty-four CSF samples were collected at the beginning, middle and end of treatment periods in seven cancer patients with pain of malignant origin. CSF concentrations of morphine-3,?-glucuronide (M3G) and morphine-6,?-glucuronide (M6G) metabolites were measured by

Gary C. Dennis; Deepa Soni; Ozra Dehkordi; Richard M. Millis; Hutchinson James; William L. West; Robert E. Taylor



Nimodipine-enhanced opiate analgesia in cancer patients requiring morphine dose escalation: a double-blind, placebo-controlled study.  


The ability of nimodipine, a dihydropyridine calcium antagonist, to reduce the daily dose of oral morphine in cancer patients who had developed dose escalation, was tested in 54 patients under randomized, double-blind, placebo-controlled conditions. We selected patients that required at least two successive increments of morphine to maintain pain relief. A possible pharmacokinetic interaction between nimodipine and morphine was also studied in 14 patients by assaying steady-state serum levels of morphine and its 3- and 6-glucuronides. A total of 30 patients completed the study, 14 and 16 in the nimodipine and placebo groups, respectively. Nimodipine controlled the escalation of the morphine dose in 9 patients (65%), and placebo in 4 (28%), the difference being statistically significant (P=0.03). The dose of morphine was reduced from 313+/-52 to 174+/-33 mg/day (P < 0.001) in the nimodipine group, and from 254+/-26 to 218+/-19 mg/day (not significant) in the placebo group. The percentages of reduction in the daily dose of morphine also showed significant differences between both groups (P=0.02). One week after introducing nimodipine or placebo, while the dose of morphine remained similar to that of the pre-test week, the serum levels of morphine and its glucuronides were not modified significantly. We conclude that the introduction of nimodipine in patients chronically treated with morphine may be a safe alternative to reduce the daily requirements of the opioid. It is suggested that interference with Ca2+-related events may attenuate the development and/or expression of tolerance to morphine in a clinically relevant way. PMID:9696455

Santillán, R; Hurlé, M A; Armijo, J A; de los Mozos, R; Flórez, J



A randomised trial of glucose tablets to aid smoking cessation  

Microsoft Academic Search

Rationale Oral glucose has been found to decrease tobacco craving among abstaining smokers. One study has demon- strated an effect of glucose on short-term abstinence. There is a need to examine any long-term benefit of glucose on abstinence. Objectives To assess whether glucose tablets improve 6-month continuous abstinence rates compared with low- calorie placebo tablets. Methods Smokers attempting to stop

Robert West; Sylvia May; Andy McEwen; Hayden McRobbie; Peter Hajek; Eleni Vangeli



Innovations in education : tablets  

Microsoft Academic Search

In this group of three separate articles the authors discuss the use of tablet PCs in educational applications at their schools. In 'Tablets: the smart medicine for teaching and learning', Lee Bond explains how Immanuel Lutheran College on the Sunshine Coast in Queensland is using ICT to make real systemic change in the delivery of education in physics, chemistry, biology

Lee Bond



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



Relative potency of controlled-release oxycodone and controlled-release morphine in a postoperative pain model  

Microsoft Academic Search

Objective: The relative analgesic potency of single doses of oral controlled-release oxycodone and oral controlled-release morphine\\u000a were compared in a randomized, double-blind trial using a postoperative pain model.\\u000a \\u000a \\u000a \\u000a Methods: Women (n?=?169) with moderate to severe pain following abdominal hysterectomy received single oral doses of controlled-release oxycodone,\\u000a 20?mg or 40?mg, or controlled-release morphine, 45?mg or 90?mg. Assessments were made at 30?min,

G. B. Curtis; G. H. Johnson; P. Clark; R. Taylor; J. Brown; R. O'Callaghan; M. Shi; P. G. Lacouture



Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia  

PubMed Central

Recent data suggest that opioids can activate immune-like cells of the central nervous system (glia). This opioid-induced glial activation is associated with decreased analgesia, owing to the release of proinflammatory mediators. Here we examine in rats whether the putative microglial inhibitor, minocycline, may affect morphine-induced respiratory depression and/or morphine-induced reward (conditioned place preference). Systemic co-administration of minocycline significantly attenuated morphine-induced reductions in tidal volume, minute volume, inspiratory force and expiratory force, but did not affect morphine-induced reductions in respiratory rate. Minocycline attenuation of respiratory depression was also paralleled with significant attenuation by minocycline of morphine-induced reductions in blood oxygen saturation. Minocycline also attenuated morphine conditioned place preference. Minocycline did not simply reduce all actions of morphine, as morphine analgesia was significantly potentiated by minocycline co-administration. Lastly, morphine dose-dependently increased cyclooxygenase-1 gene expression in a rat microglial cell line, an effect that was dose-dependently blocked by minocycline. Together, these data support that morphine can directly activate microglia in a minocycline-suppressible manner and suggest a pivotal role for minocycline-sensitive processes in the mechanisms of morphine-induced respiration depression, reward, and pain modulation.

Hutchinson, Mark R.; Northcutt, Alexis L.; Chao, Lindsey W.; Kearney, Jeffrey J.; Zhang, Yingning; Berkelhammer, Debra L.; Loram, Lisa C.; Rozeske, Robert R.; Bland, Sondra T.; Maier, Steven F.; Gleeson, Todd T.; Watkins, Linda R.



Influence of morphine on host immunity.  


Morphine is a widely used drug for analgesia and substance abuse. It has been accepted as a safe medication with great analgesic efficacy. Previous studies have reported that morphine is highly associated with the risk of immunosuppressive effects. Although the observed clinical effects suggest that morphine has the immunomodulatory capabilities, the mechanism of its action is still unclear. Here we review morphine on the bench to improve our understanding of the drug on the host immunity at the bedside. Studies of the effects of morphine on the innate and adaptive immune systems as well as immune responses are also discussed. PMID:21982172

Chang, Ming-Cheng; Fan, Shou-Zen; Hsiao, Po-Ni; Cheng, Wen-Fang; Sun, Wei-Zen



The pharmacokinetics of morphine and morphine glucuronide metabolites after subcutaneous bolus injection and subcutaneous infusion of morphine  

PubMed Central

Aims To investigate the pharmacokinetics of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) in healthy volunteers after the administration of morphine by subcutaneous bolus injection (s.c.b.) and subcutaneous infusion (s.c.i.) over 4 h, and to compare the results with the intravenous bolus (i.v.) administration of morphine. Methods Six healthy volunteers each received 5 mg morphine sulphate by i.v., s.c.b. and short s.c.i. over 4 h, on three separate occasions, in random order, each separated by at least 1 week. Plasma samples were assayed for morphine, M6G and M3G. Results After i.v. morphine, the concentrations of morphine, M6G and M3G and their pharmacokinetic parameters were similar to those we have observed previously, in other healthy volunteers (when standardized to nmol l?1, for a 10 mg dose to a 70 kg subject). After s.c.b. morphine, similar results were obtained except that the median tmax values for morphine and M3G were significantly longer than after i.v. morphine (P < 0.001 and P < 0.05, respectively), with a trend to a longer tmax for M6G (P = 0.09). The appearance half-lives after s.c.b. morphine for M6G and M3G were also significantly longer than after i.v. morphine (P = 0.03 and P < 0.05, respectively). Comparison of log-transformed AUC values indicated that i.v. and s.c.b. administration of morphine were bioequivalent with respect to morphine, M6G and M3G. In comparison with i.v. morphine, morphine by s.c.i. was associated with significantly longer median tmax values for morphine (P < 0.001), M6G (P < 0.001) and M3G (P < 0.05), and the mean standardized Cmax values significantly lower than after both i.v. and s.c.b. morphine (morphine P < 0.001, M6G P < 0.001 and M3G P < 0.01 for each comparison). Comparison of log-transformed AUC values after i.v. and s.c.i. morphine indicated that the two routes were not bioequivalent for morphine (log-transformed AUC ratio 0.78, 90% CI 0.66–0.93), M6G (0.72, 90% CI 0.63–0.82), or M3G (0.65, 90% CI 0.54–0.78). A small stability study indicated no evidence of adsorptive losses from morphine infused over 4 h using the infusion devices from the study. Conclusions Although bioequivalence was demonstrated between the s.c.b. and i.v. routes of morphine administration, the bioavailabilities of morphine, M6G and M3G after s.c.i. were significantly lower than after i.v. administration. However, despite this, the study demonstrates that the subcutaneous route is an effective method for the parenteral administration of morphine.

Stuart-harris, R; Joel, S P; McDonald, P; Currow, D; Slevin, M L



Stereoselective action of (+)-morphine over (-)-morphine in attenuating the (-)-morphine-produced antinociception via the naloxone-sensitive sigma receptor in the mouse  

PubMed Central

We have previously demonstrated that (+)-morphine and (?)-morphine given spinally stereoselectively attenuate the spinally-administered (?)-morphine-produced tail-flick inhibition in the mouse. The phenomenon has been defined as antianalgesia (Wu et al., 2005). Present studies were then undertaken to determine if the systemic administration of (+)-morphine and (?)-morphine also stereoselectively attenuates the systemic (?)-morphine-produced tail-flick inhibition and the effects of (+)-morphine and (?)-morphine are mediated by the naloxone-sensitive sigma receptor activation in male CD-1 mice. Pretreatment with (+)-morphine at a dose of 0.01–10 ng/kg given subcutaneously dose-dependently attenuated the tail-flick inhibition produced by subcutaneously-administered (?)-morphine (5 mg/kg). Pretreatment with (?)-morphine (0.01–1.0 mg/kg) given subcutaneously also attenuates the (?)-morphine-produced tail-flick inhibition. The ED50 values for (+)-morphine and (?)-morphine for inhibiting the (?)-morphine-produced tail-flick inhibition were estimated to be 30.6 pg/kg and 97.5 µg/kg, respectively. The attenuation of the (?)-morphine-produced tail-flick inhibition induced by (+)-morphine or (?)-morphine pretreatment was reversed by the pretreatment with (+)-naloxone or by the sigma receptor antagonist BD1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine dihydrobromide) given subcutaneously. Pretreatment with (+)-pentazocine, a selective sigma receptor agonist, (1–10 mg/kg) given subcutaneously also attenuates (?)-morphine-produced tail-flick inhibition, which was restored by (+)-naloxone (4 mg/kg) or BD1047 (10 mg/kg) pretreated subcutaneously. It is concluded that (+)-morphine exhibits extremely high stereoselective action over (?)-morphine given systemically in attenuating the systemic (?)-morphine-produced antinociception and the antianalgesic effect of (+)-morphine and (?)-morphine is mediated by activation of the naloxone-sensitive sigma receptor.

Wu, Hsiang-en; Hong, Jau-Shyong; Tseng, Leon F.



Safety and Effectiveness of Intravenous Morphine for Episodic Breakthrough Pain in Patients Receiving Transdermal Buprenorphine  

Microsoft Academic Search

Supplemental dosing of an opioid is the main treatment suggested to manage breakthrough pain in cancer patients. The intravenous route has been proven to be safe and effective, providing rapid analgesia in patients receiving oral morphine. Transdermal buprenorphine (TTS-BUP) is increasingly used in cancer pain management, but this drug has been labeled as a difficult drug to use in combination

Sebastiano Mercadante; Patrizia Villari; Patrizia Ferrera; Giampiero Porzio; Federica Aielli; Lucilla Verna; Alessandra Casuccio



Yokukansan inhibits morphine tolerance and physical dependence in mice: the role of ??A-adrenoceptor.  


Yokukansan (YKS) is a traditional Japanese medicine consisting of seven medicinal herbs that is used for the treatment of neurosis, insomnia, and the behavioral/psychological symptoms of dementia. This study examined the effects of YKS on morphine tolerance and physical dependence in mice. Daily oral administration of YKS (0.5 or 1.0 g/kg) for 3 weeks significantly attenuated morphine tolerance and naloxone-precipitated morphine withdrawal signs (jumps and body weight loss) without affecting the analgesic effect of morphine. The inhibitory effect of YKS on withdrawal jumps in morphine-dependent mice was blocked by a single pretreatment with an ?(2)-adrenoceptor antagonist, yohimbine, but not by an ?(1)-adrenoceptor antagonist, prazosin. A similar inhibitory effect on withdrawal jumps was observed by repeated administration of yohimbine. The membrane expression of ?(2A)-adrenoceptors in the pons/medulla was decreased in morphine withdrawn animals; this reduction was prevented by repeated administration of YKS or yohimbine. Competitive radioligand and [(35)S]guanosine-5'-O-(3-thiotriphosphate) binding assays revealed that YKS and its constituent herbs, Glycyrrhiza (GR) and Uncaria hook (UH), had specific binding affinity for and antagonist activity against the ?(2A)-adrenoceptor. Certain chemical constituents, including GR -derived glycyrrhizin and its metabolite, 18?-glycyrrhetinic acid, and UH-derived geissoschizine methyl ether (GME), shared such activities. Repeated administration of GR, UH, glycyrrhizin or GME significantly inhibited morphine withdrawal signs. These results suggest that YKS and its active constituents inhibit morphine tolerance and physical dependence, and that the latter is due at least in part to the prevention of the decreased membrane expression of the ?(2A)-adrenoceptor in the brainstem by its prolonged blockade. PMID:23069764

Nakagawa, T; Nagayasu, K; Nishitani, N; Shirakawa, H; Sekiguchi, K; Ikarashi, Y; Kase, Y; Kaneko, S




Microsoft Academic Search

Male Sprague–Dawley rats were injected daily with saline (morphine-naive rats) or 20 mg kg?1morphine (morphine-experienced rats), starting 15 days before the experiment. Subsequent taste conditioning indicated that 0.1 mg kg?1buprenorphine significantly decreased 0.025% saccharin consumption in morphine-naive, but not in morphine-experienced rats. A 10 mg kg?1dose of morphine gave similar results, whiled-amphetamine (0.75 mg kg?1) was consistently aversive. It was




Comparative bioavailability study of cefuroxime axetil (equivalent to 500 mg cefuroxime/tablet) tablets (Zednad® versus Zinnat®) in healthy male volunteers.  


This study was performed to investigate the bioequivalence of cefuroxime axetil tablets between a generic test product (A) Zednad® Tablet (500 mg cefuroxime/ tablet, Diamond Pharma, Syria), and the Reference Product (B) Zinnat® Tablet (500 mg cefuroxime/tablet, GlaxoSmithKline, Saudi Arabia). The bioavailability study was carried out for 24 healthy male volunteers. The subjects received 1 Zednad® Tablet (500 mg/ tablet) and 1 Zinnat® Tablet (500 mg/tablet) in a randomized, two-way crossover design fashion on 2 treatment days, after an overnight fast of at least 10 h, with a washout period of 7 days. 24 volunteers plus 2 alternatives completed the crossover. The bioanalysis of clinical plasma samples was accomplished by HPLC method, which was developed and validated in accordance with international guidelines. Pharmacokinetic parameters, determined by standard non-compartmental methods, and ANOVA statistics were calculated using SAS Statistical Software. The significance of a sequence effect was tested using the subjects nested in sequence as the error term. The 90% confidence intervals for the ratio between the test and reference product pharmacokinetic parameters of AUC0?t, AUC0??, and Cmax were calculated and found to be within the confidence limits of 80.00 - 125.00% for AUC0?t, AUC0?? and Cmax. The study demonstrated that the test product (A) was found bioequivalent to the reference product (B) following an oral dose of 500 mg tablet. Therefore, the two formulations were considered to be bioequivalent. PMID:21888870

Asiri, Y A; Al-Hadiya, B M; Kadi, A A; Al-Khamis, K I; Mowafy, H A; El-Sayed, Y M



Calcification Prevention Tablets.  

National Technical Information Service (NTIS)

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 i...

G. A. Lindsay M. A. Hasting M. A. Gustavson



In vitro and in vivo studies of a new sustained release formulation of morphine. Discrepancies between the in vitro release and the in vivo absorption in dogs.  


An in vivo preclinical study has been made of the oral absorption of morphine (CAS 57-27-2) from a new sustained release formulation (morphine-Eudragit L complex, MEC), which had shown good sustained release properties in in vitro dissolution studies. The absorption of morphine from capsules filled with morphine hydrochloride trihydrate (MHT) or MEC was compared in fasted and fed dogs. Mean plasma morphine concentrations obtained after administration of MHT and MEC to fasted dogs were similar, and no statistically significant differences were found in the pharmacokinetic parameters of morphine (Cmax, Tmax and area under the plasma morphine concentration versus time curve from time zero to the last time with a detectable concentration of morphine). When MHT and MEC were administered to fed animals, mean plasma morphine concentrations were again similar for both formulations, without statistically significant differences in the pharmacokinetic parameters of morphine. These results contrast with those obtained in vitro, and indicate the limited usefulness of in vitro assays for this kind of sustained release formulations in which pH and ionic strength are important factors for drug release from the polymeric structure. The plasma morphine concentrations obtained in fed dogs were generally lower than in fasted dogs, though they were detectable for a longer time, until 10 h after dosing, in contrast to up to 6 h in fasted dogs. It is postulated that the apparently prolonged absorption of morphine in fed dogs may be due to the enterohepatic recycling of the drug (excreted in bile as glucuronide, hydrolysed back to the parent compound in the intestine, and then reabsorbed) as a consequence of gallbladder emptying induced by food. PMID:19202736

Araícot, Amparo; Torres-Molina, Francisca; Saadeddin, Anas; Cárcel-Trullols, Jaime; Alvarez-Fuentes, Josefa; Holgado, Angeles; Fernández-Arévalo, Mercedes; Peris, José-Esteban



Acute and chronic morphine administration in swine.  


Functional responses to acute and chronic morphine administration in domestic swine were examined and correlated with pharmacokinetic profiles. Acute effects of morphine sulfate were monitored in pigs for 24 h and the chronic actions of morphine alkaloid were monitored for 21 days. Serum morphine levels, nociception, locomotor activity, respiratory rate, body temperature, and body weight were monitored during all studies. To assess nociception in a large laboratory animal, a portable thermal stimulating device was constructed. Morphine sulfate administered IV and SC had a half-life of approximately 1 h whereas delayed-release morphine alkaloid delivered SC had a half-life of 28 h. The degree of antinociception paralleled decline in blood morphine levels for both SC- and IV-administered animals. Tolerance occurred to both antinociception as well as weight gain despite morphine levels remaining constant over the 21-day period. Morphine dependence was demonstrated by precipitation of an abstinence syndrome using naloxone. Animals in withdrawal displayed consistent signs, including wet-dog shakes, posture changes, vocalization, and salivation. Collectively, these results indicate that swine may be reliably employed as a model to study the actions of morphine and opiate-like compounds. PMID:1448475

Risdahl, J M; Chao, C; Murtaugh, M P; Peterson, P K; Molitor, T W



Tablets containing drug-loaded polymeric nanocapsules: an innovative platform.  


The aim of the present work was to evaluate the feasibility to convert drug-loaded nanocapsule suspensions in a solid dosage form (tablets). Dexamethasone was used as a model drug due to its low aqueous solubility and fast drug release from conventional tablets. Granules containing dexamethasone-loaded nanocapsules were obtained by a wet granulation process using a dispersion of polyvinylpirrolidone/nanocapsules as a binder system. Granules were compressed in an eccentric compression machine (D-NC-T). A control formulation (tablets without nanocapsules) was also prepared (D-T). Tablets were characterized by means of mean weight, hardness, friability, diameter, thickness, disintegration time, drug content, morphological analysis by scanning electron microscopy (SEM), and in vitro drug release studies. D-NC-T showed adequate physicochemical characteristics according to the pharmacopeial requirements in terms of mean weight, hardness, friability, disintegration time and drug content. Intact nanocapsules in tablets were observed by SEM. In vitro drug release studies showed a slower release of dexamethasone from these tablets (D-NC-T) compared to the control formulation (D-T). Results showed that these tablets represent an interesting platform to the development of oral drug delivery systems containing polymeric nanocapsules. PMID:21133121

Friedrich, R B; Bastos, M O; Fontana, M C; Ourique, A F; Beck, R C R



21 CFR 520.2260c - Sulfamethazine sustained-release tablets.  

Code of Federal Regulations, 2013 CFR

...HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2260c Sulfamethazine...within 2 to 3 days, reevaluate therapy. Do not crush tablets. Treated animals must not be...



Plasma-Mediated Release of Morphine from Synthesized Prodrugs.  

National Technical Information Service (NTIS)

Two morphine prodrugs (PDA and PDB) were synthesized and the kinetics of esterase-mediated morphine release from these prodrugs were determined when incubated with plasma from different animal species. Morphine was rapidly released from PDA by all species...

A. Desai B. Huang H. Zong T. P. Thomas X. Cheng



21 CFR 862.3640 - Morphine test system.  

Code of Federal Regulations, 2010 CFR

...2009-04-01 2009-04-01 false Morphine test system. 862.3640 Section 862...Toxicology Test Systems § 862.3640 Morphine test system. (a) Identification. A morphine test system is a device intended to...



21 CFR 862.3640 - Morphine test system.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Morphine test system. 862.3640 Section 862...Toxicology Test Systems § 862.3640 Morphine test system. (a) Identification. A morphine test system is a device intended to...



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.

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



Pharmaceutical development of ondansetron tablets.  


Ondansetron tablets contain ondansetron base as the hydrochloride dihydrate, lactose, microcrystalline cellulose, starch and magnesium stearate. Tablets sampled at the beginning and end of the compression process have good content uniformity and drug content, showing that there is no segregation or loss of the drug substance during tabletting. The release of drug substance is related to the tablet disintegration time. Tablets with disintegration times of 3 and 10 min release 85% of the drug substance in approximately 6 and 20 min respectively. Satisfactory bioavailability has been demonstrated. The tablets have good stability, and have a shelf life of 2 years when stored below 30 degrees C. PMID:2533901

Leak, R E; Woodford, J D



Heroin-using drivers: importance of morphine and morphine-6-glucuronide on late clinical impairment  

Microsoft Academic Search

Objective  To evaluate the relationship between major heroin metabolites (morphine, morphine-6-glucoronide), pattern of drug use, and late impairment of psychomotor functions.Methods  From the database of the Norwegian Institute of Public Health, Oslo, blood morphine concentration in samples from heroin users (n=70) containing only morphine were correlated with results of the clinical test for impairment (CTI). For comparison, test results were explored in

Liliana Bachs; Gudrun Høiseth; Svetlana Skurtveit; Jørg Mørland



Concentration-ingestion relations of morphine-adulterated food and morphine solution  

Microsoft Academic Search

Four groups (n=16\\/group) of rats were given ad libitum access to morphine-adulterated food in one of four different concentrations (1, 2, 3, or 4 mg morphine HCl\\/g milled food). Half of the subjects in each group were given ad libitum water while the other half were provided with sucrose morphine (1 mg morphine HCl\\/ml 10% sucrose). Daily measures of body

Khalil A. Khavari; Marc E. Risner



Morphine modulates monocyte-macrophage conversion phase.  


Monocyte migration and their activation into the macrophage phenotype play a role in the modulation of tissue injury. We studied the effect of morphine on the monocyte-macrophage conversion phase (MMCP). Phorbol 12-myristate 13-acetate (PMA) activated THP-1 cells and promoted their adhesion to the substrate. Morphine inhibited PMA-induced MMCP. However, opiate receptor antagonists attenuated this effect of morphine. Interestingly, PMA as well as morphine-stimulated superoxide production by monocytes. Superoxide dismutase (SOD) not only inhibited PMA-mediated MMCP but also attenuated the inhibitory effect of morphine. PMA not only enhanced adhesion of monocytes to a filter but also promoted their migration. These findings suggest that the PMA-induced macrophage phenotype conversion may be accelerating their migration; whereas, morphine may be preventing the migration of monocytes by inhibiting MMCP. PMID:16698002

Hatsukari, Ikuske; Hitosugi, Naoko; Dinda, Amit; Singhal, Pravin C



(+)-Morphine and (-)-morphine stereoselectively attenuate the (-)-morphine-produced tail-flick inhibition via the naloxone-sensitive sigma receptor in the ventral periaqueductal gray of the rat  

PubMed Central

We have previously demonstrated that (+)-morphine and (?)-morphine pretreated spinally for 45 min stereoselectively attenuates the tail-flick inhibition produced by (?)-morphine given spinally in the mouse. The present study is then undertaken to determine if the same phenomenon observed in the mouse spinal cord can also take place in the ventral periaqueductal gray of the rat. Pretreatment with (+)-morphine for 45 min at 0.3 to 3.3 fmol dose-dependently attenuated the tail-flick inhibition produced by (?)-morphine (9 nmol) given into the ventral periaqueductal gray. Likewise, pretreatment with (?)-morphine for 45 min at a higher dose (3-900 pmol), which given alone did not affect the baseline tail-flick latency, also dose-dependently attenuated the tail-flick inhibition produced by (?)-morphine. Thus, (+)-morphine is approximately 270,000-fold more potent than (?)-morphine in attenuating the (?)-morphine-produced tail-flick inhibition. The attenuation of the (?)-morphine-produced tail-flick inhibition induced by (+)-morphine or (?)-morphine was dose-dependently reversed by (+)-naloxone (27.5 to 110 pmol) pretreatment for 50 min given into the ventral periaqueductal gray. Pretreatment with the sigma receptor antagonist BD1047 (N-[2-(3,4-Dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine dihydrobromide) (11-45 nmol) for 45 min given into the ventral periaqueductal gray also reversed dose-dependently the attenuation of the (?)-morphine-produced tail-flick inhibition induced by (+)-morphine or (?)-morphine, indicating that the effects are mediated by the activation of the sigma receptors. Since (+)-morphine, (?)-morphine and (+)-naloxone do not have any affinity for the naloxone-inaccessible sigma receptors, we therefore propose that (+)-morphine and (?)-morphine attenuate the (?)-morphine-produced tail-flick inhibition via the activation of the naloxone-sensitive sigma receptor originally proposed by Tsao and Su (1997).

Terashvili, Maia; Wu, Hsiang-en; Moore, Rachel M.; Harder, David R.; Tseng, Leon F.



Morphine, the Proteus of organic molecules.  


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



Evaluation of Water Sterilizing Tablets.  

National Technical Information Service (NTIS)

Water sterilizing tablets were evaluated for efficiency of kill of micro-organisms, effect of inhibitors and palatability. The effect of long term use is discussed. The water sterilizing tablet recommended for disinfection of personal drinking water, on t...

G. F. Thomson K. W. James G. E. Driver A. T. Hancock



Alinia (nitazoxanide) tablets and oral suspension  

Center for Drug Evaluation (CDER)

Text Version... failed to submit the sales aid to FDA ... caused by Cryptosporidium parvum in HIV-infected or ... acquired immune deficiency syndrome (AIDS) in Zambia ... More results from


NDA 22-406, rivaroxaben oral tablets  

Center for Biologics Evaluation and Research (CBER)

Text Version... I am unaware of any data that would support this hypothesis. At autopsy it was noted that there was little regeneration of the ... More results from


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 several...



21 CFR 520.2150a - Stanozolol 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 and cats. (2) Administered orally to cats and small breeds of dogs, 1/2 to 1 tablet twice...



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

PubMed Central

Objective: Some animal models apply morphine in the drinking water to generate addiction, but related reports are not free of conflicting results. Accordingly, this study aimed to figure out if chronic consumption of morphine in the drinking water can induce morphine addiction in Wistar rats. Methods: For 3 weeks, the animals received a daily morphine dose of 35 mg/kg by offering a calculated volume of sugar water (5% sucrose) with morphine (0.1 mg/ml) to each rat; animals receiving just sugar water served as controls. Immediately after the treatment phase, the tail immersion test was used to check for morphine tolerance, and all animals were then kept on tap water for one week (withdrawal phase). Afterwards, all rats were allowed to choose their drinking source by offering two bottles, containing sugar water without and with morphine, simultaneously for two days (preference phase). Results: While the chronic consumption of morphine led to a reduction in body weight and to morphine tolerance, the morphine-treated Wistar rats did not show any preference for the opiate-containing sugar water. Conclusion: Body weight loss and tolerance do not reveal a condition of drug craving, and current animal models should be re-evaluated regarding their potential to establish morphine addicted animals.

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



Differences in morphine-induced antinociception in male and female offspring born of morphine exposed mothers  

PubMed Central

Objective: Antinociceptive effect of morphine in offspring born of mothers that received saline or morphine during the gestation period was investigated. Materials and Methods: Wistar rats (200-250 g) received saline, morphine 0.5 mg/kg or 5 mg/kg during gestation days 14-16. All pups after weaning were isolated treatment/sex dependently and were allowed to fully mature. The antinociceptive effect of morphine was assessed in formalin test. Morphine (0.5-7.5 mg/kg) or saline (1 ml/kg) was injected intraperitoneally 10 min before formalin (50 ?l of 2.5% solution in right hind-paw). Results: Male offspring born of saline-treated mothers were less morphine-sensitive than females. On the contrary, male offspring exposed prenatally to morphine (5 mg/kg) were more sensitive to morphine-induced antinociceptive response in formalin test. However, no difference in antinociceptive effect was observed amongst offspring of either sex born of mothers treated with morphine 0.5 mg/kg, identifying a lower dose effect of the opioid. Conclusion: The exposure to morphine during the developmental period may result in altered development of tolerance to morphine and thus involved in drug abuse.

Biglarnia, Masoomeh; Karami, Manizheh; Hafshejani, Zahra Khodabakhshi



Possible effects of one week vitamin K (menaquinone-4) tablets intake on glucose tolerance in healthy young male volunteers with different descarboxy prothrombin levels  

Microsoft Academic Search

To clarify the roles of vitamin K (VK) in the pancreas, twice oral, glucose tolerance tests were examined in 12 healthy young male volunteers before and after 1 week of VK tablet intake. Blood were collected by venipucture at 0, 30 and 120 min after 75 g oral glucose loading. They then took VK tablets (90 mg\\/d of menaquinone-4) for




Continuous morphine infusion for end-stage lung cancer patients.  


End-stage cancer patients frequently receive continuous morphine infusion (CMI) to alleviate the various symptoms associated with cancer progression or adverse events; however, there have been a limited number of studies concerning such patients. We conducted a retrospective analysis of 79 end-stage lung cancer patients who received CMI at the Kyoto University Hospital, Kyoto, Japan between 2008 and 2010. Thirty-one patients (39%) received CMI intravenously and 48 (61%) received it subcutaneously. The patients were divided into four groups based on the indications for CMI: group A (uncontrolled pain; n=9), group B (dyspnea; n=44), group C (both dyspnea and pain; n=13) and group D (an inability to take oral medicine; n=13). The median maximum dose of morphine in groups A-D was 60.0, 25.0, 50.0 and 15.0 mg/day, respectively. The median survival time from the start of CMI was 4 days (range 0-136). In our limited experience, pain, dyspnea and the inability to take oral medicine were identified as indications for CMI in end-stage lung cancer patients, with dyspnea being the major indication for CMI. Patients in group B (dyspnea) required a lower dose of morphine for alleviation compared with those in groups A (uncontrolled pain) and C (both dyspnea and pain). The survival time from the initiation of CMI was markedly shorter in patients with dyspnea (groups B and C) than in patients without dyspnea (group A). Further studies are required to facilitate the effective and appropriate use of CMI in end-stage lung cancer patients. Dyspnea was the major indication for CMI in end-stage lung cancer patients, and the survival time was extensively limited in such patients. PMID:23426526

Kim, Young Hak; Okuda, Chiyuki; Sakamori, Yuichi; Masago, Katsuhiro; Togashi, Yosuke; Mishima, Michiaki



Obestatin prevents analgesic tolerance to morphine and reverses the effects of mild morphine withdrawal in mice.  


Obestatin is a 23-amino acid gut-derived neuropeptide, encoded by the same gene with ghrelin. The goal of this study was to examine the effects of obestatin on the acute and chronic analgesic actions of morphine and on mild morphine withdrawal. Open-field (OF) and elevated plus maze (EPM) tests were used to assess mild morphine withdrawal-induced behavior changes and the heat-radiant tail-flick assay was used to investigate analgesic actions of morphine. CFLP male mice were treated twice a day with graded doses of morphine in EPM and OF experiments and once a day in tail-flick studies. Obestatin (1.5?g/2?l) was administrated once a day in all experiments. Furthermore, 0.2mg/kg naloxone or saline was administered after the final injection of morphine at a dose of 20mg/kg in EPM and OF. These behavioral parameters were monitored in the OF: the percentage of center ambulation time and distance; whereas in the EPM: the time spent in open arms and the entries into open arms compared to the total time (%OAT) and entries (%OAE). In the OF, obestatin significantly decreased the percentage of time spent in the center in mice undergoing naloxone-precipitated mild morphine withdrawal. EPM results were similar to open field, but obestatin had no significant effect on parameters mentioned above. Besides, obestatin maintained the analgesic effect of morphine 90 and 120min after morphine injection in mice treated with morphine receiving obestatin compared to mice treated with morphine. In tolerance studies, obestatin diminished the analgesic tolerance to morphine on the 5th day. In this study we confirmed that obestatin reversed the effect of mild morphine withdrawal and enhances the analgesic effect of morphine. These data suggest that obestatin may have a role in opioid-induced analgesia and in behavioral responses induced by opioid withdrawal. PMID:23891980

Lipták, Nándor; Dochnal, Roberta; Csabafi, Krisztina; Szakács, Júlia; Szabó, Gyula



In vivo bioavailability studies of sumatriptan succinate buccal tablets  

PubMed Central

Back ground and the purpose of study Sumatriptan succinate is a Serotonin 5- HT1 receptor agonist, used in treatment of migraine. It is absorbed rapidly but incompletely when given orally and undergoes first-pass metabolism, resulting in a low absolute bioavailability of about 15%. The aim of this work was to design mucoadhesive bilayered buccal tablets of sumatriptan succinate to improve its bioavailability. Methods Mucoadhesive polymers carbopol 934 (Carbopol), HPMC K4M, HPMC K15M along with ethyl cellulose as an impermeable backing layer were used for the preparation of mucoadhesive bilayered tablets. In vivo bioavailability studies was also conducted in rabbits for optimized formulation using oral solution of sumatriptan succinate as standard. Results Bilayered buccal tablets (BBT) containing the mixture of Carbopol and HPMC K4M in the ratio 1:1 (T1) had the maximum percentage of in vitro drug release within 6 hrs. The optimized formulation (T1) followed non-Fickian release mechanism. The percentage relative bioavailability of sumatriptan succinate from selected bilayered buccal tablets (T1) was found to be 140.78%. Conclusions Bilayered buccal tablets of sumatriptan succinate was successfully prepared with improved bioavailability.

Shivanand, K; Raju, SA; Nizamuddin, S; Jayakar, B



Preparation, characterization and tableting of cilnidipine solid dispersions.  


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



Morphine versus remifentanil for intubating preterm neonates  

PubMed Central

A double?blind, randomised controlled study was conducted to evaluate the intubation conditions in 20 preterm neonates following the use of either morphine or remifentanil as premedication. The findings suggest that the overall intubation conditions were significantly better (p?=?0.0034) in the remifentanil group than in the morphine group. No severe complications were observed in either group.

e Silva, Yerkes Pereira; Gomez, Renato Santiago; de Oliveira Marcatto, Juliana; Maximo, Thadeu Alves; Barbosa, Rosilu Ferreira



Morphine induces delayed anorexia in rats  

Microsoft Academic Search

The delayed suppression of feeding caused by morphine was investigated in the rat. A single injection of morphine evoked a triphasic influence on feeding: a brief (1 h) severe anorexia was followed by hyperphagia (3 h) and a mild (20%) yet persistent (4–24h) anorexia. This latter anorexic effect was at least partially naltrexone reversible, and the duration of this antagonism

Micah Leshem



Synthetic substances with morphine-like effect  

PubMed Central

For compounds of the morphine, morphinan, pethidine, hexamethyleneimine, methadone, and dithienylbutenylamine groups, the analgesic and physical-dependence-producing properties are compared. On the basis of a parellelism in intensity of these properties, conclusions are drawn regarding their interrelationship and the chemical features common to substances with morphine-like addiction liability.

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



In vitro antioxidant properties of morphine  

Microsoft Academic Search

Morphine is implicated in diverse functions, from development to immune modulation in the central and peripheral nervous systems. It has also been used extensively in the clinical management of pain due to its potent analgesic effect. This study was designed to evaluate the in vitro antioxidant capacity of morphine using different antioxidant tests, including total antioxidant activity, reducing power, free

?lhami Gülç?n; ?ükrü Beydem?r; H. Ahmet Alici; Mahfuz Elmasta?; M. Emin Büyükokuro?lu



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



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…

Rapp, David



The Nebusarsekim Tablet  

Microsoft Academic Search

During the summer of 2007 an internet hype was unleashed by the breaking news that an Old Testament name of some importance, figuring in the Book of Jeremiah Ch. 39, had been positively identified on a cuneiform clay tablet, viz. a bill of receipt from the time of this prophet's floruit. Many a scholar of sorts was quick to claim

H. A. I. Stadhouders



Endogenous formation of morphine in human cells  

PubMed Central

Morphine is a plant (opium poppy)-derived alkaloid and one of the strongest known analgesic compounds. Studies from several laboratories have suggested that animal and human tissue or fluids contain trace amounts of morphine. Its origin in mammals has been believed to be of dietary origin. Here, we address the question of whether morphine is of endogenous origin or derived from exogenous sources. Benzylisoquinoline alkaloids present in human neuroblastoma cells (SH-SY5Y) and human pancreas carcinoma cells (DAN-G) were identified by GC/tandem MS (MS/MS) as norlaudanosoline (DAN-G), reticuline (DAN-G and SH-SY5Y), and morphine (10 nM, SH-SY5Y). The stereochemistry of reticuline was determined to be 1-(S). Growth of the SH-SY5Y cell line in the presence of 18O2 led to the [18O]-labeled morphine that had the molecular weight 4 mass units higher than if grown in 16O2, indicating the presence of two atoms of 18O per molecule of morphine. Growth of DAN-G cells in an 18O2 atmosphere yielded norlaudanosoline and (S)-reticuline, both labeled at only two of the four oxygen atoms. This result clearly demonstrates that all three alkaloids are of biosynthetic origin and suggests that norlaudanosoline and (S)-reticuline are endogenous precursors of morphine. Feeding of [ring-13C6]-tyramine, [1-13C, N-13CH3]-(S)-reticuline and [N-CD3]-thebaine to the neuroblastoma cells led each to the position-specific labeling of morphine, as established by GC/MS/MS. Without doubt, human cells can produce the alkaloid morphine. The studies presented here serve as a platform for the exploration of the function of “endogenous morphine” in the neurosciences and immunosciences.

Poeaknapo, Chotima; Schmidt, Jurgen; Brandsch, Matthias; Drager, Birgit; Zenk, Meinhart H.



A randomised trial of glucose tablets to aid smoking cessation  

Microsoft Academic Search

Rationale  Oral glucose has been found to decrease tobacco craving among abstaining smokers. One study has demonstrated an effect of\\u000a glucose on short-term abstinence. There is a need to examine any long-term benefit of glucose on abstinence.\\u000a \\u000a \\u000a \\u000a Objectives  To assess whether glucose tablets improve 6-month continuous abstinence rates compared with low-calorie placebo tablets.\\u000a \\u000a \\u000a \\u000a Methods  Smokers attempting to stop (n?=?928) were randomised to receive

Robert West; Sylvia May; Andy McEwen; Hayden McRobbie; Peter Hajek; Eleni Vangeli



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.

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



Routine determination of morphine, morphine 3-?- d-glucuronide and morphine 6-?- d-glucuronide in human serum by liquid chromatography coupled to electrospray mass spectrometry  

Microsoft Academic Search

A robust liquid chromatographic mass spectrometric method capable of quantifying morphine, morphine 3-?-d-glucuronide and morphine 6-?-d-glucuronide down to 1.0 ng\\/ml, 5.0 ng\\/ml and 2.0 ng\\/ml respectively in human serum is presented. The method was validated over linear ranges of 1.0 to 20.0 ng\\/ml for morphine, 5.0 to 500.0 ng\\/ml for morphine 3-?-d-glucuronide and 2.0 to 100.0 ng\\/ml for morphine 6-?-d-glucuronide

M Blanchet; G Bru; M Guerret; M Bromet-Petit; N Bromet



Transmucosal fentanyl vs intravenous morphine in doses proportional to basal opioid regimen for episodic-breakthrough pain  

Microsoft Academic Search

The use of supplemental doses of opioids is commonly suggested to manage breakthrough pain. A comparative study of intravenous morphine (IV-MO) and oral transmucosal fentanyl citrate (OTFC) given in doses proportional to the basal opioid regimen was performed in 25 cancer patients receiving stable opioid doses. For each episode, when it occurred and 15 and 30 min after the treatment,

S Mercadante; P Villari; P Ferrera; A Casuccio; S Mangione; G Intravaia



Pilot Study of Nasal Morphine-Chitosan for the Relief of Breakthrough Pain in Patients With Cancer  

Microsoft Academic Search

Breakthrough pain in patients with cancer is common, often unpredictable, and can rapidly become severe. Treatment using the oral administration of opioids is not optimal due to the slow onset of pain relief. Nasal administration of analgesics potentially offers more rapid pain relief. This study investigates the tolerability and efficacy of a novel morphine-chitosan formulation. Twenty episodes of breakthrough pain

Hilary Pavis; Andrew Wilcock; Jane Edgecombe; Diane Carr; Cathann Manderson; Ann Church; Anthony Fisher



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.



Desmopressin melt improves response and compliance compared with tablet in treatment of primary monosymptomatic nocturnal enuresis.  


Primary nocturnal enuresis is a prevalent childhood condition that can persist into adulthood. Desmopressin is an antidiuretic available as orally disintegrating lyophilisate (melt) or solid tablet. Recent findings suggesting different food interactions and clinical characteristics, including compliance, between desmopressin melt and tablet motivated a post hoc analysis of a previously reported randomised, crossover study. The efficacy of desmopressin melt compared with tablet was evaluated using the International Children's Continence Society (ICCS) responder definitions. Compliance was further analysed using detailed criteria, and the association between efficacy and compliance was examined. In total, 221 patients aged 5-15 years, already receiving desmopressin tablets were randomised to the treatment sequence melt (120/240 ?g)/tablet (0.2/0.4 mg) or tablet/melt in two consecutive 3-week periods. The probability of being a responder (partial or full) during either period was significantly more likely with desmopressin melt compared with tablet (odds ratio, 2.0; confidence intervals, 1.07-3.73; p?=?0.03). There was no period effect on compliance in the tablet/melt sequence and no difference in the number of completely compliant patients in each formulation group; however, more patients were >75 % compliant in period 1 compared with period 2 in the melt/tablet sequence. Increased compliance was associated with greater reductions in the number of wet nights for both formulations. Conclusions: Desmopressin melt, compared with tablet, improves the probability of being a responder. Switching from tablet to melt formulation increased patient compliance. Increased compliance was associated with increased efficacy. Switching to desmopressin melt may benefit patients with suboptimal responses to desmopressin tablet. PMID:23677249

Juul, Kristian Vinter; Van Herzeele, Charlotte; De Bruyne, Pauline; Goble, Sandra; Walle, Johan Vande; Nørgaard, Jens Peter



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.

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



Buccal absorption of ergotamine tartrate using the bioadhesive tablet system in guinea-pigs  

Microsoft Academic Search

The buccal administration of ergotamine tartrate (ET) combined with polyvinyl alcohol (PVA) gel brought about higher plasma concentration of ET compared with that of oral administration of capsules in guinea-pigs. Tm^^ of ET in plasma of buccal administration was significantly smaller than that of oral administration. For the buccal dosage form of ET, the bioadhesive tablet system (BTS) was newly

Keiko TSutsumi; Yasuko Obata; Tsuneji Nagai; Thorsteinn LOftsson; KOZO Takayama



Orexin mediates morphine place preference, but not morphine-induced hyperactivity or sensitization.  


Orexin (or hypocretin) has been implicated in mediating drug addiction and reward. Here, we investigated orexin's contribution to morphine-induced behavioral sensitization and place preference. Orexin-/- (OKO) mice and littermate wild-type (WT) controls (n=56) and C57BL/6J mice (n=67) were tested for chronic morphine-induced locomotor sensitization or for conditioned place preference (CPP) for a morphine- or a cocaine-paired environment. C57BL/6J mice received the orexin receptor 1 (Ox1r) antagonist, SB-334867, prior to test sessions. OKO mice did not significantly differ from WT controls in locomotor activity following acute- or chronic-morphine treatments. Similarly, mice treated with the Ox1r antagonist did not differ from vehicle controls in locomotor activity following acute- or chronic-morphine treatments. In contrast, while OKO mice did not differ from WT controls in preference for a morphine-paired environment, the Ox1r antagonist significantly attenuated place preference for a morphine-, but not a cocaine-paired, environment. These data suggest that orexin action is not required for locomotor responses to acute and chronic morphine, but Ox1r signaling can influence morphine-seeking in WT animals. PMID:20034477

Sharf, Ruth; Guarnieri, Douglas J; Taylor, Jane R; DiLeone, Ralph J



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



Pharmaceutical development of tablets of a new antineoplastic drug: mitonafide.  


The pharmaceutical development of tablets of a 1,8 naphtalimide with antineoplastic activity is carried out in two steps. The preformulation step includes the study of those characteristics of the drug with special importance for the successful development of the formulation step. In this way, the low moisture, the low porosity and the good flowability of the drug as raw material allow direct compression to be taken into account, together with wet granulation as methods of tablet manufacture. As a result of the formulation studies, one formulation of tablets obtained by direct compression and another one obtained by wet granulation are selected. Both of them meet all the requirements imposed to a solid pharmaceutical form for oral administration. PMID:7809172

Torres Suárez, A I; Gil Alegre, M E; Camacho Sánchez, M A



Fentanyl buccal tablet.  


Studies of populations with chronic cancer pain have shown a high prevalence of breakthrough pain (BTP), defined as transitory, severe flares of pain that occur on a background of otherwise controlled, persistent pain. High BTP prevalence rates have also been reported in patients with chronic noncancer pain, although data in these patient populations are more limited. The incidence of BTP appears to be associated with progression of chronic disease, with more than 80% of patients reporting BTP with far-advanced, end-stage cancer and noncancer terminal conditions (1). The most widely accepted therapeutic approach for the management of BTP involves use of short-acting opioids taken as needed in addition to the around-the-clock opioid regimen being used for the continuous component of the persistent pain syndrome. For some patients, an optimal treatment outcome for BTP may be unattainable because of a mismatch between the time course of the BTP episode and the onset of analgesia of short-acting opioids. Breakthrough pain typically reaches peak intensity within a few minutes, whereas the onset of analgesia with traditional, orally administered short-acting opioids is between 30 and 60 minutes (2-7). Consequently, treatment outcomes for BTP are likely to be improved with agents that have a more rapid onset of analgesia. Fentanyl buccal tablet (FBT) is a new formulation of fentanyl indicated for the management of BTP in patients with cancer who are already receiving, and who are tolerant to, opioid therapy for their underlying persistent cancer pain. The FBT formulation uses OraVescent (Cephalon, Inc., Frazer, PA, USA) drug delivery technology to provide rapid absorption of fentanyl through the buccal mucosa. In pharmacokinetic studies in healthy volunteers, FBT demonstrated high, early systemic absorption. In addition, FBT delivered a larger proportion of the fentanyl dose transmucosally and produced a greater early systemic exposure than oral transmucosal fentanyl citrate (OTFC), which is also indicated for the management of BTP in opioid-tolerant cancer patients. A number of short-term studies have evaluated the efficacy, safety and tolerability of FBT in the management of BTP in opioid-tolerant patients with chronic pain. All these studies included an open-label dose-titration phase prior to randomized, placebo-controlled, double-blind treatment. Pain Intensity of a BTP episode was measured using an 11-point scale (0 = no pain, 10 = worst pain), and the primary outcome measure was the Summed Pain Intensity Difference (SPID) at a specified time point. Secondary efficacy measures included Pain Relief, Pain Intensity Differences, and the proportion of BTP episodes demonstrating >or=33% and >or=50% improvement in Pain Intensity scores at each time point postdose, and the proportion of BTP episodes requiring supplemental medication. In a pivotal study of opioid-tolerant patients with cancer-related chronic pain and BTP, the primary outcome measure, SPID at 30 minutes (SPID(30)), significantly favored FBT compared with placebo (mean +/- SE: 3.0 +/- 0.12 vs. 1.8 +/- 0.18, p<0.0001). Better efficacy was also observed with FBT compared with placebo for pain relief, Pain Intensity Differences, and the proportion of episodes showing >or=33% and >or=50% improvement in Pain Intensity Scores. Treatment with FBT was generally well tolerated. Most adverse events were mild to moderate in severity and typical of those associated with opioid use (e.g., nausea, dizziness) (8). Similar results have been observed in studies of opioid-tolerant patients with BTP in association with noncancer-related chronic pain. In a study of patients with chronic low back pain, the primary outcome measure, SPID(60), significantly favored FBT over placebo (mean +/- SE: 8.3 +/- 0.66 vs. 3.6 +/- 0.57, p <0.0001). All secondary efficacy measures were similarly improved, with Pain Intensity Differences and Pain Relief scores showing significant differences versus placebo as early as 10 and 15 minutes, respectively. As in the study of cancer patient

Messina, John; Darwish, Mona; Fine, Perry G



Oral calcitonin.  


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



Pharmacokinetics of acetaminophen, codeine, and the codeine metabolites morphine and codeine-6-glucuronide in healthy Greyhound dogs  

PubMed Central

The purpose of this study was to determine the pharmacokinetics of codeine and the active metabolites morphine and codeine-6-glucuronide after IV codeine administration and the pharmacokinetics of acetaminophen (APAP), codeine, morphine, and codeine-6-glucuronide after oral administration of combination product containing acetaminophen and codeine to dogs. Six healthy Greyhound dogs were administered 0.734 mg/kg codeine IV and acetaminophen (10.46 mg/kg mean dose) with codeine (1.43 mg/kg mean dose) orally. Blood samples were obtained at predetermined time points for the determination of codeine, morphine, and codeine-6-glucuronide plasma concentrations by LC/MS and acetaminophen by HPLC with UV detection. Codeine was rapidly eliminated after IV administration (T½ =1.22 hr; clearance=29.94 mL/min/kg; volume of distribution=3.17 L/kg) with negligible amounts of morphine present, but large amounts of codeine-6-glucuronide (CMAX=735.75 ng/mL) were detected. The oral bioavailability of codeine was 4%, morphine concentrations were negligible, but large amounts of codeine-6-glucuronide (CMAX=1952.86 ng/mL) were detected suggesting substantial first pass metabolism. Acetaminophen was rapidly absorbed (CMAX=6.74 ?g/mL; TMAX=0.85 hr) and eliminated (T½=0.96 hr). In conclusion, the pharmacokinetics of codeine were similar to other opioids in dogs with a short half-life, rapid clearance, large volume of distribution, and poor oral bioavailability. High concentrations of codeine-6-glucuronide were detected after IV and oral administration.

KuKanich, Butch



Histopathological and biochemical changes of morphine sulphate administration on the cerebellum of albino rats.  


In this study the long-term effects of morphine sulphate treatment (MST) on histopathological and biochemical changes in the cerebellum was assessed in albino rats. Normal saline (5ml) was given orally as placebo in the control group (n=25). Morphine groups received morphine orally at a dose level of 5mg/kg body weight day after day for 10, 20 and 30 days (n=25/group). Light microscopy revealed that the molecular layer showed vacuolation. The Purkinje cells lost their specific shaped appearance, decreased in size and numbers. The granular cells highly degenerated. Electron microscopy revealed fragmentation of the cisterns of the both types of endoplasmic reticulum, resulted in a progressive depletion of total protein contents as well as general carbohydrates in all treated groups as supported by histochemical observation. Obvious destruction of mitochondrial inner membrane and cristae mediate cell death. Also, abnormal nucleus with deformed perforated nuclear membrane and deformation of the plasma membrane with degeneration of the synapses could interpreted as a sign of necrosis. Biochemical analysis revealed that dopamine (DA) and norepinephrine (NE) were significantly decreased in four brain areas (cortex striatum, thalamus/hypothalamus, and cerebellum). In contrast, serotonin (5-HT) level was increased in these brain regions; with an exception of 5-HT on day 10 and neurotransmitter levels in the pons were unaffected. The quantitative analysis showed a significant decrease (P<0.05) in the diameter of Purkinje cells and in the thickness of both molecular and granular layers treated groups. Morphine sulphate induces may be a cell death or necrosis in the rat cerebellum and modulating neurotransmitter system. Our findings pointed out the risk of increased cerebellum damage due to long-term of morphine use. PMID:20434749

Bekheet, S H; Saker, S A; Abdel-Kader, A M; Younis, A E A



In vitro-in vivo correlation for wet-milled tablet of poorly water-soluble cilostazol.  


The purpose of the present study was to investigate oral bioavailability of an immediate release tablet containing wet-milled crystals of a poorly water-soluble drug, cilostazol, and to establish in vitro-in vivo correlation. Sub-micron sized cilostazol (median diameter: 0.26 microm) was successfully prepared using a beads-mill in water in the presence of a hydrophilic polymer and an anionic surfactant. The milled suspension was solidified with a sugar alcohol as a water-soluble carrier by spray-drying method. The co-precipitate was compressed into an immediate release tablet with common excipients. Oral bioavailability of the wet-milled cilostazol tablet in male beagle dogs was 13-fold higher than the hammer-milled commercial tablet in fasted condition. Food did not increase the oral bioavailability of the wet-milled tablet, while 4-fold increase was found for the commercial tablet. Irrespective to the bioavailability enhancement, in vitro dissolution rate of the wet-milled tablet was even slower than the commercial tablet by the compendial method (USP Apparatus 2). On the other hand, a good correlation was found between the dissolution profiles obtained by a flow-through cell method (USP Apparatus 4, closed-loop system without outlet filter) using a large volume of water and sodium lauryl sulfate (SLS) solution at the concentration lower than the critical micellar concentration (cmc) as dissolution media corresponding to the fasted and fed conditions, respectively. PMID:18582979

Jinno, Jun-ichi; Kamada, Naoki; Miyake, Masateru; Yamada, Keigo; Mukai, Tadashi; Odomi, Masaaki; Toguchi, Hajime; Liversidge, Gary G; Higaki, Kazutaka; Kimura, Toshikiro



Preparation and evaluation of buccal bioadhesive tablets containing clotrimazole.  


Buccal bioadhesive tablets of clotrimazole (CTZ) and clotrimazole: hydroxypropyl-beta-cyclodextrin (CTZ-HPbetaCD) complex were prepared by using polymer xanthan gum in combination with carbopol 974P. The prepared buccal bioadhesive tablet formulations were evaluated for physicochemical characteristics (weight, hardness, friability, diameter, and drug content), swelling index, microenvironment pH, in-vitro drug release, bioadhesion strength, residence time and duration of antifungal activity (in-vitro). The dissolution of CTZ from the prepared tablets into phosphate buffer (pH 6.8) was controlled up to 8 h. All the prepared tablets gave reasonable in-vitro residence time (7.13 - 9.34 h). X-ray diffraction (XRD) studies of the CTZ-HPbetaCD complex, made by kneading and freeze-dried method, showed no CTZ crystal signals, demonstrating the inclusion of CTZ in the hydrophobic cavity of hydroxypropyl-beta-cyclodextrin (HPbetaCD) and formation of amorphous inclusion complex. Duration of the antifungal activity was measured by the inhibition zone of Candida albicans by agar diffusion assay. It is evident from the results obtained, the prepared buccal bioadhesive tablets of CTZ would markedly prolong the duration of the antifungal activity and may prove to be a viable alternative to the conventional local oral medication. PMID:18393816

Singh, S; Jain, S; Muthu, M S; Tilak, R



Formulation and evaluation of effervescent floating tablets of tizanidine hydrochloride.  


Tizanidine hydrochloride is an orally administered prokinetic agent that facilitates or restores motility through-out the length of the gastrointestinal tract. The objective of the present investigation was to develop effervescent floating matrix tablets of tizanidine hydrochloride for prolongation of gastric residence time in order to overcome its low bioavailability (34-40 %) and short biological half life (4.2 h). Tablets were prepared by the direct compression method, using different viscosity grades of hydroxypropyl methylcellulose (HPMC K4M, K15M and K100M). Tablets were evaluated for various physical parameters and floating properties. Further, tablets were studied for in vitro drug release characteristics in 12 hours. Drug release from effervescent floating matrix tablets was sustained over 12 h with buoyant properties. DSC study revealed that there is no drug excipient interaction. Based on the release kinetics, all formulations best fitted the Higuchi, first-order model and non-Fickian as the mechanism of drug release. Optimized formulation (F9) was selected based on the similarity factor (f2) (74.2), dissolution efficiency at 2, 6 and 8 h, and t50 (5.4 h) and was used in radiographic studies by incorporating BaSO4. In vivo X-ray studies in human volunteers showed that the mean gastric residence time was 6.2 ± 0.2 h. PMID:21684848

Someshwar, Komuravelly; Chithaluru, Kalyani; Ramarao, Tadikonda; Kumar, K K Kalyan



Effects of intraplantar morphine in the mouse formalin test.  


We studied the effects of intraplantar morphine in the formalin test in mice. Intraplantarly administered morphine (30 - 300 microg) induced analgesic effects at lower doses than intraperitoneally administered morphine. Following the administration of [3H]morphine, the % of radioactivity present in brain was the same by either route. In contrast, higher radioactivity values appeared in the injected paw in those mice intraplantarly injected. Since local morphine induces analgesia at doses lower than the intraperitoneally administered drug, especially in the second phase of the test, and the access to brain is undistinguishable, we propose that local morphine enhances central opiate analgesia in the formalin test in mice. PMID:10928329

Baamonde, A; Alvarez-Vega, M; Hidalgo, A; Menéndez, L



[Progress on study of clinical application of xinhuang tablet on orthopedic diseases].  


By retrieval of medical periodicals published in the recent 23 years, 155 papers concerning Xinhuang Tablet were searched, among them 28 were dealing with its clinical application in orthopedics disease, involving gouty arthritis, soft tissue injury, osteoarthritis, ankylosing spondylosis, rheumatoid arthritis, etc. Besides the traditional oral administration mode, Xinhuang Tablet may be used externally for local absorption through transcutaneous manner by mixing with some adjuvant as honey, vinegar, wine, and egg white. PMID:18822923

Chen, Shao-dong



Relationship between morphine analgesia and cortical extracellular fluid levels of morphine and its metabolites in the rat: a microdialysis study.  

PubMed Central

1. The effect of morphine (10 mg kg-1, s.c.) on the analgesic response measured by the tail-flick method was determined in male Sprague-Dawley rats. The analgesic response to morphine was correlated with the levels of morphine and its metabolites collected by microdialysis from the cortical extracellular fluid (ECF). 2. The analgesic response to morphine lasted for 4 h. The concentration of morphine during a 4 h collection period was significantly higher than the metabolites concentration. The relative concentration of morphine and its metabolites during the 4 h period was 70 and 30% respectively. 3. The analgesic response during the first 2.25 h period accounted for more than 82% of the total analgesia as determined by the area under the time-response curve (AUC). The concentration of morphine and its metabolites during the same period were 78 and 22%, respectively, but they did not differ during the 2.25-4.0 h period (52 and 48%). 4. The half-life for morphine and its metabolites were similar, the maximal achievable concentration Cmax and AUC0-4 h were lower for metabolites but the time to reach maximum concentration was higher for morphine metabolites than for morphine. The ratio of the concentration of metabolites to the concentration of morphine in the cortical ECF increased with time whereas the analgesic response to morphine decreased with time. 5. At several time points following morphine injection even though the levels of morphine were the same, the concentration of metabolites (mainly M3G) differed and thus the ratio [metabolite/morphine]. A plot of [metabolite]/[morphine] vs. analgesia gave a high correlation coefficient. Since M3G has been shown to be antianalgesic and is the only metabolite of morphine in the rat, it is concluded that the levels of this metabolite may regulate the analgesic effect of morphine in the rat.

Barjavel, M. J.; Scherrmann, J. M.; Bhargava, H. N.



Inhibition of the development of morphine tolerance by a potent dual mu-delta-opioid antagonist, H-Dmt-Tic-Lys-NH-CH2-Ph.  


Three analogues of the dual mu-/delta-antagonist, H-Dmt-Tic-R-NH-CH2-Ph (R = 1, Lys-Z; 2, Lys-Ac; 3, Lys) were examined in vivo: 1 and 2 exhibited weak bioactivity, while 3 injected intracerebroventricularly was a potent dual antagonist for morphine- and deltorphin C-induced antinociception comparable to naltrindole (delta-antagonist), but 93% as effective as naloxone (nonspecific opioid receptor antagonist) and 4% as active as CTOP, a mu antagonist. Subcutaneous or oral administration of 3 antagonized morphine-induced antinociception indicating passage across epithelial and blood-brain barriers. Mice pretreated with 3 before morphine did not develop morphine tolerance indicative of a potential clinical role to inhibit development of drug tolerance. PMID:18571706

Jinsmaa, Yunden; Marczak, Ewa D; Balboni, Gianfranco; Salvadori, Severo; Lazarus, Lawrence H



Inhibition of the Development of Morphine Tolerance by a Potent Dual ?-/?-Opioid Antagonist, H-Dmt-Tic-Lys-NH-CH2-Ph  

PubMed Central

Three analogues of the dual ?-/?-antagonist, H-Dmt-Tic-R-NH-CH2-Ph (R = 1, Lys-Z; 2, Lys-Ac; 3, Lys) were examined in vivo: 1 and 2 exhibited weak bioactivity, while 3 injected intracerebroventricularly was a potent dual antagonist for morphine- and deltorphin C-induced antinociception comparable to naltrindole (?-antagonist), but 93% as effective as naloxone (nonspecific opioid receptor antagonist) and 4% as active as CTOP, a ? antagonist. Subcutaneous or oral administration of 3 antagonized morphine-induced antinociception indicating passage across epithelial and blood-brain barriers. Mice pretreated with 3 before morphine did not develop morphine tolerance indicative of a potential clinical role to inhibit development of drug tolerance.

Jinsmaa, Yunden; Marczak, Ewa D.; Balboni, Gianfranco; Salvadori, Severo; Lazarus, Lawrence H.



Evaluation of binders in the preparation of medicinal carbon tablets by wet granule compression.  


Medicinal carbon (MC) tablets were prepared to obtain an oral dosage form that can be easily taken. The MC tablets were made by the wet granule compression method, in which hydroxypropyl cellulose (HPC), carboxymethyl cellulose sodium (CMC-Na) and maltitol (MT) were applied as binders. Brilliant Blue FCF (BB) was used as a model drug. The binders were evaluated in terms of formability of the granules and tablets, their strength, disintegration of the tablets, and their effect on the adsorption potential of MC. HPC and CMC-Na gave the strong granules at a fairly low concentration, but more MT was needed to obtain the strong granules. The tablets could be formed only when using MT at 120% (w/w) of the MC amount. The tablet displayed good hardness and rapid disintegration. The adsorption potential was not affected by CMC-Na, and slightly prevented by MT. However, the adsorption ability of MC was lowered more with the increase in HPC. The granules and tablets exhibited similar adsorption potentials, which were a little lower than that of MC suspended in MT aqueous solution. Similar adsorption characteristics were also observed in a real drug, acetaminophen. It is suggested that the MC tablets prepared by the wet granule compression using MT as a binder should be useful as a compact dosage form of MC. PMID:16596024

Ito, Akihiko; Onishi, Hiraku; Yamamoto, Kenta; Machida, Yoshiharu



Pharmacokinetics study of bio-adhesive tablet of Panax notoginseng saponins  

PubMed Central

Panax notoginseng saponin (PNS) is the main active gradient of Chinese traditional medicine Panax notoginseng. Although its prominent therapeutic efficacy has been demonstrated by various researchers, the broader application is restricted by the low bioavailability of PNS. This article aims to discuss PNS's plasma pharmacokinetics after oral administration of bio-adhesive tablet of PNS to beagle dogs and improve its bioavailability in comparison with normal tablet. The bio-adhesive tablet was prepared according to our previous patent, using chitosan as main excipient. A simple and sensitive LC-MS/MS combined with solid-phase extraction (SPE) method for the analysis of PNS in dog's plasma was developed in our previous study, and was validated to apply in the pharmacokinetics study in this work. Three ingredients: Notoginsenoside R1 (R1), Ginsenoside Rg1 (Rg1) and Ginsenoside Rb1 (Rb1) (Figure 1), were chosen as indicators of PNS to analyze it in vivo. Statistically significant increase (P < 0.05) in pharmacokinetic parameters of PNS including AUC and Tmax for R1, Rg1 and Rb1, Cmax for R1 and Rb1, MRT for Rg1 were obtained after oral administration of bio-adhesive tablet of PNS comparing with its normal tablet. The formulation modification of using chitosan to prepare bio-adhesive tablet for oral administration is effective in improving the bioavailability of PNS, thereby enhancing its potential therapeutic effect and broadening its clinical application.



Unwrapping and Visualizing Cuneiform Tablets  

Microsoft Academic Search

Thousands of historically revealing cuneiform clay tablets, which were inscribed in Mesopotamia millenia ago, still exist today. Visualizing cuneiform writing is important when deciphering what is written on the tab- lets. It is also important when reproducing the tablets in papers and books. Unfortunately, scholars have found photographs to be an inadequate visualization tool, for two reasons. First, the text

Sean Eron Anderson; Marc Levoy



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



dextro-Morphine attenuates the morphine-produced conditioned place preference via the sigma1 receptor activation in the rat  

PubMed Central

An unbiased conditioned place preference paradigm was used to evaluate the effect of dextro-morphine on the morphine-produced reward in male CD rats. Morphine sulfate (1-10 mg/kg) given intraperitoneally dose-dependently produced the conditioned place preference. Pretreatment with dextro-morphine at a dose from 0.1 to 3 ?g/kg given subcutaneously dose-dependently attenuated the morphine-produced conditioned place preference. However, dextro-morphine at a higher dose 100 ?g/kg did not affect the morphine-produced conditioned place preference. Thus, dextro-morphine pretreatment induces an U-shaped dose-response curve for attenuating the morphine-produced conditioned place preference. The attenuation of the morphine-produced conditioned place preference was reversed by the pretreatment with the sigma1 receptor antagonist BD1047 (N-[2-(3,4-Dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine dihydrobromide. dextro-Morphine or BD1047 given alone did not affect the baseline place conditioning. It is concluded that dextro-morphine attenuated the morphine-produced conditioned place preference via the sigma1 receptor activation.

Wu, Hsiang-en; Schwasinger, Emma T.; Terashvili, Maia; Tseng, Leon F.



21 CFR 862.3640 - Morphine test system.  

Code of Federal Regulations, 2013 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...



Detection and identification of 2-nitro-morphine and 2-nitro-morphine-6-glucuronide in nitrite adulterated urine specimens containing morphine and its glucuronides.  


In vitro urine adulteration is a well-documented practice adopted by individuals aiming to evade detection of drug use, when required to undergo mandatory sports and workplace drug testing. Potassium nitrite is an effective urine adulterant due to its oxidizing potential, and has been shown to mask the presence of many drugs of abuse. However, limited research has been conducted to understand its mechanism of action, and to explore the possibility of the drugs undergoing direct oxidation to form stable reaction products. In this study, opiates including morphine, codeine, morphine-3-glucuronide and morphine-6-glucuronide were exposed to potassium nitrite in water and urine to mimic the process of nitrite adulteration. It was found that two stable reaction products were detected by liquid chromatography-mass spectrometry (LC-MS) when morphine and morphine-6-glucuronide were exposed to nitrite. Isolation and elucidation using spectrometric and spectroscopic techniques revealed that they were 2-nitro-morphine and 2-nitro-morphine-6-glucuronide, respectively. These reaction products were also formed when an authentic morphine-positive urine specimen was fortified with nitrite. 2-Nitro-morphine was found to be stable enough to undergo the enzymatic hydrolysis procedure and also detectable by gas chromatography-mass spectrometry (GC-MS) after forming a trimethylsilyl derivative. On the contrary, morphine-3-glucuronide did not appear to be chemically manipulated when exposed to potassium nitrite in urine. These reaction products are not endogenously produced, are relatively stable and can be monitored with both LC-MS and GC-MS confirmatory techniques. As a result, these findings have revealed the possibility for the use of 2-nitro-morphine and 2-nitro-morphine-6-glucuronide as markers for the indirect monitoring of morphine and morphine-6-glucuronide in urine specimens adulterated with nitrite. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23592389

Luong, Susan; Fu, Shanlin



Hyperglycemic suppression of morphine withdrawal signs in the rat  

Microsoft Academic Search

Male Sprague-Dawley rats maintained under controlled lighting and temperature conditions were used in this experiment. Morphine\\u000a dependency was induced by giving increasing doses of morphine by intraperitoneal injection (IP group) or by the ingestion\\u000a of morphine through drinking water (PO group). Animals were injected with 10, 20, 30 and 50 mg\\/kg morphine sulfate at days\\u000a 1, 2, 3 and 4,

Hyacinth C. Akunne; Karam F. A. Soliman



A Bacoside containing Bacopa monnieri extract reduces both morphine hyperactivity plus the elevated striatal dopamine and serotonin turnover.  


Bacopa monnieri (BM) has been used in Ayurvedic medicine as a nootropic, anxiolytic, antiepileptic and antidepressant. An n-butanol extract of the plant (nBt-ext BM) was analysed and found to contain Bacoside A (Bacoside A3, Bacopaside II and Bacopasaponin C). The effects of the BM extract were then studied on morphine-induced hyperactivity as well as dopamine and serotonin turnover in the striatum since these parameters have a role in opioid sensitivity and dependence. Mice were pretreated with saline or nBt-ext BM (5, 10 and 15 mg/kg, orally), 60 min before morphine administration and locomotor activity was subsequently recorded. Immediately after testing, striatal tissues were analysed for dopamine (DA), serotonin (5HT) and their metabolites using HPLC coupled with electrochemical detection. The results indicated that nBt-ext BM significantly (p < 0.001) decreased locomotor activity in both the saline and morphine treated groups. Additionally, nBt-ext BM significantly lowered morphine-induced dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-H1AA) upsurges in the striatum but failed to affect DA, 5-HT and their metabolites in the saline treated group. These findings suggest that nBt-ext BM has an antidopaminergic/serotonergic effect and may have potential beneficial effects in the treatment of morphine dependence. PMID:22105846

Rauf, Khalid; Subhan, Fazal; Sewell, Robert D E



Orodispersible tablets: A new trend in drug delivery  

PubMed Central

The most common and preferred route of drug administration is through the oral route. Orodispersible tablets are gaining importance among novel oral drug-delivery system as they have improved patient compliance and have some additional advantages compared to other oral formulation. They are also solid unit dosage forms, which disintegrate in the mouth within a minute in the presence of saliva due to super disintegrants in the formulation. Thus this type of drug delivery helps a proper peroral administration in pediatric and geriatric population where swallowing is a matter of trouble. Various scientists have prepared orodispersible tablets by following various methods. However, the most common method of preparation is the compression method. Other special methods are molding, melt granulation, phase-transition process, sublimation, freeze-drying, spray-drying, and effervescent method. Since these tablets dissolve directly in the mouth, so, their taste is also an important factor. Various approaches have been taken in order to mask the bitter taste of the drug. A number of scientists have explored several drugs in this field. Like all other solid dosage forms, they are also evaluated in the field of hardness, friability, wetting time, moisture uptake, disintegration test, and dissolution test.

Dey, Paramita; Maiti, Sabyasachi



The Role of Morphine in Animal Models of Human Cancer: Does Morphine Promote or Inhibit the Tumor Growth?  

PubMed Central

Morphine, a highly potent analgesic agent, is widely used to relieve pain and suffering of patients with cancer. Additionally, it has been reported that morphine is important in the regulation of cancerous tissue. Morphine relieves pain by acting directly on the central nervous system, although its activities on peripheral tissues are responsible for many adverse side effects. For these reasons, it is very important also to understand the role of morphine in cancer treatment. The published literature reporting the effect of morphine on tumor growth presents some discrepancies, with reports suggesting that morphine may either promote or inhibit the tumor growth. It has been also demonstrated that morphine modulates angiogenesis which is important for primary tumour growth, invasiveness, and the development of metastasis. This review will focus on the latest findings on the role of morphine in the regulation of cancer cell growth and angiogenesis.

Bimonte, Sabrina; Barbieri, Antonio; Palma, Giuseppe; Arra, Claudio



Discriminative stimulus effects of morphine: central versus peripheral training  

Microsoft Academic Search

While it is well known that rats can discriminate a peripheral injection of morphine from a saline injection, to our knowledge no one has trained rats to discriminate a direct brain-site injection of morphine from saline. In the present series of studies, one group of rats was trained to discriminate morphine (0.3 ?g) from saline injected into the perifornical area

James P. Cleary; Eugene O'Hare; James D. Pomonis; Patricia L. Dittel; Jacki J. Hofmeister; Melinda M. Fritz; Charles J. Billington; Allen S. Levine



Tolerance to and physical dependence on morphine in rats  

Microsoft Academic Search

The effects of large doses of morphine in nontolerant and tolerant rats as well as the effects of abruptly withdrawing morphine in rats experimentally addicted to large doses of morphine have been studied on body weight, temperature, metabolic rate, respiratory rate, water consumption and various forms of motor activity and behavior. In confirmation of many early reports, tolerance develops to

W. R. Martin; A. Wikler; C. G. Eades; F. T. Pescor



Presence and Formation of Codeine and Morphine in the Rat  

Microsoft Academic Search

Endogenous codeine and morphine were identified in rat brain by immunological determination following HPLC. To demonstrate occurrence of a biosynthetic pathway to morphine in mammals similar to that used by the poppy plant, (+)-salutaridine, (-)-thebaine, and (-)-codeine were administered to rats intravenously. These compounds, which are intermediates in the synthesis of morphine in Papaver somniferum, caused a marked increase in

Josef Donnerer; Kazuhiro Oka; Arnold Brossi; Kenner C. Rice; Sydney Spector



Magnesium Sulfate Potentiates Morphine Antinociception at the Spinal Level  

Microsoft Academic Search

Intrathecal magnesium sulfate coinfusion with morphine increases antinociception in normal rats; however, be- cause magnesium also delays the onset of tolerance, it is not clear whether this additional antinociception is a re- sult of potentiated analgesia or tolerance abatement. We examined the antinociceptive interaction of intrathecal (IT) bolus magnesium sulfate and morphine in morphine naive rats and those with mechanical

Jeffrey S. Kroin; Robert J. McCarthy; Natasha Von Roenn; Brady Schwab; Kenneth J. Tuman; Anthony D. Ivankovich



Morphine in cancer pain management: a practical guide  

Microsoft Academic Search

Morphine is the most practical and versatile analgesic for the relief of severe pain associated with advanced cancer. Information is available in the literature about its use in routine clinical practice. Morphine induces analgesia by reducing neurotransmitter release presynaptically and hyperpolarizing dorsal horn neurons at the postsynaptic level, thus preventing rostral transmission of nociception. Morphine has a unique metabolism via

Sinead Donnelly; Mellar P. Davis; Declan Walsh; Michael Naughton



Continuous intraventricular clonidine infusion in controlled morphine withdrawal – case report  

Microsoft Academic Search

A patient with atypical bilateral facial pain reported the loss of analgesic effect of intracerebroventricular morphine delivered continuously via an implanted pump, accompanied by intolerable adverse side effects associated with the administered high dose of morphine. Clonidine was substituted for morphine over a period of 3 weeks to achieve a drug holiday. The patient did not have significant withdrawal symptoms

M Lorenz; S Hussein; L Verner



Changes in morphine-induced activation of cerebral Na(+),K(+)-ATPase during morphine tolerance: biochemical and behavioral consequences.  


There is ample evidence of the biological changes produced by the sustained activation of opioid receptors. We evaluated the adaptive changes of cerebral Na(+),K(+)-ATPase in response to the sustained administration of morphine (minipumps, 45mg/kg/day, 6 days) in CD-1 mice and the functional role of these changes in opioid antinociception. The antinociceptive effect of morphine as determined with tail-flick tests was reduced in morphine-tolerant mice. There were no significant changes in the density of high-affinity Na(+),K(+)-ATPase ? subunits labeled with [(3)H]ouabain in forebrain membranes from morphine-tolerant compared to those of morphine-naive animals. Western blot analysis showed that there were no significant differences between groups in the changes in relative abundance of ?(1) and ?(3) subunits of Na(+),K(+)-ATPase in the spinal cord or forebrain. However, the morphine-induced stimulation of Na(+),K(+)-ATPase activity was significantly lower in brain synaptosomes from morphine-tolerant mice (EC(50)=1.79±0.10?M) than in synaptosomes from morphine-naive mice (EC(50)=0.69±0.12?M). Furthermore, adaptive alterations in the time-course of basal Na(+),K(+)-ATPase activity were observed after sustained morphine treatment, with a change from a bi-exponential decay model (morphine-naive mice) to a mono-exponential model (morphine-tolerant mice). In behavioral studies the antinociceptive effects of morphine (s.c.) in the tail-flick test were dose-dependently antagonized by ouabain (1 and 10ng/mouse, i.c.v.) in morphine-naive mice, but not in morphine-tolerant mice. These findings suggest that during morphine tolerance, adaptive cellular changes take place in cerebral Na(+),K(+)-ATPase activity which are of functional relevance for morphine-induced antinociception. PMID:22410004

Gonzalez, Luis G; Masocha, Willias; Sánchez-Fernández, Cristina; Agil, Ahmad; Ocaña, Maria; Del Pozo, Esperanza; Baeyens, José M



Tianeptine reduces morphine antinociceptive tolerance and physical dependence.  


Long-term use of morphine can cause neuronal dystrophic changes in specific areas of the brain. These changes may underlie the mechanism for developing morphine antinociceptive tolerance and physical dependence. We evaluated the effect of tianeptine, an antidepressant with prominent neuroprotective and neuroplastic properties, on the development of morphine antinociceptive tolerance and physical dependence. Male C57BL/6 mice were rendered tolerant to or dependent on morphine by subcutaneously injecting them with morphine (10 mg/kg) and intraperitoneally with saline or tianeptine (1, 3, or 5 mg/kg) twice daily for 6 days. The mice were given a daily tail-flick test 1 h after the first morphine injection to evaluate the development of their tolerance to morphine antinociception. To evaluate their physical dependence on morphine, 3 h after the final morphine injection on day 6, naloxone-HCl-precipitated (2 mg/kg, intraperitoneally) withdrawal symptoms were counted for 30 min, and body weight was checked 1 h after the naloxone injection. Tianeptine per se produced no antinociception, neither did it modify the antinociception produced by morphine, nor did it evoke the behavioral responses different from those in the saline controls. The combination of tianeptine with morphine significantly reduced the development of morphine antinociceptive tolerance and suppressed the incidence of naloxone-precipitated withdrawal symptoms. We conclude that tianeptine is an effective inhibitor of morphine-induced antinociceptive tolerance and physical dependence in mice. Our results would imply that comedication with tianeptine and morphine might benefit those who need long-term morphine treatment. PMID:20679893

Chu, Chin-Chen; Shieh, Ja-Ping; Shui, Hao-Ai; Chen, Jen-Yin; Hsing, Chung-Hsi; Tzeng, Jann-Inn; Wang, Jhi-Joung; Ho, Shung-Tai



Redesign of a dioxygenase in morphine biosynthesis.  


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



Risedronate-loaded Eudragit S100 microparticles formulated into tablets.  


Abstract 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



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



Wheel running attenuates the antinociceptive properties of morphine and its metabolite, morphine-6-glucuronide, in rats  

Microsoft Academic Search

Recent work has shown that chronic exercise is associated with a reduction in the pain-relieving actions of opioid drugs in experimental animals. To determine whether this reduction represents an interaction between exogenously administered opioids and the endogenous opioid system, or is the result of altered drug pharmacokenitics, the antinociceptive actions of morphine and its metabolite, morphine-6-glucuronide (M6G), were compared in

Wendy Foulds Mathes; Robin B Kanarek



A comparison between spontaneous electroencephalographic activities induced by morphine and morphine-related environment in rats  

Microsoft Academic Search

Previous studies demonstrated that drug cues could elicit drug-like or withdrawal-like effect, both subjectively and physiologically. However, few studies have compared the central activities induced by a drug-related environment and the drug itself. The aim of this study was to observe and compare electroencephalographic (EEG) changes induced by acute morphine administration and by the morphine-related environment. EEG activities were recorded

Yan-Fang Zuo; Jin-Yan Wang; Ji-Huan Chen; Zhi-Mei Qiao; Ji-Sheng Han; Cai-Lian Cui; Fei Luo



Determination of morphine, morphine-3-glucuronide and morphine-6-glucuronide in monkey and dog plasma by high-performance liquid chromatography–electrospray ionization tandem mass spectrometry  

Microsoft Academic Search

A specific and simultaneous assay of morphine, morphine-3-glucuronide (M-3-G) and morphine-6-glucuronide (M-6-G) in monkey and dog plasma has been developed. These methods are based on rapid isolation using solid phase extraction cartridge, and high-performance liquid chromatography (HPLC)–electrospray ionization (ESI)-tandem mass spectrometric (MSMS) detection. Analytes were separated on a semi-micro ODS column in acetonitrile–formic (or acetic) acid mixed solution. The selected

Masanari Mabuchi; Satomi Takatsuka; Masayuki Matsuoka; Kozo Tagawa



Fast relief from migraine attacks using fast-disintegrating sublingual zolmitriptan tablets.  


Zolmitriptan is a potent molecule for treatment of migraine. Its current oral therapies present drawbacks such as slow onset of action, low bioavailability and large inter-subject variability. Fast disintegrating sublingual zolmitriptan tablet (FDST) using freeze-drying technique has been developed to enhance tablet disintegration and dissolution with the intention of speeding drug absorption and onset of effect, hence mitigating the effects on the gastrointestinal dysmotility that typically accompanies the migraine attack. The FDSTs were prepared using different concentrations of gelatin as binder and mannitol or L-alanine as matrix supporting/disintegration enhancing agents. The effect of formulation variables on the physicochemical and solid-state properties, as well as the dissolution behaviour of the tablets, was studied. The formulated FDSTs disintegrated within 30 s and showed significantly faster dissolution rate of zolmitriptan compared to the zolmitriptan oral tablet. Tablet containing 2% gelatin and mannitol showed acceptable weight variation, drug content and friability values. Furthermore, it had a low in-vitro and in-vivo disintegration time (11 s) and it reached 100% of drug release within 30 s. This sublingual formulation gave faster and higher zolmitriptan plasma concentration in rabbits compared to the oral zolmetriptan market product. Zolmitriptan FDST may therefore constitute an advance in the management of acute migraine attacks. PMID:22023340

Mahmoud, Azza A; Salah, Salwa



Medicinal carbon tablets for treatment of acetaminophen intoxication: adsorption characteristics of medicinal carbon powder and its tablets.  


Adsorption characteristics of medicinal carbon powder (JP 14) for acetaminophen were examined at 37 degrees C using conventional incubation in an attempt to obtain an effective oral dosage form. Hydroxypropyl cellulose (HPC) and maltitol (MT), being able to act as a binding agent, were tested as additives. Tablets of medicinal carbon were produced by the wet granulation method. The rate and extent of adsorption of the medicinal carbon powder were roughly similar in water, JP 14 1st fluid (pH 1.2) and JP 14 2nd fluid (pH 6.8). The relationship between concentrations of free and adsorbed acetaminophen indicated that the adsorption followed the Langmuir mode. The maximal adsorption of acetaminophen in water was 0.219 g per gram medicinal carbon powder, little influenced by the addition of MT, but slightly reduced by the addition of HPC. The tablet prepared using MT as a binding agent displayed a favorable hardness and adequate disintegration time. The tablet showed good adsorption potential for acetaminophen, though the adsorption rate and extent of the tablet were reduced to some extent as compared with powder. PMID:16508192

Yamamoto, Kenta; Onishi, Hiraku; Ito, Akihiko; Machida, Yoshiharu



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



Study of the clomipramine-morphine interaction in the forced swimming test in mice  

Microsoft Academic Search

Tricyclic antidepressant-morphine interactions have been extensively studied on pain tests but less often on tests predictive of antidepressant activity. The effects of clomipramine (CMI) and morphine were tested on the forced swimming test in mice after pretreatment with CMI, morphine or saline. Like CMI, though less so, morphine was significantly active. Morphine pretreatment partially inhibited the effect of CMI irrespective

A. Eschalier; J. Fialip; O. Varoquaux; M.-C. Makambila



Morphine and Antibodies to ?-Opiate Receptors in Ultralow Doses: Effect on Oxygen Consumption  

Microsoft Academic Search

The degree of oxygen consumption in rats was determined after intraperitoneal injection of morphine in a single dose of 5 mg\\/kg. Some animals were injected with morphine and perorally received morphine or antibodies to µ-opiate receptors in ultralow doses obtained by the technology of potentiation. Potentiated substances significantly reduced oxygen consumption intensified after morphinization. Potentiated morphine decreased the intensity of

I. F. Pavlov; O. I. Epstein



Technological evaluation and equivalence assessment of lorazepam tablets in rabbits.  


Four different oral lorazepam tablets (Tavor tablets as reference preparation and three generic tablet formulations, A, B and C) were investigated after administration to 12 rabbits to evaluate their bioequivalence. A single 2 mg/kg dose was administered orally as powder and lorazepam plasma concentrations were determined by a validated HPLC method. Maximum plasma concentrations (Cmax), of 207 ng/ml (reference), 198 ng/ml (A), 166 ng/ml (B) and 169 ng/ml (C) were achieved. Lorazepam appeared in the plasma at 0.66 h (Tmax) for all formulations, probably because the disintegration step was bypassed due to the pulverization of the administered doses. Areas under the plasma concentration-time curves (AUC(0-t) and AUC(0-infinity)) were determined. The obtained AUC(0-t) values were 556.57 ng h/ml (reference), 554.70 ng h/ml (A), 493.08 ng h/ml (B), and 487.88 ng h/ml (C). ANOVA results (P > or = 0.05) and 90% confidence intervals for the mean ratio (T/R) of AUC(0-t), AUC(0-infinity), and Cmax were within the EMEA acceptance range. Pharmacokinetic and statistical results of this study show that the four tested drug products (Tavor, A, B, C) are to be considered bioequivalent and interchangeable in medical practice. PMID:17718192

Ventura, C A; Giannone, I; Musumeci, T; Pignatello, R; Puglisi, G



Optical properties of aqueous morphine solutions  

NASA Astrophysics Data System (ADS)

We have studied morphine action on mobility and structure of water by means of fluorescent investigations and light scattering analysis. Wave-like concentration dependences have been plotted in the both cases. Theoretical description of the discovered effect has been made based on the formalism of N.N.Bogolubov.

Kuznetsov, Pavel E.; Gracheva, Anna A.; Zlobin, Vladimir A.; Nazarov, Georgy V.; Kuznetsova, Nina B.; Rogacheva, Svetlana M.



Intrathecal Morphine Plus General Anesthesia in Cardiac Surgery: Effects on Pulmonary Function, Postoperative Analgesia, and Plasma Morphine Concentration  

PubMed Central

OBJECTIVES: To evaluate the effects of intrathecal morphine on pulmonary function, analgesia, and morphine plasma concentrations after cardiac surgery. INTRODUCTION: Lung dysfunction increases morbidity and mortality after cardiac surgery. Regional analgesia may improve pulmonary outcomes by reducing pain, but the occurrence of this benefit remains controversial. METHODS: Forty-two patients were randomized for general anesthesia (control group n=22) or 400 ?g of intrathecal morphine followed by general anesthesia (morphine group n=20). Postoperative analgesia was accomplished with an intravenous, patient-controlled morphine pump. Blood gas measurements, forced vital capacity (FVC), forced expiratory volume (FEV), and FVC/FEV ratio were obtained preoperatively, as well as on the first and second postoperative days. Pain at rest, profound inspiration, amount of coughing, morphine solicitation, consumption, and plasma morphine concentration were evaluated for 36 hours postoperatively. Statistical analyses were performed using the repeated measures ANOVA or Mann-Whiney tests (*p<0.05). RESULTS: Both groups experienced reduced FVC postoperatively (3.24 L to 1.38 L in control group; 2.72 L to 1.18 L in morphine FEV1 (p=0.085), group), with no significant decreases observed between groups. The two groups also exhibited similar results for FEV1/FVC (p=0.68) and PaO2/FiO2 ratio (p=0.08). The morphine group reported less pain intensity (evaluated using a visual numeric scale), especially when coughing (18 hours postoperatively: control group= 4.73 and morphine group= 1.80, p=0.001). Cumulative morphine consumption was reduced after 18 hours in the morphine group (control group= 20.14 and morphine group= 14.20 mg, p=0.037). The plasma morphine concentration was also reduced in the morphine group 24 hours after surgery (control group= 15.87 ng.mL?1 and morphine group= 4.08 ng.mL?1, p=0.029). CONCLUSIONS: Intrathecal morphine administration did not significantly alter pulmonary function; however, it improved patient analgesia and reduced morphine consumption and morphine plasma concentration.

dos Santos, Luciana Moraes; Santos, Veronica Cavani Jorge; Santos, Silvia Regina Cavani Jorge; Malbouisson, Luiz Marcelo Sa; Carmona, Maria Jose Carvalho



Morphine depression and tolerance of nerve-induced parotid secretion.  

PubMed Central

1 The nerve-induced secretion produced by the rat parotid gland is proportional to the frequency of stimulation. Morphine decreased the flow rate during stimulation at 2.5 and 5 Hz, but not at 20 Hz. This frequency-dependent action of morphine and was partially reversed by naloxone. 2 The secretion produced by the rat parotid gland during an intravenous infusion of acetylcholine was not diminished by morphine. Therefore, the action of morphine on nerve-induced secretion is most probably on the motor nerve terminals, which release acetylcholine. 3 Animals that had been implanted with morphine base pellets tolerated 4 times as much morphine as controls; after 6 days the minute ventilation was less depressed by graded doses of morphine than non-implanted controls. 4 Nerve-induced secretion in morphine-implanted animals was less depressed by morphine than control animals 6 and 24 h after the pellets were removed. The flow rates in the 6 h group treated with morphine were greater after naloxone than control (precipitated withdrawal) but at 24 h when withdrawal symptoms were no longer evident, naloxone produced only a slight reversal.

Bowen, S R; Carpenter, F G



Acupuncture at SI5 attenuates morphine seeking behavior after extinction.  


Our previous studies have shown that acupuncture attenuates morphine self-administration and sensitization behavior as well as withdrawal signs. The present study was designed to investigate the role of acupuncture in the reinstatement of morphine seeking. Male Sprague-Dawley rats weighing 270-300 g were subjected to intravenous catheterization after food training. The animals were trained to self-administer morphine (1.0mg/kg, 3 weeks), followed by extinction (1 week). Extinction conditions were introduced by substituting saline for morphine. The rats were then tested for reinstatement of morphine self-administration by a priming injection of morphine (0.25mg/kg). To see whether acupuncture can reduce morphine reinstatement, acupuncture was performed at SI5 or LI5 for 1 min immediately before a morphine injection. To further test the involvement of gamma aminobutyric acid (GABA) receptors in acupuncture effects, GABA receptor antagonists were injected before acupuncture. In the present results, acupuncture at SI5, but not at control acupoint LI5 attenuated the reinstatement of morphine seeking behavior, which was blocked by the GABA receptor antagonists. It suggests that acupuncture can reduce the reinstatement of morphine seeking, possibly due to the mediation of GABA receptor system. PMID:22995180

Lee, Bong Hyo; Ma, Jeong Hun; In, Sunghyun; Kim, Hee Young; Yoon, Seong Shoon; Jang, Eun Young; Yang, Chae Ha



Morphine: new aspects in the study of an ancient compound.  


Morphine is the most widely used compound among narcotic analgesics and remains the gold standard when the effects of other analgetic drugs are compared. Apart from its presence in the poppy plant Papaver somniferum, morphine has been shown to be present in milk, cerebrospinal fluid and also in nervous tissue extracts. Recent evidence suggests that biosynthetic pathways for morphine exist in animal and even human tissues such as liver, blood and brain. The most characteristic effect of morphine is the modulation of pain perception resulting in an increase in the threshold of noxious stimuli. Antinociception induced by morphine is mediated via opioid receptors and therefore can be inhibited by opioid antagonists, e.g., naloxone. Nevertheless, consideration of morphine as endogenous ligand for opioid receptors seems to be speculative. Recently, the primary receptor for morphine-type drugs called the mu-opioid receptor has been cloned from rat brain. There is accumulating evidence that morphine actions are, at least partly, due to one of its major metabolite morphine-6-glucuronide in man. It is concluded that further investigations are necessary to elucidate the mechanisms, whereby multiple actions of morphine are expressed in the nervous system. PMID:8084213

Benyhe, S



Early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects  

Microsoft Academic Search

BACKGROUND: Efforts to ease administration and enhance acceptability of the oral anti-malarial artemether-lumefantrine (A-L) crushed tablet to infants and children triggered the development of a novel dispersible tablet of A-L. During early development of this new formulation, two studies were performed in healthy subjects, one to evaluate the palatability of three flavours of A-L, and a second one to compare

Salim Abdulla; Baraka Amuri; Abdunoor M Kabanywanyi; David Ubben; Christine Reynolds; Steve Pascoe; Serge Fitoussi; Ching-Ming Yeh; Marja Nuortti; Romain Séchaud; Günther Kaiser; Gilbert Lefèvre



Development, characterization and permeability assessment based on caco-2 monolayers of self-microemulsifying floating tablets of tetrahydrocurcumin.  


Novel self-microemulsifying floating tablets were developed to enhance the dissolution and oral absorption of the poorly water-soluble tetrahydrocurcumin (THC). Their physicochemical properties and THC permeability across Caco-2 cell monolayers were assessed. The self-microemulsifying liquid containing THC was adsorbed onto colloidal silicon dioxide, mixed with HPMC, gas-generating agents (sodium bicarbonate and tartaric acid), lactose and silicified-microcrystalline cellulose and transformed into tablets by direct compression. The use of different types/concentrations of HPMC and sodium bicarbonate in tablet formulations had different effects on the floating characteristics and in vitro THC release. The optimum tablet formulation (F2) provided a short floating lag time (?23 s) together with a prolonged buoyancy (>12 h). About 72% of THC was released in 12 h with an emulsion droplet size in aqueous media of 33.9±1.0 nm while that of a self-microemulsifying liquid was 29.9±0.3 nm. The tablet formulation was stable under intermediate and accelerated storage conditions for up to 6 months. The THC released from the self-microemulsifying liquid and tablet formulations provided an approximately three- to fivefold greater permeability across the Caco-2 cell monolayers than the unformulated THC and indicated an enhanced absorption of THC by the formulations. The self-microemulsifying floating tablet could provide a dosage form with the potential to improve the oral bioavailability of THC and other hydrophobic compounds. PMID:23319299

Sermkaew, Namfa; Wiwattanawongsa, Kamonthip; Ketjinda, Wichan; Wiwattanapatapee, Ruedeekorn



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



21 CFR 520.312 - Carnidazole tablets.  

Code of Federal Regulations, 2010 CFR

...Conditions of use â(1) Amount. Adult pigeons: 1 tablet (10 milligrams); newly weaned pigeons: 1/2 tablet (5 milligrams). (2...trichomoniasis (canker) in ornamental and homing pigeons. (3) Limitations. Not for...



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.



Multispectral imaging of tablets in blister packaging  

Microsoft Academic Search

This experiment tested the hypothesis that using near-infrared (IR) imaging spectrometry on tablets through blister packs\\u000a permits the identification and composition of multiple individual tablets to be determined simultaneously. Aspirin was selected\\u000a for this study because its breakdown mechanism is well understood. Near-IR cameras were used to collect thousands of spectra\\u000a simultaneously from a field of packaged aspirin tablets. Tablets

Imran Malik; Mela Poonacha; Jennifer Moses; Robert A. Lodder



[Preparation of sucking tablet of shengmei] off.  


The Sucking Tablet of Shengmei is made from eight Chinese traditional drugs including Radix Adenophorae, Fructus Mume, etc. The effective rate of the tablet in treating chronic pharyngitis reaches up to 96 percent. The working mechanism related to the fact that the tablet is bacteria-resistant and helps to strengthen the body function. This paper presents the preparation process of the Sucking Tablet along with solutions for some problems encountered in the process and appropriate standards for quality control. PMID:1418578

Jiang, J; Shao, J; Zhu, Z; Dai, Y; Xu, C



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



Pharmacokinetic analysis of a new acenocoumarol tablet formulation during a bioequivalence study  

Microsoft Academic Search

Summary  The pharmacokinetics of a new tablet formulation of acenocoumarol racemate, an oral anticoagulant agent, has been investigated\\u000a in 8 normal healthy subjects. The drug was given as a single oral dose of 12 mg. 12 blood samples were collected after administration.\\u000a Plasma acenocoumarol concentrations were determined by a sensitive HPLC method. Areas under the plasma level-time curves for\\u000a each subject

J. Popovi?; M. Mikov; V. Jakovljevi?



Immunotoxicological screening of morphine and methadone in an extended 28 day study in rats.  


Drug addicts are prone to infection with viruses including hepatitis-B and HIV. Besides indirect effects as a consequence of lifestyle, heroin and methadone may also enhance the risk of infections by a direct immunotoxic effect affecting resistance. In addition to general toxicological screening, we therefore performed a screening for potential immunotoxicity of morphine and methadone. Rats treated orally with different dosages of morphine or methadone for 6 weeks showed only a minor effect of overt toxicity on liver and spleen at the high dose, whereas at lower doses an increase in the relative weight of the mesenteric lymph nodes and an increase in cell density in the medullary cords were observed histopathologically, indicating a specific effect on humoral immunity. This specific immunotoxic effect was corroborated by an increased IgG concentration in serum (significant for the methadone-treated group). Further immunotoxicological research is needed aimed at revealing the potential risk of opiate use with respect to immune function. In conclusion, the present paper showed the toxicological profile of morphine and methadone in an extended 28 day subchronic study. Specific immunotoxicological effects were observed at doses where no effects were seen in routine toxicological evaluation, suggesting that the immune system is sensitive to opiates. PMID:7499032

van der Laan, J W; Krajnc, E I; Krajnc-Franken, M A; van Loveren, H



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



Mathematics instruction and the tablet PC  

Microsoft Academic Search

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

K. Renee Fister; Maeve L. McCarthy



Using Tablet PCs in Engineering Education  

Microsoft Academic Search

This paper describes the experiences of using Tablet PCs along with associated software, such as Classroom Presenter and OneNote, in a course entitled Introduction to Computer Engineering. Twenty tablet PCs were distributed in a classroom of 40 students. Students used the tablets on a daily basis throughout the semester to take notes, to respond to in-class exercises, and to perform

Joseph G. Tront


JWA regulates chronic morphine dependence via the delta opioid receptor.  


Opioid dependence is correlated with the adaptive changes at the cellular level following chronic opioid use, and believed to be the main cause for the relapse of drug taking behavior of addicts. Despite decades of intensive studies, the underlying mechanisms of morphine dependence are still unclear. Here, we present evidence that JWA was induced by chronic morphine treatment in specific brain regions, and knockdown of JWA expression significantly reduced the withdrawal response to chronic morphine treatment in rats. We further demonstrated that the morphine induced DOR expression, while activation of DARPP-32 and MAP kinase was suppressed by JWA knockdown. Through an in vitro cell model of chronic morphine exposure, we also found that JWA is required for maintaining the stability of DOR via the ubiquitin-proteasome pathway. These observations suggest that JWA is directly involved in the regulation of chronic morphine dependence. PMID:21600884

Wu, Yu; Chen, Rui; Zhao, Xiaojia; Li, Aiping; Li, Gang; Zhou, Jianwei



Isolation and identification of morphine n-oxide alpha- and beta-dihydromorphines, beta- or gamma-isomorphine, and hydroxylated morphine as morphine metabolites in several mammalian species.  


New morphine metabolites in the urine of guinea pigs, rats, rabbits, cats, monkeys, and humans were isolated with column chromatography, solvent extraction, and TLC and identified with TLC, GLC, and GLC-mass spectrometry. In addition to the known morphine metabolites, morphine N-oxide was isolated from the urine of guinea pigs, and alpha- and beta-dihydromorphines were isolated or detected in the urine of guinea pigs, rats, and rabbits. Monohydroxymorphine was identified tentatively in the urine of guinea pigs, rats, rabbits, and cats. Dihydroxymorphine was identified tentatively in the urine of guinea pigs, rats, and possibly, rabbits. Finally, beta- or gamma-isomorphine was identified tentatively in the urine of guinea pigs. The newly described morphine metabolites may be involved in some long lasting pharmacological effects of morphine. PMID:106104

Yeh, S Y; Krebs, H A; Gorodetzky, C W



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.

Aasmundstad, T A; Xu, B Q; Johansson, I; Ripel, A; Bj?rneboe, A; Christophersen, A S; Bodd, E; M?rland, J



Renal failure does not impair the metabolism of morphine.  

PubMed Central

The pharmacokinetics of morphine were measured using gas chromatography-mass spectrometry (GCMS) with specific ion monitoring after the intramuscular administration of papaveretum to four patients with renal failure (one anephric) and three normals. The apparent t1/2 of absorption and t1/2 of elimination were significantly shorter in the patients with renal failure (P less than 0.05). Morphine glucuronides are eliminated slowly in these patients as expected. Renal failure does not impair the elimination of morphine.

Woolner, D F; Winter, D; Frendin, T J; Begg, E J; Lynn, K L; Wright, G J



Potentiation of morphine analgesia by BQ123, an endothelin antagonist  

Microsoft Academic Search

Several neurotransmitter mechanisms have been proposed to play a role in the actions of morphine. The present study is the first to provide evidence that central endothelin (ET) mechanisms are involved in the modulation of pharmacological actions of morphine. The effect of intracerebroventricular (i.c.v.) administration of endothelin-A (ETA) antagonist, BQ123, on morphine-induced analgesia, hyperthermia, and catalepsy was determined in the

Shaifali Bhalla; George Matwyshyn; Anil Gulati



A specific immunoassay for the determination of morphine and its glucuronides in human blood  

Microsoft Academic Search

The development of specific antisera for immunochemical determination of morphine, morphine-3-glucuronide and morphine-6-glucuronide\\u000a is described. Morphine was N-demethylated to normorphine and N-alkylated to give N-aminopropyl-normorphine as hapten for antisera\\u000a against morphine. As haptens for antisera against morphine-3-glucuronide and morphine-6-glucuronide, N-aminopropyl-nor-morphine\\u000a was glucuronidated in position 3 or 6 respectively. Each of these three haptens were coupled to BSA employing the glutaraldehyde

J. Beike; G. Blaschke; A. Mertz; H. Köhler; B. Brinkmann



Attitudes of Polish Physicians and Medical Students toward Breaking Bad News, Euthanasia and Morphine Administration in Cancer Patients.  


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



Calcium phosphates in pharmaceutical tableting. 2. Comparison of tableting properties.  


Ten calcium phosphates suitable for direct compression (dibasic calcium phosphate dihydrate, dibasic calcium phosphate anhydrous and hydroxylapatite) were investigated with respect to their compressional behaviour. Except for Di-Cafos A all products gave tablets with sufficient to good mechanical strength. Nevertheless, there were differences between the products. All tablets prepared from the different products showed a high friability. This seems to be a problem of the calcium phosphates in general. On the other hand, the influence of magnesium stearate on the mechanical strength of the tablets was negligible for all products investigated. Moreover, a considerable effect of the particle size on the tensile strength of the tablets was found. The ejection forces and residual pressures were high in general, but critical only in the case of hydroxylapatites. Heckel plots were used to differentiate between plastic deformation and brittle fracture of the particles. In the case of calcium phosphates the slope of the Heckel plots indicated the hardness of the particles rather than their deformation behaviour. PMID:8348107

Schmidt, P C; Herzog, R



Parkinson's disease, L-DOPA, and endogenous morphine: A revisit  

PubMed Central

Summary Clinical observations stemming from widespread employment of restorative L-3,4-dihydroxyphenylalanine (L-DOPA) therapy for management of dyskinesia in Parkinson’s Disease (PD) patients implicate a regulatory role for endogenous morphine in central nervous system dopamine neurotransmission. Reciprocally, it appears that restorative L-DOPA administration has provided us with a compelling in vivo pharmacological model for targeting peripheral sites involved in endogenous morphine expression in human subjects. The biological activities underlying endogenous morphine expression and its interaction with its major precursor dopamine strongly suggest that endogenous morphine systems are reciprocally dysregulated in PD. These critical issues are examined from historical and current perspectives within our short review.

Stefano, George B.; Mantione, Kirk J.; Kralickova, Milena; Ptacek, Radek; Kuzelova, Hana; Esch, Tobias; Kream, Richard M.



Effect of morphine on PC12 cells with molecular radar  

NASA Astrophysics Data System (ADS)

Molecular Radar (MR) is a new method to detect biological processes in living cells at the level of molecular, it is also the newest means to get intracellular information. In this paper we study the effect of morphine on PC12 cells using MR. The results show that the effect of morphine on PC12 cells is time- and concentration-dependent. Morphine treating for short time induces the increase and fluctuation of intracellular (CA2+), while morphine treating for long time induces chromatin condensation, loss of mitochondria membrane potential apoptosis.

Shi, Chen; Yu, Xiaoli; Lu, Jiuyi; Zhang, Chun-Yang; Jin, Lei; Ma, Hui; Zhang, Dacheng; Chen, Dieyan



Involvement of glial glutamate transporters in morphine dependence.  


There are several lines of evidence implying the involvement of the central glutamatergic system in morphine dependence. Extracellular glutamate released from nerve terminals is counterbalanced by glutamate transporters in neurons (EAAC1 and EAAT4) and glial cells (GLT-1 and GLAST), thereby modulating the glutamatergic system and protecting neurons from an excitotoxic action of glutamate. Here we show that a glial glutamate transporter GLT-1 could be involved in physical and psychological morphine dependence. By Northern blot analysis, the expression of glial glutamate transporter GLT-1, but not GLAST, mRNA was decreased in the striatum/nucleus accumbens (NAc) and thalamus of morphine-dependent rats. Subcutaneous administration of a glutamate transporter activator suppressed the development of physical morphine dependence and morphine-induced conditioned place preference. Intracerebroventricular administration of a glutamate transporter inhibitor to morphine-dependent rats facilitated the expression of naloxone-precipitated morphine withdrawal-induced somatic signs and conditioned place aversion. Furthermore, gene transfer techniques using recombinant adenoviruses revealed that GLT-1 in the locus coeruleus and NAc shell plays inhibitory roles in physical and psychological morphine dependence, respectively. These findings may provide evidence that a glial glutamate transporter GLT-1 could be a new target for preventing physical and psychological morphine dependence. PMID:15542740

Nakagawa, Takayuki; Satoh, Masamichi



Development of controlled release oral drug delivery system by membrane-coating method-I  

Microsoft Academic Search

In order to develop a controlled-release oral drug delivery system (DDS) which sustains the plasma acetaminophen (AAP) concentration\\u000a for a certain period of time, microporous membrane-coated tablets were prepared and evaluatedin vitro. Firstly, highly water-soluble core tablets of AAP were prepared with various formulations by wet granulation and compression\\u000a technique. Then the core tablets were coated with polyvinylchloride (PVC) in

Chang-Koo Shim; Ki-Man Kim; Young-Il Kim; Chong-Kook Kim



Constipation in cancer patients on morphine  

Microsoft Academic Search

Goals of work  Constipation is a significant problem in patients taking morphine for cancer pain. The aims of this study were (1) to assess\\u000a the magnitude of constipation in this study cohort, (2) to analyse the constipation treatment strategies and (3) to look for\\u000a evidence of inter-individual variation in both susceptibility to constipation and response to treatment with laxatives in\\u000a this

Joanne Droney; Joy Ross; Sophy Gretton; Ken Welsh; Hiroe Sato; Julia Riley



Continuous Subcutaneous Infusion of Morphine vs. Hydromorphone  

Microsoft Academic Search

Seventy-four patients were included in a double-blind, randomized, controlled trial comparing the analgesic efficacy and adverse effects of hydromorphone and morphine delivered by continuous subcutaneous infusion. Patients completed the Memorial Pain Assessment Card and a checklist of opioid-related adverse effects immediately before commencing subcutaneous infusion and 24, 48, and 72 hours later. An assessment tool was developed for the 60

Mary G. Miller; Noel McCarthy; Ciarán A. O'Boyle; Michael Kearney



Use of oral clonidine for sedation in ventilated paediatric intensive care patients  

Microsoft Academic Search

Objectives We aimed to document our experience with oral clonidine when used as a sedative in combination with intravenous morphine and lorazepam in a group of mechanically ventilated children with single-organ, respiratory failure. In particular, our objectives were to establish the relationship between oral dose, plasma concentration, and sedative effect, and second, to document the side-effect profile. Design Prospective, cohort

Sara Arenas-López; Shelley Riphagen; Shane M. Tibby; Andrew Durward; Steve Tomlin; Graham Davies; Ian A. Murdoch



Biomarkers of morphine tolerance and dependence are prevented by morphine-induced endocytosis of a mutant ?-opioid receptor  

PubMed Central

Growing evidence shows that trafficking of the ?-opioid receptor (MOR) is a critical process in functional recovery from desensitization following activation and plays important roles in morphine tolerance and dependence largely because of the failure of morphine to promote such trafficking. However, morphine tolerance and dependence are believed to be mediated by multiple mechanisms, including well-documented biochemical changes in cAMP activity, N-methyl-d-aspartate receptors (NMDARs), glucocorticoid receptors (GRs), and c-fos. Here, we assess the consequences of promoting morphine-induced endocytosis on these biochemical changes utilizing a knock-in mouse model, RMOR, in which MORs undergo morphine-induced endocytosis. Chronic morphine treatment of wild-type (WT) mice promoted superactivation of adenylyl cyclase, alterations in NMDARs, and up-regulation of GR and c-fos in distinct brain regions. Notably, none of these biochemical changes occurred in the RMOR-knock-in mice. Together, these data demonstrate that morphine tolerance and dependence are mediated by multiple biochemical mechanisms and that MOR endocytosis plays a critical role in each of these mechanisms.—He, L., Kim, J. A., Whistler, J. L. Biomarkers of morphine tolerance and dependence are prevented by morphine-induced endocytosis of a mutant ?-opioid receptor.

He, Li; Kim, Joseph A.; Whistler, Jennifer L.



Tablet PCs in undergraduate mathematics  

Microsoft Academic Search

Undergraduate students often struggle to learn mathematics because introductory classes are taught in large lectures that do not engage students in active problem-solving. These students do not connect mathematics to their lives and feel that learning mathematics is a solitary undertaking. We now use Tablet PCs in a networked classroom to address these challenges. Students in classes that use the

Carla A. Romney



The Venus Tablet and Refraction  

Microsoft Academic Search

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

V. G. Gurzadyan



Respiratory depression following morphine and morphine-6-glucuronide in normal subjects.  

PubMed Central

1. Morphine 6-glucuronide (M6G) is a metabolite of morphine with analgesic activity. A double-blind, randomised comparison of the effects of morphine and M6G on respiratory function was carried out in 10 normal subjects after i.v. morphine (10 mg 70 kg-1) or M6G (1, 3.3 and 5 mg 70 kg-1). Analgesic potency was also assessed using an ischaemic pain test and other toxic effects were monitored. 2. Following morphine there was a significant increase in arterial PCO2, as measured by blood gases 45 min post dose (0.54 +/- 0.24 (s.d.) kPa, P < 0.001), and in transcutaneous PCO2 from 15 min post dose until the end of the study period (4 h), whereas blood gas and transcutaneous PCO2 were unchanged after M6G at 1.0, 3.3 and 5.0 mg 70 kg-1. This increased PCO2 following morphine was associated with an increase in expired CO2 concentration (FECO2) (0.20 +/- 0.14% expired air at 15 min post dose, P = 0.002), compared with small but significant reductions in FECO2 following morphine 6-glucuronide (-0.15 +/- 0.17% at 1 mg 70 kg-1 P = 0.030, -0.14 +/- 0.15% at 3.3 mg 70 kg-1 P = 0.017, -0.18 +/- 0.11% at 5 mg 70 kg-1 P = 0.024). Maximum transcutaneous PCO2 was significantly increased after morphine (0.63 +/- 0.28 kPa P = 0.009), but was not changed after M6G at 1 mg (0.10 +/- 0.34 kPa P = 0.11) 3.3 mg (0.06 +/- 0.37 kPa P = 0.34) or 5 mg (0.26 +/- 0.07 kPa P = 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)

Thompson, P I; Joel, S P; John, L; Wedzicha, J A; Maclean, M; Slevin, M L



Suppression of transmission of nociceptive impulses by morphine  

PubMed Central

1 In spinal cats anaesthetized with ?-chloralose, a study was made of the effects of morphine and naloxone, administered electrophoretically from micropipettes, on the responses of dorsal horn neurones to noxious (raising of skin temperature above 45°C) and innocuous (deflection of hairs) peripheral stimuli. 2 Administered near cell bodies, morphine reduced the nociceptive responses of only 2 of 37 cells. Excitation occurred more commonly than depression and abnormalities in action potentials were commonly observed following ejection of morphine. None of these effects of morphine was antagonized by electrophoretically applied naloxone. 3 Administered in the substantia gelatinosa from one micropipette while recording responses of deeper neurones with a second micropipette, morphine reduced the nociceptive responses of 15 of 19 neurones. Firing in response to deflection of hairs was not reduced by morphine. Depression of nociceptive responses by morphine was long lasting (>20 minutes). Naloxone ejected into the substantia gelatinosa or given intravenously in doses as low as 0.1 mg/kg antagonized the effects of morphine. The effectiveness of this dose of intravenous naloxone suggests that the concentrations of morphine in the substantia gelatinosa which reduced nociceptive responses were not unlike those present after analgesic doses of systemic morphine. Naloxone alone, and excitant and depressant amino acids ejected into the substantia gelatinosa had little effect on cell firing. 4 Both the selective action of morphine on nociceptive responses and the reversal of this action by intravenous naloxone suggest that the opiate receptor present in the substantia gelatinosa is relevant to analgesia produced by opiates given systemically.

Duggan, A.W.; Hall, J.G.; Headley, P.M.



Carboxymethyl high amylose starch (CM-HAS) as excipient for Escherichia coli oral formulations  

Microsoft Academic Search

Carboxymethyl high amylose starch (CM-HAS) is proposed as a novel excipient for oral tablet formulation of bioactive agents ensuring their protection in the stomach and delivery in the intestine. Three variants of CM-HAS, with different degrees of substitution, were synthesized by starch treatment with various amounts of monochloroacetic acid. The products were dried in powder form and tablets were obtained

Carmen Calinescu; Jérôme Mulhbacher; Éric Nadeau; John Morris Fairbrother; Mircea Alexandru Mateescu



Application of guar gum biopolymer in the prescription of tablets with sodium ibuprofen--quality tests and pharmaceutical availability in vitro.  


The increasing interest of the technology of drug form in natural biopolymers has become the reason for undertaking investigations on the possibility of guar gum application in the prescription of oral solid form of a drug. Alternative compositions and technology of the production of tablets of regulated in time sodium ibuprofen release were worked out for children. Two series of tablets were prepared with guar gum (5 and 10% content) and a series without the biopolymer. The tablet mass in each case contained keryostatic sorbitol and bioadhesive polyvinylpyrrolidone. All tablets were tested as regards the quality of production, compliance with the requirements of Polish Pharmacopoeia VI and potential therapeutic usefulness, manifestation of which is pharmaceutical availability of the therapeutic agent (sodium ibuprofen). The tests demonstrated that the produced tablets with sodium ibuprofen have proper physicochemical properties, in compliance with Polish Pharmacopoeia VI requirements. Application of biopolymer of guar gum type as adjuvant substance contributes to the improvement of the tablet hardness parameters and prevents technological problems (lining mixture of powders to tableting machine punch). The designed tablets demonstrate proper pharmaceutical availability of over 80%. Introduction of guar gum into their prescription prolonged their disintegration time and the rate of sodium ibuprofen release, which predisposes the produced form of a drug to have the function of a tablet with slowed-down release. PMID:17402228

Berner-Strzelczyk, Aneta; Ko?odziejska, Justyna; Zgoda, Marian Miko?aj



Pharmaceutical and analytical evaluation of triphalaguggulkalpa tablets  

PubMed Central

Aim of the Study: Development of standardized, synergistic, safe and effective traditional herbal formulations with robust scientific evidence can offer faster and more economical alternatives for the treatment of disease. The main objective was to develop a method of preparation of guggulkalpa tablets so that the tablets meet the criteria of efficacy, stability, and safety. Materials and Methods: Triphalaguggulkalpa tablet, described in sharangdharsanhita and containing guggul and triphala powder, was used as a model drug. Preliminary experiments on marketed triphalaguggulkalpa tablets exhibited delayed in vitro disintegration that indicated probable delayed in vivo disintegration. The study involved preparation of triphalaguggulkalpa tablets by Ayurvedic text methods and by wet granulation, dry granulation, and direct compression method. The tablets were evaluated for loss on drying, volatile oil content, % solubility, and steroidal content. The tablets were evaluated for performance tests like weight variation, disintegration, and hardness. Results: It was observed that triphalaguggulkalpa tablets, prepared by direct compression method, complied with the hardness and disintegration tests, whereas tablets prepared by Ayurvedic text methods failed. Conclusion: Direct compression is the best method of preparing triphalaguggulkalpa tablets.

Savarikar, Shreeram S.; Barbhind, Maneesha M.; Halde, Umakant K.; Kulkarni, Alpana P.



Brain stress system response after morphine-conditioned place preference.  


This study examined the involvement of the brain stress system in the reinforcing effects of morphine. One group of mice was conditioned to morphine using the conditioned place preference (CPP) paradigm and the other group received morphine in a home-cage (non-conditioned). Adrenocorticotropic hormone and corticosterone levels were measured by radioimmunoassay; phospho (p) CREB expression and the number of corticotropin-releasing factor (CRF) neurons and fibres were measured by immunohistochemistry in different brain areas. We observed that the number of CRF neurons in the paraventricular nucleus (PVN) was increased after morphine-induced CPP, which was paralleled with enhanced CRF-immunoreactivity fibres in the nucleus tractus solitarius (NTS) and ventral tegmental area (VTA) vs. home-cage group injected with morphine. Morphine exposure induced an increase in CREB phosphorylated at Ser133 in the PVN and central amygdale (CeA), whereas mice exhibiting morphine CPP had higher levels of pCREB in the PVN, CeA and bed nucleus of the stria terminalis (BNST). We also found that most of the CRF-positive neurons in the PVN, CeA and BNST co-express pCREB after morphine CPP expression, suggesting that the drug-associated environmental contexts can elicit neuronal activity in the brain stress system. From the present results it is clear that exposure to a drug-associated context remains a potent activator of signalling pathways leading to CRF activation in the brain stress system. PMID:23745716

García-Carmona, Juan-Antonio; Milanés, María-Victoria; Laorden, María-Luisa



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



Plasma morphine levels produced by continuous infusion in children.  


Blood samples were taken from six children aged between 10 months and 15 years, at intervals over a period of 40 hours while they were receiving continuous morphine infusions. The plasma morphine values obtained showed similar and consistent levels 15-30 minutes after starting the infusions. PMID:3752440

Bray, R J; Beeton, C; Hinton, W; Seviour, J A



Synthesis and analgetic activity of nicotinic esters of morphine derivatives.  


The synthesis of morphine nicotinates is described using nicotinyl chloride in the presence of pyridine. Isomorphine and isocodeine nicotinates were prepared from the corresponding morphine and codeine derivatives with nicotinic acid in the presence of triphenylphosphine and diethyl azodicarboxylate. Unexpectedly the reaction of 14-hydroxy-dihydromorphinone derivatives was anomalous, enolesters were formed. The analgetic activity of selected compounds was determined. PMID:7904819

Hosztafi, S; Köhegyi, I; Simon, C; Fürst, Z



Neuroimmunomodulatory Effects of Morphine in Leishmania donovani-Infected Hamsters  

Microsoft Academic Search

Objective: The effect of morphine on host defense during Leishmania donovani infection in golden hamsters was studied. Methods: Hamsters were intracardially infected with L. donovani amastigotes and then monitored by spleen touch print microscopic examination. Morphine and naloxone were administered subcutaneously and intraperitoneally, respectively. Leukocytes were counted by a hemocytometer, and ex vivo phagocytosis was determined by the examination of

Priya Singal; Arvind G. Kinhikar; Savita Singh; Prati Pal Singh



Negative and positive intracranial reinforcement tresholds: Effects of morphine  

Microsoft Academic Search

Negative (aversive) and positive (self-stimulation) intracranial reinforcement thresholds were determined in rats using a “double staircase” psychophysical procedure. Morphine raised aversive thresholds at all doses tested, while the drug lowered positive reinforcement thresholds at low or moderate doses. The results suggest the possible involvement of central motivational systems in the mediation of morphine-induced analgesia, the narcotic “high”, and narcotic addiction.

Richard Marcus; Conan Kornetsky



BDNF is a Negative Modulator of Morphine Action  

PubMed Central

Summary Brain-derived neurotrophic factor (BDNF) is a key positive regulator of neural plasticity, promoting for example, the actions of stimulant drugs of abuse such as cocaine. We discovered a surprising opposite role for BDNF in countering responses to chronic morphine. The suppression of BDNF in the ventral tegmental area (VTA) enhanced the ability of morphine to increase dopamine (DA) neuron excitability and promote reward. In contrast, optical stimulation of VTA DA terminals in nucleus accumbens (NAc) completely reversed the suppressive effect of BDNF on morphine reward. Furthermore, we identified numerous genes in NAc, a major target region of VTA DA neurons, whose regulation by BDNF in the context of chronic morphine exposure mediated this counteractive function. These findings provide insight into the molecular basis of morphine-induced neuroadaptations in the brain’s reward circuitry.

Koo, Ja Wook; Mazei-Robison, Michelle S.; Chaudhury, Dipesh; Juarez, Barbara; LaPlant, Quincey; Ferguson, Deveroux; Feng, Jian; Sun, Haosheng; Scobie, Kimberly N.; Damez-Werno, Diane; Crumiller, Marshall; Ohnishi, Yoshinori N.; Ohnishi, Yoko H.; Mouzon, Ezekiell; Dietz, David M.; Lobo, Mary Kay; Neve, Rachael L.; Russo, Scott J.; Han, Ming-Hu; Nestler, Eric J.



Modulation of drug release kinetics of shellac-based matrix tablets by in-situ polymerization through annealing process.  


A new oral-controlled release matrix tablet based on shellac polymer was designed and developed, using metronidazole (MZ) as a model drug. The shellac-based matrix tablets were prepared by wet granulation using different amounts of shellac and lactose. The effect of annealing temperature and pH of medium on drug release from matrix tablets was investigated. The increased amount of shellac and increased annealing temperature significantly affected the physical properties (i.e., tablet hardness and tablet disintegration) and MZ release from the matrix tablets. The in-situ polymerization played a major role on the changes in shellac properties during annealing process. Though the shellac did not dissolve in acid medium, the MZ release in 0.1N HCl was faster than in pH 7.3 buffer, resulting from a higher solubility of MZ in acid medium. The modulation of MZ release kinetics from shellac-based matrix tablets could be accomplished by varying the amount of shellac or annealing temperature. The release kinetics was shifted from relaxation-controlled release to diffusion-controlled release when the amount of shellac or the annealing temperature was increased. PMID:18362064

Limmatvapirat, Sontaya; Limmatvapirat, Chutima; Puttipipatkhachorn, Satit; Nunthanid, Jurairat; Luangtana-anan, Manee; Sriamornsak, Pornsak



Comparison of sustained-release morphine with sustained-release oxycodone in advanced cancer patients  

Microsoft Academic Search

The antinociceptive effect of morphine and oxycodone is mediated preferentially at ? and ? receptors, respectively. The aim of this study was to evaluate the analgesic profile of the combination of morphine and oxycodone in cancer pain, compared to the standard administration of morphine alone. Controlled-release formulations of oxycodone (CRO) and morphine (CRM) were compared in 26 patients. The study

G R Lauretti; G M Oliveira; N L Pereira



The role of nitric oxide in diabetes-induced changes of morphine tolerance in rats  

Microsoft Academic Search

Several neuroendocrine complications including diabetes change the morphine antinociception and the development of tolerance to the drug. Morphine antinociception was reduced significantly in morphine tolerant diabetic rats compared to the non-diabetic animals. The exact mechanism of this effect is not known. This study was performed to determine the role of nitric oxide (NO) on morphine tolerance in diabetic state. Nociceptive

Khojasteh Joharchi; Masoumeh Jorjani



Morphine acts in the parabrachial nucleus, a pontine viscerosensory relay, to produce discriminative stimulus effects  

Microsoft Academic Search

Morphine is known to act centrally to produce discriminative stimulus effects, but the specific neuroanatomical sites mediating this action have not been identified. We used morphine as a discriminative stimulus in a taste aversion paradigm to elucidate the neural basis of morphine's cueing properties. Rats were injected subcutaneously with 5 mg\\/kg morphine 15 min prior to the presentation of a

Thomas V. Jaeger; Derek van der Kooy



Early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects  

PubMed Central

Background Efforts to ease administration and enhance acceptability of the oral anti-malarial artemether-lumefantrine (A-L) crushed tablet to infants and children triggered the development of a novel dispersible tablet of A-L. During early development of this new formulation, two studies were performed in healthy subjects, one to evaluate the palatability of three flavours of A-L, and a second one to compare the bioavailability of active principles between the dispersible tablet and the tablet (administered crushed and intact). Methods Study 1 was performed in 48 healthy schoolchildren in Tanzania. Within 1 day, all subjects tasted a strawberry-, orange- and cherry-flavoured oral A-L suspension for 10 seconds (without swallowing) in a randomized, single-blind, crossover fashion. The palatability of each formulation was rated using a visual analogue scale (VAS). Study 2 was an open, randomized crossover trial in 48 healthy adults given single doses of A-L (80 mg artemether + 480 mg lumefantrine) with food. The objectives were to compare the bioavailability of artemether, dihydroartemisinin (DHA) and lumefantrine between the dispersible tablet and the tablet administered crushed (primary objective) and intact (secondary objective). Results Study 1 showed no statistically significant difference in VAS scores between the three flavours but cherry had the highest score in several ratings (particularly for overall liking). Study 2 demonstrated that the dispersible and crushed tablets delivered bioequivalent artemether, DHA and lumefantrine systemic exposure (area under the curve [AUC]); mean ± SD AUC0-tlast were 208 ± 113 vs 195 ± 93 for artemether, 206 ± 81 vs 199 ± 84 for DHA and 262 ± 107 vs 291 ± 106 h.?g/ml for lumefantrine. Bioequivalence was also shown for peak plasma concentrations (Cmax) of DHA and lumefantrine. Compared with the intact tablet, the dispersible tablet resulted in bioequivalent lumefantrine exposure, but AUC and Cmax values of artemether and DHA were 20-35% lower. Conclusions Considering that cherry was the preferred flavour, and that the novel A-L dispersible tablet demonstrated similar pharmacokinetic performances to the tablet administered crushed, a cherry-flavoured A-L dispersible tablet formulation was selected for further development and testing in a large efficacy and safety study in African children with malaria.



[Simultaneous determination of 5 kinds of alkaloids in Kechuanning tablets by SPE-UPLC under different UV-vis wavelength].  


The paper is to establish a method for simultaneous determination of 5 kinds of alkaloids in ephedra and poppy which are in Kechuanning tablets. Solid-phase extraction (SPE) was adopted in pretreatment, and a UPLC method with 2 different wavelengths had been developed: 210 nm for the detection of morphine, codeine phosphate, ephedrine hydrochloride and pseudoephedrine hydrochloride, and 251 nm for papaverine hydrochloride. The column used was Acquity UPLC BEH C18 (100 mm x 2.1 mm ID, 1.7 microm) with linear gradient elution using acetonitrile and 0.1% phosphoric acid. The flow rate was 0.4 mL.min-1, and the column temperature was 30 degrees C. The linear response range was 0.375 0 - 12.50 microg.mL-1 for morphine, 0.064 32 - 2.144 microg.mL-1 for codeine phosphate, 0.030 06 - 1.002 microg.mL-1 for papaverine hydrochloride, 1.126 - 37.52 microg.mL-1 for ephedrine hydrochloride, 0.287 8 - 9.592 microg.mL-1 for pseudoephedrine hydrochloride (r = 0.999 7). The average recoveries of these compounds were 99.26%, 100.6%, 95.29%, 100.1% and 97.48%, respectively. This is a more reasonable and credible method of quality control for Kechuanning tablets. PMID:21800548

Liu, Yong-li; Li, Dong-mei; Feng, Li; Yuan, Hao



Characteristics of Distribution of Morphine and Metabolites in Cerebrospinal Fluid and Plasma with Chronic Intrathecal Morphine Infusion in Humans  

PubMed Central

Background Despite widespread use of chronic intrathecal (IT) infusions of morphine, there is little systematic human work evaluating the steady-state morphine concentrations or cerebrospinal (CSF) chemistry after long-term IT morphine delivery. We sought to address these issues in patients receiving chronic IT morphine infusion. Methods Pain patients with implanted catheters and pumps (range: 127–2165 days), receiving a stable dosing (> 1 week) of IT morphine by infusion, were entered into the study. The following sequence was performed: 1) estimation of pain score; 2) radiograph localization of catheter tip; 3) Percutaneous sampling of lumbar CSF at the L4-5 or L5-S1 space. CSF/plasma samples were assayed for chemistry, and morphine and its 3/6 glucuronide metabolites (M3G, M6G) by liquid chromatography mass spectrometry. Results Nineteen patients were enrolled. CSF samples were obtained from 16 subjects. Three patients were not included in the primary analysis because one catheter was epidural, one catheter was fractured and one had a granuloma at the catheter tip. Of the 13 sampled patients, the range of daily doses, rates and concentrations were 1.6–25 mg/d and 0.1–1 ml/d, 5–50 mg/mL, respectively. The principal observations were: i) morphine, M3G and M6G were present in the CSF and plasma and showed a significant regression slope when plotted versus daily dose; ii) in contrast, the regression slope of the group ratio Morphine: M3G: M6G plotted versus daily dose in CSF or plasma was not different from zero; iii) plotting “normalized” CSF analyte concentration (e.g., concentration at site/daily IT morphine dose) against the segmental distance of the sampling site from the catheter tip revealed a significant decline in concentration of morphine, but not of conjugates as a function of distance from the catheter tip; iv) plotting CSF protein, glucose, red and white cell counts versus daily morphine dose or morphine concentration at the sampling site revealed no significant regression; and v) patients with a catheter failure or a granuloma showed reduced concentrations of morphine in their CSF. Conclusion Chronic infusion of morphine shows high concentrations which correlate with the infusion dose and the proximity of the sampling site to the infusion site with no effects on CSF chemistry.

Wallace, Mark; Yaksh, Tony L.



PolyMorphine: an innovative biodegradable polymer drug for extended pain relief  

PubMed Central

Morphine, a potent narcotic analgesic used for the treatment of acute and chronic pain, was chemically incorporated into a poly(anhydride-ester) backbone. The polymer termed “PolyMorphine”, was designed to degrade hydrolytically releasing morphine in a controlled manner to ultimately provide analgesia for an extended time period. PolyMorphine was synthesized via melt-condensation polymerization and its structure was characterized using proton and carbon nuclear magnetic resonance spectroscopies, and infrared spectroscopy. The weight-average molecular weight and the thermal properties were determined. The hydrolytic degradation pathway of the polymer was determined by in vitro studies, showing that free morphine is released. In vitro cytocompatibility studies demonstrated that PolyMorphine is non-cytotoxic towards fibroblasts. In vivo studies using mice showed that PolyMorphine provides analgesia for 3 days, 20 times the analgesic window of free morphine. The animals retained full responsiveness to morphine after being subjected to an acute morphine challenge.

Rosario-Melendez, Roselin; Harris, Carolyn L.; Delgado-Rivera, Roberto; Yu, Lei; Uhrich, Kathryn E.



Disruption of temporally organized behavior by morphine.  

PubMed Central

Four pigeons pecked keys in two different procedures commonly used in the study of timing, or temporal discrimination. Sessions consisted of 40 trials. During half of the trials, two keys were presented for 50 s. Left-key pecks were reinforced according to a variable-interval 67.86-s schedule during the first 25 s of the trial, and right-key pecks were not reinforced. During the second 25 s of the trial, right-key pecks were reinforced according to the same schedule, and left-key pecks were not reinforced. In the other half of the 40-trial session, the center key was presented. The majority of these trials arranged fixed-interval 2.5-s schedules. Occasionally a probe, or peak-interval, trial was presented. These trials were 100 s in duration and terminated without reinforcement. These two procedures were used to examine the effects of morphine on indexes of timing and on patterns of responding. Morphine altered behavior in a race-dependent manner in both procedures. Low baseline (saline) response rates were increased following morphine administration, and high baseline rates were either unaffected or decreased slightly. Rate-dependent effects appeared as leftward shifts in the timing index for two-key trials and decreases in the index of curvature for fixed-interval trials. Despite large changes in response rates, no consistent shift of the peak time was observed during peak-interval trials. These results are discussed primarily in terms of rate dependency; that is, rates of responding following drug administration tend to be determined in large part by rates of responding under baseline conditions.

Knealing, Todd W; Schaal, David W



The Venus Tablet and Refraction  

Microsoft Academic Search

It is shown that the refraction near the horizon is introducing an additional\\u000abias into the Venus Tablet of Ammisaduqa, which is able to influence the\\u000ainterpretation of the data. We then discuss the attempts to link certain solar\\u000aeclipses to the birth of Shamshi-Adad and conclude that a record of a single\\u000asolar eclipse without description of details and\\/or

V. G. Gurzadyan




Microsoft Academic Search

This research focuses on the use of the Tablet PC in education. The research explores the development of the Tablet PC and introduces the Classroom Presenter software. Implementation efforts of both the Tablet PC and the Classroom Presenter software at Coastal Carolina University are explored.



Potentiation of morphine analgesia by caffeine.  

PubMed Central

Significant potentiation of morphine (5 mg kg-1 s.c. or 1 mg kg-1 i.v.) analgesia (tail-withdrawal reflex at 55 degrees C) was observed in caffeine-treated (100 mg kg-1 i.p.) rats as compared to the control group and lower doses of caffeine (2mg kg-1 i.p.) did not show this effect. Potentiated analgesia was reversed by naloxone. Pharmacokinetic or dispositional factors appear to be involved in part in this potentiation.

Misra, A. L.; Pontani, R. B.; Vadlamani, N. L.



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.


Effects of morphine and morphine withdrawal on brainstem neurons innervating hypothalamic nuclei that control thepituitary-adrenocortical axis in rats  

PubMed Central

Different data support a role for brainstem noradrenergic inputs to the hypothalamic paraventricular nucleus (PVN) in the control of hypothalamus?–?pituitary?–?adrenocortical (HPA) axis. However, little is known regarding the functional adaptive changes of noradrenergic afferent innervating the PVN and supraoptic nucleus (SON) during chronic opioid exposure and upon morphine withdrawal.Here we have studied the expression of Fos after administration of morphine and during morphine withdrawal in the rat hypothalamic PVN and SON. Fos production was also studied in brainstem regions that innervate hypothalamic nuclei: the nucleus of solitary tract (NTS?–?A2) and the ventrolateral medulla (VLM?–?A1) and combined with immunostaining for tyrosine hydroxylase (TH) for immunohistochemical identification of active neurons during morphine withdrawal. Male rats were implanted with s.c. placebo or morphine (tolerant/dependent) pellets for 7 days. On day 8 rats received an injection of saline i.p., morphine i.p., saline s.c. or naloxone s.c.Acute morphine administration produced an increase in Fos expression at hypothalamic nuclei and in the brainstem regions, and tolerance developed towards this effect. Precipitated morphine withdrawal induced marked Fos immunoreactivity within the PVN and SON. Concomitantly, numerous neurons in the brainstem were stimulated by morphine withdrawal. Moreover, catecholaminergic-positive neurons in the brainstem showed a significant increase in Fos expression in response to morphine withdrawal.These findings demonstrate that chronic activation of opioid receptors results in altered patterns of immediate-early genes (IEG) expression in the PVN and SON, which occurs concurrently with an increased activity of their inputs from the brainstem.

Laorden, Maria Luisa; Castells, Maria Teresa; Milanes, Maria Victoria



Morphine Withdrawal in the Rat: Assessment by Quantitation of Diarrhea and Modification by Ethanol  

Microsoft Academic Search

A procedure to quantitatively assess diarrhea during morphine withdrawal in rats has been developed. Physical dependence on morphine was produced either by pellet implantation (75 mg morphine\\/rat) or by a single subcutaneous injection of morphine (150 mg\\/kg in oil). The gross morphine abstinence signs observed after naloxone administration included diarrhea, body weight loss, jumping, wet-dog shakes, hypothermia, teeth chattering, and

Andrew K. S. Ho; Raymond C. A. Chen; Mary Jeanne Kreek



Electroacupuncture Treatment Normalized Sleep Disturbance in Morphine Withdrawal Rats  

PubMed Central

Sleep disturbance is considered as an important symptom of acute and protracted opiate withdrawal. Current results suggest that sleep disturbance may be taken as a predictor of relapse. Appropriate sleep enhancement therapy will be in favor of the retention in treatment for opiate addicts. Our previous studies have shown that electroacupuncture (EA) is effective in suppressing morphine withdrawal syndrome. The aim of the present study is to investigate the effect of 2 and 100?Hz EA on the sleep disturbance during morphine withdrawal. Rats were made dependent on morphine by repeated morphine injections (escalating doses of 5–80?mg?kg?1, subcutaneously, twice a day) for 5 days. EA of 2 or 100?Hz was given twice a day for 3 days, starting at 48?h after the last morphine injection. Electroencephalogram and electromyogram were monitored at the end of the first and the last EA treatments, respectively. Results showed that non-rapid eye movement (NREM) sleep, REM sleep and total sleep time decreased dramatically, while the sleep latency prolonged significantly during acute morphine withdrawal. Both 2 and 100?Hz EA produced a significant increase in NREM sleep, REM sleep and total sleep time. It was suggested that EA could be a potential treatment for sleep disturbance during morphine withdrawal.

Li, Yi-Jing; Zhong, Fei; Yu, Peng; Han, Ji-Sheng; Cui, Cai-Lian; Wu, Liu-Zhen



Effect of Bacopasides on acquisition and expression of morphine tolerance.  


Opioids are extensively used for the management of both chronic malignant and non malignant pains. One major serious limitation associated with chronic use of opioids is the development of tolerance to its analgesic effect. The effect of Bacopa monnieri, a renowned ayurvedic medicine for acquisition and expression of morphine tolerance in mice, was investigated. Bacopa monnieri, n-Butanol fraction was analyzed on High performance liquid chromatography (HPLC), for Bacopaside A major components i.e. Bacoside A(3), Bacopaside ll and Bacosaponin C. Antinociceptive effect of n-Butanol extract of Bacopa monnieri (n Bt-ext BM) (5, 10 and 15 mg/kg) was assessed on hot plate. Effect of different doses of n Bt-ext BM on morphine antinociception was also assessed. n Bt-ext BM was also screened for development of tolerance to antinociceptive effect of Bacopa monnieri by administering 15 mg/kg n Bt-ext BM for seven days. Tolerance to morphine analgesia was induced in mice by administering intraperitoneally (I.P.) 20 mg/kg morphine twice daily for five days. Acute and Chronic administration of 5, 10 and 15 mg/kg n Bt-ext BM significantly reduced both expression and development of tolerance to morphine analgesia in mice. Additionally, Bacopa monnieri was found to enhance antinociceptive effect of morphine in intolerant animals. However, no tolerance to Bacopa monnieri antinociceptive effect was observed in seven days treatment schedule. These findings indicate effectiveness of Bacopa monnieri for management of morphine tolerance. PMID:21377853

Rauf, Khalid; Subhan, Fazal; Abbas, Muzaffar; Badshah, Amir; Ullah, Ihsan; Ullah, Sami



Changes in morphine reward in a model of neuropathic pain.  


In addition to sensory disturbances, neuropathic pain is associated with an ongoing and persistent negative affective state. This condition may be reflected as altered sensitivity to rewarding stimuli. We examined this hypothesis by testing whether the rewarding properties of morphine are altered in a rat model of neuropathic pain. Neuropathic pain was induced by chronic constriction of the common sciatic nerve. Drug reward was assessed using an unbiased, three-compartment conditioned place preference (CPP) paradigm. The rats underwent two habituation sessions beginning 6 days after surgery. Over the next 8 days, they were injected with drug or vehicle and were confined to one CPP compartment for 30 min. On the following test day, the rats had access to all three compartments for 30 min. Consistent with the literature, systemic administration of morphine dose-dependently increased the CPP in pain-naive animals. In rats with neuropathic pain, however, the dose-dependent effects of morphine were in a bell-shaped curve, with a low dose of morphine (2 mg/kg) producing a greater CPP than a higher dose of morphine (8 mg/kg). In a separate group of animals, acute administration of morphine reversed mechanical allodynia in animals with neuropathic pain at the same doses that produced a CPP. The increased potency of systemic morphine to produce a CPP in animals with neuropathic pain suggests that the motivation for opioid-induced reward is different in the two states. PMID:23591124

Cahill, Catherine M; Xue, Lihua; Grenier, Patrick; Magnussen, Claire; Lecour, Samantha; Olmstead, Mary C



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.



Powerful behavioral interactions between methamphetamine and morphine.  


Use of drugs of abuse in combination is common among recreational users and addicts. The combination of a psychomotor stimulant with an opiate, known as a 'speedball,' reportedly produces greater effects than either drug alone and has been responsible for numerous deaths. Historically, the most popular speedball combination is that of cocaine and heroin. However, with the growing popularity of methamphetamine in recent years, there has been increased use of this drug in combination with other drugs of abuse, including opiates. Despite this, relatively little research has examined interactions between methamphetamine and opiates. In the current research, behavioral interactions between methamphetamine and the prototypical opiate, morphine, were examined across a variety of dose combinations in Sprague-Dawley rats. The combination of methamphetamine and morphine produced stimulation of behavior that was dramatically higher than either drug alone; however, the magnitude of the interaction was dependent on the dose of the drugs and the specific behaviors examined. The results demonstrate complex behavioral interactions between these drugs, but are consistent with the idea that this combination is used because it produces a greater effect than either drug alone. PMID:21549146

Trujillo, Keith A; Smith, Monique L; Guaderrama, Melissa M



Episodic withdrawal promotes psychomotor sensitization to morphine.  


The relative intermittency or continuity of drug delivery is a major determinant of addictive liability, and also influences the impact of drug exposure on brain function and behavior. Events that occur during the offset of drug action (ie, acute withdrawal) may have an important role in the consequences of intermittent drug exposure. We assessed whether recurrent episodes of acute withdrawal contribute to the development of psychomotor sensitization in rodents during daily morphine exposure. The acoustic startle reflex--a measure of anxiety induced by opiate withdrawal-was used to resolve and quantify discrete withdrawal episodes, and pharmacological interventions were used to manipulate withdrawal severity. Startle potentiation was observed during spontaneous withdrawal from a single morphine exposure, and individual differences in initial withdrawal severity positively predicted the subsequent development of sensitization. Manipulations that reduce or exacerbate withdrawal severity also produced parallel changes in the degree of sensitization. These results demonstrate that the episodic experience of withdrawal during daily drug exposure has a novel role in promoting the development of psychomotor sensitization--a prominent model of drug-induced neurobehavioral plasticity. Episodic withdrawal may have a pervasive role in many effects of intermittent drug exposure and contribute to the development of addiction. PMID:20811341

Rothwell, Patrick E; Gewirtz, Jonathan C; Thomas, Mark J



Morphine in ventilated neonates: its effects on arterial blood pressure  

PubMed Central

Objective To study the effects of continuous morphine infusion on arterial blood pressure in ventilated neonates. Design Blinded randomised placebo controlled trial. Setting Level III neonatal intensive care unit in two centres. Patients A total of 144 ventilated neonates. Inclusion criteria were postnatal age <3?days, ventilation <8?hours, and indwelling arterial line. Exclusion criteria were severe asphyxia, severe intraventricular haemorrhage, major congenital anomalies, neuromuscular blockers. Intervention Arterial blood pressure was measured before the start and during the first 48?hours of masked infusion of drug (morphine/placebo; 100??g/kg + 10??g/kg/h). Outcome measures Arterial blood pressure and blood pressure variability. Results There were no significant differences in overall mean arterial blood pressure between the morphine group (median (interquartile range) 36?mm?Hg (6) and the placebo group (38?mm?Hg (6)) (p ?=? 0.11). Although significantly more morphine treated patients (70%) showed hypotension than the placebo group (47%) (p ?=? 0.004), the use of volume expanders and vasopressor drugs was not significantly different (morphine group, 44%; placebo group, 48%; p ?=? 0.87), indicating the limited clinical significance of this side effect. Blood pressure variability was not influenced by routine morphine analgesia (p ?=? 0.81) or additional morphine (p ?=? 0.80). Patients with and without intraventricular haemorrhage showed no differences in blood pressure (Mann?Whitney U test 1953; p ?=? 0.14) or incidence of hypotension (?2 test 1.16; df 1; p ?=? 0.28). Conclusions Overall arterial blood pressure, use of inotropes, and blood pressure variability were not influenced by morphine infusion. Therefore the clinical impact of hypotension as a side effect of low dose morphine treatment in neonates is negligible.

Simons, S H P; Roofthooft, D W E; van Dijk, M; van Lingen, R A; Duivenvoorden, H J; van den Anker, J N; Tibboel, D



Examination of Acute Sensitivity to Morphine and Morphine Self- Administration Following Physical and Environmental Stressors in Fischer-344 and Lewis Female Rats.  

National Technical Information Service (NTIS)

The present experiments examined the effects of different environmental conditions on acute morphine sensitivity and morphine self- administration in two genetically diverse inbred strains of rats. Fischer-344 and Lewis rats were subjects because they are...

K. Brown



Increase in Plasma Concentrations of Geranylgeranoic Acid after Turmeric Tablet Intake by Healthy Volunteers  

PubMed Central

Geranylgeranoic acid (GGA) is one of the most potent cancer-preventive acyclic retinoids. GGA has been shown to induce cell death in human hepatoma-derived HuH-7 cells. We have recently reported the natural occurrence of GGA and its related compounds in several medicinal herbs such as turmeric, basil, rosehip, cinnamon and others [Shidoji and Ogawa, J. Lipid Res., 45: 1092–1103, 2004]. In the present study, we performed oral administration of turmeric tablets to healthy volunteers in order to investigate bioavailability of natural GGA. By using liquid chromatography/mass spectrometry, authentic GGA was eluted at a retention time of around 18 min as a negative ion of m/z 303.4. With healthy volunteers, plasma GGA was detected prior to the tablet intake and its concentrations were increased at 2 h after its intake and maintained at higher level until 4 h, suggesting an efficient bioavailability of preformed GGA in the turmeric tablets through oral administration. These results indicated that GGA in the turmeric tablet was absorbed as an intact form from intestinal mucosa. The present study provides a clue to conduct a research for cancer preventive roles of GGA in a number of spices.

Mitake, Maiko; Ogawa, Hiroko; Uebaba, Kazuo; Shidoji, Yoshihiro



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.



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


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.



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


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 (10mg/kg increasing to 30mg/kg, twice a day for 5days) showed a twofold 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 (10mg/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



Relationship Between Gelation Rate of Controlled-release Acetaminophen Tablets Containing Polyethylene Oxide and Colonic Drug Release in Dogs  

Microsoft Academic Search

Purpose. We hypothesized that sufficient gelation of orally administered hydrophilic matrix tablets before they reach the colon could, as a result of continuous erosion of the gelated matrix, prevent the decrease in colonic drug release which normally occurs here. The purpose of this study was to elucidate the effect of gelation of hydrophilic matrices containing polyethylene oxide on colonic drug

Kazuhiro Sako; Hiroshi Nakashima; Toyohiro Sawada; Muneo Fukui



Comparison of Risperidone Orodispersible Tablet and Intramuscular Haloperidol in the Treatment of Acute Psychotic Agitation: A Randomized Open, Prospective Study  

Microsoft Academic Search

Objectives: Psychotic agitation of psychiatric patients is a common manifestation that needs emergent management. Traditionally, parenteral or intramuscular injection of antipsychotics was conducted for treatment of psychotic agitation. Considering that the rapidly absorbed form of risperidone (risperidone orodispersible tablet) could be used for the agitated patient, comparison of oral risperidone and intramuscular haloperidol was performed in emergency treatment of psychotic

Hyun Kook Lim; Jung Jin Kim; Chi Un Pae; Chang Uk Lee; Chul Lee; In Ho Paik



An in vitro and in vivo comparative study of directly compressed solid dispersions and freeze dried sildenafil citrate sublingual tablets for management of pulmonary arterial hypertension.  


Sildenafilcitrate (SILD) orodispersable sublingual tablets (ODSTs) have been developed using two comparative techniques for improving their oral disintegration, dissolution and bioavailability in order to manage acute attacks of pulmonary arterial hypertension (PAH). The techniques employed were direct compression of SILD-poloxamer 188 solid dispersions (SDs) and freeze drying using various excipients. The physicochemical and solid-state properties, as well as the dissolution behavior of the tablets were evaluated. Moreover, SILD bioavailability in human volunteers from the prepared ODSTs was compared to that of the conventional oral tablet. Incorporation of SD of poloxamer188 in sublingual tablets together with Pharmaburst using the direct compression technique enhanced the extent and dissolution rate of SILD with 100% of drug being dissolved after 7 minutes. However, the lyophilization process was superior in enhancing dissolution and 100% of SILD was dissolved after only one minute. Moreover, the in vivo study showed that the AUC???? of lyophilized tablets was significantly higher than that of directly compressed tablets, with bioavailability values of 159.81 and 140.85%, respectively, compared to the commercial oral product. PMID:23470352

Zayed, Reham; Kamel, Amany O; Shukr, Marwa; El-Shamy, Abd El-Hamid



Blockade of toll-like receptor 4 attenuates morphine tolerance and facilitates the pain relieving properties of morphine.  


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; Murphy, Anne Z



Improved Packaging of Water Purification Tablet.  

National Technical Information Service (NTIS)

The new method of packaging the iodine tablets consists of sealing the individual tablets in a blister sheet and packaging two blister sheets in an overwrapper packet. The blister sheet measures 1 3/4 in x 2 1/8 in and contains 12 transparent blister unit...

J. L. Carney



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...FORM NEW ANIMAL DRUGS § 520.1870 Praziquantel tablets. (a) Specifications ...contains: (1) 34 milligrams (mg) praziquantel. (2) 11.5 or 23 mg...



Fluoride Tablets and Salivary Fluoride Levels  

Microsoft Academic Search

Mixed salivary fluoride levels have been measured after 9 subjects sucked or slowly dissolved three different brands of 1 mg F–– fluoride tablets. Results indicate that for all preparations the maximum salivary F–– concentration was obtained when a tablet was sucked rather than dissolved. However, salivary F–– retention was greatly enhanced under conditions which allowed undisturbed disintegration of each formulation.

D. McCall; K. W. Stephen; S. G. McNee



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.



Tablet computers in the veterinary curriculum.  


Tablet computers offer a new method of information management in veterinary medical education. With the tablet computer, students can annotate class notes using electronic ink, search for keywords, and convert handwriting to text as needed. Additional electronic learning resources, such as medical dictionaries and electronic textbooks, can be readily available. Eleven first-year veterinary students purchased tablet computers and participated in an investigation of their working methods and perceptions of the tablet computer as an educational tool. Most students found the technology useful. The small size and portability of the tablet allowed easy transport and use in a variety of environments. Most students adapted to electronic notetaking by the second week of classes; negative experiences with the tablet centered on a failure to become comfortable with taking notes and navigating on the computer as opposed to writing and searching on paper. A few performance-related problems, including short battery life, were reported. Tablet software allowed conversion of faculty course notes from a variety of original formats, meaning that instructors could maintain their original methods of note preparation. Adopting a consistent naming convention for files helped students to locate the files on their computers, and smaller file sizes helped with computer performance. Collaboration between students was fostered by tablet use, which offers possibilities for future development of collaborative learning environments. PMID:15834829

Eurell, Jo Ann C; Diamond, Nancy A; Buie, Brandon; Grant, David; Pijanowski, Gerald J



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



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



Using a Tablet PC for Classroom Instruction  

Microsoft Academic Search

An increasing trend for lecture-based courses is for instructors to convert their lecture notes to slides that can be projected electronically. While there are many advantages to electronic projection, a large drawback is the loss of interactivity and spontaneity that can result. The use of a tablet PC by the instructor promises to overcome this difficulty. The tablet PC, combined

Carol C. W. Hulls



Analysis of fatty acids in ecstasy tablets  

Microsoft Academic Search

Fatty acids are the basis of so-called stearates which are frequently used as lubricants in the production of ecstasy tablets. Being a product added at the initial tablet production step its composition does not change once the compression is performed. The analysis of fatty acids can therefore provide useful information for a drug intelligence purpose. In this context an appropriate

Ines Baer; Pierre Margot



Spinal mitochondrial-derived peroxynitrite enhances neuroimmune activation during morphine hyperalgesia and antinociceptive tolerance.  


Treatment of severe pain by morphine, the gold-standard opioid and a potent drug in our arsenal of analgesic medications, is limited by the eventual development of hyperalgesia and analgesic tolerance. We recently reported that systemic administration of a peroxynitrite (PN) decomposition catalyst (PNDC) or superoxide dismutase mimetic attenuates morphine hyperalgesia and antinociceptive tolerance and reduces PN-mediated mitochondrial nitroxidative stress in the spinal cord. These results suggest the potential involvement of spinal PN signaling in this setting; which was examined in the present study. PN removal with intrathecal delivery of manganese porphyrin-based dual-activity superoxide/PNDCs, MnTE-2-PyP(5+) and the more lipophilic MnTnHex-2-PyP(5+), blocked hyperalgesia and antinociceptive tolerance in rats. Noteworthy is that intrathecal MnTnHex-2-PyP(5+) prevented nitration and inactivation of mitochondrial manganese superoxide dismutase. Mitochondrial manganese superoxide dismutase inactivation enhances the superoxide-to-PN pathway by preventing the dismutation of superoxide to hydrogen peroxide, thus providing an important enzymatic source for PN formation. Additionally, intrathecal MnTnHex-2-PyP(5+) attenuated neuroimmune activation by preventing the activation of nuclear factor kappa B, extracellular-signal-regulated kinase and p38 mitogen activated protein kinases, and the enhanced levels of proinflammatory cytokines, interleukin (IL)-1? and IL-6, while increasing anti-inflammatory cytokines, IL-4 and IL-10. The role of PN was further confirmed using intrathecal or oral delivery of the superoxide-sparing PNDC, SRI-110. These results suggest that mitochondrial-derived PN triggers the activation of several biochemical pathways engaged in the development of neuroinflammation in the spinal cord that are critical to morphine hyperalgesia and tolerance, further supporting the potential of targeting PN as an adjunct to opiates to maintain pain relief. PMID:23590939

Little, Joshua W; Cuzzocrea, Salvatore; Bryant, Leesa; Esposito, Emanuela; Doyle, Timothy; Rausaria, Smita; Neumann, William L; Salvemini, Daniela



[Reactogenicity and immunological effectiveness of an oral cholera chemical vaccine in a limited controlled experiment with human revaccination].  


Oral cholera chemical vaccine in the doses tested (2 and 3 tablets) proved to be areactogenic, harmless and immunologically effective in a controlled limited trial in 150 volunteers. By the results of titration of specific antitoxins and vibriocidal antibodies in the blood serum, as well as of coproantibodies a dose of 2 tablets was chosen as the optimal one. PMID:371293

Sumarokov, A A; Ivanov, N R; Lelikov, V L; Dzhaparidze, M N; Karaeva, L T



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.

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



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.



Discriminative stimulus effects of nalbuphine in nontreated and morphine-treated pigeons.  


In the present study, the stimulus effects of the low efficacy agonist nalbuphine were examined under two conditions: nontreated and morphine treated. In the first experiment, five pigeons were trained to discriminate among 3.2 mg/kg morphine, 5.6 mg/kg nalbuphine, and saline. Nalbuphine produced nalbuphine-like responding. Low doses of morphine produced nalbuphine-like responding, whereas high doses produced morphine-like responding. Naltrexone produced saline-like responding and reversed the stimulus effects produced by the training doses of morphine and nalbuphine. Five different pigeons were treated daily with 10 mg/kg morphine (i.m.) and trained 6 h later to discriminate among 10 mg/kg morphine, 1.0 mg/kg nalbuphine and saline. In these pigeons, morphine produced morphine-like responding and nalbuphine produced nalbuphine-like responding. Morphine abstinence produced nalbuphine-like responding that was reversed by morphine. Additionally, naltrexone produced nalbuphine-like responding. These data suggest that the discrimination between morphine and nalbuphine in the nontreated and morphine-treated pigeons may be based on the relative efficacy differences between morphine, a higher efficacy mu-agonist, and nalbuphine a lower efficacy mu-agonist. PMID:10515328

Walker, E A; Hawkins, E R; Tiano, M J; Picker, M J; Dykstra, L A



Systemic Absorption of Rifamycin SV MMX Administered as Modified-Release Tablets in Healthy Volunteers?  

PubMed Central

The new oral 200-mg rifamycin SV MMX modified-release tablets, designed to deliver rifamycin SV directly into the colonic lumen, offer considerable advantages over the existing immediate-release antidiarrheic formulations. In two pharmacokinetics studies of healthy volunteers, the absorption, urinary excretion, and fecal elimination of rifamycin SV after single- and multiple-dose regimens of the new formulation were investigated. Concentrations in plasma of >2 ng/ml were infrequently and randomly quantifiable after single and multiple oral doses. The systemic exposure to rifamycin SV after single and multiple oral doses of MMX tablets under fasting and fed conditions or following a four-times-a-day (q.i.d.) or a twice-a-day (b.i.d.) regimen could be considered negligible. With both oral regimens, the drug was confirmed to be very poorly absorbable systemically. The amount of systemically absorbed antibiotic excreted by the renal route is far lower than 0.01% of the administered dose after both the single- and multiple-dose regimens. The absolute bioavailability, calculated as the mean percent ratio between total urinary excretion amounts (?Xu) after a single intravenous injection and after a single oral dose under fasting conditions, was 0.0410 ± 0.0617. The total elimination of the unchanged rifamycin SV with feces was 87% of the administered oral dose. No significant effect of rifamycin SV on vital signs, electrocardiograms, or laboratory parameters was observed.

Di Stefano, A. F. D.; Rusca, A.; Loprete, L.; Droge, M. J.; Moro, L.; Assandri, A.



Procainamide Oral  


Procainamide is used to treat abnormal heart rhythms. It works by making your heart more resistant to ... Procainamide comes as a capsule and tablet to take by mouth. Immediate-acting procainamide usually is taken ...


[Antisecretory effect of the H2-histamine receptor antagonist ranitidine in water-soluble tablets and film-coated tablets. Results of a randomized, placebo-controlled crossover study in humans].  


This clinico-pharmacological trial aimed to prove equivalence between the known film-coated tablets of ranitidine (Sostril Filmtabletten) and the novel dispersible tablets for the preparation of a drinkable solution (Sostril Aquatabs) on a pharmacodynamic level. Therefore, the influence of single oral doses of the two ranitidine preparations (2 X 150 mg p.e.m. each) and placebo on the gastric hydrogen ion concentration was studied in 12 healthy volunteers using a randomized cross-over design. pH-values of the gastric juice were measured and recorded continuously for 24 h. Median pH-values for the entire study period were 2.20, 2.15 and 1.40 for dispersible tablets, filmcoated tablets and placebo, respectively. During the night-time median pH-values of 3.45 for both ranitidine preparations and 1.40 for placebo were calculated. From these results it can be concluded that the novel dispersible tablets are equivalent to the ranitidine filmcoated tablets with regard to their pharmacodynamic potency. PMID:2192716

Witzel, L; Röhmel, J



[Nonspecific effect of morphine on the erythrocyte membrane].  


The effect of low morphine concentrations on the plasmatic membranes of erythrocytes without opiate receptors was investigated. It was shown that the ATPase activity and hemolytic stability of erythrocytes, which characterize the state of cell membranes and the mobility of the near-membrane water phase, depend on the concentration of morphine, and this dependence is wave-like. The nonmonotonous dependence of the biological response was suggested to be due to changes in the structure of water hydrogen links near the membrane surface, induced by opiate molecules. The hypothesis was confirmed by the results of studies of morphine water solutions using the methods of fluorescent probe and light scattering. It was found that the intensity of light scattering by water and the mobility of its molecules considerably increase in the presence of strictly specified concentrations of morphine. PMID:15458252

Kuznetsov, P E; Zlobin, V A; Nazarov, G V; Kuznetsova, N B; Rogacheva, S M; Gracheva, A A


Chronic alcohol exposure increases ganglia endogenous morphine levels  

PubMed Central

Introduction We have previously demonstrated that alcohol has the ability to release low levels of endogenously expressed, chemically authentic, morphine from neural tissues. Material and methods Presently, we demonstrate that chronic exposure of Mytilus edulis pedal ganglia tissues maintained in organotypic culture to very concentrations of 1 mM and 10 mM ethanol induces a time dependent increase in both endogenous morphine and dopamine (DA) levels. Results Chronic incubation of M. edulis pedal ganglia with 3 concentrations of DA resulted in statistically significant elevations of cellular morphine levels, thereby confirming previous studies from our laboratory establishing DA as an essential precursor in the morphine biosynthetic pathway. Conclusions By understanding multiple debilitating effects of alcohol on “morphinergic” signaling, we may understand the ravages of neural processes associated with alcohol abuse and how its treatment may be made more effective.

Li, Yiqing; Kream, Richard M.; Stefano, George B.



Enduring Effects of Morphine Pellets Revealed by Conditioned Taste Aversion.  

National Technical Information Service (NTIS)

Morphine pellets (75 mg) were implanted subcutaneously in albino rats. Three days later, following 24 h without water, these rats (Group MSN) were given access to a saccharin solution for 30 min, then injected with naloxone hydrochloride. The classical ab...

F. J. Manning M. C. Jackson



Localization of the Antinociceptive Action of Morphine in Primate Brain.  

National Technical Information Service (NTIS)

Microinjections of morphine sulfate (20 to 40 micrograms were made into various subcortical regions of the rhesus monkey brain. The effects of these injections were evaluated on the nociceptive threshold, as defined by the shock titration technique. The r...

A. Pert T. Yaksh



Design and evaluation of matrix-based controlled release tablets of diclofenac sodium and chondroitin sulphate  

Microsoft Academic Search

The purpose of the present study was to develop and characterize an oral controlled release drug delivery system for concomitant\\u000a administration of diclofenac sodium (DS) and chondroitin sulfate (CS). A hydrophilic matrix-based tablet using different concentrations\\u000a of hydroxypropylmethylcellulose (HPMC) was developed using wet granulation technique to contain 100 mg of DS and 400 mg of\\u000a CS. Formulations prepared were evaluated

Amelia Avachat; Vikram Kotwal



Investigations on mefenamic acid sustained release tablets with water-insoluble gel  

Microsoft Academic Search

Mefenamic acid (MA) has analgesic, anti-inflammatory and antipyretic properties. Available conventional dosage forms are capsules and film-coated tablets. No commercial sustained release preparation of MA exists in the market. The usual oral dose is 250 or 500 mg and reported half-life is 2 h. Sodium alginate (NaAL) is the sodium salt of alginic acid, a natural polysaccharide extracted from marine

S. Güngör; A. Y?ld?z; Y. Özsoy; E. Cevher; A. Araman



Pharmacokinetics of multi-dose D-polymannuronicate tablets in Chinese healthy volunteers  

Microsoft Academic Search

Aim To investigate the pharmacokinetics of multi-dose D-polymannuronicate tablet in Chinese healthy male volunteers. Methods The protocol was designed according to GCP principle after ethics committee passed. It's necessary that all volunteers sign the informed consents. 12 volunteers passed health and laboratory examinations took orally D-polymannuronicate 400mg once a day for 10 days. The activated part thromboplastin time (aPTT) assay

Rui Wang; Yi Fang; Mei-Yu Geng; Gui-Ling Li; Xian-Liang Xin; Xin Qi; Dong Chai; Fei Pei; Sen-Yang Lang; Xiao-Mei Qin; Sheng-Jie Chen; Nai-Dong Wang


Fangchinoline inhibited the antinociceptive effect of morphine in mice  

Microsoft Academic Search

Fangchinoline (FAN), a non-specific calcium antagonist, is a major alkaloidal component of the creeper Stephania tetrandra S. Moore (or fenfangji). It has been shown to possess antagonistic activity on morphine-induced antinociception in mice. This study was undertaken to assess the antagonistic mechanism. The results demonstrated that FAN (IP) attenuated morphine (SC)-induced antinociception in a dose-dependent manner with significant effect at

L.-H. Fang; Y.-H. Zhang; B.-S. Ku



Signaling pathway of morphine induced acute thermal hyperalgesia in mice  

Microsoft Academic Search

Systemic administration of morphine induced a hyperalgesic response in the hot plate test, at an extremely low dose (1–10?g\\/kg). We have examined in vivo whether morphine, at an extremely low dose, induces acute central hypernociception following activation of the opioid receptor-mediated PLC\\/PKC inositol-lipid signaling pathway. The PLC inhibitor U73122 and the PKC blocker, calphostin C, dose dependently prevented the thermal

Nicoletta Galeotti; George B. Stefano; Massimo Guarna; Enrica Bianchi; Carla Ghelardini



Enhanced Immune Sensitivity to Stress Following Chronic Morphine Exposure  

Microsoft Academic Search

Chronic administration of escalating doses ofmorphine leads to neuroadaptive changes precipitating development of tolerance\\u000a to many of the acute effects of morphine, such as analgesia, activation of the hypothalamic–pituitary–adrenal (HPA) axis and\\u000a suppression of immune cell activities. Interestingly, morphine tolerance has also been shown to be accompanied by heightened\\u000a immunosuppressive effects of restraint stress using a rodent model. These observations

Kimberly A. Ballard; Trisha C. Pellegrino; Norma C. Alonzo; Alexandria L. Nugent; Barbara M. Bayer



Temporal effects of topical morphine application on cutaneous wound healing  

PubMed Central

Background Studies have shown that topical administration of exogenous opioid drugs impairs wound healing by inhibiting the peripheral release of neuropeptides, thereby inhibiting neurogenic inflammation. This delay is immediate and peaks during the first days of wound closure. This study examined the effects of topical morphine treatment in a cutaneous wound healing model in the rat. Methods Full-thickness 4mm diameter wounds were placed on the periscapular region of rats that subsequently received twice-daily topical applications of IntraSite Gel (Smith+Nephew, Hull, United Kingdom) alone or gel infused with 5 mM morphine sulfate on days 0–3 or 4–10 post-wounding or throughout the time course. Wound tissue was taken on days 1, 3, 5, 8, and 18 post-wounding and immunostained for myofibroblast and macrophage markers or stained with hematoxylin and eosin. Results Delays in wound closure observed during morphine application on days 0–3 post-wounding mimicked those seen in wounds treated with morphine throughout the entire healing process. However, no significant delays in closure were seen in wounds treated with morphine beginning on day 4 post-wounding. Treatment of wounds with morphine significantly reduced the number of myofibroblasts and macrophages in the closing wound. Additionally, morphine application resulted in decreases in skin thickness and an increase in residual scar tissue in healed skin. Conclusions These findings demonstrate the time-dependent and persistent nature of the detrimental effects of topical morphine on cutaneous wound healing. The data identify specific limitations that could be ameliorated to optimize topical opioid administration as an analgesic therapeutic strategy in the treatment of painful cutaneous wounds.

Rook, Jerri M.; Hasan, Wohaib; McCarson, Kenneth E.



Quantitative analysis of morphine in dried blood spots by using morphine-d3 pre-impregnated dried blood spot cards.  


Two different internal standard dried blood spot (DBS) pre-impregnation procedures (prior to blood spotting) were investigated. In the first procedure DBS pre-impregnation is performed by immersing the DBS card fully into an internal standard solution. In the second procedure pre-impregnation is performed by pipetting a certain volume of an internal standard solution onto the DBS card. Morphine-d3 was used as the model compound for all experiments. The pre-impregnation procedure by immersing was further investigated with respect to homogeneity of impregnation, influence of different blood spotting techniques and the influence of spotting different blood volumes on the internal standard distribution, calibration and stability of pre-impregnated cards. Finally, the immersing procedure was used for the analysis of morphine in dried blood spots and the results were compared to the conventional procedure in which the internal standard morphine-d3 was added to the extraction solvent. The new pre-impregnated cards couple simplicity of operation and convenient use in the field to results equivalent to the conventional procedure. PMID:23567113

Mommers, John; Mengerink, Ynze; Ritzen, Erik; Weusten, Jos; van der Heijden, Jac; van der Wal, Sjoerd



The development and in vitro evaluation of sustained release tablet formulations of benzydamine hydrochloride and its determination.  


A novel oral controlled delivery system for benzydamine hydrochloride (BN) was developed and optimized. Hydrophilic matrix tablets of BN were prepared by using hydroxypropylmethylcellulose (HPMC) and chitosan as polymer substance to achieve required sustained release profile. The matrix tablets were prepared both direct compression and wet granulation method. The influence of matrix forming agents and binary mixtures of them on BN release was investigated. The formulated tablets were characterized by hardness, friability, thickness, weight variation and in vitro drug release. The formulated tablets had acceptable physicochemical characters. The quantity of BN present in the tablets and the release medium were estimated by a simple, sensitive, rapid and validated HPLC method. The dissolution results show that increased amount of polymer resulted in reduced and extended drug release. F7 formulation containing 12.5% HPMC and 12.5 % chitosan with direct compression method is the optimum formulation due to its better targeting profile in terms of release. Higuchi (diffusion) and Hixon-Crowell (erosion) kinetic profiles were achieved and this codependent mechanism of drug release was established. This formulation may provide an alternative for oral controlled delivery of BN and be helpful in the future treatment of primary normoreactive types of inflammation. PMID:20426743

Kose-Ozkan, Cansel; Savaser, Ayhan; Tas, Cetin; Ozkan, Yalcin



Role of repeated exposure to morphine in determining its affective properties: place and taste conditioning studies in rats  

Microsoft Academic Search

Male Sprague Dawley rats were injected daily with saline (morphine naive rats) or 20 mg\\/kg morphine (morphine experienced rats), starting at least 12 days before training. Subsequent place and taste conditioning indicated that 2.5 mg\\/kg morphine caused a significant increase in the amount of time spent on the least preferred side by morphine experienced but not by morphine naive rats;

M. Gaiardi; M. Bartoletti; A. Bacchi; C. Gubellini; M. Costa; M. Babbini



Teaching dynamics using interactive tablet PC instruction software  

Microsoft Academic Search

Is there an advantage of using interactive tablet PC software as opposed to more traditional teaching methods? This work is an innovative use of tablet PC technology to teach an introductory dynamics course. Each student in the classroom used a tablet PC as did the instructor. In addition to using the tablet PCs, each lecture was recorded using screen capture

David Fisher; Phillip Cornwell; Julia Williams



DDMAC Letter: Letairis™ (ambrisentan) tablets for oral use  

Center for Drug Evaluation (CDER)

Text Version... by misleadingly suggesting that the risks associated with the drug's risk management plan (potential liver injury and the risk of birth defects) do not ... More results from


Celexa (escitalopram oxalate) tablets/oral solution label  

Center for Drug Evaluation (CDER)

Text Version... Do not take Lexapro if you: • are allergic to escitalopram oxalate or citalopram hydrobromide or any of the ingredients in Lexapro. ... More results from


[Oral and formulated pharmaceutical preparations before the invention of tablets].  


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



Active ingredient: Zolpidem Form/Route: Tablets/Oral ...  

Center for Biologics Evaluation and Research (CBER)

Text Version... this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You ... More results from


Active ingredient: Zaleplon Form/Route: Tablets/Oral ...  

Center for Biologics Evaluation and Research (CBER)

Text Version... this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You ... More results from


Active ingredient: Irbesartan Form/Route: Tablet/Oral ...  

Center for Drug Evaluation (CDER)

Text Version... 1. Type of study: Fasting Design: Single-dose, two-treatment, two-period crossover in-vivo Strength: 300 mg Subjects: Normal healthy males and ... More results from


[Tramadol/acetaminophen combination tablets].  


Tramadol/acetaminophen fixed-dose combination tablets (Tramse) combine tramadol, a centrally acting week opioid analgesic, with low-dose acetaminophen. The action of tramadol may be described as a weak agonist at the mu-opioid receptor, inhibition of serotonin reuptake, and inhibition of noradrenaline reuptake. The second component in these tablets, acetaminophen mainly appears to act through central mechanism. Chronic pain may be broadly classified into nociceptive, neuropathic and mixed. Tramset may exert additive or synergic benefits in treating the multiple mechanism of pain. Clinical studies have revealed its efficacy and safety for a variety of pain condition such as chronic low back pain, rheumatoid arthritis, fibromyalgia and painful diabetic peripheral neuropathy. It is expected that Tramset is going to induce pain relief and to improve disturbance of daily life in patients with intractable chronic pain. However overuse of Tramset may induce severe adverse effects such as addiction, abuse and hepatotoxicity. Therefore clinician should continuously assess pain intensity, activity of daily life, mode of its consumption, and adverse effects after prescription. PMID:23905401

Yokotsuka, Shoko; Kato, Jitsu



Prolonged morphine administration alters protein expression in the rat myocardium  

PubMed Central

Background Morphine is used in clinical practice as a highly effective painkiller as well as the drug of choice for treatment of certain heart diseases. However, there is lack of information about its effect on protein expression in the heart. Therefore, here we aimed to identify the presumed alterations in rat myocardial protein levels after prolonged morphine treatment. Methods Morphine was administered to adult male Wistar rats in high doses (10 mg/kg per day) for 10 days. Proteins from the plasma membrane- and mitochondria-enriched fractions or cytosolic proteins isolated from left ventricles were run on 2D gel electrophoresis, scanned and quantified with specific software to reveal differentially expressed proteins. Results Nine proteins were found to show markedly altered expression levels in samples from morphine-treaded rats and these proteins were identified by mass spectrometric analysis. They belong to different cell pathways including signaling, cytoprotective, and structural elements. Conclusions The present identification of several important myocardial proteins altered by prolonged morphine treatment points to global effects of this drug on heart tissue. These findings represent an initial step toward a more complex view on the action of morphine on the heart.



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.

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



Mitragynine attenuates withdrawal syndrome in morphine-withdrawn zebrafish.  


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



Analysis of Biologic Samples for Morphine and Morphine-Related Compounds by Gas Chromatographic-Mass Spectrometric Methods.  

National Technical Information Service (NTIS)

Methods were investigated for the analysis of biologic samples containing morphinee and morphine-related compounds through use of bioanalytical systems involving gas chromatograph-mass spectrometer-computer combined instruments. Most of the work was carri...

E. C. Horning J. P. Thenot M. G. Horning



The effects of morphine treatment and morphine withdrawal on the dynorphin and enkephalin systems in sprague-dawley rats  

Microsoft Academic Search

The effect of morphine tolerance and withdrawal on prodynorphin peptides was studied in relevant brain areas and in the pituitary gland of male Sprague-Dawley rats, and compared with effects on the proenkephalin-derived peptide Met-enkephalin. After 8 days of morphine injections (twice daily), dynorphin A and B levels increased in the nucleus accumbens and dynorphin A levels increased also in the

Ingrid Nylander; M. Vlaskovska; L. Terenius



Postoperative hypoxaemia: continuous extradural infusion of bupivacaine and morphine vs patient-controlled analgesia with intravenous morphine  

Microsoft Academic Search

Summary We carried out a randomized prospective study in 60 patients who had undergone major abdominal surgery for cancer. For postoperative pain control, 30 patients received continuous extradural infusion of 0.125% bupivacaine 12.5 mg h1 and morphine 0.25 mg h1 (EXI group) and 30 received patient-controlled analgesia (PCA) with intravenous morphine (1 mg bolus, 5-min lock-out and maximum dose 20



Terahertz Technology: A Boon to Tablet Analysis  

PubMed Central

The terahertz gap has a frequency ranges from ?0.3 THz to ?10 THz in the electromagnetic spectrum which is in between microwave and infrared. The terahertz radiations are invisible to naked eye. In comparison with x-ray they are intrinsically safe, non-destructive and non-invasive. Terahertz spectroscopy enables 3D imaging of structures and materials, and the measurement of the unique spectral fingerprints of chemical and physical forms. Terahertz radiations are produced by a dendrimer based high power terahertz source and spectroscopy technologies. It resolves many of the questions left unanswered by complementary techniques, such as optical imaging, Raman and infrared spectra. In the pharmaceutical industries it enables nondestructive, internal, chemical analysis of tablets, capsules, and other dosage forms. Tablet coatings are a major factor in drug bioavailability. Therefore tablet coatings integrity and uniformity are of crucial importance to quality. Terahertz imaging gives an unparalleled certainty about the integrity of tablet coatings and the matrix performance of tablet cores. This article demonstrates the potential of terahertz pulse imaging for the analysis of tablet coating thickness by illustrating the technique on tablets.

Wagh, M. P.; Sonawane, Y. H.; Joshi, O. U.



Effect of chronic morphine on the dentate gyrus neurogenic microenvironment.  


Opiates, such as morphine, decrease neurogenesis in the postnatal hippocampal subgranular zone (SGZ) by inhibiting progenitor proliferation and maturation. However, it is not known how morphine influences the growth factors and vasculature that encompass the neurogenic SGZ microenvironment. We examined morphine's effect on pro- and anti-proliferative factors in the dentate gyrus (DG; Experiment 1) as well as the DG neurovasculature itself (Experiment 2). For Experiment 1, mice were implanted with subcutaneous sham or morphine pellets (0 and 48 h) and were decapitated 24 or 96 h later. One brain hemisphere was postfixed to examine proliferation by immunohistochemistry, and a DG-enriched sample was dissected from the other hemisphere to examine the neurogenic microenvironment via immunoblotting for known pro- and anti-proliferative factors. Consistent with previous results, morphine decreased the number of proliferating cells in the SGZ, as the number of Ki67-immunoreactive (IR) cells was decreased at 96 h. Morphine did not alter DG levels of the pro-proliferative factor brain-derived neurotrophic factor, anti-proliferative factor interleukin-1 beta, or their receptors TrkB and IL1R1 at either time point. However, morphine increased the pro-proliferative factor vascular endothelial growth factor (VEGF) at 96 h. Given that VEGF is also a potent angiogenic factor, Experiment 2 examined whether the morphine-induced increase in VEGF correlated with altered DG neurovasculature. Mice were implanted with morphine pellets as in Experiment 1, and 2 h before perfusion (24 or 96 h) were administered bromodeoxyuridine (BrdU; intraperitoneal, 150 mg/kg). Tissue was co-stained for BrdU and the endothelial cell marker endoglin to enable examination of DG vessels and proximity of BrdU-IR cells to endoglin-IR vessels. At 96 h, endoglin-IR vessel area and perimeter were increased, but proximity of BrdU-IR cells to endoglin-IR vessels remained unchanged. These data suggest that following chronic morphine exposure, factors within the neurogenic microenvironment are maintained or upregulated to compensate for decreased SGZ proliferation. PMID:19356684

Arguello, A A; Fischer, S J; Schonborn, J R; Markus, R W; Brekken, R A; Eisch, A J



A single blind normal volunteer bioavailability study of a new microencapsulated potassium chloride tablet compared with two reference potassium formulations  

Microsoft Academic Search

Summary  A single blind placebo controlled, cross-over study comparing a new microencapsulated potassium chloride tablet (MET) with\\u000a two reference formulations of oral potassium, potassium chloride solution (PS) and potassium chloride wax-matrix tablets (WMT),\\u000a was performed in 12 normal healthy volunteers. Urinary potassium excretion was the main criterion of comparison.\\u000a \\u000a \\u000a Results showed that all three formulations have excellent bioavailability. This indicates that

H. Caplain; R. Dahan; R. Pamphile; J. J. Thebault



Tyzeka (telbivudine) tablets medication guide  

Center for Drug Evaluation (CDER)

Text Version... Tyzeka also comes as a liquid (oral solution) that you can drink. ... Tell your healthcare provider about any side effect that bothers you or that ... More results from


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



The relative expressed estrogenicity of oral contraceptives.  


Total effective estrogenicity of several human oral contraceptives was investigated through a method determining uterine weight in immature rats. The preparations, normally given to human females in tablet, form were Norinyl-1 (.05 mg mestranol, 1mg norethindrone), Norinyl-2 (.10 mg mestranol, 2 mg norethindrone), Ovulen (.10 mg mestranol, 1mg ethynodiol diacetate), Enovid-E (.10 mg mestranol, 2.5 mg norethynodrel), and Enovid-5 (.075 mg mestranol, 5mg norethynodrel). Each products was administered in total doses of .0025, .005, and .01 of a tablet. Each dose had 3 trials, approximately 10 mice to a trial. Each mouse was given the compound in .2 ml aqueous vehicle orally, daily for a 3-day period so that the sum of the daily doses equaled 1 of the tablet fractions above. Autopsy, on Day 4, discovered the ratio of mg uterus/gm body weight. A .0025 fraction of a tablet of Norinyl-1 produced a mean uterine ratio of 1.79, while control (untreated) mice had a mean ratio of 1.06. Norinyl-2, Ovulen, Enovid-5 and Enovid-E, judging from the corresponding increases in ratios from the control ratio, were found to be 2.1, 2.7, 6, and 8 times, respectively, more estrogenic than Norinyl-1. The relatively high estrogenicity of the Enovids is probably due to the conversion of norethynodrel to estrogenic compounds. PMID:5647620

Rooks, W H; Kugler, S L; Dorfman, R I


Effects of Morphine Sulfate on Agglutination, Clot Formation and Hemolysis in Packed Red Blood Cells.  

National Technical Information Service (NTIS)

Morphine sulfate is an opium alkaloid narcotic frequently used on patients suffering from acute and chronic disease processes. Often patients receiving either acute or long- term pain therapy with morphine require concomitant blood transfusion therapy. Ba...

B. K. Estavillo



Development of Fluorescence Based Systems for Detection of Morphine in Urine.  

National Technical Information Service (NTIS)

The report contains the results of efforts toward devising an improved method for fluorescent determination of morphine in urine. One of the initial problems investigated was a method for hydrolysis of morphine-3-glucuronide in urine without loss of morph...

D. A. Knowlton D. L. Marshall M. B. Neher



Effect of Chronic Administration of Morphine on the Activity of Brain Monoamine Oxidase in the Rat.  

National Technical Information Service (NTIS)

The effect of chronic administration of morphine on the activity of monoamine oxidase in specific regions of the brain of rats has been investigated. It was found that, shortly after the last administration of morphine, brain monoamine oxidase was drastic...

C. G. McHale G. N. Catravas J. Takenaga



Asymmetrical Cross-Tolerance Between Morphine- and Scopolamine-Induced Antinociception in the Primate.  

National Technical Information Service (NTIS)

Two experiments were designed to explore further the role of the cholinergic system in mediating morphine-induced analgesia in the Rhesus monkey. Experiment 1 tested for cross-tolerance between morphine and scopolamine using the shock titration technique....

A. Pert G. Maxey



Action of Reserpine in Morphine Tolerant Rats: Absence of an Antagonism of Catecholamine Depletion.  

National Technical Information Service (NTIS)

The mechanism of resistance to the catecholamine depleting effects of reserpine in morphine tolerant rats was examined. In vitro, morphine did not alter reserpine inhibition of 3H-norepinephrine uptake by synaptic vesicles. Similarly, uptake by vesicles i...

J. C. Blosser G. N. Catravas



Influence of Morphine on Pericyte-Endothelial Interaction: Implications for Antiangiogenic Therapy  

PubMed Central

Morphine stimulates tumor angiogenesis and cancer progression in mice. We examined if morphine influences endothelial-pericyte interaction via platelet-derived growth factor-BB (PDGF-BB) and PDGF receptor-? (PDGFR-?). Clinically relevant doses of morphine stimulated PDGF-BB secretion from human umbilical vein endothelial cells and activated PDGFR-? and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) phosphorylation in human pericytes. These in vitro effects of morphine were translated into promotion of tumor angiogenesis in a transgenic mice model of breast cancer when treated with clinically used dose of morphine. Increased vessel-associated immunoreactivity of desmin and PDGFR-? was observed on pericytes in tumors of morphine-treated mice. These data suggest that morphine potentiates endothelial-pericyte interaction via PDGF-BB/PDGFR-? signaling and promotes tumor angiogenesis, pericyte recruitment, and coverage of tumor vessels. We speculate that morphine may impair the effectiveness of antiangiogenic therapy by influencing vascular pericyte coverage.

Luk, Kathryn; Boatman, Sonja; Johnson, Katherine N.; Dudek, Olivia A.; Ristau, Natalie; Vang, Derek; Nguyen, Julia; Gupta, Kalpna



Oral Candidiasis  


... . Oral Candidiasis Oropharyngeal / Esophageal Candidiasis ("Thrush") Candidiasis that develops in the mouth or ... other Fungal topics, visit the Fungal Homepage. Oral Candidiasis Topics Definition What is oral candidiasis? Symptoms Redness ...


Fentanyl buccal tablet: faster rescue analgesia for breakthrough pain?  


Breakthrough pain (BTP) is an unmet clinical need that is still poorly diagnosed, evaluated and inadequately treated. The prevalence of BTP has been estimated to affect at least 64% of cancer patients. Two pain-relief strategies were proposed: preventive and active ('rescue'). Oral short-acting opioid seems to be the most popular approach for BTP treatment, however, it is likely to be inadequate for a substantial proportion of patients as a result of the slow-onset of most available opioid preparations. Fentanyl buccal tablet (FBT) is a novel delivery system for fentanyl citrate. FBT utilizes OraVescent technology to improve bioavailability and speed of drug delivery. Recent studies have demonstrated superior pharmacokinetic profiles when compared with other available transmucosal opioids (OTFC), however, pharmacodynamic data are still somewhat limited. PMID:17661711

Lecybyl, Remigiusz; Hanna, Magdi



21 CFR 520.531 - Cythioate tablets.  

Code of Federal Regulations, 2013 CFR

...tablet. (c) Special considerations. Cythioate is a cholinesterase inhibitor. Do not use this product in animals simultaneously...a few days before or after treatment with or exposure to cholinesterase-inhibiting drugs, insecticides, pesticides, or...



Fentanyl Buccal Tablets (marketed as Fentora) Information  

Center for Drug Evaluation (CDER)

... Fentora (fentanyl buccal tablets) is a an opioid pain medication used for the treatment of breakthrough pain in cancer patients receiving opioid ... More results from


Chocolate Tablet Aspects of Cytherean Meshkenet Tessera.  

National Technical Information Service (NTIS)

Meshkenet Tessera structures were mapped from Magellan data and several resemblances to chocolate tablet boudinage were found. The complex fault sets display polyphase tectonic sequences of a few main deformation phases. Shear and tension have contributed...

J. Raitala



? 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



Discriminative Stimulus Effects of Nalbuphine in Nontreated and Morphine-Treated Pigeons  

Microsoft Academic Search

In the present study, the stimulus effects of the low efficacy agonist nalbuphine were examined under two conditions: nontreated and morphine treated. In the first experiment, five pigeons were trained to discriminate among 3.2 mg\\/kg morphine, 5.6 mg\\/kg nalbuphine, and saline. Nalbuphine produced nalbuphine-like responding. Low doses of morphine produced nalbuphine-like responding, whereas high doses produced morphine-like responding. Naltrexone produced

Ellen A Walker; Eric R Hawkins; Michael J Tiano; Mitchell J Picker; Linda A Dykstra