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Sample records for oral morphine tablets

  1. Morphine Oral

    MedlinePLUS

    Morphine is used to relieve moderate to severe pain. Morphine extended-release tablets and capsules are only used ... controlled by the use of other pain medications. Morphine extended-release tablets and capsules should not be ...

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2012-12-01

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

  4. High prevalence of 6-acetylmorphine in morphine-positive oral fluid specimens.

    PubMed

    Presley, Lance; Lehrer, Michael; Seiter, William; Hahn, Dawn; Rowland, Barbara; Smith, Melissa; Kardos, Keith W; Fritch, Dean; Salamone, Sal; Niedbala, R Sam; Cone, Edward J

    2003-04-23

    Identification of 6-acetylmorphine, a specific metabolite of heroin, is considered to be definitive evidence of heroin use. Although 6-acetylmorphine has been identified in oral fluid following controlled heroin administration, no prevalence data is available for oral fluid specimens collected in the workplace. We evaluated the prevalence of positive test results for 6-acetylmorphine in 77,218 oral fluid specimens collected over a 10-month period (January-October 2001) from private workplace testing programs. Specimens were analyzed by Intercept immunoassay (cutoff concentration=30 ng/ml) and confirmed by GC-MS-MS (cutoff concentrations=30 ng/ml for morphine and codeine, and 3 ng/ml for 6-acetylmorphine). Only morphine-positive oral fluid specimens were tested by GC-MS-MS for 6-acetylmorphine. A total of 48 confirmed positive morphine results were identified. An additional 107 specimens were confirmed for codeine only. Of the 48 morphine-positive specimens, 32 (66.7%) specimens were positive for 6-acetylmorphine. Mean concentrations (+/-S.E.M.) of morphine, 6-acetylmorphine and codeine in the 32 specimens were 755+/-201, 416+/-168 and 196+/-36 ng/ml, respectively. Concentrations of 6-acetylmorphine in oral fluid ranged from 3 to 4095 ng/ml. The mean ratio (+/-S.E.M.) of 6-acetylmorphine/morphine was 0.33+/-0.06. It is suggested that, based on controlled dose studies of heroin administration, ratios >1 of 6-acetylmorphine/morphine in oral fluid are consistent with heroin use within the last hour before specimen collection. The confirmation of 6-acetylmorphine in 66.7% of morphine-positive oral fluid specimens indicates that oral fluid testing for opioids may offer advantages over urine in workplace drug testing programs and in testing drugged drivers for recent heroin use. PMID:12742685

  5. Potentiating effect of morphine on oral Salmonella enterica serovar Typhimurium infection is ?-opioid receptor-dependent.

    PubMed

    Breslow, Jessica M; Feng, Pu; Meissler, Joseph J; Pintar, John E; Gaughan, John; Adler, Martin W; Eisenstein, Toby K

    2010-12-01

    Previous studies from our laboratory demonstrated that mice treated with morphine pellets are sensitized to Salmonella enterica, serovar Typhimurium infection. However, the opioid receptor antagonist, naltrexone, only partially blocked the effect of morphine, raising the possibility that the opioid might have some of its effects through a nonopioid receptor. To further clarify whether sensitization to infection is an opioid receptor-dependent phenomenon, ?-opioid receptor knockout (MORKO) mice were used in the present study. Wild-type (WT) and MORKO mice were treated with morphine and their sensitivity to oral Salmonella infection was assessed by mortality, bacterial burdens in gut associated lymphoid tissue and in blood and peritoneal fluid, and by levels of pro-inflammatory cytokines in plasma. MORKO animals treated with morphine were refractory to a sublethal dose of Salmonella, while similar treatment of WT animals resulted in 100% mortality. WT animals treated with morphine had high bacterial loads in all organs tested, while morphine-treated MORKO animals had no culturable Salmonella in any organs. Pro-inflammatory cytokine levels were elevated in morphine-treated WT but not MORKO mice infected with Salmonella. These results provide definitive evidence that the morphine-mediated enhancement of oral Salmonella infection is dependent on the ?-opioid receptor. PMID:20688146

  6. Mucoadhesive tablet releasing iodine for treating oral infections.

    PubMed

    Mizrahi, Boaz; Domb, Abraham J

    2007-11-01

    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

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

    PubMed

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

    2010-01-01

    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

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

    PubMed

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

    2010-01-01

    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

  9. The Effect of Oral Morphine on Pain-Related Brain Activation - An Experimental Functional Magnetic Resonance Imaging Study.

    PubMed

    Hansen, Tine Maria; Olesen, Anne Estrup; Graversen, Carina; Drewes, Asbjørn Mohr; Frøkjaer, Jens Brøndum

    2015-11-01

    Knowledge about cerebral mechanisms underlying pain perception and effect of analgesic drugs is important for developing methods for diagnosis and treatment of pain. The aim was to explore altered brain activation before and after morphine treatment using functional magnetic resonance imaging recorded during experimental painful heat stimulation. Functional magnetic resonance imaging data were recorded and analysed in 20 healthy volunteers (13 men and 7 women, 24.9 ± 2.6 years) in a randomized, double-blind, placebo-controlled, cross-over study. Painful stimulations were applied to the right forearm using a contact heat evoked potential stimulator (CHEPS) before and after treatment with 30 mg oral morphine and placebo. CHEPS stimulations before treatment induced activation in the anterior cingulate cortex, secondary somatosensory cortex/insula, thalamus and cerebellum (n = 16, p < 0.05). In response to morphine treatment, the spatial extent of these pain-specific areas decreased (n = 20). Reduced pain-induced activation was seen in the right insula, anterior cingulate cortex and inferior parietal cortex after morphine treatment compared to before treatment (n = 16, p < 0.05), and sensory ratings of pain perception were significantly reduced after morphine treatment (p = 0.02). No effect on pain-induced brain activation was seen after placebo treatment compared to before treatment (n = 12, p > 0.05). In conclusion, heat stimulation activated areas in the 'pain matrix' and a clinically relevant dose of orally administered morphine revealed significant changes in brain areas where opioidergic pathways are predominant. The method may be useful to investigate the mechanisms of analgesics. PMID:25924691

  10. 77 FR 1695 - Determination That AVALIDE (Hydrochlorothiazide and Irbesartan), Oral Tablets, 25 Milligrams/300...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... SERVICES Food and Drug Administration Determination That AVALIDE (Hydrochlorothiazide and Irbesartan), Oral... Food and Drug Administration (FDA) has determined that AVALIDE (hydrochlorothiazide and irbesartan... (ANDAs) for hydrochlorothiazide and irbesartan, oral tablets, 25 mg/300 mg and 12.5 mg/75 mg, if...

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

    PubMed

    Preis, Maren

    2015-04-01

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

  12. Development and evaluation of cetirizine HCl taste-masked oral disintegrating tablets.

    PubMed

    Douroumis, Dionysios Dennis; Gryczke, Andreas; Schminke, Silke

    2011-03-01

    The purpose of the current study was to mask the taste of cetirizine HCl and to incorporate the granules produced in oral disintegrating tablets (ODT). The bitter, active substance was coated by fluidized bed coating using Eudragit® RL30-D at levels between 15% and 40% w/w. The ODTs were developed by varying the ratio of superdisintegrants such as sodium croscarmellose, crospovidone grades and low substituted hydroxypropyl cellulose (L-HPC). A direct compression process was used to compress the ODTs under various compaction forces to optimize tablet robustness. The properties of the compressed tablets including porosity, hardness, friability and dissolution profiles were further investigated. The in vitro and in vivo evaluation of the tablet disintegration times showed almost identical rapid disintegration below 10 s at the optimal levels of each superdisintegrant. Finally, the taste and sensory evaluation in human volunteers demonstrated excellence in masking the bitter active and tablet palatability. PMID:21181510

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

    PubMed

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

    2011-09-01

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

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

    PubMed Central

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

    2012-01-01

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

  15. Development of oral dispersible tablets containing prednisolone nanoparticles for the management of pediatric asthma

    PubMed Central

    Chen, Yi-Dan; Liang, Zhong-Yuan; Cen, Yan-Yan; Zhang, He; Han, Mei-Gui; Tian, Yun-Qiao; Zhang, Jie; Li, Shu-Jun; Yang, Da-Sheng

    2015-01-01

    The purpose of the present study was to develop oral dispersible tablets containing prednisolone (PDS)-loaded chitosan nanoparticles using microcrystalline cellulose (MCC 101), lactose, and croscarmellose sodium (CCS). The PDS-loaded chitosan nanoparticles were formulated by ionotropic external gelation technique in order to enhance the solubility of PDS in salivary pH. Prepared nanoparticles were used for the development of oral fast disintegrating tablets by direct compression method. The prepared tablets were evaluated for disintegration time (DT), in vitro drug release (DR), thickness, weight variation, drug content uniformity, friability, and hardness. The effect of concentrations of the dependent variables (MCC, lactose, CCS) on DT and in vitro DR was studied. Fast disintegrating tablets of PDS can be prepared by using MCC, CCS, and lactose with enhanced solubility of PDS. The minimum DT was found to be 15 seconds, and the maximum DR within 30 minutes was 98.50%. All independent variables selected for the study were statistically significant. Oral fast disintegrating tablets containing PDS nanoparticles could be the better choice for the pediatric patients that would result in better patient compliance. From this study, it can be concluded that fast disintegrating tablets could be a potential drug delivery technology for the management of asthma in pediatrics. PMID:26640367

  16. Development of oral dispersible tablets containing prednisolone nanoparticles for the management of pediatric asthma.

    PubMed

    Chen, Yi-Dan; Liang, Zhong-Yuan; Cen, Yan-Yan; Zhang, He; Han, Mei-Gui; Tian, Yun-Qiao; Zhang, Jie; Li, Shu-Jun; Yang, Da-Sheng

    2015-01-01

    The purpose of the present study was to develop oral dispersible tablets containing prednisolone (PDS)-loaded chitosan nanoparticles using microcrystalline cellulose (MCC 101), lactose, and croscarmellose sodium (CCS). The PDS-loaded chitosan nanoparticles were formulated by ionotropic external gelation technique in order to enhance the solubility of PDS in salivary pH. Prepared nanoparticles were used for the development of oral fast disintegrating tablets by direct compression method. The prepared tablets were evaluated for disintegration time (DT), in vitro drug release (DR), thickness, weight variation, drug content uniformity, friability, and hardness. The effect of concentrations of the dependent variables (MCC, lactose, CCS) on DT and in vitro DR was studied. Fast disintegrating tablets of PDS can be prepared by using MCC, CCS, and lactose with enhanced solubility of PDS. The minimum DT was found to be 15 seconds, and the maximum DR within 30 minutes was 98.50%. All independent variables selected for the study were statistically significant. Oral fast disintegrating tablets containing PDS nanoparticles could be the better choice for the pediatric patients that would result in better patient compliance. From this study, it can be concluded that fast disintegrating tablets could be a potential drug delivery technology for the management of asthma in pediatrics. PMID:26640367

  17. Opioid addicts at admission vs. slow-release oral morphine, methadone, and sublingual buprenorphine maintenance treatment participants.

    PubMed

    Giacomuzzi, S; Kemmler, G; Ertl, M; Riemer, Y

    2006-01-01

    With use of a randomized study design, quality of life (QOL) and physical symptoms of opioid addicts at admission were compared with slow-release oral morphine, methadone, and sublingual buprenorphine maintenance program participants after 6 months of treatment. The study was conducted from February to July 2004 in the outpatient drug user treatment center at University Department of Psychiatry at Innsbruck, providing maintenance treatment programs and detoxification in Tyrol, Austria. One hundred twenty opioid users seeking treatment were compared with 120 opioid-dependent patients retained for 6 months on a slow-release oral morphine, methadone, or sublingual buprenorphine maintenance program. The German version ("Berlin Quality of Life Profile") of the Lancashire Quality of Life Profile was used, and illicit opioid use was determined by urinalysis. Physical symptoms were measured by using the Opioid Withdrawal Scale. Urinalyses revealed a significantly lower consumption of cocaine and opioids in all three substitution groups than in patients at admission (p < 0.001 and p < or = 0.004, respectively). Both the buprenorphine and the methadone maintenance group showed significantly more favorable values than opioid clients at admission for stomach cramps (p < or = 0.002), muscular tension (p < or = 0.027), general pain (p < or = 0.001), feelings of coldness (p < or = 0.000), heart pounding (p < or = 0.008), runny eyes (p < or = 0.047), and aggressions (p < or = 0.009). Patients who received slow-release oral morphine treatment generally showed the least favorable QOL scores compared with patients at admission or sublingual buprenorphine and methadone clients. Patients in the sublingual buprenorphine or methadone program showed nearly the same QOL scores. The buprenorphine and the methadone maintenance group showed significantly more favorable values than opioid clients at admission regarding leisure time (p < or = 0.019), finances (p < or = 0.014), mental health (p < or = 0.010), and overall satisfaction (p < or = 0.010). Slow-release oral morphine is a well-established treatment for pain, but more research is required to evaluate it as a treatment for heroin dependence. The present data indicate that slow-release oral morphine could have some disadvantages compared with sublingual buprenorphine and methadone in QOL, physical symptoms, and additional consumption. The results further suggest that buprenorphine treatment is as effective as methadone in effects on quality of life and physical symptoms. PMID:16393744

  18. The effects of preoperative oral pregabalin and perioperative intravenous lidocaine infusion on postoperative morphine requirement in patients undergoing laparatomy

    PubMed Central

    Zengin, Senniye Ulgen; Saracoglu, Ayten; Eti, Zeynep; Umuroglu, Tumay; Gogus, Fevzi Yilmaz

    2015-01-01

    OBJECTIVES: To evaluate and compare the effects of preoperative oral pregabalin and perioperative intravenous lidocaine infusion on postoperative morphine requirement, adverse effects, patients’ satisfaction, mobilization, time to first defecation and time to discharge in patients undergoing laparotomy. METHODS: Eighty patients (18 to 65 years of age) undergoing elective laparotomy were randomly divided into four groups (n=20 in each group): group C, placebo capsules and normal saline infusion perioperatively (control); group L, placebo capsules and lidocaine 1 mg/kg intravenous bolus dose followed by 2 mg/kg/h infusion until skin closure; group P, 150 mg oral pregabalin and normal saline infusion perioperatively; and group PL, 150 mg oral pregabalin and lidocaine 2 mg/kg/h infusion until skin closure. Hemodynamic parameters, visual analogue scale (VAS) scores, analgesic consumption, side effects, time to mobilization, time to first defecation, time to discharge and patients’ satisfaction were recorded. RESULTS: VAS scores of group L, group P and group PL were lower than group C (P<0.05). Morphine consumption of group P and group PL was lower than group C (P<0.05). Incidence of nausea in group C was higher than group L and group PL. Time to first defecation and mobilization were shorter in group L and group PL compared with group C (P<0.05). CONCLUSION: Preoperative oral pregabalin and perioperative intravenous lidocaine infusion decreased postoperative VAS scores. Preoperative oral pregabalin decreased morphine requirement and perioperative intravenous lidocaine infusion hastened gastrointestinal motility and mobilization, and decreased the incidence of nausea in patients undergoing laparotomy. Therefore, preoperative pregabalin with or without lidocaine provides superior pain relief in patients undergoing laparatomy. PMID:25950425

  19. Formulation and Characterization of Oral Mucoadhesive Chlorhexidine Tablets Using Cordia myxa Mucilage

    PubMed Central

    Moghimipour, Eskandar; Aghel, Nasrin; Adelpour, Akram

    2012-01-01

    Background The dilution and rapid elimination of topically applied drugs due to the flushing action of saliva is a major difficulty in the effort to eradicate infections of oral cavity. Utilization a proper delivery system for incorporation of drugs has a major impact on drug delivery and such a system should be formulated for prolonged drug retention in oral cavity. Objectives The aim of the present study was the use of mucilage of Cordia myxa as a mucoadhesive material in production of chlorhexidine buccal tablets and its substitution for synthetic polymers such as HPMC. Materials and Methods The influence of mucilage concentration on the physicochemical responses (hardness, friability, disintegration time, dissolution, swelling, and muco-adhesiveness strength) was studied and swelling of mucilage and HPMC were compared. The evaluated responses included pharmacopoeial characteristics of tablets, the force needed to separate tablets from mucosa, and the amount of water absorbed by tablets. Results In comparison to HPMC, the rise of mucilage concentration in the formulations increased disintegration time, drug dissolution rate, and reduced MDT. Also, compared to 30% HPMC, muco-adhesiveness strength of buccal tablets containing 20% mucilage was significantly higher. Conclusions It can be concluded that the presence of Cordia myxa powdered mucilage may significantly affect the tablet characteristics, and increasing in muco-adhesiveness may be achieved by using 20% w/w mucilage. PMID:24624170

  20. Hair testing in postmortem diagnosis of substance abuse: An unusual case of slow-release oral morphine abuse in an adolescent.

    PubMed

    Baillif-Couniou, Valérie; Kintz, Pascal; Sastre, Caroline; Pok, Phak-Rop Pos; Chèze, Marjorie; Pépin, Gilbert; Leonetti, Georges; Pelissier-Alicot, Anne-Laure

    2015-11-01

    Morphine sulfate misuse is essentially observed among regular heroin injectors. To our knowledge, primary addiction to morphine sulfate is exceptional, especially among young adolescents. A 13-year-old girl, with no history of addiction, was found dead with three empty blisters of Skenan(®) LP 30 mg at her side. Opiates were detected in biological fluids and hair by chromatographic methods. Blood analyses confirmed morphine overdose (free morphine: 428 ng/mL; total morphine: 584 ng/mL) and segmental hair analysis confirmed regular exposure over several months (maximum morphine concentration 250 pg/mg). Suspecting the victim's mother of recreational use of Skenan(®), the magistrate ordered analysis of her hair, with negative results. From an epidemiological viewpoint, this case of oral morphine sulfate abuse in an adolescent with no previous history suggests the emergence of a new trend of morphine sulfate consumption. From a toxicological viewpoint, it demonstrates the value of hair testing, which documented the victim's regular exposure and made an important contribution to the police investigation. PMID:26492165

  1. Orally administered nanocurcumin to attenuate morphine tolerance: comparison between negatively charged PLGA and partially and fully PEGylated nanoparticles.

    PubMed

    Shen, Hao; Hu, Xiaoyu; Szymusiak, Magdalena; Wang, Zaijie Jim; Liu, Ying

    2013-12-01

    We have formulated hydrophobic curcurmin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] into stable nanoparticle suspensions (nanocurcumin) to overcome its relatively low bioavailability, high rate of metabolism, and rapid elimination and clearance from the body. Employing the curcumin nanoformulations as the platform, we discovered that curcumin has the potential to alleviate morphine tolerance. The two types of stable polymeric nanoparticles, poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA), and the hybrid of the two were generated using flash nanoprecipitation integrated with spray drying. The optimized formulations have high drug loading (>45%), small particles size with narrow distribution, and controlled surface properties. Mice behavioral studies (tail-flick and hot-plate tests) were conducted to verify the effects of nanocurcumin on attenuating morphine tolerance. Significant analgesia was observed in mice during both tail-flick and hot-plate tests using orally administered nanocurcumin following subcutaneous injections of morphine. However, unformulated curcumin at the same dose showed no effect. Compared with PEGylated nanocurcumin, negatively charged PLGA nanoparticles showed better functionality. PMID:24195658

  2. Risperidone oral disintegrating mini-tablets: A robust-product for pediatrics.

    PubMed

    El-Say, Khalid M; Ahmed, Tarek A; Abdelbary, Maged F; Ali, Bahaa E; Aljaeid, Bader M; Zidan, Ahmed S

    2015-12-01

    This study was aimed at developing risperidone oral disintegrating mini-tablets (OD-mini-tablets) as age-appropriate formulations and to assess their suitability for infants and pediatric use. An experimental Box-Behnken design was applied to assure high quality of the OD-mini-tablets and reduce product variability. The design was employed to understand the influence of the critical excipient combinations on the production of OD-mini-tablets and thus guarantee the feasibility of obtaining products with dosage form uniformity. The variables selected were mannitol percent in Avicel (X1), swelling pressure of the superdisintegrant (X2), and the surface area of Aerosil as a glidant (X3). Risperidone-excipient compatibilities were investigated using FTIR and the spectra did not display any interaction. Fifteen formulations were prepared and evaluated for preand post-compression characteristics. The prepared ODmini- tablet batches were also assessed for disintegration in simulated salivary fluid (SSF, pH 6.2) and in reconstituted skimmed milk. The optimized formula fulfilled the requirements for crushing strength of 5 kN with minimal friability, disintegration times of 8.4 and 53.7 s in SSF and skimmed milk, respectively. This study therefore proposes the risperidone OD-mini-tablet formula having robust mechanical properties, uniform and precise dosing of medication with short disintegration time suitable for pediatric use. PMID:26677895

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

    PubMed

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

    2013-05-01

    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

  4. Formulation of cyclodextrin inclusion complex-based orally disintegrating tablet of eslicarbazepine acetate for improved oral bioavailability.

    PubMed

    Desai, Samixa; Poddar, Aditi; Sawant, Krutika

    2016-01-01

    The present investigation was aimed towards developing a beta-cyclodextrin (?-CD) solid dispersion (SD) based orally disintegrating tablet (ODT) of eslicarbazepine acetate (ESL), for improving the dissolution and providing fast onset of anti-epileptic action. Optimum ratio of ESL and ?-CD was determined by Job's plot. Thereafter, solid dispersions were prepared by solvent evaporation method and evaluated for yield, assay, Differential scanning calorimetry (DSC), Fourier transform infra red spectroscopy (FTIR), X-ray diffraction (XRD), and in vitro dissolution. Optimized SD was compressed into ODT by direct compression using super disintegrants and evaluated for wetting time, drug content, in vitro drug release and in vivo studies. The results of DSC, FTIR and XRD analysis supported the formation of inclusion complex. An improved dissolution with 99.95±2.80% drug release in 60min was observed in comparison to 24.85±2.96% release from a plain drug suspension. Tablets with crosspovidone as a super disintegrant showed the least disintegration time of 24.66±1.52s and higher in vitro drug release against marketed tablets. In vivo studies indicated that the formulated tablets had 2 times higher bioavailability than marketed tablets. Thus, the developed ?-CD-ESL SD-ODT could provide faster onset of action and higher bioavailability, which would be beneficial in case of epileptic seizures. PMID:26478377

  5. Investigation of Formulation and Process of Lyophilised Orally Disintegrating Tablet (ODT) Using Novel Amino Acid Combination

    PubMed Central

    AlHusban, Farhan; ElShaer, Amr M.; Kansara, Jiteen H.; Smith, Alan M.; Grover, Liam M.; Perrie, Yvonne; Mohammed, Afzal R.

    2010-01-01

    Lyophilised orally disintegrating tablets (ODTs) have achieved a great success in overcoming dysphagia associated with conventional solid dosage forms. However, the extensive use of saccharides within the formulation limits their use in treatment of chronic illnesses. The current study demonstrates the feasibility of using combination of proline and serine to formulate zero sacharide ODTs and investigates the effect of freezing protocol on sublimation rate and tablets characteristics. The results showed that inclusion of proline and serine improved ODT properties when compared to individual counterparts. Additionally, annealing the ODTs facilitated the sublimation process and shortened the disintegration time.

  6. Orally fast disintegrating tablets: developments, technologies, taste-masking and clinical studies.

    PubMed

    Fu, Yourong; Yang, Shicheng; Jeong, Seong Hoon; Kimura, Susumu; Park, Kinam

    2004-01-01

    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. 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. 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, moisture treatment, sintering, and use of sugar-based disintegrants. In addition, taste-masking technologies, experimental measurements of disintegration times, and clinical studies are also discussed. PMID:15658933

  7. Determination of the in vitro disintegration profile of rapidly disintegrating tablets and correlation with oral disintegration.

    PubMed

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

    2005-03-23

    The assessment of the in vitro disintegration profile of rapidly disintegrating tablets (RDT) is very important in the evaluation and the development of new formulations of this type. So far neither the US Pharmacopoeia nor the European Pharmacopoeia has defined a specific disintegration test for RDT; currently, it is only possible to refer to the tests on dispersible or effervescent tablets for the evaluation of RDT's disintegration capacity. In the present study, we have evaluated the disintegration profile of RDT manufactured by main commercialised technologies, using the texture analyser (TA). In order to simulate as much as possible the oral disintegration of these dosage forms, a new operating structure was developed. This structure mimics the situation in the patient's mouth and provides a gradual elimination of the detached particles during the disintegration process. The obtained time-distance profiles or disintegration profiles enabled the calculation of certain quantitative values as the disintegration onset (t1) and the total disintegration time (t2). These values were used in the characterisation of the effect of test variables as the disintegration medium and temperature on the disintegration time of RDT. Moreover, the oral disintegration time of the same products was evaluated by 14 healthy volunteers. Results obtained when artificial saliva at 37 degrees C was employed as disintegration medium were used to correlate the in vitro (t2) and oral disintegration times. Excellent correlation was found and in addition, we were able to achieve a qualitative measure of the mouthfeel by comparing the thickness of the tablets and the penetration distance obtained from the disintegration profile. This method also permitted the discrimination between different RDT, where differences in the disintegration mechanism were reflected on the disintegration profile achieved for each tablet. PMID:15725551

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2009-01-01

    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

  10. Morphine Rectal

    MedlinePLUS

    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 ...

  11. The simultaneous determination of codeine, morphine, hydrocodone, hydromorphone, 6-acetylmorphine, and oxycodone in hair and oral fluid.

    PubMed

    Jones, Joseph; Tomlinson, Kimberly; Moore, Christine

    2002-04-01

    Recently, the abuse of prescription opiates as alternatives to heroin has become a national concern. The determination of a six-drug opiate panel, codeine, morphine, 6-acetylmorphine, hydrocodone, hydromorphone, and oxycodone, in hair and oral fluid using solid-phase extraction and capillary gas chromatography-mass spectrometry (GC-MS) is described. Oral fluid was obtained from the donor by insertion of absorptive collectors into the mouth. Hair was collected from the patient and powdered using stainless steel ball bearings in a mini bead-beater apparatus. Opiates present in the samples were extracted from a buffered, aqueous matrix using a solid-phase cartridge. The extracts were concentrated and the methoxime/BSTFA derivatives prepared in order to eliminate interference from the keto-opiates. The extracts were separated by GC-MS in electron impact mode. By utilizing methoxyamine, we were able to produce the methoxime derivatives required for single derivative production and chromatographically separate all six opiates. The routine analysis of these opiates in hair and oral fluid using GC-MS is described for the first time. PMID:11991534

  12. Design, development, and optimization of orally disintegrating tablets of etoricoxib using vacuum-drying approach.

    PubMed

    Patel, Dharmesh; Shah, Mohit; Shah, Sunny; Shah, Tejal; Amin, Avani

    2008-01-01

    Etoricoxib is a cyclooxygenase 2 (COX-2) inhibitor that selectively inhibits the COX-2 enzyme and decreases the incidences of side effects associated with these agents. It is commonly prescribed for acute pain, gouty arthritis, and rheumatoid arthritis. Conventional tablets of etoricoxib are not capable of rapid action, which is required for faster drug effect onset and immediate relief from pain. Thus, the aim of the present investigation is to formulate orally disintegrating tablets (ODTs) of etoricoxib. A combination of the superdisintegrants with a sublimation technique was used to prepare the tablets. Tablets were prepared using a direct compression method employing superdisintegrants such as low substituted hydroxylpropyl methyl cellulose (L-HPMC), low substituted hydroxyl-propyl cellulose (L-HPC), crospovidone, croscarmellose sodium, and sodium starch glycolate. Tablets of etoricoxib prepared using L-HPC exhibited the least friability and disintegration time (approximately 65 s). To decrease the disintegration time further, a sublimation technique was used along with the superdisintegrants for the preparation of ODTs. The use of sublimating agents including camphor, menthol, and thymol was explored. The addition of camphor lowered the disintegration time (approximately 30 s) further, but the percent friability was increased. A 3(2) full factorial design was employed to study the joint influence of the amount of superdisintegrant (L-HPC) and the amount of sublimating agent (camphor) on the percent of friability and the disintegration time. The results of multiple linear regression analysis revealed that for obtaining an effective ODT of etoricoxib, higher percentages of L-HPC and camphor should be used. Checkpoint batches were prepared to validate the evolved mathematical model. A response surface plot is also presented to graphically represent the effect of the independent variables on the percent of friability and the disintegration time. The approach using the optimization technique helped to produce a detailed understanding of the effects of formulation parameters. PMID:18661871

  13. Concentrations of Morphine and Codeine in Paired Oral Fluid and Urine Specimens Following Ingestion of a Poppy Seed Roll and Raw Poppy Seeds.

    PubMed

    Samano, Kimberly L; Clouette, Randal E; Rowland, Barbara J; Sample, R H Barry

    2015-10-01

    Interpretation of opiate drug test results can be challenging due to casual dietary consumption of poppy seeds, which may contain variable opiate content. Opiate concentrations in paired oral fluid (OF), collected with the Oral-Eze(®) Oral Fluid Collection System, and urine were analyzed after ingestion of poppy seeds from the same source, consumed raw or contained in a roll. In Part 1, 12 individuals consumed equal portions of a poppy seed roll. For Part 2, the same individuals consumed an equivalent quantity of raw poppy seeds, containing ?3.2 mg of morphine and 0.6 mg of codeine. Specimens were analyzed both by enzyme immunoassay (opiates) and by GC-MS (morphine/codeine). Urinary morphine was between 155-1,408 (roll) and 294-4,213 ng/mL (raw), measured at 2, 4, 6 and 20 h post-ingestion. Urinary codeine concentrations between 140-194 (roll) and 121-664 ng/mL (raw) were observed up to 6 h post-ingestion. Following consumption of raw poppy seeds, OF specimens were positive, above LOQ, from 0.25 to 3.0 h with morphine ranging from 7 to 600 ng/mL and codeine from 8 to 112 ng/mL. After poppy seed roll consumption, morphine concentrations of 7-143 ng/mL were observed up to 1.5 h with codeine detected in only 5.5% of OF specimens and ranging from 8 to 28 ng/mL. Combined with the existing poppy seed literature, these results support previous findings and provide guidance for interpretation of OF opiate testing. PMID:26378141

  14. Concentrations of Morphine and Codeine in Paired Oral Fluid and Urine Specimens Following Ingestion of a Poppy Seed Roll and Raw Poppy Seeds

    PubMed Central

    Samano, Kimberly L.; Clouette, Randal E.; Rowland, Barbara J.; Sample, R.H. Barry

    2015-01-01

    Interpretation of opiate drug test results can be challenging due to casual dietary consumption of poppy seeds, which may contain variable opiate content. Opiate concentrations in paired oral fluid (OF), collected with the Oral-Eze® Oral Fluid Collection System, and urine were analyzed after ingestion of poppy seeds from the same source, consumed raw or contained in a roll. In Part 1, 12 individuals consumed equal portions of a poppy seed roll. For Part 2, the same individuals consumed an equivalent quantity of raw poppy seeds, containing ?3.2 mg of morphine and 0.6 mg of codeine. Specimens were analyzed both by enzyme immunoassay (opiates) and by GC–MS (morphine/codeine). Urinary morphine was between 155–1,408 (roll) and 294–4,213 ng/mL (raw), measured at 2, 4, 6 and 20 h post-ingestion. Urinary codeine concentrations between 140–194 (roll) and 121–664 ng/mL (raw) were observed up to 6 h post-ingestion. Following consumption of raw poppy seeds, OF specimens were positive, above LOQ, from 0.25 to 3.0 h with morphine ranging from 7 to 600 ng/mL and codeine from 8 to 112 ng/mL. After poppy seed roll consumption, morphine concentrations of 7–143 ng/mL were observed up to 1.5 h with codeine detected in only 5.5% of OF specimens and ranging from 8 to 28 ng/mL. Combined with the existing poppy seed literature, these results support previous findings and provide guidance for interpretation of OF opiate testing. PMID:26378141

  15. Safety and tolerability of slow-release oral morphine versus methadone in the treatment of opioid dependence.

    PubMed

    Hämmig, Robert; Köhler, Wilfried; Bonorden-Kleij, Karin; Weber, Bernd; Lebentrau, Karin; Berthel, Toni; Babic-Hohnjec, Lucija; Vollmert, Christian; Höpner, Doris; Gholami, Najibulah; Verthein, Uwe; Haasen, Christian; Reimer, Jens; Ruckes, Christian

    2014-10-01

    Opioid substitution treatment (OST) for opioid dependence may be limited by adverse events (AEs). Increasing the range of therapeutic options optimizes outcomes and facilitates patient management. An international, multi-center, two-phase study investigated the efficacy and safety of slow-release oral morphine (SROM) versus methadone in patients receiving methadone therapy for opioid dependence. In phase 1 (two way cross-over, 11 weeks each period) patients were randomized to SROM or methadone oral solution. In phase 2 (25 weeks), patients continued treatment with SROM (group A) or switched from methadone to SROM (group B). In total, 211 out of 276 completed phase 1 and 198 entered phase 2 (n=95 group A, n=103 group B). Treatment with both SROM and methadone was well tolerated. However, the mean QTc-interval associated with methadone was significantly longer than that under SROM. Higher treatment satisfaction, fewer cravings for heroin, and lower mental stress were reported with SROM. This study adds a significant further weight of evidence that SROM is an effective and well tolerated long-term maintenance treatment for opioid dependence with a beneficial risk profile compared to methadone regarding cardiac effects and supports its clinical utility. PMID:25064422

  16. Development of orally disintegrating tablets comprising controlled-release multiparticulate beads

    PubMed Central

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  18. Formulation and Evaluation of a Novel Matrix-Type Orally Disintegrating Ibuprofen Tablet

    PubMed Central

    Tayebi, Hoda; Mortazavi, Seyed Alireza

    2011-01-01

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

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

    PubMed

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

    2015-04-01

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

  20. Development and optimization of dextromethorphan hydrobromide oral disintegrating tablets: effect of formulation and process variables.

    PubMed

    Mostafa, Haitham Fady; Ibrahim, Mohamed Abbas; Sakr, Adel

    2013-01-01

    Orally disintegrating tablets (ODTs), which disintegrate rapidly (<1?min) in the mouth and do not require water for administration, have become a very popular dosage form. The study aims to develop a simple and inexpensive method of manufacturing ODTs of a sparingly water-soluble drug, Dextromethorphan hydrobromide. Two factors, three levels (3(2)) full factorial design was used to optimize the diluent, microcrystalline cellulose (X(1)) and superdisintegrant, croscarmellose sodium (X(2)) concentrations. Disintegration time, hardness and T(50) values for all the formulations varied from 12.5 to 152.6 s, 3.58 to 4.92 kp and 0.8 to 2.8?min, respectively. The results indicated that the selected variables have a strong influence on disintegration time, hardness and T(50) of the ODTs. The manufactured ODTs formula composed of 30% microcrystalline cellulose in combination with 3% croscarmellose sodium was chosen as optimized formula, as it showed the lowest disintegration time (12.5?±?1.22 s), low T(50) (0.8?min.) and hard tablets (4.92?±?0.28 kp) amongst other tested ODTs formulations. Hardness of DM ODTs was not affected by changing the type of superdisintegrant and lubricant. The disintegration time was significantly (p < 0.05) increased by using sodium starch glycolate instead of croscarmellose sodium. PMID:22881389

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

    PubMed

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

    2010-01-01

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

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

    PubMed

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

    2014-06-01

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

  3. Effect of a High-Fat Meal on the Pharmacokinetics of 300-Milligram Posaconazole in a Solid Oral Tablet Formulation

    PubMed Central

    Kersemaekers, Wendy M.; Dogterom, Peter; Xu, Jialin; de Greef, Rik; Waskin, Hetty; van Iersel, Marlou L. P. S.

    2015-01-01

    Posaconazole in oral suspension must be taken multiple times a day with food (preferably a high-fat meal) to ensure adequate exposure among patients. We evaluated the effect of food on the bioavailability of a new delayed-release tablet formulation of posaconazole at the proposed clinical dose of 300 mg once daily in a randomized, open-label, single-dose, two-period crossover study with 18 healthy volunteers. When a single 300-mg dose of posaconazole in tablet form (3 tablets × 100 mg) was administered with a high-fat meal, the posaconazole area under the concentration-time curve from 0 to 72 h (AUC0–72) and maximum concentration in plasma (Cmax) increased 51% and 16%, respectively, compared to those after administration in the fasted state. The median time to Cmax (Tmax) shifted from 5 h in the fasted state to 6 h under fed conditions. No serious adverse events were reported, and no subject discontinued the study due to an adverse event. Six of the 18 subjects reported at least one clinical adverse event; all of these events were mild and short lasting. The results of this study demonstrate that a high-fat meal only modestly increases the mean posaconazole exposure (AUC), ?1.5-fold, after administration of posaconazole tablets, in contrast to the 4-fold increase in AUC observed previously for a posaconazole oral suspension given with a high-fat meal. PMID:25824210

  4. Gastrointestinal transit of model mini-tablet controlled release oral dosage forms in fasted human volunteers.

    PubMed

    Podczeck, F; Course, N; Newton, J M; Short, M B

    2007-07-01

    The aim of this study was to compare the gastrointestinal transit of multiple unit, small diameter (3.2 mm), non-disintegrating tablets of differing densities with results previously reported in the same volunteers in the fasted state for larger diameter (6.6 and 12.2 mm) tablets. The gastrointestinal transit was observed with gamma-scintigraphy at various intervals over a 9-h period to give an accurate assessment of the transit characteristics. The value for the median emptying time of the first light tablet was significantly shorter than that for the dense tablet, but the total emptying time and the time for the last tablet to empty for both sets of tablets were not statistically different. The value of the median time for initial and final emptying of the small tablets from the stomach was significantly longer than that for the larger diameter tablets. The 9-h time limit of the observations limited the estimation of the time taken to enter the caecum and consequently the small intestine transit times. There was clear evidence that for the dense tablets of all sizes, the value for the small intestine transit time was longer than the 3-4 h reported in the literature. The only tablet system to enter the caecum within the time limit of the study was the normal density 12.2-mm tablets. PMID:17637188

  5. Freeze drying of orally disintegrating tablets containing taste masked naproxen sodium granules in blisters.

    PubMed

    Stange, Ulrike; Führling, Christian; Gieseler, Henning

    2014-09-15

    Abstract Orally disintegrating tablets (ODTs) were freeze dried in blisters using the Lyostar® II SMART™ Freeze Dryer Technology. ODT formulations either without non-water soluble particles (placebo) or containing large fractions (717?mg) of taste-masked naproxen sodium (NaS) granules were freeze dried. The process data revealed differences between ODTs with and without embedded granules in the pressure rise curves as well as in the shelf (inlet) temperature adjustments during freeze-drying. Pressure rise curves of the placebo ODTs from eight hours process time showed no distinct temperature-dominated part, and the last optimization step of the shelf temperature to achieve -24.4?°C might be prone to errors. The final shelf temperature of ODTs containing granules was -23.3?°C. The detection of primary drying endpoints using SMART™ Technology or comparative pressure measurements was reliable for both ODT formulations, whereas the application of thermocouples resulted in premature endpoint indication. Product resistance of ODTs containing granules was generally elevated in comparison to ODTs without granules, but increased only slightly over the course of the drying process. In summary, the developed freeze-drying cycle was found applicable for production of elegant ODTs with incorporated taste masked NaS granules. PMID:25220888

  6. Nanocrystals as tool to improve piroxicam dissolution rate in novel orally disintegrating tablets.

    PubMed

    Lai, F; Pini, E; Angioni, G; Manca, M L; Perricci, J; Sinico, C; Fadda, A M

    2011-11-01

    In this paper, orally disintegrating tablets (ODT) were prepared using nanocrystal formulations in order to optimise dissolution properties of lipophilic, poorly soluble drug piroxicam (PRX). Different nanocrystal formulations were prepared using a high pressure homogenisation technique and poloxamer 188 as stabiliser. Characterisation of PRX nanocrystal ODT was carried out by infrared spectroscopy (FTIR), X-ray powder diffractometry (XRPD), differential scanning calorimetry and photon correlation spectroscopy. Dissolution study of PRX ODT was performed in distilled water (pH 5.5) and was compared to that of PRX coarse suspension ODT, PRX/poloxamer 188 physical mixture and bulk PRX samples. The XRPD and FTIR studies demonstrated that the homogenisation process led to a polymorphic transition from form I (bulk commercial PRX) to form III and monohydrate form of the nanocrystals. All ODT formulations prepared using PRX nanosuspensions showed a higher PRX dissolution rate compared with the ODT prepared with the coarse PRX. Since the solubility of the different PRX polymorphic forms increased only slightly from bulk PRX (form I) to monohydrate, form II and form III, we can conclude that the improvement in PRX dissolution rate is mainly caused by the increased surface-to-volume ratio due to the submicron dimension of the drug particles. PMID:21820052

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

    PubMed Central

    Nabais, Teresa; Leclair, Grégoire

    2014-01-01

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

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

    PubMed

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

    2015-06-01

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

  9. Population pharmacokinetics of levodopa in subjects with advanced Parkinson's disease: levodopa-carbidopa intestinal gel infusion vs. oral tablets

    PubMed Central

    Othman, Ahmed A; Dutta, Sandeep

    2014-01-01

    Aims Levodopa-carbidopa intestinal gel (LCIG) provides continuous levodopa-carbidopa delivery through intrajejunal infusion. This study characterized the population pharmacokinetics of levodopa following a 16 h jejunal infusion of LCIG or frequent oral administration of levodopa-carbidopa tablets (LC-oral) in subjects with advanced Parkinson's disease (PD). Methods A non-linear mixed-effects model of levodopa pharmacokinetics was developed using serial plasma concentrations from an LCIG phase 1 study and a phase 3 double-blind, double-dummy study of the efficacy and safety of LCIG compared with LC-oral in advanced PD patients (n = 68 for model development; 45 on LCIG and 23 on LC-oral). The final model was internally evaluated using stochastic simulations and bootstrap and externally evaluated using sparse pharmacokinetic data from 311 subjects treated in a long term safety study of LCIG. Results The final model was a two compartment model with a transit compartment for absorption, first order elimination, bioavailability for LCIG (97%; confidence interval = 95% to 98%) relative to LC-oral, different first order transit absorption rate constants (LCIG = 9.2 h–1 vs. LC-oral = 2.4 h–1; corresponding mean absorption time of 7 min for LCIG?vs. 25 min for LC-oral) and different residual (intra-subject) variability for LCIG (15% proportional error, 0.3 ?g ml?1 additive error) vs.?LC-oral (29% proportional error, 0.59 ?g ml?1 additive error). Estimated oral clearance and steady-state volume of distribution for levodopa were 24.8 l h?1 and 131 l, respectively. Conclusions LCIG administration results in faster absorption, comparable levodopa bioavailability and significantly reduced intra-subject variability in levodopa concentrations relative to LC-oral administration. PMID:24433449

  10. Single-Dose Phase I Study To Evaluate the Pharmacokinetics of Posaconazole in New Tablet and Capsule Formulations Relative to Oral Suspension

    PubMed Central

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

    2012-01-01

    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 [AUC0–?], 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 AUC0–?, 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 AUC0–?, 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 AUC0–?, 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

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

    PubMed

    Ramadhani, Nisrina; Shabir, Mehwish; McConville, Christopher

    2014-11-20

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

  12. Pharmacokinetics of ketoconazole administered intravenously to dogs and orally as tablet and solution to humans and dogs.

    PubMed

    Baxter, J G; Brass, C; Schentag, J J; Slaughter, R L

    1986-05-01

    The single-dose pharmacokinetics and bioavailability of three ketoconazole formulations were evaluated using HPLC in five healthy human volunteers and six male mongrel dogs. The human volunteers received 400 mg po of ketoconazole as tablet (Ktab) and solution (Ksol) formulations. The dogs received 400 mg po of Ktab and Ksol, and 376 mg iv of an intravenous dose (Kiv). In humans the AUC value for Ksol (62.21 +/- 21.2 microgram X h/ml; mean +/- SD) was significantly greater than for Ktab (50.0 +/- 15.2 micrograms X h/ml; p less than 0.05). Peak serum concentrations (Cmax), time to peak serum concentrations (tmax), t1/2, and the terminal elimination rate constant (kel) did not differ between Ktab and Ksol. This suggests that the administration of Ksol may be a useful alternative to dosage increases in situations where low bioavailability of ketoconazole in tablet form is suspected. The mean systemic clearance (CLs) of Kiv in dogs was 2.74 +/- 1.10 mL/min/kg, the volume of distribution at steady state (Vdss) was 0.72 +/- 0.28 L/kg, and the half-life was 2.7 +/- 1.6 h. Considerable variability was seen in the AUC of ketoconazole, particularly with the oral preparations. The absolute bioavailability of Ktab was 0.50 +/- 0.38, which did not differ statistically from that of Ksol, 0.56 +/- 0.23. The Ksol showed less variability in AUC, Cmax, and F values than did Ktab, and two dogs with low bioavailability with Ktab (0.04 and 0.07) had substantially greater bioavailability with Ksol (F = 0.96 and 0.57, respectively). Evaluation of Kiv in dogs confirms decreased bioavailability from orally administered tablet formulations of ketoconazole. PMID:3735080

  13. Development and characterisation of sustained release solid dispersion oral tablets containing the poorly water soluble drug disulfiram.

    PubMed

    Shergill, Mandip; Patel, Mina; Khan, Siraj; Bashir, Ayesha; McConville, Christopher

    2016-01-30

    Administration of drugs via the oral route is the most common and preferred route due to its ease of administration, cost-effectiveness and flexibility in design. However, if the drug being administered has limited aqueous solubility it can result in poor bioavailability. Furthermore, the low pH of the stomach as well as enzymatic activity can result in drugs delivered via the oral route being rapidly metabolised and degraded. Here we demonstrate the development and characterisation of sustained release solid dispersion oral tablets, containing the poorly water-soluble drug disulfiram (DSF). The tablets, which are manufactured from two different polymers (Kolliphor(®) P 188 and P 237) specifically designed for the manufacture of solid dispersions and two different polymers (Kollidon(®) SR and HPMC) specifically designed to provide sustained release, can enhance the solubility of DSF, sustain its release, while protecting it from degradation in simulated gastric fluid (SGF). The paper demonstrates that when using the hot melt method at 80°C the DSF loading capacity of the Kolliphor(®) P 188 and P 237 polymers is approximately 43 and 46% respectively, with the DSF completely in an amorphous state. The addition of 80% Kollidon(®) SR to the formulation completely protected the DSF in SGF for up to 70min with 16% degradation after 120min, while 75% degradation occurred after 120min with the addition of 80% HPMC. The release rate of DSF can be manipulated by both the loading and type of sustained release polymer used, with HPMC providing for a much faster release rate compared to Kollidon(®) SR. PMID:26608620

  14. Potential use of 2-hydroxypropyl-beta-cyclodextrin for preparation of orally disintegrating tablets containing dl-alpha-tocopheryl acetate, an oily drug.

    PubMed

    Motoyama, Keiichi; Nagatomo, Kiyoshi; Abd Elazim, Soliman Osama; Hirayama, Fumitoshi; Uekama, Kaneto; Arima, Hidetoshi

    2009-11-01

    To expand the application of a drug in orally disintegrating tablets, the potential use of beta-cyclodextrin (beta-CyD) and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) as excipients for the tablets containing dl-alpha-tocopheryl acetate (VE), an oily drug, was evaluated. HP-beta-CyD, not beta-CyD, solubilized VE in water through the formation of higher order of complexes at the molar ratio of 1 : 2 (VE : HP-beta-CyD). When prepared under the optimal preparation conditions, the VE tablets containing lactose and 5% (w/w) of HP-beta-CyD, not beta-CyD, had high hardness more than 4 kg and rapid disintegration within 100 s both in vitro and in vivo. In addition, VE tablets containing lactose and 5% (w/w) of HP-beta-CyD, not beta-CyD, maintained the high hardness and rapid disintegration under the accelerated stability test using different conditions for 4 weeks. Therefore, these results suggest the potential use of HP-beta-CyD, not beta-CyD, as an excipient for orally disintegrating tablets containing VE, an oily drug, in the molding method. PMID:19881268

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

    PubMed Central

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

    2014-01-01

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

  16. Morphine: Myths and Reality

    MedlinePLUS

    ... training. The reality is that Morphine (and other opiates that work in the same way, such as ... doctor) are afraid to use Morphine or other opiates. Here are some common misunderstandings about Morphine and ...

  17. Enteric-coated tablet of risedronate sodium in combination with phytic acid, a natural chelating agent, for improved oral bioavailability.

    PubMed

    Kim, Jeong S; Jang, Sun W; Son, Miwon; Kim, Byoung M; Kang, Myung J

    2016-01-20

    The oral bioavailability (BA) of risedronate sodium (RS), an antiresorptive agent, is less than 1% due to its low membrane permeability as well as the formation of non-absorbable complexes with multivalent cations such as calcium ion (Ca(2+)) in the gastrointestinal tract. In the present study, to increase oral BA of the bisphosphonate, a novel enteric-coated tablet (ECT) dosage form of RS in combination with phytic acid (IP6), a natural chelating agent recognized as safe, was formulated. The chelating behavior of IP6 against Ca(2+), including a stability constant for complex formulation was characterized using the continuous variation method. Subsequently, in vitro dissolution profile and in vivo pharmacokinetic profile of the novel ECT were evaluated comparatively with that of the marketed product (Altevia, Sanofi, US), an ECT containing ethylenediaminetetraacetic acid (EDTA) as a chelating agent, in beagle dogs. The logarithm of stability constant for Ca(2+)-IP6 complex, an equilibrium constant approximating the strength of the interaction between two chemicals to form complex, was 19.05, which was 3.9-fold (p<0.05) and 1.7-fold (p<0.05) higher than those of Ca(2+)-RS and Ca(2+)-EDTA complexes. The release profile of RS from both enteric-coated dosage forms was equivalent, regardless of the type of chelating agent. An in vivo absorption study in beagle dogs revealed that the maximum plasma concentration and area under the curve of RS after oral administration of IP6-containing ECT were approximately 7.9- (p<0.05) and 5.0-fold (p<0.05) higher than those of the marketed product at the same dose (35mg as RS). Therefore, our study demonstrates the potential usefulness of the ECT system in combination with IP6 for an oral therapy with the bisphosphonate for improved BA. PMID:26594027

  18. Risperidone solid dispersion for orally disintegrating tablet: its formulation design and non-destructive methods of evaluation.

    PubMed

    Rahman, Ziyaur; Zidan, Ahmed S; Khan, Mansoor A

    2010-11-15

    The focus of present investigation was to assess the utility of non-destructive techniques in the evaluation of risperidone solid dispersions (SD) with methyl-?-cyclodextrin (MBCD) and subsequent incorporation of the SD into orally disintegrating tablets (ODT) for a faster release of risperidone. The SD was prepared by a solvent evaporation method and evaluated by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), near infrared spectroscopy (NIR), NIR-chemical imaging (NIR-CI), powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). DSC and XRD analysis indicated that crystallinity of SD has reduced significantly. FTIR showed no interaction between risperidone and MBCD. Partial least square (PLS) was applied to the NIR data for the construction of chemometric models to determine both components of the SD. Good correlations were obtained for calibration and prediction as indicated by correlation coefficients >0.9965. The model was more accurate and less biased in predicting the MBCD than risperidone as indicated by its lower mean accuracy and mean bias values. SD-3 (risperidone:MBCD, 1:3) was incorporated into ODT tablets containing diluent (D-mannitol, FlowLac(®) 100 or galenIQ™-721) and superdisintegrant (Kollidon(®) CL-SF, Ac-Di-Sol or sodium starch glycolate). Disintegration time, T(50) and T(90) were decreased in the formulations containing mannitol and Kollidon(®) CL-SF, but increased with galenIQ™-721 and sodium starch glycolate, respectively. NIR-CI images confirmed the homogeneity of SD and ODT formulations. PMID:20801200

  19. Swimming reduces the severity of physical and psychological dependence and voluntary morphine consumption in morphine dependent rats.

    PubMed

    Fadaei, Atefeh; Gorji, Hossein Miladi; Hosseini, Shahrokh Makvand

    2015-01-15

    Previous studies have indicated that voluntary exercise decreases the severity of the anxiogenic-like behaviors in both morphine-dependent and withdrawn rats. This study examined the effects of regular swimming exercise during the development of dependency and spontaneous morphine withdrawal on the anxiety-depression profile and voluntary morphine consumption in morphine dependent rats. The rats were chronically treated with bi-daily doses (10 mg/kg, at 12h intervals) of morphine over a period of 14 days. The exercising rats were allowed to swim (45 min/d, five days per a week, for 14 or 21 days) during the development of morphine dependence and withdrawal. Then, rats were tested for the severity of morphine dependence, the elevated plus-maze (EPM), sucrose preference test (SPT) and voluntary morphine consumption using a two-bottle choice paradigm in animal models of craving. The results showed that withdrawal signs were decreased in swimmer morphine dependent rats than sedentary rats (P<0.05). Also, the swimmer morphine-dependent and withdrawn rats exhibited an increase in EPM open arm time and entries (P<0.05), higher levels of sucrose preference (P<0.001) than sedentary rats. Voluntary consumption of oral morphine was less in the swimmer morphine-withdrawn rats than the sedentary groups during four periods of the intake of drug (P<0.01). We conclude that regular swimming exercise reduces the severity of morphine dependence and voluntary morphine consumption with reducing anxiety and depression in morphine-dependent and withdrawn rats. Thus, swimming exercise may be a potential method to ameliorate some of the deleterious behavioral consequences of morphine dependence. PMID:25498794

  20. Formulation, preparation, and evaluation of novel orally disintegrating tablets containing taste-masked naproxen sodium granules and naratriptan hydrochloride.

    PubMed

    Stange, Ulrike; Führling, Christian; Gieseler, Henning

    2014-04-01

    The purpose of this study was to develop and manufacture novel freeze-dried orally disintegrating tablets (ODTs) for migraine therapy containing taste-masked naproxen sodium and naratriptan hydrochloride. The formulation was optimized based on freeze-drying of sucrose solutions with different binders (hydroxyethylstarch, sodium alginate, methylcellulose, and gelatin) and varying amounts of Eudragit® E-coated naproxen sodium granules. Excellent product performance of the ODTs in terms of hardness and disintegration time (<10 s) independent of the mass of particles embedded was found for the solution consisting of sucrose and hydroxyethylstarch. Poloxamer 188, menthol flavor, naratriptan hydrochloride, and taste-masked naproxen sodium granules corresponding to 200 mg of naproxen were then added, and the final batches of ODTs for migraine therapy were produced. The ODTs were fully characterized, and subsequently stored for 1 month at room temperature and at 40°C. The amount of free naproxen sodium after freeze-drying and storage was below the threshold bitterness value, and the coating remained intact. Additionally, the particle size distribution of taste-masked granules was preserved, and more than 90 % naproxen sodium was released after 30 min. Naratriptan hydrochloride was dissolved immediately after disintegration, hence facilitating buccal absorption of the active pharmaceutical ingredient. PMID:24532095

  1. Enhancement of Solubility of Lamotrigine by Solid Dispersion and Development of Orally Disintegrating Tablets Using 32 Full Factorial Design

    PubMed Central

    Singh, Jatinderpal; Garg, Rajeev; Gupta, Ghanshyam Das

    2015-01-01

    Present investigation deals with the preparation and evaluation of orally disintegrating tablets (ODTs) of lamotrigine using ?-cyclodextrin and PVP-K30 as polymers for the preparation of solid dispersion which help in enhancement of aqueous solubility of this BCS CLASS-II drug and sodium starch glycolate (SSG) and crospovidone as a superdisintegrating agent, to reduce disintegration time. The ODTs were prepared by direct compression method. Nine formulations were developed with different ratios of superdisintegrating agents. All the formulations were evaluated for disintegration time, weight variation, hardness, friability, drug content uniformity, wetting time, and in vitro drug release study. In vitro drug release study was performed using United States Pharmacopoeia (USP) type 2 dissolution test apparatus employing paddle stirrer at 50?rpm using 900?mL of 0.1?N HCl maintained at 37°C ± 0.5°C as the dissolution medium. On the basis of evaluation parameters formulations were prepared using ?-CD 1?:?1 solid dispersion. Then 32 full factorial design was applied using SSG and crospovidone in different ratios suggested by using design expert 8.0.7.1 and optimized formulation was prepared using amount of SSG and crospovidone as suggested by the software. The optimized formulation prepared had disintegrating time of 15?s, wetting time of 24?s, and % friability of 0.55. PMID:26634173

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

    PubMed Central

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

    2011-01-01

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

  3. Application of the BCS biowaiver approach to assessing bioequivalence of orally disintegrating tablets with immediate release formulations.

    PubMed

    Ono, Asami; Sugano, Kiyohiko

    2014-11-20

    The aim of this study was to compare the dissolution profiles of oral disintegrating tablets (ODTs) and immediate release (IR) formulations in order to experimentally validate the regulatory biowaiver scheme (BWS) for biopharmaceutical classification system (BCS) class III drugs. We examined six drugs that show clinical bioequivalence between the ODTs and IR formulations: taltirelin, olopatadine, droxidopa, famotidine, fexofenadine, and hydrochlorothiazide. The dissolution profiles of these drugs were evaluated using the compendium paddle apparatus at pH 1.2 and 6.8. Taltirelin and olopatadine showed very rapid dissolution and met the dissolution criteria in the BWS, whereas droxidopa, famotidine, fexofenadine, and hydrochlorothiazide did not. Furthermore, in the case of famotidine, fexofenadine, and hydrochlorothiazide, the ODTs and IR formulations showed dissimilar dissolution profiles. The dose-to-solubility ratio (D:S) of these drugs was larger than that of the other drugs. The results of this study suggest that extension of the BCS-BWS to ODTs and IR formulations of BCS class III drugs is appropriate. Furthermore, for BCS class III drugs with relatively high D:S, clinical bioequivalence would be achievable even when two formulations showed different dissolution profiles in vitro. PMID:25151946

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

    PubMed

    Vora, Nishant; Rana, Vikas

    2008-01-01

    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

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

    PubMed

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

    2008-06-01

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

  6. The Effects of Screw Configuration and Polymeric Carriers on Hot-Melt Extruded Taste-Masked Formulations Incorporated into Orally Disintegrating Tablets

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  8. Oral Doxycycline in the Management of Acne Vulgaris: Current Perspectives on Clinical Use and Recent Findings with a New Double-scored Small Tablet Formulation

    PubMed Central

    2015-01-01

    Oral antibiotics have been used for the treatment of acne vulgaris for six decades. Among dermatologists, tetracyclines represent at least three-fourths of the oral antibiotics prescribed in clinical practice. Unlike other specialties, antibiotic use in dermatology is predominantly for the treatment of noninfectious disorders, such as acne vulgaris and rosacea, which usually involves prolonged therapy over several weeks to months as compared to short courses used to treat cutaneous infections. At the present time, doxycycline and minocycline are the most commonly prescribed tetracyclines in dermatology, used primarily for treatment of acne vulgaris with a long overall favorable track record of effectiveness and safety. Although both are commonly used, doxycycline may be chosen by clinicians more readily as there is a lower risk of rare yet potentially serious adverse reactions, although doxycycline does warrant preventative measures to reduce the risks of esophagitis and phototoxicity reactions. This article reviews data with a new double-scored small 150mg tablet of doxycycline hyclate that has proven functional scoring, exhibits bioavailability similar to enteric-coated doxycycline, and has been shown to be associated with a low potential for gastrointestinal adverse reactions very comparable to what is achieved with enteric-coated tablets. PMID:26029331

  9. 21 CFR 520.1870 - Praziquantel tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1870 Praziquantel tablets. (a) Specifications. Each tablet contains: (1) 34 milligrams (mg) praziquantel. (2) 11.5 or 23 mg praziquantel. (b... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Praziquantel tablets. 520.1870 Section...

  10. 21 CFR 520.928 - Firocoxib tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Firocoxib tablets. 520.928 Section 520.928 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.928 Firocoxib tablets. (a) Specifications. Each chewable tablet contains 57...

  11. Morphine Sulfate Injection

    MedlinePLUS

    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 ...

  12. 21 CFR 520.1284 - Sodium liothyronine tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sodium liothyronine tablets. 520.1284 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of tablets intended for...

  13. [New option in the management of cancer pain in Hungary: short acting oral opioid therapy].

    PubMed

    Kullmann, Tamás; Sip?cz, István; Csikós, Ágnes; Pintér, Tamás

    2015-06-21

    Short acting oral morphine has recently been registered again in Hungary. Short acting oral morphine has two essential indications: dose titration at initiation of major analgesic therapy and treatment of breakthrough pain appearing beside round the clock major analgesic therapy. The clinical management of short acting oral morphine is summarised in this article. PMID:26170088

  14. 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.

    PubMed

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

    2013-01-01

    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

  15. In vitro and in vivo correlation of disintegration and bitter taste masking using orally disintegrating tablet containing ion exchange resin-drug complex.

    PubMed

    Kim, Jong-Il; Cho, Sang-Min; Cui, Jing-Hao; Cao, Qing-Ri; Oh, Euichaul; Lee, Beom-Jin

    2013-10-15

    Although the taste-masking of bitter drug using ion exchange resin has been recognized, in vitro testing using an electronic tongue (e-Tongue) and in vivo bitterness test by human panel test was not fully understood. In case of orally disintegrating tablet (ODT) containing bitter medicine, in vitro and in vivo disintegration is also importance for dosage performance. Donepezil hydrochloride was chosen as a model drug due to its bitterness and requires rapid disintegration for the preparation of ODT. In this study, ion exchange resin drug complex (IRDC) at three different ratios (1:2, 1:1, 2:1) was prepared using a spray-drying method and then IRDC-loaded ODT containing superdisintegrants (crospovidone, croscarmellose sodium, and sodium starch glycolate) were prepared by the direct compression method. The physical properties and morphologies were then characterized by scanning electron microscopy (SEM), X-ray powder diffraction (PXRD) and electrophoretic laser scattering (ELS), respectively. The in vitro taste-masking efficiency was measured with an electronic tongue (e-Tongue). In vivo bitterness scale was also evaluated by human volunteers and then we defined new term, "bitterness index (BI)" to link in vitro e-Tongue. There was a good correlation of IRDC between in vitro e-Tongue values and in vivo BI. Furthermore, IRDC-loaded ODT showed good in vitro/in vivo correlation in the disintegration time. The optimal IRDC-loaded ODTs displayed similar drug release profiles to the reference tablet (Aricept(®) ODT) in release media of pH 1.2, pH 4.0, pH 6.8 and distilled water but had significantly better palatability in vivo taste-masking evaluation. The current IRDC-loaded ODT according to the in vitro and in vivo correlation of disintegration and bitter taste masking could provide platforms in ODT dosage formulations of donepezil hydrochloride for improved patient compliances. PMID:23933050

  16. Influence of food on the oral bioavailability of loratadine and pseudoephedrine from extended-release tablets in healthy volunteers.

    PubMed

    Nomeir, A A; Mojaverian, P; Kosoglou, T; Affrime, M B; Nezamis, J; Rodwanski, E; Lin, C C; Cayen, M N

    1996-10-01

    The effect of a high-fat breakfast on the bioavailability of the components of an extended-release tablet containing 10 mg loratadine in the immediate-release coating and 240 mg pseudoephedrine sulfate in the extended-release core was studied in 24 healthy male volunteers in a single-dose, two-way crossover study. The drug was administered after a 10-hour overnight fast or within 5 minutes of consuming a standardized high-fat breakfast. Serial blood samples were collected over a 48-hour period, and plasma was analyzed for loratadine and its active metabolite descarboethoxyloratadine (DCL), and pseudoephedrine. For pseudoephedrine, maximum concentration (Cmax) and area under the concentration-time curve extrapolated to infinity (AUCzero-infinity) were similar after both treatments, indicating no relevant food effect on the bioavailability of pseudoephedrine. Also, the absorption profiles of pseudoephedrine (from Wagner-Nelson analysis) were similar for the fed and fasted treatments, indicating no apparent differences in absorption. Plasma concentration-time profiles and values for Cmax and AUCzero-infinity of DCL were similar for the two treatments, indicating no relevant food effect on the pharmacokinetics of DCL. In contrast, for loratadine, administration with food resulted in a significantly increased mean Cmax (53%) and AUC from time zero to the final quantifiable sample (AUCif) (76%). However, the resultant Cmax and AUC of loratadine under fed conditions were well below those previously obtained at steady-state after multiple-dose administration of loratadine (40 mg/day) that were shown to be safe and well-tolerated in several clinical studies. The effect of food on the bioavailability and pharmacokinetic profiles of the components of a combination loratadine/pseudoephedrine extended-release tablet is not likely to be clinically significant. PMID:8930779

  17. Estrogen and Progestin (Oral Contraceptives)

    MedlinePLUS

    ... many different brands. Different brands of oral contraceptives contain slightly different medications or doses, are taken in ... 28-tablet packets have certain color tablets that contain different amounts of estrogen and progestin, but also ...

  18. LC-MS/MS determination and urinary excretion study of seven alkaloids in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets.

    PubMed

    Cheng, Minlu; Liu, Ruijuan; Wu, Yao; Gu, Pan; Zheng, Lu; Liu, Yujie; Ma, Pengcheng; Ding, Li

    2016-01-25

    An LC-MS/MS method was developed and validated for the simultaneous determination of magnoflorine, berberrubine, jatrorrhizine, coptisine, epiberberine, palmatine and berberine in human urine. The sample preparation procedure involved the four-fold dilution of the urine samples with acetonitrile/water (1:3, v/v). The chromatographic separation was achieved on a Hedera ODS-2 column under gradient elution at a flow rate of 0.4mL/min with acetonitrile and water containing 0.5% formic acid as the mobile phase. The mass detection was performed in the positive mode. Calibration curves of the seven alkaloids showed good linearity (correlation coefficients>0.9973) over their concentration ranges. To meet the requirements of urinary excretion study for each alkaloid in human, the lower limit of quantification was set at different values from 0.05063ng/mL to 2.034ng/mL for the seven alkaloids, respectively. The intra- and inter-batch precision and accuracy were all within ±15%. No matrix effect was observed for the analytes. The validated method was applied to the excretion study for the seven alkaloids in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets. The average 72h cumulative urinary excretion of magnoflorine, berberrubine, jatrorrhizine, coptisine, epiberberine, palmatine and berberine accounted for 1.81%, 0.27%, 0.29%, 0.046%, 0.027%, 0.010% and 0.021% of the respective administered dose. PMID:26519688

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

    PubMed

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

    2009-04-01

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

  20. 21 CFR 520.804 - Enalapril tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Enalapril tablets. 520.804 Section 520.804 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.804 Enalapril tablets. (a) Specifications. Each tablet contains either 1.0, 2.5, 5.0, 10.0, or 20.0 milligrams of enalapril maleate....

  1. 21 CFR 520.804 - Enalapril tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Enalapril tablets. 520.804 Section 520.804 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.804 Enalapril tablets. (a) Specifications. Each tablet contains either 1.0, 2.5, 5.0, 10.0, or 20.0 milligrams of enalapril maleate....

  2. A double-blind, randomized, parallel group study to compare the efficacy, safety and tolerability of slow-release oral morphine versus methadone in opioid-dependent in-patients willing to undergo detoxification

    PubMed Central

    Madlung-Kratzer, Ekkehard; Spitzer, Berhard; Brosch, Renate; Dunkel, Dirk; Haring, Christian

    2009-01-01

    Aims Evaluation of the efficacy and safety of slow-release oral morphine (SROM) compared with methadone for detoxification from methadone and SROM maintenance treatment. Design Randomized, double-blind, double-dummy, comparative multi-centre study with parallel groups. Setting Three psychiatric hospitals in Austria specializing in in-patient detoxification. Participants Male and female opioid dependents (age > 18 years) willing to undergo detoxification from maintenance therapy in order to reach abstinence. Interventions Abstinence was reached from maintenance treatment by tapered dose reduction of either SROM or methadone over a period of 16 days. Measurements Efficacy analyses were based on the number of patients per treatment group completing the study, as well as on the control of signs and symptoms of withdrawal [measured using Short Opioid Withdrawal Scale (SOWS)] and suppression of opiate craving. In addition, self-reported somatic and psychic symptoms (measured using Symptom Checklist SCL-90-R) were monitored. Findings Of the 208 patients enrolled into the study, 202 were eligible for analysis (SROM: n = 102, methadone: n = 100). Completion rates were 51% in the SROM group and 49% in the methadone group [difference between groups: 2%; 95% confidence interval (CI): ?12% to 16%]. The rate of discontinuation in the study was high mainly because of patients voluntarily withdrawing from treatment. No statistically significant differences between treatment groups were found in terms of signs and symptoms of opiate withdrawal, craving for opiates or self-reported symptoms. SROM and methadone were both well tolerated. Conclusions Detoxification from maintenance treatment with tapered dose reduction of SROM is non-inferior to methadone. PMID:19686525

  3. 21 CFR 520.1331 - Meclofenamic acid tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Meclofenamic acid tablets. 520.1331 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1331 Meclofenamic acid tablets. (a) Specifications. Each tablet contains either 10 or 20 milligrams of meclofenamic acid....

  4. 21 CFR 520.1331 - Meclofenamic acid tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Meclofenamic acid tablets. 520.1331 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1331 Meclofenamic acid tablets. (a) Specifications. Each tablet contains either 10 or 20 milligrams of meclofenamic acid....

  5. 21 CFR 520.1331 - Meclofenamic acid tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Meclofenamic acid tablets. 520.1331 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1331 Meclofenamic acid tablets. (a) Specifications. Each tablet contains either 10 or 20 milligrams of meclofenamic acid....

  6. 21 CFR 520.1331 - Meclofenamic acid tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Meclofenamic acid tablets. 520.1331 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1331 Meclofenamic acid tablets. (a) Specifications. Each tablet contains either 10 or 20 milligrams of meclofenamic acid....

  7. 21 CFR 520.2150a - Stanozolol tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Stanozolol tablets. 520.2150a Section 520.2150a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2150a Stanozolol tablets. (a) Specifications. Each tablet contains...

  8. 21 CFR 520.1331 - Meclofenamic acid tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Meclofenamic acid tablets. 520.1331 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1331 Meclofenamic acid tablets. (a) Specifications. Each tablet contains either 10 or 20 milligrams of meclofenamic acid....

  9. 21 CFR 520.1696d - Penicillin V tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin V tablets. 520.1696d Section 520.1696d... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696d Penicillin V tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125 milligrams...

  10. 21 CFR 520.1696d - Penicillin V tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Penicillin V tablets. 520.1696d Section 520.1696d... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696d Penicillin V tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125 milligrams...

  11. 21 CFR 520.1380 - Methocarbamol tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Methocarbamol tablets. 520.1380 Section 520.1380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1380 Methocarbamol tablets. (a) Chemical name....

  12. 21 CFR 520.1380 - Methocarbamol tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Methocarbamol tablets. 520.1380 Section 520.1380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1380 Methocarbamol tablets. (a) Chemical name....

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

    PubMed Central

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

    2014-01-01

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

  14. 21 CFR 520.370 - Cefpodoxime tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.370 Cefpodoxime tablets...S. aureus , Streptococcus canis (group G, -hemolytic), Escherichia coli...

  15. 21 CFR 520.370 - Cefpodoxime tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.370 Cefpodoxime tablets...S. aureus , Streptococcus canis (group G, -hemolytic), Escherichia coli...

  16. 21 CFR 520.370 - Cefpodoxime tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.370 Cefpodoxime tablets...S. aureus , Streptococcus canis (group G, -hemolytic), Escherichia coli...

  17. 21 CFR 520.370 - Cefpodoxime tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.370 Cefpodoxime tablets...S. aureus , Streptococcus canis (group G, -hemolytic), Escherichia coli...

  18. 21 CFR 520.370 - Cefpodoxime tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.370 Cefpodoxime tablets...S. aureus , Streptococcus canis (group G, -hemolytic), Escherichia coli...

  19. Dose-response relationship after single oral dose administrations of morphine and oxycodone using laser-evoked potentials on UVB- and capsaicin-irritated skin in healthy male subjects.

    PubMed

    Hoeben, Eef; Smit, Johan W; Upmalis, David; Rusch, Sarah; Schaffler, Klaus; Reitmeir, Peter; Mangold, Bernhard

    2012-08-01

    The aim of the study was to evaluate the analgesic/antihyperalgesic efficacy and to establish the dose-response relationship of morphine immediate release (IR) and oxycodone IR in a human experimental algesimetric model. Calculated effect ratios for peak-to-peak (PtP) amplitudes of laser-evoked potentials (LEPs) and visual analog scales (VAS) postlaser pain on UVB-irradiated skin (main target variables) were 1.68 and 1.18 respectively for oxycodone 10mg/morphine 20mg, 3.00 and 1.63 respectively for oxycodone 15 mg/morphine 30 mg, and 1.12 and 1.25 respectively for oxycodone 20mg/morphine 40 mg. The effect on the laser-PtP amplitude of morphine at the highest dose (40 mg) and of oxycodone at all doses (10, 15, 20mg) was considered to be clinically relevant based on a difference from placebo of ? 2.5 ?V. For both compounds, a statistically significant linear trend was observed between dose groups in at least 1 of the 2 main target variables (adjusted P value for both end points <.001 at all doses). Hyperalgesia developed over time vs baseline due to acute exposure to UVB irradiation and to topical/occlusive 1% capsaicin solution. For both compounds, the principal onset of analgesic/antihyperalgesic drug effects was around 0.5 hours with an average peak at about 1 to 2 hours and the effect lasting for more than 3 hours (morphine 20 and 30 mg) or 6 hours (morphine 40 mg and oxycodone all doses). In conclusion, the study demonstrated a solid outcome of a mixed objective/subjective human experimental algesimetric model to approach dose-response relationships and analgesic/antihyperalgesic effects of 2 opioids. PMID:22703892

  20. Tablet Weaving

    ERIC Educational Resources Information Center

    Kren, Margo

    1976-01-01

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

  1. [Study of Preparation and Utility of Suppository Containing Carbamazepine Tablet for Hospital Use in Rabbits].

    PubMed

    Murata, Isamu; Arai, Narutoshi; Fukushima, Aishi; Saito, Astuko; Inoue, Yutaka; Kimura, Masayuki; Kanamoto, Ikuo

    2015-01-01

    Cancer patients often report a decreased quality of life due to cancer-related pain, especially neuropathic pain, which is difficult to manage and often develops resistance to morphine. Thus a supplementary analgesic can play an important role in the treatment of cancer-related pain. Carbamazepine (CBZ), for example, can be effective, but only if the patient can take medication orally because it is limited to oral administration. In this study we investigated the efficacy of a suppository containing CBZ tablet in hospital preparations. We selected a base for the suppository of either polyethylene glycol (P), Witepsol VOSCO(®) H-15 (H), or Witepsol VOSCO(®) S-55 (S). Six to eight in vitro and in vivo groups were divided randomly based on route of administration and treatment: intravenous (i.v.), per os (p.o.), and intrarectal administration (i.r.) (composed of CBZ powder and tablet formulations, CBZp and CBZt) prepared in either a base of P, H, or S (CBZp/P, CBZp/H, CBZp/S, CBZt/P, CBZt/H, and CBZt/S). The hardness levels of the CBZt suppository group were significantly lower than the CBZp suppository group. The drug release profiles of the CBZt suppository group were high in order of P, H, and S; there were no significant differences between these groups and the CBZp suppository group. The maximum drug concentration time levels of the CBZt suppository group significantly increased compared with the p.o. group. These two groups had equivalent maximum drug concentration and bioavailability levels. These results suggest that a suppository containing CBZ tablet can be useful for hospital preparations. PMID:26329551

  2. Three-way, three-period, crossover bioequivalence study of single oral dose of three brands of 300 mg phenytoin sodium tablets marketed in India, on healthy Indian human volunteers

    PubMed Central

    Doshi, Maulik S.; Naik, Anuja A.; Mehta, Mohit R.; Gogtay, Nithya J.; Thatte, Urmila M.; Menon, Mala D.

    2013-01-01

    Objective: To compare the bioavailability of two brands of phenytoin sodium tablets available in the Indian market using Eptoin™ as the reference. Materials and Methods: A randomized, assessor-blind, three-way crossover design study was carried out over a period of 6 months after approval from the Institutional Review Board (IRB). Twenty-two healthy male participants received a single oral 300 mg oral tablet of either of the formulations with a 2-week washout. Blood samples were collected predose and at regular intervals postdose. Plasma phenytoin levels were estimated by high-performance liquid chromatography. Calculation of Cmax, AUC0-t, and AUC0-? was done by the linear trapezoidal rule and 90-110% margin (90% confidence interval (CI)) was used to assess bioequivalence. Results: Twenty volunteers completed the study. It was seen that the log-transformed values of Cmax, AUC0-t, and AUC0-? of the test formulations were not within the specified limits. Conclusion: Bioinequivalence of available phenytoin brands indicates that switching brands could lead to variations in blood concentrations and thus impact safety and efficacy. If a brand switch is done for any reason, stringent drug-level monitoring is advised. PMID:24250200

  3. Simultaneous determination of calycosin-7-O-?-d-glucoside, calycosin, formononetin, astragaloside IV and schisandrin in rat plasma by LC-MS/MS: application to a pharmacokinetic study after oral administration of Shenqi Wuwei chewable tablets.

    PubMed

    Sun, Xuehui; Zhang, Pingping; Wu, Xiujun; Wu, Qiong; Zhang, Mengmeng; An, Ye; Shi, Guobing

    2014-08-01

    A rapid, sensitive and reliable high-performance liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous quantification of the five main bioactive components, calycosin, calycosin-7-O-?-d-glucoside, formononetin, astragaloside IV and schisandrin in rat plasma after oral administration of Shenqi Wuwei chewable tablets. Plasma samples were extracted using solid-phase extraction separated on a CEC18 column and detected by MS with an electrospray ionization interface in multiple-reaction monitoring mode. Calibration curves offered linear ranges of two orders of magnitude with r > 0.995. The method had a lower limit of quantitation of 0.1, 0.02, 0.1, 1 and 0.1 ng/mL for calycosin, calycosin-7-O-?-d-glucoside, formononetin, astragaloside IV and schisandrin, respectively. Intra- and inter-day precisions (relative standard deviation) for all analytes ranged from 0.97 to 7.63% and from 3.45 to 10.89%, respectively. This method was successfully applied to the pharmacokinetic study of the five compounds in rats after oral administration of Shenqi Wuwei chewable tablets. PMID:24652759

  4. Investigation of the bioequivalence of montelukast chewable tablets after a single oral administration using a validated LC-MS/MS method

    PubMed Central

    Zaid, Abdel Naser; Abualhasan, Murad N; Watson, David G; Mousa, Ayman; Ghazal, Nadia; Bustami, Rana

    2015-01-01

    Background Montelukast (MT) is a leukotriene D4 antagonist. It is an effective and safe medicine for the prophylaxis and treatment of chronic asthma. It is also used to prevent acute exercise-induced bronchoconstriction and as a symptomatic relief of seasonal allergic rhinitis and perennial allergic rhinitis. Objective The aim of this study was to evaluate the bioequivalence (BE) of two drug products: generic MT 5 mg chewable tablets versus the branded drug Singulair® pediatric 5 mg chewable tablets among Mediterranean volunteers. Methods An open-label, randomized two-period crossover BE design was conducted in 32 healthy male volunteers with a 9-day washout period between doses and under fasting conditions. The drug concentrations in plasma were quantified by using a newly developed and fully validated liquid chromatography tandem mass spectrometry method, and the pharmacokinetic parameters were calculated using a non-compartmental model. The ratio for generic/branded tablets using geometric least squares means was calculated for both the MT products. Results The relationship between concentration and peak area ratio was found to be linear within the range 6.098–365.855 ng/mL. The correlation coefficient (R2) was always greater than 0.99 during the course of the validation. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between the generic and branded products. The point estimates (ratios of geometric means) were 101.2%, 101.6%, and 98.11% for area under the curve (AUC)0?last, AUC0?inf, and Cmax, respectively. The 90% confidence intervals were within the predefined limits of 80.00%–125.00% as specified by the US Food and Drug Administration and European Medicines Agency for BE studies. Conclusion Broncast® pediatric chewable tablets (5 mg/tablet) are bioequivalent to Singulair® pediatric chewable tablets (5 mg/tablet), with a similar safety profile. This suggests that these two formulations can be considered interchangeable in clinical practice. PMID:26451086

  5. Peripheral postmortem redistribution of morphine.

    PubMed

    Hargrove, Veronica M; Molina, D Kimberley

    2014-06-01

    It is known that postmortem drug concentrations can vary depending on the sampling site and that, in general, central sites have higher drug concentrations than do peripheral sites. It has also been suggested that clamping the femoral vessel before drawing the sample may eliminate possible contribution from central sites. Morphine is a commonly prescribed and commonly encountered opiate medication that is often found in postmortem examinations, both as a cause of death and also as an incidental finding. It is important to understand the degree of postmortem redistribution of morphine to peripheral sites and whether clamping the femoral vessel can eliminate postmortem redistribution of morphine to ensure the correct interpretation of postmortem morphine concentrations. Morphine drug concentrations were evaluated in clamped and unclamped femoral vein blood samples at 3 different times before autopsy, and no significant change in either the clamped or the unclamped femoral vein morphine concentration was seen over time. Furthermore, no significant difference was found between the clamped and unclamped blood concentrations at any period. Therefore, it can be concluded that for morphine, unclamped femoral blood samples do not show significant redistribution from central sites within the first 24 hours after death in bodies kept refrigerated at 4°C. PMID:24781405

  6. 21 CFR 520.531 - Cythioate tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.531 Cythioate tablets. (a) (b...) Limitations. For oral use in dogs only. Do not use in greyhounds or in animals that are pregnant, sick, under stress, or recovering from surgery. Federal law restricts this drug to use by or on the order of...

  7. 21 CFR 520.531 - Cythioate tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.531 Cythioate tablets. (a) (b...) Limitations. For oral use in dogs only. Do not use in greyhounds or in animals that are pregnant, sick, under stress, or recovering from surgery. Federal law restricts this drug to use by or on the order of...

  8. 21 CFR 520.531 - Cythioate tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.531 Cythioate tablets. (a) (b...) Limitations. For oral use in dogs only. Do not use in greyhounds or in animals that are pregnant, sick, under stress, or recovering from surgery. Federal law restricts this drug to use by or on the order of...

  9. 21 CFR 520.531 - Cythioate tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.531 Cythioate tablets. (a) (b...) Limitations. For oral use in dogs only. Do not use in greyhounds or in animals that are pregnant, sick, under stress, or recovering from surgery. Federal law restricts this drug to use by or on the order of...

  10. [Cancer pain therapy in children and adolescents using morphine].

    PubMed

    Sittl, R; Richter, R

    1991-02-01

    Systematic treatment in children suffering from cancer pain is a field of pediatric oncology that was neglected for a long time. Investigations have shown that pain therapy oriented to the special situation of the child's body is urgently necessary. In Germany, an unpublished study by Fengler (Berlin), who reviewed all pediatric cancer centers, revealed serious deficiencies in the therapy of pain in children. In our study, we attempted to develop a new concept of cancer pain management, with the emphasis on cooperation between pediatric oncologist and anesthesiological pain therapists. PATIENTS AND METHODS. A total of 36 children and adolescents suffering from malignant tumors and in whom pain therapy according to WHO stage III was necessary were treated. After being seen by a pediatric oncologist and an anesthetist (pain therapist) each patient received either slow release oral morphine (MST, 0.5-1 mg/kg per dose) two to three times a day or a continuous infusion of morphine (0.05 mg/kg per h). The amount of morphine administered was quickly raised until the young patients were free of pain. Drug actions (pain score) and side effects were registered continuously with a documentation form. The morphine was combined with dipyrone 5-15 mg/kg per dose five times a day. The intravenous dosage of oral dipyrone was 2-5 mg/kg per h. RESULTS. The average age of the patients treated was 12 years (1.5-19 years); 10 were inpatients, and 26 were outpatients. All patients were treated successfully. The doses of morphine required for pain relief varied substantially (1-25 mg/kg per day p.o. and 0.05 mg-1 mg/kg per h i.v.). We did not observe extreme sedation or respiratory depression. In our patients we did not observe opioid-induced nausea such as is frequently seen in adults. All children needed laxatives. In 2 children, intolerable itching was experienced after oral administration of slow-release morphine. In 20 patients cortisone was given as adjuvant therapy, in 5 patients with neuropathic pain, anticonvulsants e.g., carbamazepine. In 6 patients we administered benzodiazepines successfully for sedation and anxiolysis. CONCLUSIONS. Therapy of pain in children with advanced cancer requires interdisciplinary cooperation. In most children therapy of pain can be successfully administered with slow-release morphine in combination with dipyrone, so that the children can remain in their usual social environment. PMID:2048710

  11. A (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer)-dispersed sustained-release tablet for imperialine to simultaneously prolong the drug release and improve the oral bioavailability.

    PubMed

    Lin, Qing; Fu, Yu; Li, Jia; Qu, Mengke; Deng, Li; Gong, Tao; Zhang, Zhirong

    2015-11-15

    Imperialine, extracted from Bulbus Fritillariae Cirrhosae, is an efficient antitussive and expectorant medicine. However, its short half-life and stomach degradation limited imperialine from further clinical use. The current study was conducted to develop a sustained-release tablet for imperialine both to prolong absorption time and to improve the oral bioavailability of the drug. The tablets were prepared by a direct compression method formulated on optimized solid dispersion (SD) for imperialine based on polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus(®)) with imperialine/Soluplus(®) ratio of 1:8 (w/w). In order to obtain the optimized formulation, factors that affected the drug release were investigated by in vitro dissolution studies in the media of pH1.2, 5.8, 7.0 and 7.4. Powder X-ray diffraction and scanning electron microscope confirmed that the imperialine in SD was amorphous instead of crystalline, and still stayed amorphous even after the direct compression. And besides, pharmacokinetic study in Beagle dogs was performed to inspect the in vivo sustained release. Plasma concentration-time curves and pharmacokinetic parameters were gained. As a result, the Cmax of imperialine was one-fold reduced and Tmax was two-fold prolonged, and the mean AUC0-24 was expressed as 89.581±21.243?gh/L, which showed that the oral bioavailability of imperialine was 2.46-fold improved. Moreover, the in vitro-in vivo correlation was recommended to carry out, demonstrating the percentages of drug release in vitro were well-correlated with the absorptive fraction in vivo with the correlation coefficients above 0.9900. By mathematically modeling and moment imaging of the drug release, Peppas equation was selected as the most fitted model for the sustained-release tablets with the diffusional coefficient in the range of 0.59-0.62, indicating the release of imperialine from the sustained-release tablets was an anomalous process involving polymer swelling, drug diffusion and matrix erosion. PMID:26349052

  12. Combination of morphine with nortriptyline for neuropathic pain.

    PubMed

    Gilron, Ian; Tu, Dongsheng; Holden, Ronald R; Jackson, Alan C; DuMerton-Shore, Deborah

    2015-08-01

    First-line neuropathic pain drugs, including tricyclic antidepressants, are not always effective, and opioids have been recommended as second line. This trial evaluates a nortriptyline-morphine combination, compared with each monotherapy. In this randomized, double-blind crossover trial, patients with neuropathic pain were enrolled at 1 site between January 25, 2010, and May 22, 2014, and randomized in a 1:1:1 ratio using a balanced Latin square design to receive oral nortriptyline, morphine, and their combination. During each of three 6-week periods, doses were titrated toward maximal tolerated dose (MTD). The primary outcome was average daily pain at MTD, and secondary outcomes included other pain, mood and quality of life measures, and adverse effects. Sixty-two patients were screened, 52 enrolled, and 39 completed at least 2 treatment periods. Average daily pain (0-10) at baseline was 5.3 and at MTD was 2.6 for combination vs 3.1 for nortriptyline (P = 0.046) and 3.4 for morphine (P = 0.002). Brief Pain Inventory scores for average and present pain were also significantly lower for combination vs each monotherapy. Combination treatment resulted in moderate-severe constipation in 43% vs 46% with morphine (P = 0.82) and 5% with nortriptyline (P < 0.0001). Combination treatment resulted in moderate-severe dry mouth in 58% vs 49% with nortriptyline (P = 0.84) and 13% with morphine (P < 0.0001). This trial suggests superior efficacy of a nortriptyline-morphine combination over either monotherapy with constipation, dry mouth, and somnolence as the most frequent adverse effects. PMID:25749306

  13. [History of opium poppy and morphine].

    PubMed

    Norn, Svend; Kruse, Poul R; Kruse, Edith

    2005-01-01

    Opium has been known for millennia to relieve pain and its use for surgical analgesia has been recorded for several centuries. The Sumerian clay tablet (about 2100 BC) is considered to be the world's oldest recorded list of medical prescriptions. It is believed by some scholars that the opium poppy is referred to on the tablet. Some objects from the ancient Greek Minoan culture may also suggest the knowledge of the poppy. A goddess from about 1500 BC shows her hair adorned probably with poppy-capsules and her closed eyes disclose sedation. Also juglets probably imitating the poppy-capsules were found in that period in both Cyprus and Egypt. The first authentic reference to the milky juice of the poppy we find by Theophrastus at the beginning of the third century BC. In the first century the opium poppy and opium was known by Dioscorides, Pliny and Celsus and later on by Galen. Celsus suggests the use of opium before surgery and Dioscorides recommended patients should take mandrake (contains scopolamine and atropine) mixed with wine, before limb amputation. The Arabic physicians used opium very extensively and about 1000 AD it was recommended by Avicenna especially in diarrhoea and diseases of the eye. Polypharmacy, including a mixture of nonsensical medications were often used. Fortunately for both patients and physicians many of the preparations contained opium. The goal was a panacea for all diseases. A famous and expensive panacea was theriaca containing up to sixty drugs including opium. Simplified preparations of opium such as tinctura opii were used up to about 2000 in Denmark. In the early 1800s sciences developed and Sertürner isolated morphine from opium and was the founder of alkaloid research. A more safe and standardized effect was obtained by the pure opium. Several morphine-like drugs have been synthesized to minimize adverse effects and abuse potential. Opioid receptors were identified and characterized in binding assays and their localization examined. However, the complexity of the system including interaction with several neurons and transmitters indicate the goal of nonaddictive opiates to be elusive. Combination therapy, innovative delivery systems and long-acting formulations may improve clinical utility. PMID:17152761

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

    PubMed Central

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

    2014-01-01

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

  15. 21 CFR 520.531 - Cythioate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Cythioate tablets. 520.531 Section 520.531 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.531 Cythioate tablets. (a) (b) Sponsors. See No. 000859 in § 510.600(c)...

  16. Analgesic effects of dextromethorphan and morphine in patients with chronic pain.

    PubMed

    Heiskanen, Tarja; Härtel, Brita; Dahl, Marja-Liisa; Seppälä, Timo; Kalso, Eija

    2002-04-01

    N-methyl-aspartate (NMDA) receptor antagonists have been shown to improve opioid analgesia in the animal model. The cough suppressant dextromethorphan is a clinically available NMDA-receptor antagonist. In this randomised, double-blind, placebo-controlled study 20 patients with chronic pain of several years duration were given 100 mg of oral dextromethorphan or matching placebo 4 h prior to an intravenous infusion of morphine 15 mg. Pain intensity and adverse effects were assessed at 0, 4, 5 and 7 h. Dextromethorphan had no effect on morphine analgesia: the mean (+/-SEM) visual analogue scores for pain relief (VAS, 0-100 mm) at the end of the morphine infusion were 38 (+/-6) for dextromethorphan+morphine and 38 (+/-7) for placebo+morphine. VAS scores for pain intensity were comparable both at rest and at movement at all time points. The most common adverse effects reported were dizziness, nausea and sedation. There were no significant differences in either the incidence or severity of adverse effects. In conclusion, oral dextromethorphan 100 mg had no effect on pain relief by intravenous morphine 15 mg in patients with chronic pain. PMID:11972998

  17. 76 FR 45267 - Determination That INVERSINE (Mecamylamine Hydrochloride) Tablet and Six Other Drug Products Were...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-28

    ...) Oral Solution in the Federal Register of July 21, 2010 (75 FR 42455).) Application No. Drug Applicant.... NDA 019201 VOLTAREN (diclofenac Novartis sodium) Delayed- Pharmaceuticals Release Tablet, 75...

  18. 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.

    PubMed

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

    2013-01-16

    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

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

    PubMed

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

    2012-01-01

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

  20. Morphine Induces Splenocyte Trafficking into the CNS

    PubMed Central

    Olin, Michael R; Oh, Seunguk; Roy, Sabita; Peterson, Phillip K; Molitor, Thomas

    2013-01-01

    Opioids significantly alter functional responses of lymphocytes following activation. Morphine, an opioid derivative, alters the Th1 to Th2 response and modulates functional responses such as cytolytic activity and proliferation. Although there has been extensive research involving morphine’s effects on lymphocytes, little is known about the effects morphine has on lymphocyte trafficking. The objective of the study was to use in vivo bioluminescent imaging to determine morphine’s effect on the trafficking pattern of splenocytes systemically and into the CNS following a neuroinflammatory stimulus. A neuroinflammatory response was induced by intracerebrally administering a DNA plasmid producing IFN-? in morphine-dependent or placebo wildtype mice. Mice with or without a neurostimulus received adoptively transferred firefly luciferase transgenic splenocytes and were imaged using a charge-coupled device camera. Morphine dependence significantly altered the inherent ability of splenocytes to traffic into the spleen, and lead to non-directed chaotic trafficking throughout the animal, including the CNS. The morphine-mediated effects on trafficking were blocked by naltrexone. Morphine dependence intensified splenocyte infiltration into the CNS following neuroinflammation induced by IFN-? gene transfer. The study determined that morphine severely altered the ability of non-activated splenocytes to home to the spleen, inducing chaotic extrasplenic trafficking thoughout the animals. Following a neuroinflammatory response, morphine exacerbated infiltration into the CNS. PMID:21858458

  1. 21 CFR 520.2150b - Stanozolol chewable tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Stanozolol chewable tablets. 520.2150b Section 520.2150b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2150b Stanozolol chewable tablets. (a) Specifications....

  2. 21 CFR 520.390a - Chloramphenicol tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Chloramphenicol tablets. 520.390a Section 520.390a... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.390a Chloramphenicol tablets... chloramphenicol. (2) Sponsor. In § 510.600(c) of this chapter: No. 000010 for 100-, 250-, and 500-milligram and...

  3. 21 CFR 520.390a - Chloramphenicol tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Chloramphenicol tablets. 520.390a Section 520.390a... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.390a Chloramphenicol tablets... chloramphenicol. (2) Sponsor. In § 510.600(c) of this chapter: No. 000010 for 100-, 250-, and 500-milligram and...

  4. 21 CFR 520.446 - Clindamycin capsules and tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Clindamycin capsules and tablets. 520.446 Section 520.446 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.446 Clindamycin capsules and tablets. (a)...

  5. 21 CFR 520.1284 - Sodium liothyronine tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium liothyronine tablets. 520.1284 Section 520.1284 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications....

  6. 21 CFR 520.1445 - Milbemycin oxime tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Milbemycin oxime tablets. 520.1445 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1445 Milbemycin oxime... milbemycin oxime. (2) Cats. Each tablet contains 5.75, 11.5, or 23.0 milligrams of milbemycin oxime....

  7. 21 CFR 520.1445 - Milbemycin oxime tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Milbemycin oxime tablets. 520.1445 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1445 Milbemycin oxime... milbemycin oxime. (2) Cats. Each tablet contains 5.75, 11.5, or 23.0 milligrams of milbemycin oxime....

  8. 21 CFR 520.1445 - Milbemycin oxime tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Milbemycin oxime tablets. 520.1445 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1445 Milbemycin oxime... milbemycin oxime. (2) Cats. Each tablet contains 5.75, 11.5, or 23.0 milligrams of milbemycin oxime....

  9. 21 CFR 520.2610 - Trimethoprim and sulfadiazine tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Trimethoprim and sulfadiazine tablets. 520.2610 Section 520.2610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2610 Trimethoprim and sulfadiazine tablets....

  10. 21 CFR 520.434 - Chlorphenesin carbamate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Chlorphenesin carbamate tablets. 520.434 Section 520.434 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.434 Chlorphenesin carbamate tablets. (a) Specifications....

  11. 21 CFR 520.1341 - Megestrol acetate tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Megestrol acetate tablets. 520.1341 Section 520.1341 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1341 Megestrol acetate tablets. (a) Specifications. Each...

  12. Morphine inhalation by cancer patients: a comparison of different nebulization techniques using pharmacokinetic, spirometric, and gasometric parameters.

    PubMed

    Krajnik, Ma?gorzata; Podolec, Zygmunt; Siekierka, Monika; Sykutera, Marzena; Pufal, Ewa; Sobanski, Piotr; Makarewicz, Roman; Neef, Cees; Punt, Nieko; Zylicz, Zbigniew

    2009-11-01

    Despite numerous case reports suggesting the value of morphine (M) nebulization in the treatment of breathlessness, only a few clinical trials have been able to support this. The reason for this could lie in the lack of understanding of the localization of opioid receptors in the airways and the biopharmaceutics and pharmacokinetics of nebulized morphine. In the present study, we compared two different methods of pneumodosimetric nebulization: the Bronchial Control Treatment System-Sidestream (BCTS-S) and the Bronchial Control Treatment System-Micro Cirrus (BCTS-MC). The first method delivers relatively large aerosol particles (2-5microm) preferentially to the bronchial tree and trachea. In the BCTS-MC method, small aerosol particles (0.5-2microm) mostly reach the alveoli. Ten patients with cancer were randomly assigned to either the BCTS-S or BCTS-MC inhalation of 5 mg morphine HCl. Patients using the BCTS-S method inhaled a morphine dose in 6.6+/-2 minutes, whereas with the BCTS-MC method, the inhalation time was 28.8+/-8 minutes. The areas under the curve of morphine and glucuronides were several times higher after BCTS-S than after BCTS-MC. The proportion of morphine-3-glucuronide to morphine-6-glucuronide (M6) was, on average, close to one for both methods. From the same amount of morphine in the BCTS-S method, five times more M6 was produced. In both methods, the time to maximum concentration for morphine metabolites was 20-40 minutes, much shorter than expected from oral, intranasal, or intravenous administration. The study shows that the method of inhalation may have a profound effect on the pharmacokinetics of morphine. It is possible that the lungs metabolize morphine to glucuronides themselves and in different proportions from those seen after systemic administration. The BCTS-S method was found to be potentially superior to the BCTS-MC method in local action in the lungs. PMID:19783397

  13. 21 CFR 520.2150a - Stanozolol tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 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 daily for several weeks; to...

  14. 21 CFR 520.2362 - Thenium closylate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...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...

  15. 21 CFR 520.2362 - Thenium closylate tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...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...

  16. 21 CFR 520.2362 - Thenium closylate tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...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...

  17. 21 CFR 520.2362 - Thenium closylate tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...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...

  18. 21 CFR 520.2362 - Thenium closylate tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...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...

  19. 21 CFR 520.2150a - Stanozolol tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 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 daily for several weeks; to...

  20. 21 CFR 520.2150a - Stanozolol tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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 daily for several weeks; to...

  1. 21 CFR 520.2604 - Trimeprazine tartrate and prednisolone tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...administered to dogs suffering from acute or chronic bacterial infections, provided the infection is controlled by appropriate antibiotic or chemotherapeutic agents.1 (2) The drug is administered orally at an initial dosage level of 1/2 tablet...

  2. 21 CFR 520.2604 - Trimeprazine tartrate and prednisolone tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...administered to dogs suffering from acute or chronic bacterial infections, provided the infection is controlled by appropriate antibiotic or chemotherapeutic agents.1 (2) The drug is administered orally at an initial dosage level of 1/2 tablet...

  3. 21 CFR 520.2604 - Trimeprazine tartrate and prednisolone tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...administered to dogs suffering from acute or chronic bacterial infections, provided the infection is controlled by appropriate antibiotic or chemotherapeutic agents.1 (2) The drug is administered orally at an initial dosage level of 1/2 tablet...

  4. 21 CFR 520.2604 - Trimeprazine tartrate and prednisolone tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...administered to dogs suffering from acute or chronic bacterial infections, provided the infection is controlled by appropriate antibiotic or chemotherapeutic agents.1 (2) The drug is administered orally at an initial dosage level of 1/2 tablet...

  5. 21 CFR 520.928 - Firocoxib tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.928 Firocoxib tablets. (a... surgery. (2) Indications for use. For the control of pain and inflammation associated with osteoarthritis... surgery. (3) Limitations. Federal law restricts this drug to use by or on the order of a...

  6. 21 CFR 520.928 - Firocoxib tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.928 Firocoxib tablets. (a... surgery. (2) Indications for use. For the control of pain and inflammation associated with osteoarthritis... surgery. (3) Limitations. Federal law restricts this drug to use by or on the order of a...

  7. 21 CFR 520.928 - Firocoxib tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.928 Firocoxib tablets. (a... surgery. (2) Indications for use. For the control of pain and inflammation associated with osteoarthritis... surgery. (3) Limitations. Federal law restricts this drug to use by or on the order of a...

  8. 21 CFR 520.928 - Firocoxib tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.928 Firocoxib tablets. (a... surgery. (2) Indications for use. For the control of pain and inflammation associated with osteoarthritis... surgery. (3) Limitations. Federal law restricts this drug to use by or on the order of a...

  9. Clavulanic acid reduces rewarding, hyperthermic and locomotor-sensitizing effects of morphine in rats: a new indication for an old drug?

    PubMed Central

    Schroeder, Joseph A.; Tolman, Nicholas G.; McKenna, Faye F.; Watkins, Kelly L.; Passeri, Sara M.; Hsu, Alexander H.; Shinn, Brittany R.; Rawls, Scott M.

    2014-01-01

    Background Despite the efficacy of ceftriaxone (CTX) in animal models of CNS diseases, including drug addiction, its utility as a CNS-active therapeutic may be limited by poor brain penetrability and cumbersome parenteral administration. An alternative is the ?-lactamase inhibitor clavulanic acid (CA), a constituent of Augmentin that prevents antibiotic degradation. CA possesses the ?-lactam core necessary for CNS activity but, relative to CTX, possesses: 1) oral activity; 2) 2.5-fold greater brain penetrability; and 3) negligible antibiotic activity. Methods To compare the effectiveness of CA (10 mg/kg) and CTX (200 mg/kg) against centrally-mediated endpoints, we investigated their effects against morphine’s rewarding, hyperthermic, and locomotor-sensitizing actions. Endpoints were based on prior evidence that CTX attenuates morphine-induced physical dependence, tolerance, and hyperthermia. Results As expected, rats treated with morphine (4 mg/kg) displayed hyperthermia and conditioned place preference (CPP). Co-treatment with CTX or CA inhibited development of morphine-induced CPP by approximately 70%. Morphine’s hyperthermic effect was also suppressed, with CTX and CA producing 57% and 47% inhibition, respectively. Locomotor sensitization induced by repeated morphine exposures was inhibited by CA but not CTX. Conclusions The present findings are the first to suggest that CA disrupts the in vivo actions of morphine and point toward further studying CA as a potential therapy for drug addiction. Further, its ability to disrupt morphine’s rewarding effects at 20-fold lower doses than CTX identifies CA as an existing, orally-active alternative to direct CTX therapy for CNS diseases. PMID:24998018

  10. Morphine-3-glucuronide: silent regulator of morphine actions.

    PubMed

    Lipkowski, A W; Carr, D B; Langlade, A; Osgood, P F; Szyfelbein, S K

    1994-01-01

    To assess whether stoichiometric manipulation of morphine (M) metabolism can enhance analgesia or slow the development of M tolerance we co-administered M-3- glucuronide (M3G) during single or repeated doses of morphine in rats. Although M3G itself lacked analgesic activity, co-injection of M3G with M increased and prolonged analgesia beyond that seen with M. In addition, diminution of the acute analgesic effect of M after 3 once-daily doses of M did not occur after daily co-injection of M3G and M. Thus the traditional view that tolerance to the effects of M is due solely to effects mediated through opioid receptors must be broadened to include the contributions of enzyme induction or stoichiometric equilibration of M3G in this process. PMID:8015358

  11. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...2012-04-01 2012-04-01 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...

  12. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...2011-04-01 2011-04-01 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...

  13. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...2013-04-01 2013-04-01 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...

  14. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...2014-04-01 2014-04-01 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...

  15. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...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...

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

    PubMed

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

    2015-02-01

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

  17. Simultaneous determination of four phenolic acids and seven alkaloids in rat plasma after oral administration of traditional Chinese medicinal preparation Jinqi Jiangtang Tablet by LC-ESI-MS/MS.

    PubMed

    Chang, Yan-Xu; Ge, Ai-Hua; Yu, Xie-An; Jiao, Xiu-Cheng; Li, Jin; He, Jun; Tian, Ji; Liu, Wei; Azietaku, John Teye; Zhang, Bo-Li; Gao, Xiu-Mei

    2016-01-01

    A rapid, sensitive and selective high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of four phenolic acids (neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid and ferulic acid) and seven alkaloids (berberine, epiberberine, coptisine, magnoflorine, berberubine, palmatine and jatrorrhizine) in rat plasma. After mixing with the internal standards tetrahydropalmatine (IS1) and rosmarinic acid (IS2), plasma samples were pretreated by protein precipitation using acetonitrile. The HPLC analysis was performed on an Agilent Eclipse plus C18 (4.6mm×100mm, 1.8?m) column with mobile phase consisting of 0.1% formic acid aqueous solution and acetonitrile at a flow rate of 0.3mLmin(-1). The detection was accomplished for the analytes and internal standards using positive electrospray ionization for the alkaloids and negative electrospray ionization for the phenolic acids in multiple-reaction monitoring mode. The method showed a good linearity over a wide concentration range (r(2)>0.99). The lower limit of quantification of seven alkaloids was lower than 2ngmL(-1) and that of four phenolic acids was less than 20ngmL(-1). The developed method was applied to the pharmacokinetic study of 11 components after oral administration of traditional Chinese medicinal preparation Jinqi Jiangtang Tablet in rats. PMID:26340557

  18. [Modern polymers in matrix tablets technology].

    PubMed

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

    2014-01-01

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

  19. Redesign of a Dioxygenase in Morphine Biosynthesis

    E-print Network

    Runguphan, Weerawat

    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 ...

  20. Presence of morphine metabolites in human cerebrospinal fluid after intracerebroventricular administration of morphine.

    PubMed

    Sandouk, P; Serrie, A; Scherrmann, J M; Langlade, A; Bourre, J M

    1991-01-01

    After intracerebroventricular administration of morphine in four cancer patients, cerebrospinal fluid (CSF) was analyzed by two morphine radioimmunoassays (RIA), liquid chromatography (LC) and radioreceptor assay (RRA) to evaluate the presence of morphine metabolites. Immunoreactive morphine-like substances were detected by differential RIA's. The maximum concentrations of these compounds were achieved 3 hours after drug administration. These concentrations, according to the specificity of the antiserum, represent a mixture of several metabolites in which only morphine 3-glucuronide(M 3-G) and morphine 6-glucuronide (M 6-G) were identified by LC, and M 6-G by LC-RRA. These results confirm that brain is able to metabolize morphine to inactive (M 3-G) or more potent (M 6-G) derivatives. PMID:1820872

  1. Delay of Morphine Tolerance by Palmitoylethanolamide

    PubMed Central

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

    2015-01-01

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

  2. Synthetic substances with morphine-like effect

    PubMed Central

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

    1955-01-01

    For morphine-, morphinan-, pethidine-, methadone-, and dithienyl-butenylamine groups of analgesic compounds a systematic survey is given of how analgesic activity is quantitatively affected by alteration of the chemical constitution. Features common to the structural formulae of substances with morphine-like analgesic effect are pointed out. ImagesFIG. 1FIG. 1(Contd.) PMID:13284565

  3. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Morphine test system. 862.3640 Section 862.3640....3640 Morphine test system. (a) Identification. A morphine test system is a device intended to measure morphine, an addictive narcotic pain-relieving drug, and its analogs in serum, urine, and gastric...

  4. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Morphine test system. 862.3640 Section 862.3640....3640 Morphine test system. (a) Identification. A morphine test system is a device intended to measure morphine, an addictive narcotic pain-relieving drug, and its analogs in serum, urine, and gastric...

  5. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Morphine test system. 862.3640 Section 862.3640....3640 Morphine test system. (a) Identification. A morphine test system is a device intended to measure morphine, an addictive narcotic pain-relieving drug, and its analogs in serum, urine, and gastric...

  6. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Morphine test system. 862.3640 Section 862.3640....3640 Morphine test system. (a) Identification. A morphine test system is a device intended to measure morphine, an addictive narcotic pain-relieving drug, and its analogs in serum, urine, and gastric...

  7. 21 CFR 862.3640 - Morphine test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Morphine test system. 862.3640 Section 862.3640....3640 Morphine test system. (a) Identification. A morphine test system is a device intended to measure morphine, an addictive narcotic pain-relieving drug, and its analogs in serum, urine, and gastric...

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

    PubMed

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

    2013-01-01

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

  9. Driving under the influence of opiates: concentration relationships between morphine, codeine, 6-acetyl morphine, and ethyl morphine in blood.

    PubMed

    Jones, A Wayne; Holmgren, Anita; Kugelberg, Fredrik C

    2008-05-01

    Morphine and codeine are frequently identified in blood samples from impaired drivers. But whether these opiates reflect the use of prescription analgesics or abuse of the illicit drug heroin (diacetyl morphine) is not always obvious. Opiates, either alone or together with other drugs, were determined in 2,573 blood specimens from impaired drivers by sensitive and specific methods of analysis. The specific metabolite of heroin 6-acetyl morphine (6-AM) was quantifiable in only 52 cases (2%) at mean, median, and highest concentrations of 0.015, 0.010, and 0.10 mg/L, respectively. The mean, median, and highest concentrations of morphine were 0.046, 0.03, and 1.13 mg/L, respectively (N = 2,029). The corresponding concentrations of codeine (N = 1,391) were 0.047, 0.01, and 2.40 mg/L. Ethyl morphine was identified in 63 cases at a mean concentration of 0.055 mg/L (median 0.03 mg/L). When 6-AM was present in urine (N = 324), the mean morphine/codeine ratio in blood was 7.5 (median 6.7), and this important ratio was less than unity in only two cases. This study finds compelling evidence that approximately 90% of apprehended drivers in Sweden with morphine and codeine in their blood had used heroin. PMID:18430293

  10. Novel approach of aceclofenac fast dissolving tablet.

    PubMed

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

    2015-01-01

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

  11. The Trouble with Tablets.

    PubMed

    Espinoza, Kathy

    2015-09-01

    The biggest recommendation is to get your tablet screen up. This can be done by using a case or a tablet stand. Avoid using the tablet on your lap because posture follows vision. If you must use it on your lap, try placing it on a pillow to raise its height and reduce dangerous neck flexion. Whenever possible, set the tablet on a table rather than holding it with your hands because hands and forearms fatigue quickly. Consider finding an external keyboard that can be separated from the tablet screen. This way, you can set the tablet on a higher surface to elevate the screen and have a lower keyboard to eliminate some of the wrist extension when keying. PMID:26495616

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

    SciTech Connect

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

    1982-05-01

    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.

  13. Oral contraceptive tablets containing 20 and 30 micrograms of ethinyl estradiol with 150 micrograms desogestrel. Their influence on lipids, lipoproteins, sex hormone binding globulin and testosterone.

    PubMed

    Akerlund, M; Almström, E; Högstedt, S; Nabrink, M

    1994-02-01

    The effect of two oral contraceptive (OC) pills, both containing 150 micrograms of desogestrel, but with 20 (Mercilon) or 30 micrograms (Marvelon/Desolett) of ethinyl estradiol on plasma levels of lipids, lipoproteins and sex hormone binding globulin (SHBG), total and free testosterone were compared in a double-blind, randomized, two-center study in a total of 60 women over one year. A significant rise with Marvelon but not with Mercilon was seen in total cholesterol, HDL cholesterol, HDL-3 and apolipoprotein B, whereas LDL cholesterol decreased with Mercilon only. These effects resulted in significant differences between the two groups in the magnitude of responses in all these parameters except HDL-3. HDL-2, apolipoprotein A-1 and total phospholipids were elevated with both pills after treatment and with no difference in the degree of response between groups. The HDL/LDL cholesterol ratio tended to increase in both groups and that of apolipoproteins A-1/B in the women on Mercilon. Total triglycerides increased in both groups, but more in the women on Marvelon. Total testosterone decreased, particularly in the Marvelon group, whereas the two pills caused a similar increase in SHBG and decrease in free testosterone. It is concluded that the direction of changes in plasma lipids and lipoproteins with both these pills may as a whole be interpreted as beneficial, and that the differences in effect on LDL cholesterol and apolipoprotein B may suggest a slightly advantageous effect of Mercilon in this aspect. However, the clinical significance of these changes is uncertain. The results indicate a lack of androgenicity of both pills. PMID:8116352

  14. Physicochemical characterization and evaluation of buccal adhesive tablets containing omeprazole.

    PubMed

    Yong, C S; Jung, J H; Rhee, J D; Kim, C K; Choi, H G

    2001-05-01

    The objective of this study was to develop an effective omeprazole buccal adhesive tablet with excellent bioadhesive force and good drug stability in human saliva. The omeprazole buccal adhesive tablets were prepared with various bioadhesive polymers, alkali materials, and croscarmellose sodium. Their physicochemical properties, such as bioadhesive force and drug stability in human saliva, were investigated. The release and bioavailability of omeprazole delivered by the buccal adhesive tablets were studied. As bioadhesive additives for the omeprazole tablet, a mixture of sodium alginate and hydroxypropylmethylcellulose (HPMC) was selected. The omeprazole tablets prepared with bioadhesive polymers alone had bioadhesive forces suitable for a buccal adhesive tablet, but the stability of omeprazole in human saliva was not satisfactory. Among alkali materials, only magnesium oxide could be an alkali stabilizerfor omeprazole buccal adhesive tablets due to its strong waterproofing effect. Croscarmellose sodium enhanced the release of omeprazole from the tablets; however, it decreased the bioadhesive forces and stability of omeprazole tablets in human saliva. The tablet composed of omeprazole/sodium alginate/HPMC/magnesium oxide/croscarmellose sodium (20/24/6/50/10 mg) could be attached on the human cheek without disintegration, and it enhanced the stability of omeprazole in human saliva for at least 4 h and gave fast release of omeprazole. The plasma concentration of omeprazole in hamsters increased to a maximum of 370 ng/ml at 45 min after buccal administration and continuously maintained a high level of 146-366 ng/ml until 6 h. The buccal bioavailability of omeprazole in hamsters was 13.7% +/- 3.2%. These results demonstrate that the omeprazole buccal adhesive tablet would be useful for delivery of an omeprazole that degrades very rapidly in acidic aqueous medium and undergoes hepatic first-pass metabolism after oral administration. PMID:11448052

  15. Dipyrone potentiates morphine-induced antinociception in dipyrone-treated and morphine-tolerant rats.

    PubMed

    Hernández-Delgadillo, Gloria P; Cruz, Silvia L

    2004-10-11

    Coadministration of morphine and dipyrone produces acute and chronic antinociceptive potentiation in drug-naive rats. In this work, the effectiveness of the combination was determined in rats pretreated with morphine or dipyrone. Nine groups of male rats received (i.v.) 3.1 mg/kg morphine, 600 mg/kg dipyrone, or the morphine-dipyrone combination twice a day for five administrations (three groups per treatment). From the 6th to the 10th administration, one group out of each treatment continued without change, while the other two were switched to one of the other two possible treatments. In morphine-tolerant rats, morphine plus dipyrone produced a transient antinociceptive potentiation. In dipyrone-treated animals, this combination produced a long-lasting potentiation. In animals only treated with the combination, antinociception was clear since the beginning, although it decreased after the 6th injection. No cross-tolerance was seen between morphine and dipyrone. These data suggest that dipyrone potentiates morphine-induced antinociception in dipyrone-treated as well as in morphine-tolerant rats. PMID:15464091

  16. Levels of morphine and metabolites in CSF during respiratory depression after intraventricular morphine injection.

    PubMed

    Langlade, A; Serrie, A; Sandouk, P; Thurel, C; Cunin, G

    1991-02-01

    We report a case of respiratory depression after intracerebroventricular morphine administration of a dose inadvertently 10 times greater than the typical daily dose. At the time of the respiratory dysfunction, the concentrations of morphine and its metabolites in cerebrospinal fluid (CSF) and plasma samples were determined. On comparison of these results with previous clinical studies in which there was no respiratory depression, no relationship was found between the occurrence of respiratory depression and the concentration of morphine or its metabolites in the CSF. The occurrence and characteristics of respiratory depression may be related to the concentrations of morphine and its metabolites in bulbar tissue. PMID:2052385

  17. Is intramuscular morphine satisfying frontline medical personnels’ requirement for battlefield analgesia in Helmand Province, Afghanistan? A questionnaire study

    PubMed Central

    Gibson, Lorna M; Claydon, Michael A

    2015-01-01

    Background: All deployed British Army personnel carry intramuscular (IM) morphine auto-injectors to treat battlefield casualties. No other nation supplies parenteral opiate analgesia on individual issue. Studies highlight this agent’s inefficacy and safety issues, but are limited by a relative lack of inclusion of frontline personnel. We aimed to determine the opinions of frontline medical personnel on current battlefield analgesia. Methods: We surveyed 88 British Army frontline medical personnel (medical officers (n = 12), nurses (n = 7), combat medical technicians (CMTs) (n = 67), paramedics (n = 1) and health-care assistants (n = 1)) upon completion of a six-month deployment (September 2011 to April 2012) to Helmand Province, Afghanistan, using Likert scale questions on the efficacy of battlefield analgesia, complications of IM morphine, safety of morphine auto-injectors and its suitability for treating child casualties. Results: A total of 88/88 questionnaires were returned. Of these, 61/88 had treated casualties on the battlefield, 26/86 agreed that current battlefield analgesia is effective, 80/87 agreed that a more potent analgesic with a faster onset than IM morphine is desirable in the first hour following injury, 47/65 CMTs agreed that they can manage complications of current battlefield analgesia and 53/86 respondents correctly disagreed that current battlefield analgesia is suitable for child casualties. The potential for accidental self-injection was reported. Conclusions: A more potent, faster onset analgesic than IM morphine is desirable in the first hour following injury. Pre-deployment training should emphasise management of complications of opiate analgesics and treatment of child casualties. Oral transmucosal fentanyl citrate is now being issued to all frontline medical personnel. IM morphine will remain on individual issue to all deployed soldiers for environments where an oral agent is not suitable, for example, chemical, biological, radiological and nuclear warfare. Summary points Frontline medical personnel agree that a more potent, faster onset analgesic than IM morphine is desirable in the first hour following injury. The two most desirable features of the ideal analgesic were ranked as rapid onset of action, and when fully onset produces a high degree of pain relief. Oral transmucosal fentanyl citrate (OTFC) has now been issued to all frontline medical personnel as an adjunct to IM morphine. IM morphine will remain on individual issue for situations where parenteral analgesia is required. Consideration should be given to individual issue of OTFC to all deployed personnel in the future. Pre-deployment training should emphasise management of complications of opiate analgesics and treatment of child casualties. PMID:26516566

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

    PubMed Central

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

    1995-01-01

    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. PMID:8719797

  19. Morphine and Codeine Concentrations in Human Urine following Controlled Poppy Seeds Administration of Known Opiate Content

    PubMed Central

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

    2014-01-01

    Opiates are an important component for drug testing due to their high abuse potential. Proper urine opiate interpretation includes ruling out poppy seed ingestion; however, detailed elimination studies after controlled poppy seed administration with known morphine and codeine doses are not available. Therefore, we investigated urine opiate pharmacokinetics after controlled oral administration of uncooked poppy seeds with known morphine and codeine content. Participants were administered two 45g oral poppy seed doses 8h apart, each containing 15.7mg morphine and 3mg codeine. Urine was collected ad libitum up to 32h after the first dose. Specimens were analyzed with the Roche Opiates II immunoassay at 2,000 and 300?g/L cutoffs, and the ThermoFisher CEDIA® Heroin Metabolite (6-acetylmorphine, 6AM) and Lin-Zhi 6AM immunoassays with 10?g/L cutoffs to determine if poppy seed ingestion could produce positive results in these heroin marker assays. In addition, all specimens were quantified for morphine and codeine by GC/MS. Participants (N=22) provided 391 urine specimens over 32h following dosing; 26.6% and 83.4% were positive for morphine at 2,000 and 300?g/L GC/MS cutoffs, respectively. For the 19 subjects who completed the study, morphine concentrations ranged from <300 to 7,522?g/L with a median peak concentration of 5,239?g/L. The median first morphine-positive urine sample at 2,000?g/L cutoff concentration occurred at 6.6h (1.2-12.1), with the last positive from 2.6 to 18h after the second dose. No specimens were positive for codeine at a cutoff concentration of 2,000?g/L, but 20.2% exceeded 300?g/L, with peak concentrations of 658 ?g/L (284-1540). The Roche Opiates II immunoassay had efficiencies greater than 96% for the 2000 and 300?g/L cutoffs. The CEDIA 6AM immunoassay had a specificity of 91%, while the Lin-Zhi assay had no false positive results. These data provide valuable information for interpreting urine opiate results. PMID:24887324

  20. Pleiotrophin modulates morphine withdrawal but has no effects on morphine-conditioned place preference.

    PubMed

    Gramage, Esther; Vicente-Rodríguez, Marta; Herradón, Gonzalo

    2015-09-14

    Pleiotrophin (PTN) is a neurotrophic factor with important functions in addiction and neurodegenerative disorders. Morphine administration induces an increase in the expression of PTN and Midkine (MK), the only other member of this family of cytokines, in brain areas related with the addictive effects of drug of abuse, like the Ventral Tegmental Area or the hippocampus. In spite of previous studies showing that PTN modulates amphetamine and ethanol rewarding effects, and that PTN is involved in morphine-induced analgesia, it was still unknown if the rewarding effects of morphine may be regulated by endogenous PTN. Thus, we aim to study the role of PTN in the reward and physical dependence induced by morphine. We used the Conditioned Place Preference (CPP) paradigm in PTN genetically deficient (PTN-/-) and wild type (WT) mice to assess the rewarding effects of morphine in absence of endogenous PTN. Second, to study if PTN may be involved in morphine physical dependence, naloxone-precipitated withdrawal syndrome was induced in PTN-/- and WT morphine dependent mice. Although the increase in the time spent in the morphine-paired compartment after conditioning tended to be more pronounced in PTN-/- mice, statistical significance was not achieved. The data suggest that PTN does not exert an important role in morphine reward. However, our results clearly indicate that PTN-/- mice develop a more severe withdrawal syndrome than WT mice, characterized as a significant increase in the time standing and in the total incidences of forepaw licking, forepaw tremors, wet dog shake and writhing. The data presented here suggest that PTN is a novel genetic factor that plays a role in morphine withdrawal syndrome. PMID:26222257

  1. Fast disintegrating tablets: Opportunity in drug delivery system

    PubMed Central

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

    2011-01-01

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

  2. Calcification prevention tablets

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

  3. Morphine-6-glucuronide: actions and mechanisms.

    PubMed

    Kilpatrick, Gavin J; Smith, Terry W

    2005-09-01

    Morphine-6-glucuronide (M6G) appears to show equivalent analgesia to morphine but to have a superior side-effect profile in terms of reduced liability to induce nausea and vomiting and respiratory depression. The purpose of this review is to examine the evidence behind this statement and to identify the possible reasons that may contribute to the profile of M6G. The vast majority of available data supports the notion that both M6G and morphine mediate their effects by activating the micro-opioid receptor. The differences for which there is a reasonable consensus in the literature can be summarized as: (1) Morphine has a slightly higher affinity for the micro-opioid receptor than M6G, (2) M6G shows a slightly higher efficacy at the micro-opioid receptor, (3) M6G has a lower affinity for the kappa-opioid receptor than morphine, and (4) M6G has a very different absorption, distribution, metabolism, and excretion (ADME) profile from morphine. However, none of these are adequate alone to explain the clinical differences between M6G and morphine. The ADME differences are perhaps most likely to explain some of the differences but seem unlikely to be the whole story. Further work is required to examine further the profile of M6G, notably whether M6G penetrates differentially to areas of the brain involved in pain and those involved in nausea, vomiting, and respiratory control or whether micro-opioid receptors in these brain areas differ in either their regulation or pharmacology. PMID:15952175

  4. Pharmacokinetic comparison of a dextromethorphan-salbutamol combination tablet and a plain dextromethorphan tablet.

    PubMed

    Silvasti, M; Karttunen, P; Happonen, P; Mykkänen, M; Romppanen, T; Tukiainen, H

    1990-06-01

    We compared in this double-blind crossover study the bioavailability of dextromethorphan from a dextromethorphan-salbutamol combination tablet (Redol comp) and from a plain dextromethorphan tablet (Extuson) by determining dextrorphan concentrations after single-dose oral administration in 10 healthy volunteers. The absorption of salbutamol from the combined preparation was also determined. The absorption of dextromethorphan was slightly faster from the plain dextromethorphan preparation. The peak concentration of dextrorphan was achieved at 1.5 h after Extuson and at 2 h after Redol comp (1,053.0 +/- 366.5 ng/ml and 901.5 +/- 210.9 ng/ml, NS). AUC0-12 values of dextrorphan were 4,315.6 +/- 295.0 (ng/ml)h after Extuson and 3,983.8 +/- 205.6 (ng/ml)h after Redol comp (p less than 0.05). Salbutamol was well absorbed from the combined preparation and the peak concentration was achieved at 3 h (6.57 +/- 2.95 ng/ml). Four subjects reported side-effects typical for salbutamol after the combination tablet. No side-effects were reported after the plain dextromethorphan tablet. On the basis of the present study, we conclude that the absorption of dextromethorphan from the preparations tested is almost equal and the dextromethorphan-salbutamol combination can be administered in tablet form for the treatment of cough. PMID:2376428

  5. Oral calcitonin.

    PubMed

    Hamdy, Ronald C; Daley, Dane N

    2012-01-01

    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

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

    PubMed

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

    2012-05-01

    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

  7. 21 CFR 520.1696d - Penicillin V potassium tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin V potassium tablets. 520.1696d Section 520.1696d Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS §...

  8. 21 CFR 520.2150b - Stanozolol chewable tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...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...

  9. 21 CFR 520.2150b - Stanozolol chewable tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...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...

  10. 21 CFR 520.2150b - Stanozolol chewable tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...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...

  11. 21 CFR 520.1720a - Phenylbutazone tablets and boluses.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Phenylbutazone tablets and boluses. 520.1720a Section 520.1720a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS §...

  12. A Randomized Controlled Trial on the Effect of Tapentadol and Morphine on Conditioned Pain Modulation in Healthy Volunteers

    PubMed Central

    Martini, Chris; van Velzen, Monique; Drewes, Asbjørn; Aarts, Leon; Dahan, Albert; Niesters, Marieke

    2015-01-01

    Background Modulatory descending pathways, originating at supraspinal sites that converge at dorsal horn neurons, influence pain perception in humans. Defects in descending pain control are linked to chronic pain states and its restoration may be a valuable analgesic tool. Conditioned pain modulation (CPM) is a surrogate marker of descending inhibition that reduces the perception of pain from a primary test stimulus during application of a conditioning stimulus. Here the effects of the analgesics tapentadol, a combined mu-opioid receptor agonist and noradrenaline reuptake inhibitor, and morphine, a strong mu-opioid receptor agonist, were tested on CPM in a randomized, double-blind, placebo-controlled crossover trial in 12 healthy pain-free volunteers, to understand possible differences in mechanism of action between these opioids. Methods and Results On three occasions CPM responses were obtained 60-90 and 120-150 min following intake of tapentadol (100 mg immediate release tablet), morphine (40 mg immediate release tablet) or placebo. At both time points, CPM was detectable after treatment with placebo and tapentadol (peak pain ratings reduced by 20-30% after application of the conditioning stimulus) but not after morphine. Compared to placebo morphine displayed significantly less CPM: mean treatment difference 18.2% (95% CI 3.4 to 32.9%) at 60-90 min after drug intake and 19.5% (95% CI 5.7 to 33.2%) at 120-150 min after drug intake (p = 0.001). No difference in CPM between placebo and tapentadol was detected: mean treatment difference 1.5% (95% CI -11.6 to 14.6%) at 60-90 min after drug intake and 1.5% (95% CI -16.0 to 18.9%) at 120-150 min after drug intake (p = 0.60). Conclusions Our data show that in volunteers morphine affects CPM, while tapentadol was without effect despite identical experimental conditions. These data confirm that tapentadol’s main mechanism of action is distinct from that of morphine and likely related to the effect of adrenergic stimulation on descending controls. Trial Registration Netherlands Trial Register NTR2716 PMID:26076171

  13. Abuse liability of prescription opioids compared to heroin in morphine-maintained heroin abusers.

    PubMed

    Comer, Sandra D; Sullivan, Maria A; Whittington, Robert A; Vosburg, Suzanne K; Kowalczyk, William J

    2008-04-01

    Abuse of prescription opioid medications has increased dramatically in the United States during the past decade, as indicated by a variety of epidemiological sources. However, few studies have systematically examined the relative reinforcing effects of commonly abused opioid medications. The current double-blind, placebo-controlled in-patient study was designed to compare the effects of intravenously delivered fentanyl (0, 0.0625, 0.125, 0.187, and 0.250 mg/70 kg), oxycodone (0, 6.25, 12.5, 25, and 50 mg/70 kg), morphine (0, 6.25, 12.5, 25, and 50 mg/70 kg), buprenorphine (0, 0.125, 0.5, 2, and 8 mg/70 kg), and heroin (0, 3.125, 6.25, 12.5, and 25 mg/70 kg) in morphine-maintained heroin abusers (N=8 completers maintained on 120 mg per day oral morphine in divided doses (30 mg q.i.d.)). All of the participants received all of the drugs tested; drugs and doses were administered in non-systematic order. All of the drugs produced statistically significant, dose-related increases in positive subjective ratings, such as 'I feel a good drug effect' and 'I like the drug.' In general, the order of potency in producing these effects, from most to least potent, was fentanyl>buprenorphine>or=heroin >morphine=oxycodone. In contrast, buprenorphine was the only drug that produced statistically significant increases in ratings of 'I feel a bad drug effect' and it was the only drug that was not self-administered above placebo levels at any dose tested. These data suggest that the abuse liability of buprenorphine in heroin-dependent individuals may be low, despite the fact that it produces increases in positive subjective ratings. The abuse liabilities of fentanyl, morphine, oxycodone, and heroin, however, appear to be similar under these experimental conditions. PMID:17581533

  14. The involvement of noradrenergic transmission in the morphine-induced locomotor hyperactivity in mice withdrawn from repeated morphine treatment

    PubMed Central

    Airio, Juha; Ahtee, Liisa

    1999-01-01

    Our previous studies suggest that in addition to the cerebral dopaminergic systems the noradrenergic ones have a crucial role in the morphine-induced behavioural sensitization in mice. Therefore the effects of ?2-adrenoceptor antagonist, idazoxan (1 and 3?mg?kg?1, i.p.) on morphine-induced locomotor hyperactivity as well as on morphine-induced changes in cerebral noradrenaline (NA) and striatal dopamine (DA) metabolism were studied in mice withdrawn for 3 days from 5 day repeated morphine treatment. The concentrations of NA, free 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG), DA, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 3-methoxytyramine (3-MT) were determined. Acute morphine (10?mg?kg?1, s.c.) increased locomotor activity in control and in morphine-withdrawn mice; idazoxan alone did not alter the activity. Idazoxan pretreatment did not alter the locomotor hyperactivity induced by acute morphine in control mice but potentiated it in morphine-withdrawn mice. Acute morphine elevated MOPEG less but increased DOPAC and HVA more clearly in morphine-withdrawn mice than in controls, and decreased 3-MT only in controls. Idazoxan alone did not alter the NA or DA metabolite concentrations in control mice, but elevated MOPEG as well as DOPAC in morphine-withdrawn mice. In control mice idazoxan enhanced acute morphine's elevating effect on MOPEG. In withdrawn mice idazoxan counteracted the tolerance so that acute morphine elevated MOPEG in these mice to about similar level as in controls. Idazoxan pretreatment abolished the HVA increasing effect of acute morphine both in control and withdrawn mice. In control mice idazoxan enhanced morphine's elevating effect on DOPAC and abolished morphine's decreasing effect on 3-MT. Idazoxan did not alter morphine's effects on DOPAC or 3-MT concentrations in withdrawn mice. Our results show that in morphine-withdrawn mice idazoxan pretreatment reveals the morphine-induced locomotor sensitization. This most probably occurs by overcoming the tolerance towards the acute morphine-induced increase of cerebral NA turnover and release. It is suggested that in mice the cerebral noradrenergic in addition to the dopaminergic systems are major determinants of the behavioural sensitization to morphine. PMID:10323593

  15. Synthetic substances with morphine-like effect

    PubMed Central

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

    1957-01-01

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

  16. Microstructural investigation of tablet compaction and tablet pharmacological properties

    E-print Network

    Mao, Kangyi

    2010-01-01

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

  17. The Use of D-Optimal Mixture Design in Optimizing Development of Okara Tablet Formulation as a Dietary Supplement

    PubMed Central

    Mohamad Zen, Nur Izzati; Abd Gani, Siti Salwa; Shamsudin, Rosnah; Fard Masoumi, Hamid Reza

    2015-01-01

    The usage of soy is increasing year by year. It increases the problem of financial crisis due to the limited sources of soybeans. Therefore, production of oral tablets containing the nutritious leftover of soymilk production, called okara, as the main ingredient was investigated. The okara tablets were produced using the direct compression method. The percentage of okara, guar gum, microcrystalline cellulose (Avicel PH-101), and maltodextrin influenced tablets' hardness and friability which are analyzed using a D-optimal mixture design. Composition of Avicel PH-101 had positive effects for both hardness and friability tests of the tablets. Maltodextrin and okara composition had a significant positive effect on tablets' hardness, but not on percentage of friability of tablets. However, guar gum had a negative effect on both physical tests. The optimum tablet formulation was obtained: 47.0% of okara, 2.0% of guar gum, 35.0% of Avicel PH-101, and 14.0% of maltodextrin. PMID:26171418

  18. The Use of D-Optimal Mixture Design in Optimizing Development of Okara Tablet Formulation as a Dietary Supplement.

    PubMed

    Zen, Nur Izzati Mohamad; Abd Gani, Siti Salwa; Shamsudin, Rosnah; Masoumi, Hamid Reza Fard

    2015-01-01

    The usage of soy is increasing year by year. It increases the problem of financial crisis due to the limited sources of soybeans. Therefore, production of oral tablets containing the nutritious leftover of soymilk production, called okara, as the main ingredient was investigated. The okara tablets were produced using the direct compression method. The percentage of okara, guar gum, microcrystalline cellulose (Avicel PH-101), and maltodextrin influenced tablets' hardness and friability which are analyzed using a D-optimal mixture design. Composition of Avicel PH-101 had positive effects for both hardness and friability tests of the tablets. Maltodextrin and okara composition had a significant positive effect on tablets' hardness, but not on percentage of friability of tablets. However, guar gum had a negative effect on both physical tests. The optimum tablet formulation was obtained: 47.0% of okara, 2.0% of guar gum, 35.0% of Avicel PH-101, and 14.0% of maltodextrin. PMID:26171418

  19. Morphine Promotes Tumor Angiogenesis and Increases Breast Cancer Progression

    PubMed Central

    Bimonte, Sabrina; Barbieri, Antonio; Palma, Giuseppe; Luciano, Antonio; Cuomo, Arturo; Arra, Claudio; Izzo, Francesco

    2015-01-01

    Morphine is considered a highly potent analgesic agent used to relieve suffering of patients with cancer. Several in vitro and in vivo studies showed that morphine also modulates angiogenesis and regulates tumour cell growth. Unfortunately, the results obtained by these studies are still contradictory. In order to better dissect the role of morphine in cancer cell growth and angiogenesis we performed in vitro studies on ER-negative human breast carcinoma cells, MDA.MB231 and in vivo studies on heterotopic mouse model of human triple negative breast cancer, TNBC. We demonstrated that morphine in vitro enhanced the proliferation and inhibited the apoptosis of MDA.MB231 cells. In vivo studies performed on xenograft mouse model of TNBC revealed that tumours of mice treated with morphine were larger than those observed in other groups. Moreover, morphine was able to enhance the neoangiogenesis. Our data showed that morphine at clinical relevant doses promotes angiogenesis and increases breast cancer progression. PMID:26064880

  20. In vivo bioavailability studies of sumatriptan succinate buccal tablets

    PubMed Central

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

    2011-01-01

    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. PMID:22615661

  1. Optical properties of aqueous morphine solutions

    NASA Astrophysics Data System (ADS)

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

    2003-10-01

    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.

  2. Morphine-related metabolites dierentially activate adenylyl cyclase isozymes after acute and chronic administration

    E-print Network

    Vogel, Zvi

    Morphine-related metabolites di¡erentially activate adenylyl cyclase isozymes after acute Abstract Morphine-3- and morphine-6-glucuronide are mor- phine's major metabolites. As morphine-6-glucuronide produces stronger analgesia than morphine, we investigated the effects of acute and chronic

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  5. Morphine upregulates kappa-opioid receptors of human lymphocytes.

    PubMed

    Suzuki, S; Chuang, T K; Chuang, L F; Doi, R H; Chuang, R Y

    2001-01-01

    Opioids such as morphine are potent analgesic and addictive compounds. Chronic morphine use also induces immunomodulatory and immunosuppressive effects, as especially evident in HIV-infected patients. Morphine acts on the immune cells primarily through its binding to mu-opioid receptors on the plasma membrane. However, morphine modulation of immune functions still exists in mu-opioid receptor knockout mice, suggesting that in addition to the mu opioid receptors, morphine may also act by mechanisms mediated by either delta or kappa opioid receptors. To determine whether morphine activates kappa opioid receptors (KOR), a quantitative competitive RT-PCR procedure was utilized to quantify the KOR gene expression of morphine-treated cells. A segment of KOR transcript spanning the second extracellular loop, which has the reported dynorphin specificity, and the seventh transmembrane domain of the receptor was amplified from the total RNA of morphine-treated CEM x174 lymphocytes, along with a competitor molecule. The competitor was constructed by deleting a 33-nucleotide fragment from KOR. The results of the competitive RT/PCR indicated that CEM x174 cells expressed KOR mRNA constitutively, in the order of femto-grams. Treatment of 10 microM of morphine resulted in the up-regulation of KOR gene expression 24 hr post-treatment. The observed morphine effect could be reversed by treating the cells with either naloxone (a KOR-partially selective antagonist) or nor-Binaltorphimine (a KOR-selective antagonist). PMID:11727785

  6. Mini-tablets versus pellets as promising multiparticulate modified release delivery systems for highly soluble drugs.

    PubMed

    Gaber, Dina M; Nafee, Noha; Abdallah, Osama Y

    2015-07-01

    Whether mini-tablets (tablets, diameters ?6mm) belong to single- or multiple-unit dosage forms is still questionable. Accordingly, Pharmacopoeial evaluation procedures for mini-tablets are lacking. In this study, the aforementioned points were discussed. Moreover, their potential for oral controlled delivery was assessed. The antidepressant venlafaxine hydrochloride (Vx), a highly soluble drug undergoing first pass effect, low bioavailability and short half-life was selected as a challenging payload. In an attempt to weigh up mini-tablets versus pellets as multiparticulate carriers, Vx-loaded mini-tablets were compared to formulated pellets of the same composition and the innovator Effexor(®)XR pellets. Formulations were prepared using various polymer hydrogels in the core and ethyl cellulose film coating with increasing thickness. Mini-tablets (diameter 2mm) showed extended Vx release (<60%, 8h). Indeed, release profiles comparable to Effexor(®)XR pellets were obtained. Remarkably higher coating thickness was required for pellets to provide equivalent retardation. Ethyl cellulose in the core ensured faster release due to polymer migration to the surface and pore formation in the coat. mini-tablets showed higher stability to pellets upon storage. Industrially speaking, mini-tablets proved to be superior to pellets in terms of manufacturing, product quality and economical aspects. Results point out the urgent need for standardized evaluation procedures for mini-tablets. PMID:25869450

  7. 77 FR 3927 - Oral Dosage Form New Animal Drugs; Deracoxib

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-26

    ... SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Deracoxib AGENCY... with dental surgery and the addition of a 12-milligram (mg) size tablet. DATES: This rule is effective... associated with dental surgery and the addition of a 12-mg size tablet. The supplemental NADA is ]...

  8. CES 2011: Tablet Crazy

    ERIC Educational Resources Information Center

    Rapp, David

    2011-01-01

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

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

    PubMed Central

    Teng, Renli; Carlson, Glenn; Hsia, Judith

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  11. The Neurodevelopmental Impact of Neonatal Morphine Administration

    PubMed Central

    Attarian, Stephanie; Tran, Lan Chi; Moore, Aimee; Stanton, George; Meyer, Eric; Moore, Robert P.

    2014-01-01

    Medical management of newborn infants often necessitates recurrent painful procedures, which may alter nociceptive pathways during a critical developmental period and adversely effect neuropsychological outcomes. To mitigate the effects of repeated painful stimuli, opioid administration for peri-procedural analgesia and ICU (intensive care unit) sedation is common in the NICU (neonatal intensive care unit). A growing body of basic and animal evidence suggests potential long-term harm associated with neonatal opioid therapy. Morphine increases apoptosis in human microglial cells, and animal studies demonstrate long-term changes in behavior, brain function, and spatial recognition memory following morphine exposure. This comprehensive review examines existing preclinical and clinical evidence on the long-term impacts of neonatal pain and opioid therapy. PMID:24961764

  12. Morphine in the treatment of acute pulmonary oedema - Why?

    PubMed

    Ellingsrud, C; Agewall, S

    2016-01-01

    Morphine has for a long time, been used in patients with acute pulmonary oedema due to its anticipated anxiolytic and vasodilatory properties, however a discussion about the benefits and risks has been raised recently. A literature search in Medline and Embase using the keywords "pulmonary oedema" OR "lung oedema" OR "acute heart failure" AND "morphine" was performed. A certain vasodilation has been described after morphine administration, but the evidence for this mechanism is relatively poor and morphine-induced anxiolysis may possibly be the most important factor of morphine in pulmonary oedema and therefore some authors have suggested benzodiazepines as an alternative treatment. Respiratory depression seems to be a less relevant clinical problem according to the literature, whereas vomiting is common, which may cause aspiration. In the largest outcome study, based on the ADHERE registry, morphine given in acute decompensated heart failure was an independent predictor of increased hospital mortality, with an odds ratio of 4.8 (95% CI: 4.52-5.18, p<0.001). Other, smaller studies have shown a significant association between morphine administration and mortality, which was lost after adjusting for confounding factors. Morphine is still used for pulmonary oedema in spite of poor scientific background data. A randomised, controlled study is necessary in order to determine the effect - and especially the risk - when using morphine for pulmonary oedema. Since the positive effects are not sufficiently documented, and since the risk for increased mortality cannot be ruled out, one can advocate that the use should be avoided. PMID:26476045

  13. Effect of morphine on PC12 cells with molecular radar

    NASA Astrophysics Data System (ADS)

    Shi, Chen; Yu, Xiaoli; Lu, Jiuyi; Zhang, Chunyang; Jin, Lei; Ma, Hui; Zhang, Dacheng; Chen, Die Yan

    2000-10-01

    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.

  14. Heroin vs morphine for cancer pain?

    PubMed

    Levine, M N; Sackett, D L; Bush, H

    1986-02-01

    Narcotic analgesics are the mainstay of pain control in patients with cancer. A controversy has been raging in the United States and Canada as to the legalization of heroin. We have reviewed the literature in order to determine the relative efficacy of heroin and morphine in cancer pain. We applied the following methodologic criteria: Was the assignment of patients to the different opiates randomized? Were all clinically relevant outcomes reported? Were the patients recognizable? Were both clinical and statistical significance considered? Was the opiate regimen feasible in routine clinical practice? Were all patients who entered the study accounted for at its conclusion? Two trials satisfied our first standard. The first, a double-blind cross-over trial, failed to meet standard 4 (the negative conclusion may represent a type 2 error) and only 21% of patients completed both treatment periods. The second study, which compared intramuscular heroin and morphine among patients with postoperative pain, failed to meet standards 3 (patients not described in sufficient detail and only tangentially related to chronic cancer pain) and 4 (type 2 error). Thus the relative efficacy of heroin and morphine in the relief of chronic cancer pain remains unknown. Randomized trials that meet all six methodologic standards must therefore be carried out for this controversy to be resolved. PMID:2418799

  15. Catecholamines bind to enkephalins, morphiceptin, and morphine.

    PubMed

    Root-Bernstein, R S

    1987-04-01

    Nuclear magnetic resonance spectroscopy, pH titration, and color reactions demonstrate that the catecholamines dopamine, epinephrine, and norepinephrine bind to the enkephalins. Binding constants are c. 6 X 10(3) per mole. Catecholamines also bound to the mu opiate receptor agonist morphiceptin (Tyr-Pro-Phe-Pro-NH2). Very little binding was found to enkephalin and morphiceptin fragments and analogues, indicating that the entire molecules are necessary. Serotonin binding peptides do not bind the catecholamines. Morphine and apomorphine, however, do bind these catecholamines (with a binding constant for morphine of c. 4 X 10(4) per mole). The opiate antagonist naloxone and a number of other drugs do not bind catecholamines. Morphine, morphiceptin, and the enkephalins also retard the formation of colored reaction products by catecholamines in vitro. These results may help to explain observations that the enkephalins are co-stored and co-transmitted with dopamine and norepinephrine, and may provide a basis for the elucidation of other known cases of peptide-monoamine co-transmission. Possible implications for understanding opiate effects on catecholamines during addiction and withdrawal are discussed, and suggestions concerning drug design are made. PMID:3607522

  16. Zomepirac sodium -- a new oral analgesic.

    PubMed

    1981-01-01

    Zomepirac sodium is a new oral analgesic that is more effective than aspirin, with no apparent tolerance or potential for addiction. It causes gastrointestinal bleeding similar to that caused by large doses of aspirin. For occasional moderate pain not responsive to aspirin, zomepirac may prove to be preferable to oral narcotics such as codeine, oxycodone, propoxyphene, pentazocine and meperidine. For chronic use, the safety and continued effectiveness of the new drug remain to be determined; it probably cannot replace oral narcotics in narcotic-dependent patients. For severe pain, as in myocardial infarction, renal colic and after some operations, zomepirac is no substitute for parenteral morphine. PMID:7005639

  17. The Comparison of Intrathecal Morphine and IV Morphine PCA on Pain Control, Patient Satisfaction, Morphine Consumption, and Adverse Effects in Patients Undergoing Reduction Mammoplasty

    PubMed Central

    Akda?, Osman; Kara, ?nci; Y?ld?ran, Gokce Unal; Tosun, Zekeriya

    2015-01-01

    Background: Following breast reduction procedures, the level of postoperative pain can be severe, and sufficient pain control influences a patient's physiological, immunological, and psychological status. Objective: The aim of this study was to examine the use of intrathecal morphine (ITM) in breast reduction surgery with patient-controlled analgesia (PCA). Methods: Sixty-two female patients who underwent breast reductions with the same technique participated in this study. The study group (ITM + PCA) included 32 patients; a single shot (0.2 mg) of ITM and intravenous morphine with PCA were administered. In the control group, morphine PCA alone was intravenously administered to 30 patients. Comparisons between the groups of cumulative morphine consumption, visual analog scale scores, and patient satisfaction scores, which were the primary outcome measures, and adverse effects, which were the secondary outcome measures, were conducted. Results: The patients in the 2 groups had similar degrees of pain and satisfaction scores. The study group had lower cumulative morphine consumption (P = .001) than the PCA-only control group; there was no statistically significant difference in adverse effects between the 2 groups. Conclusion: Intrathecal morphine may effectively control pain with lower total morphine consumption following breast reduction surgery. PMID:25987940

  18. Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose.

    PubMed Central

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

    1995-01-01

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

  19. Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose.

    PubMed

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

    1995-06-01

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

  20. Novel levocetirizine HCl tablets with enhanced palatability: synergistic effect of combining taste modifiers and effervescence technique

    PubMed Central

    Labib, Gihan S

    2015-01-01

    Objectives Levocetirizine HCl, a second-generation piperazine derivative and H1-selective antihistaminic agent, possesses few side effects. The first objective of the study was to compare and evaluate the taste-masking effect of different ratios of 2-hydroxypropyl-?-cyclodextrin and mannitol on levocetirizine HCl using an inclusion complex and solid dispersion, respectively. The second objective was to study the possibility of preparing and evaluating effervescent tablets from the best-chosen taste-masked blends for the purpose of their use either as orodispersible tablets or as water-soluble effervescent tablets, according to patients’ will. Materials and methods Prepared taste-masked blends were prepared and subjected to palatability, Fourier-transform infrared spectroscopy, and differential scanning calorimetry studies. Tablets containing different percentages of effervescent mixtures were prepared by direct compression on the selected taste-modified blends. Evaluation tests were conducted, including flowability and compressibility on the precompressed blends and hardness, friability, wetting time, effervescent time, in vitro, in vivo disintegration time, and in vitro dissolution study on the compressed tablets. Formulated tablets were evaluated and compared to marketed orodispersible tablets for mouth feel and palatability. Results All prepared tablets showed convenient physical and palatability properties compared to the selected brand. The in vitro drug-release study revealed fast release of levocetirizine HCl within 5 minutes from all prepared tablets. Conclusion Levocetirizine HCl effervescent tablets are likely to increase patient compliance with drug administration. Moreover, the use of these effervescent tablets in an orodispersible dosage form can improve oral drug bioavailability and act as an attractive pediatric dosage form. PMID:26379426

  1. Evaluation of enteric-coated tablets as a whole cell inactivated vaccine candidate against Vibrio cholerae.

    PubMed

    Fernández, Sonsire; Año, Gemma; Castaño, Jorge; Pino, Yadira; Uribarri, Evangelina; Riverón, Luis A; Cedré, Bárbara; Valmaseda, Tania; Falero, Gustavo; Pérez, José L; Infante, Juan F; García, Luis G; Solís, Rosa L; Sierra, Gustavo; Talavera, Arturo

    2013-01-01

    A vaccine candidate against cholera was developed in the form of oral tablets to avoid difficulties during application exhibited by current whole cell inactivated cholera vaccines. In this study, enteric-coated tablets were used to improve the protection of the active compound from gastric acidity. Tablets containing heat-killed whole cells of Vibrio cholerae strain C7258 as the active pharmaceutical compound was enteric-coated with the polymer Kollicoat(®) MAE-100P, which protected them efficiently from acidity when a disintegration test was carried out. Enzyme-linked immunosorbent assay (ELISA) anti-lipopolysaccharide (LPS) inhibition test and Western blot assay revealed the presence of V. cholerae antigens as LPS, mannose-sensitive haemagglutinin (MSHA) and outer membrane protein U (Omp U) in enteric-coated tablets. Immunogenicity studies (ELISA and vibriocidal test) carried out by intraduodenal administration in rabbits showed that the coating process of tablets did not affect the immunogenicity of V. cholerae-inactivated cells. In addition, no differences were observed in the immune response elicited by enteric-coated or uncoated tablets, particularly because the animal model and immunization route used did not allow discriminating between acid resistances of both tablets formulations in vivo. Clinical studies with volunteers will be required to elucidate this aspect, but the results suggest the possibility of using enteric-coated tablets as a final pharmaceutical product for a cholera vaccine. PMID:23492079

  2. Pharmaceutical and pharmacokinetic characterization of a novel sublingual buprenorphine/naloxone tablet formulation in healthy volunteers

    PubMed Central

    Fischer, Andreas; Hjelmström, Peter

    2015-01-01

    Abstract Context Bitter taste, as well as dissolve time, presents a significant challenge for the acceptability of formulations for oral transmucosal drug delivery. Objective To characterize a novel sublingual tablet formulation of buprenorphine/naloxone with regards to pharmacokinetics, dissolve time and formulation acceptability. Methods Dry mixing techniques were employed to produce a small and fast dissolving buprenorphine/naloxone sublingual tablet formulation, OX219 (Zubsolv®), using sucralose and menthol as sweetener and flavor to mask the bitter taste of the active ingredients. Two cross-over studies were performed in healthy volunteers to evaluate pharmacokinetics, dissolve time and acceptability of OX219 5.7/1.4?mg tablets compared to the commercially available buprenorphine/naloxone formulations Suboxone® tablets and films (8/2?mg). Results Buprenorphine exposure was equivalent in OX219 and Suboxone tablets. Sublingual dissolve times were significantly shorter for OX219 than for Suboxone tablets and were similar to Suboxone films. The OX219 formulation received significantly higher subjective ratings for taste and overall acceptability than both Suboxone formulations. OX219 was preferred over Suboxone tablet and film formulations by 77.4% and 88.9% of subjects, respectively. Conclusions A sublingual tablet formulation with an improved acceptability has been successfully developed. PMID:24099551

  3. A Traditional Chinese Medicine Xiao-Ai-Tong Suppresses Pain through Modulation of Cytokines and Prevents Adverse Reactions of Morphine Treatment in Bone Cancer Pain Patients

    PubMed Central

    Cong, Yan; Sun, Kefu; He, Xueming; Li, Jinxuan; Dong, Yanbin; Zheng, Bin; Tan, Xiao; Song, Xue-Jun

    2015-01-01

    Treating cancer pain continues to possess a major challenge. Here, we report that a traditional Chinese medicine Xiao-Ai-Tong (XAT) can effectively suppress pain and adverse reactions following morphine treatment in patients with bone cancer pain. Visual Analogue Scale (VAS) and Quality of Life Questionnaire (EORTC QLQ-C30) were used for patient's self-evaluation of pain intensity and evaluating changes of adverse reactions including constipation, nausea, fatigue, and anorexia, respectively, before and after treatment prescriptions. The clinical trials showed that repetitive oral administration of XAT (200?mL, bid, for 7 consecutive days) alone greatly reduced cancer pain. Repetitive treatment with a combination of XAT and morphine (20?mg and 30?mg, resp.) produced significant synergistic analgesic effects. Meanwhile, XAT greatly reduced the adverse reactions associated with cancer and/or morphine treatment. In addition, XAT treatment significantly reduced the proinflammatory cytokines interleukin-1? and tumor necrosis factor-? and increased the endogenous anti-inflammatory cytokine interleukin-10 in blood. These findings demonstrate that XAT can effectively reduce bone cancer pain probably mediated by the cytokine mechanisms, facilitate analgesic effect of morphine, and prevent or reduce the associated adverse reactions, supporting a use of XAT, alone or with morphine, in treating bone cancer pain in clinic. PMID:26617438

  4. Tests for addiction (chronic intoxication) of morphine type

    PubMed Central

    Halbach, H.; Eddy, Nathan B.

    1963-01-01

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

  5. Efficiency of postoperative pain management after gynecologic oncological surgeries with the use of morphine + acetaminophen + ketoprofen versus morphine + metamizol + ketoprofen.

    PubMed

    Samulak, D; Michalska, M; Gaca, M; Wilczak, M; Mojs, E; Chuchracki, M

    2011-01-01

    Surgical treatment used in gynecological oncology involves acute postoperative pain which requires efficient treatment. This study covered a group of 128 patients who were randomly divided into two groups. In the postoperative period patients in group I were administered morphine subcutaneously, acetaminophen intravenously and naproxen per rectum. The pain intensity level was checked by means of the pain intensity numeric rating scale (NRS). In the instances of pain rated at 5 or more, patients were additionally administered ketoprofen intravenously. Patients in group II were administered morphine, naproxen, and metamizole instead of acetaminophen and ketoprofen additionally. In group I after the administration of morphine and acetaminophen 22 patients (34.37%) needed additional doses of ketoprofen. In group II 33 women (51.56%) required ketoprofen after the administration of morphine and metamizole (N1 = 22 vs N2 = 33, p < 0.05). The use of metamizol with morphine (without ketoprofen) gave worse analgesic results than acetaminophen with morphine, but the combination of morphine, acetaminophen and ketoprofen or morphine, metamizol and ketoprofen gave satisfactory analgesic results. PMID:21614906

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

    PubMed

    Mather, S J; Peutrell, J M

    1995-01-01

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

  7. Assessing Student Writing on Tablets

    ERIC Educational Resources Information Center

    Davis, Laurie Laughlin; Orr, Aline; Kong, Xiaojing; Lin, Chow-Hong

    2015-01-01

    There is increasing expectation that schools should be able to use tablets for a range of instructional and assessment purposes. This article considers the comparability of student writing on tablets and laptops to ensure that writing assessment is conducted in a way that is fair to all students. Data were collected from a sample of 826 students…

  8. Tablet PCs: The Write Approach

    ERIC Educational Resources Information Center

    Milner, Jacob

    2006-01-01

    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…

  9. Oral Warts

    MedlinePLUS

    ... for providing oral care. NIDCR > Image Gallery > Oral Health > Oral Warts Oral Warts Main Content Title: Oral Warts Description: Warts are small, white, gray, or pinkish rough bumps that look like cauliflower. They can appear inside the lips and on ...

  10. Endogenous Cholinergic Neurotransmission Contributes to Behavioral Sensitization to Morphine

    PubMed Central

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

    2015-01-01

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

  11. Morphine tolerance offers protection from radiogenic performance deficits

    SciTech Connect

    Mickley, G.A.; Stevens, K.E.; Burrows, J.M.; White, G.A.; Gibbs, G.L.

    1983-02-01

    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.

  12. Morphine versus Hydromorphone: Does Choice of Opioid Influence Outcomes?

    PubMed Central

    Gulur, Padma; Koury, Katharine; Arnstein, Paul; Lee, Hang; McCarthy, Patricia; Coley, Christopher; Mort, Elizabeth

    2015-01-01

    Morphine has traditionally been considered the first line agent for analgesia in hospitals; however, in the last few years there has been a shift towards the use of hydromorphone as a first line agent. We conducted a hospital population based observational study to evaluate the increasing use of hydromorphone over morphine in both medical and surgical populations. Additionally, we assessed the effect of this trend on three key outcomes, including adverse events, length of stay, and readmission rates. We evaluated data from the University Health Systems Consortium. Data from 38 hospitals from October 2010 to September 2013 was analyzed for patients treated with either hydromorphone or morphine. The use of morphine steadily decreased while use of hydromorphone increased in both medical and surgical groups. Rescue drugs were used more frequently in patients treated with hydromorphone in comparison to patients treated with morphine (p < 0.01). Patients receiving morphine tended to stay in the hospital for almost one day longer than patients receiving hydromorphone. However, 30-day all cause readmission rates were significantly higher in patients treated with hydromorphone (p < 0.01). Our study highlights that the choice of hydromorphone versus morphine may influence outcomes. There are implications related to resource utilization and these outcomes. PMID:26609431

  13. Cholescintigraphy in acute cholecystitis: use of intravenous morphine

    SciTech Connect

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

    1984-04-01

    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.

  14. Recent Advances in the Synthesis of Morphine and Related Alkaloids

    NASA Astrophysics Data System (ADS)

    Chida, Noritaka

    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.

  15. Effects of morphine and naloxone on feline colonic transit

    SciTech Connect

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

    1989-01-01

    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.

  16. Stress antagonizes morphine-induced analgesia in rats

    NASA Technical Reports Server (NTRS)

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

    1981-01-01

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

  17. Enhanced potency of intravenous, but not intrathecal, morphine and morphine-6-glucuronide after burn trauma.

    PubMed

    Langlade, A; Carr, D B; Serrie, A; Silbert, B S; Szyfelbein, S K; Lipkowski, A W

    1994-01-01

    We examined the analgesic effect of morphine (M) and its metabolite morphine-6-glucuronide (M6G) in a rat model of acute thermal trauma. M or M6G were given by intrathecal (IT) or intravenous (i.v.) routes after brief burn or sham burn delivered during inhalational anesthesia. In the sham group, M6G was significantly less potent than M when given i.v., yet tended to be more potent than M when given IT. For both drugs, thermal injury increased i.v. potency, yet decreased (for M) or displayed a trend to decrease (for M6G) It potency. The increased potency seen with i.v. but not IT opioid administration may reflect pharmacokinetic (e.g., diminished clearance) and/or pharmacodynamic responses (e.g., activation of peripheral opioid receptors) after thermal injury. PMID:8177011

  18. Next generation effects of female adolescent morphine exposure: sex-specific alterations in response to acute morphine emerge before puberty

    PubMed Central

    Vassoler, Fair M.; Johnson-Collins, Nicole L.; Carini, Lindsay M.; Byrnes, Elizabeth M.

    2014-01-01

    Prescription opiate use by adolescent girls has increased significantly in the past decade. Preclinical studies using rats report alterations in morphine sensitivity in the adult offspring of adolescent morphine-exposed females (MOR-F1) when compared with the offspring of adolescent saline-exposed females (SAL-F1). To begin to elucidate the development of these next generation modifications, the present study examined the effects of acute morphine administration on sedation and corticosterone secretion in prepubescent SAL-F1 and MOR-F1 male and female rats. In addition, alterations in proopiomelanocortin (POMC) gene expression in the arcuate nucleus, as well as in tyrosine hydroxylase (TH) and ?-opioid receptor (OPRM1) gene expressions in the ventral tegmental area, were analyzed using quantitative PCR, to determine whether differential regulation of these genes was correlated with the observed behavioral and/or endocrine effects. Increased morphine-induced sedation, coupled with an attenuation of morphine-induced corticosterone secretion, was observed in MOR-F1 males. Significant alterations in both POMC and OPRM1 gene expressions were also observed in MOR-F1 males, with no change in TH mRNA expression. Overall, these data suggest that the transgenerational effects of adolescent morphine exposure can be discerned before pubertal development and are more pronounced in males, and suggest dysregulation of the hypothalamic–pituitary–adrenal axis in the offspring of adolescent morphine-exposed females. PMID:24561499

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

    PubMed

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

    2009-12-01

    Growing evidence shows that trafficking of the mu-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. PMID:19679639

  20. Formulation, Characterization and Physicochemical Evaluation of Ranitidine Effervescent Tablets

    PubMed Central

    Aslani, Abolfazl; Jahangiri, Hajar

    2013-01-01

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

  1. FDA-Approved Natural Polymers for Fast Dissolving Tablets

    PubMed Central

    Alam, Md Tausif; Parvez, Nayyar; Sharma, Pramod Kumar

    2014-01-01

    Oral route is the most preferred route for administration of different drugs because it is regarded as safest, most convenient, and economical route. Fast disintegrating tablets are very popular nowadays as they get dissolved or facilely disintegrated in mouth within few seconds of administration without the need of water. The disadvantages of conventional dosage form, especially dysphagia (arduousness in swallowing), in pediatric and geriatric patients have been overcome by fast dissolving tablets. Natural materials have advantages over synthetic ones since they are chemically inert, non-toxic, less expensive, biodegradable and widely available. Natural polymers like locust bean gum, banana powder, mango peel pectin, Mangifera indica gum, and Hibiscus rosa-sinenses mucilage ameliorate the properties of tablet and utilized as binder, diluent, and superdisintegrants increase the solubility of poorly water soluble drug, decrease the disintegration time, and provide nutritional supplement. Natural polymers are obtained from the natural origin and they are cost efficacious, nontoxic, biodegradable, eco-friendly, devoid of any side effect, renewable, and provide nutritional supplement. It is proved from the studies that natural polymers are more safe and efficacious than the synthetic polymers. The aim of the present article is to study the FDA-approved natural polymers utilized in fast dissolving tablets. PMID:26556207

  2. FDA-Approved Natural Polymers for Fast Dissolving Tablets.

    PubMed

    Alam, Md Tausif; Parvez, Nayyar; Sharma, Pramod Kumar

    2014-01-01

    Oral route is the most preferred route for administration of different drugs because it is regarded as safest, most convenient, and economical route. Fast disintegrating tablets are very popular nowadays as they get dissolved or facilely disintegrated in mouth within few seconds of administration without the need of water. The disadvantages of conventional dosage form, especially dysphagia (arduousness in swallowing), in pediatric and geriatric patients have been overcome by fast dissolving tablets. Natural materials have advantages over synthetic ones since they are chemically inert, non-toxic, less expensive, biodegradable and widely available. Natural polymers like locust bean gum, banana powder, mango peel pectin, Mangifera indica gum, and Hibiscus rosa-sinenses mucilage ameliorate the properties of tablet and utilized as binder, diluent, and superdisintegrants increase the solubility of poorly water soluble drug, decrease the disintegration time, and provide nutritional supplement. Natural polymers are obtained from the natural origin and they are cost efficacious, nontoxic, biodegradable, eco-friendly, devoid of any side effect, renewable, and provide nutritional supplement. It is proved from the studies that natural polymers are more safe and efficacious than the synthetic polymers. The aim of the present article is to study the FDA-approved natural polymers utilized in fast dissolving tablets. PMID:26556207

  3. Expression of spinal cord GABA transporter 1 in morphine-tolerant male Wistar rats.

    PubMed

    Shokoofeh, Siroosi; Homa, Manaheji; Leila, Dargahi; Samira, Daniali

    2015-11-15

    Chronic morphine exposure produces morphine tolerance. One of the mechanisms of morphine tolerance involves ?-aminobutric acid (GABA), whose level is regulated by GABA transporter 1 (GAT-1). The aim of this study was to investigate the expression of GAT-1 in the spinal cord during morphine treatment. Morphine was administrated to rats via drinking water for 21 days. On day 21, a single dose of morphine (10mg/kg) was injected, followed by the administration of 5% formalin after 30min. Expression of GAT-1 in the lumbar spinal cord during morphine treatment was analyzed by Western blotting and immunohistochemistry assay. In another set of experiments, a morphine-tolerant group was treated with a GAT-1 inhibitor, ethyl nipecotate (60mg/kg), 5min prior to the formalin test. To assess a possible analgesic effect of the GAT-1 inhibitor, a non-tolerant group was injected only with ethyl nipecotate 5min prior to the formalin test. Our results indicated that a chronic consumption of morphine led to morphine tolerance. Morphine tolerance was also concomitant with GAT-1 up-regulation in the lumbar spinal cord. The GAT-1 inhibitor ethyl nipecotate improved the antinociceptive effect of morphine in the morphine-tolerant group. Ethyl nipecotate also had an antinociceptive effect on the non-tolerant group. Thus, our data suggest that GAT-1 overexpression in the spinal cord plays an important role in morphine tolerance. PMID:26463038

  4. The ?2 Adrenergic Receptor Regulates Morphine Tolerance and Physical Dependence

    PubMed Central

    Liang, De-Yong; Shi, Xiaoyou; Li, Xiangqi; Li, Jun; Clark, J. David

    2007-01-01

    Adaptations to the chronic administration of opioids reduce the utility of these drugs in treating pain and support addiction. Recent genetics-based approaches have implicated the ?2 adrenergic receptor (?2-AR) in controlling some of these responses. We do not know, however, whether this receptor can modulate tolerance, dependence or changes in gene expression caused by chronic opioid administration. For our studies we used C57BL/6 mice and ?2-AR knockout mice in the FVB background. Morphine dose response relationships were established both prior to and after chronic morphine treatment. In some cases, the selective ?2-AR antagonist butoxamine was administered along with or after morphine. Physical dependence was assessed using naloxone-precipitated withdrawal. The expression of calcitonin gene related peptide (CGRP) and substance P (SP) were measured in spinal cord and dorsal root ganglion (DRG) tissues using both real-time PCR and enzyme-linked immunoassay (ELISA). Both the co-administration of butoxamine with morphine and the administration of butoxamine after chronic morphine reversed morphine tolerance. Morphine failed to cause tolerance in ?2-AR knockout mice. Physical dependence was reduced under the same circumstances. The chronic administration of butoxamine with morphine reduced or eliminated the normally observed up-regulation of CGRP and SP in spinal cord and DRG tissues. Our results suggest that the ?2-AR modulates both opioid tolerance and physical dependence. Activation of ?2-ARs appears to be required for some of the key neurochemical changes which characterize chronic opioid administration. Therefore ?2-AR antagonists show some promise as agents to enhance chronic opioid analgesic therapy. PMID:17498818

  5. Mechanical properties and structure of swollen crosslinked high amylose starch tablets

    E-print Network

    Buschmann, Michael

    and then compressed into a tablet provides a slow- release drug delivery system (Fig. 1). This is due to slow water as an excipient for controlled oral drug delivery. The kinetics of delivery is governed by the diffusion branched version. The respective proportion of each in industrially used starch is usually ca. 30% amylose

  6. 76 FR 51037 - Determination That Halflytely and Bisacodyl Tablets Bowel Prep Kit (Containing Two Bisacodyl...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... (polyethylene glycol (PEG) 3350, sodium chloride, sodium bicarbonate, and potassium chloride for oral solution... applications (ANDAs) for bowel prep kits containing PEG-3350, sodium chloride, sodium bicarbonate, and... Bisacodyl Tablets Bowel Prep Kit (PEG- 3350, sodium chloride, sodium bicarbonate, and potassium chloride...

  7. 21 CFR 520.1196 - Ivermectin and pyrantel pamoate chewable tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ivermectin and pyrantel pamoate chewable tablets. 520.1196 Section 520.1196 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1196 Ivermectin and pyrantel pamoate...

  8. Oral Cancer

    MedlinePLUS

    ... kinds of oral cancer: oral cavity cancer and oropharyngeal cancer. The most common symptom of oral cancer ... the oral cavity. • HPV infection The number of oropharyngeal cancers linked to human papilloma virus (HPV) has ...

  9. Mitragynine Attenuates Withdrawal Syndrome in Morphine-Withdrawn Zebrafish

    PubMed Central

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

    2011-01-01

    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

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

    SciTech Connect

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

    1982-09-01

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

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

    PubMed

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

    1991-02-01

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

  12. 76 FR 12563 - Oral Dosage Form New Animal Drugs; Spinosad and Milbemycin Oxime

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-08

    ...Oral Dosage Form New Animal Drugs; Spinosad and Milbemycin Oxime AGENCY: Food and...prescription use of chewable tablets containing spinosad and milbemycin oxime in dogs for the...veterinary prescription use of TRIFEXIS (spinosad and milbemycin oxime) Chewable...

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

    PubMed Central

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

    2015-01-01

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

  14. Spray drying of a poorly water-soluble drug nanosuspension for tablet preparation: formulation and process optimization with bioavailability evaluation.

    PubMed

    Sun, Wei; Ni, Rui; Zhang, Xin; Li, Luk Chiu; Mao, Shirui

    2015-06-01

    Spray drying experiments of an itraconazole nanosuspension were conducted to generate a dry nanocrystal powder which was subsequently formulated into a tablet formulation for direct compression. The nanosuspension was prepared by high pressure homogenization and characterized for particle-size distribution and surface morphology. A central composite statistical design approach was applied to identify the optimal drug-to-excipient ratio and spray drying temperature. It was demonstrated that the spray drying of a nanosuspension with a mannitol-to-drug mass ratio of 4.5 and at an inlet temperature of 120?°C resulted in a dry powder with the smallest increase in particle size as compared with that of the nanosuspension. X-ray diffraction results indicated that the crystalline structure of the drug was not altered during the spray-drying process. The tablet formulation was identified by determining the micromeritic properties such as flowability and compressibility of the powder mixtures composed of the spray dried nanocrystal powder and other commonly used direct compression excipients. The dissolution rate of the nanocrystal tablets was significantly enhanced and was found to be comparable to that of the marketed Sporanox®. No statistically significant difference in oral absorption between the nanocrystal tablets and Sporanox® capsules was found. In conclusion, the nanosuspension approach is feasible to improve the oral absorption of a BCS Class II drug in a tablet formulation and capable of achieving oral bioavailability equivalent to other well established oral absorption enhancement method. PMID:24785575

  15. Metamizol potentiates morphine antinociception but not constipation after chronic treatment.

    PubMed

    Hernández-Delgadillo, Gloria P; Ventura Martínez, Rosa; Díaz Reval, Ma Irene; Domínguez Ramírez, Adriana M; López-Muñoz, Francisco J

    2002-04-26

    This work evaluates the antinociceptive and constipating effects of the combination of 3.2 mg/kg s.c. morphine with 177.8 mg/kg s.c. metamizol in acutely and chronically treated (once a day for 12 days) rats. On the 13th day, antinociceptive effects were assessed using a model of inflammatory nociception, pain-induced functional impairment model, and the charcoal meal test was used to evaluate the intestinal transit. Simultaneous administration of morphine with metamizol resulted in a markedly antinociceptive potentiation and an increasing of the duration of action after a single (298+/-7 vs. 139+/-36 units area (ua); P<0.001) and repeated administration (280+/-17 vs. 131+/-22 ua; P<0.001). Antinociceptive effect of morphine was reduced in chronically treated rats (39+/-10 vs. 18+/-5 au) while the combination-induced antinociception was remained similar as an acute treatment (298+/-7 vs. 280+/-17 au). Acute antinociceptive effects of the combination were partially prevented by 3.2 mg/kg naloxone s.c. (P<0.05), suggesting the partial involvement of the opioidergic system in the synergism observed. In independent groups, morphine inhibited the intestinal transit in 48+/-4% and 38+/-4% after acute and chronic treatment, respectively, suggesting that tolerance did not develop to the constipating effects. The combination inhibited intestinal transit similar to that produced by morphine regardless of the time of treatment, suggesting that metamizol did not potentiate morphine-induced constipation. These findings show a significant interaction between morphine and metamizol in chronically treated rats, suggesting that this combination could be useful for the treatment of chronic pain. PMID:12063090

  16. Intrathecal ketorolac enhances intrathecal morphine analgesia following total knee arthroplasty

    PubMed Central

    Lauretti, Gabriela R; Righeti, Claudia C F; Mattos, Anita L

    2013-01-01

    Background: Total knee arthroplasty represents one of the most painful surgeries. The aim of the study was to compare analgesia and adverse effects of intrathecal (IT) ketorolac versus IT morphine, versus the combination of IT ketorolac and morphine. Materials and Methods: After ethical approval and patient consent, 80 patients undergoing knee arthroplasty were randomized to one of 4 groups. All groups received 15 mg IT bupivacaine plus IT test drug (2 ml). The control group (CG) received saline as IT test drug. The morphine group (MG) received IT 200 g morphine, the ketorolac group (KG) IT 2 mg ketorolac and the morphine-ketorolac group (MKG) 200 g morphine + 2 mg ketorolac as test drugs. Pain and adverse effects were evaluated. P > 0.05 was considered significant. Results: The MG and KG were similar in their times to time to first rescue analgesic (440 ± 38 min and 381 ± 44 min, respectively). Both groups were longer when compared to the CG (170 ± 13 min) (P > 0.01). The MG and KG had lesser ketoprofen consumption compared to the CG (P > 0.05). The time to first rescue analgesic was longer to the MKG (926 ± 222 min) (15 h) compared to CG (P > 0.001) and to the MG and the KG (P > 0.01). MKG displayed lesser ketoprofen consumption compared to MG and KG (P > 0.05) and to the CG (P > 0.02). Conclusions: The data suggest a role for spinal ketorolac and morphine in orthopaedic surgery because this combination of agents provided 15 h of analgesia compared to 7 h after each drug alone, with no significant side-effects. PMID:24249988

  17. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...Conditions of use —(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...

  18. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...Conditions of use —(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...

  19. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...Conditions of use —(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...

  20. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...Conditions of use —(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...

  1. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...Conditions of use (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...

  2. 21 CFR 520.1380 - Methocarbamol tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...DRUGS § 520.1380 Methocarbamol tablets. (a) Chemical name. 3-(O-Methoxyphenoxy)-1,2-propanediol 1-carbamate. (b) Specifications. Each tablet contains 500 milligrams of methocarbamol. (c) Sponsor. See No. 000856...

  3. 21 CFR 520.1380 - Methocarbamol tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...DRUGS § 520.1380 Methocarbamol tablets. (a) Chemical name. 3-(O-Methoxyphenoxy)-1,2-propanediol 1-carbamate. (b) Specifications. Each tablet contains 500 milligrams of methocarbamol. (c) Sponsor. See No. 000856...

  4. 21 CFR 520.1380 - Methocarbamol tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...DRUGS § 520.1380 Methocarbamol tablets. (a) Chemical name. 3-(O-Methoxyphenoxy)-1,2-propanediol 1-carbamate. (b) Specifications. Each tablet contains 500 milligrams of methocarbamol. (c) Sponsor. See No. 000856...

  5. Galileo's Telescopy and Jupiter's Tablet

    NASA Astrophysics Data System (ADS)

    Usher, P. D.

    2003-12-01

    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.

  6. Characterization of omega-3 tablets.

    PubMed

    Vestland, Tina Lien; Jacobsen, Øyvind; Sande, Sverre Arne; Myrset, Astrid Hilde; Klaveness, Jo

    2016-04-15

    Omega-3 nutraceuticals are extensively used as health supplements worldwide. Various administration forms for delivery of omega-3 are available. However, the niche omega-3 tablets have so far remained unexplored. In this work tablets containing 25-40% (w/w) omega-3 oil as triglycerides or ethyl esters were prepared utilizing a direct compaction grade powder with ?-cyclodextrin as encapsulating agent. It was found that powders with up to 35% (w/w) triglyceride oil and 30% (w/w) ethyl ester oil, respectively, can be directly compressed into tablets of excellent quality. Physical properties of omega-3 containing powders and tablets are described. The powder X-ray diffractograms of the powders and crushed tablets show evidence of the formation of new crystalline phases not present in ?-cyclodextrin. In addition, (1)H NMR data suggest that the ethyl esters form inclusion complexes with ?-cyclodextrin. Compaction of other, commercially available, omega-3 powders was performed as a comparison and deemed unsuccessful. PMID:26616980

  7. Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections

    PubMed Central

    Wiederhold, Nathan P

    2016-01-01

    Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data regarding clinical efficacy are needed.

  8. Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections.

    PubMed

    Wiederhold, Nathan P

    2016-01-01

    Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data regarding clinical efficacy are needed. PMID:26730212

  9. Cardiovascular effects of epidurally administered morphine and a xylazine-morphine combination in isoflurane-anesthetized dogs.

    PubMed

    Keegan, R D; Greene, S A; Weil, A B

    1995-04-01

    Cardiovascular effects of epidurally administered morphine, a morphine-xylazine combination, and saline solution (control) during isoflurane-maintained anesthesia were assessed in 6 healthy dogs. Anesthesia was induced with isoflurane in O2 and was maintained at 2.0% end-tidal isoflurane concentration. Ventilation was controlled to maintain PaCO2 at 35 to 45 mm of Hg. The dorsal pedal artery was cannulated for measurement of systolic, mean, and diastolic pressures, and for blood sample collection. Arterial blood pH and gas tensions were determined every 30 minutes. Cardiac output was determined by thermodilution. The ECG, heart rate, body temperature, central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, end-tidal isoflurane concentration, and CO2 tension were monitored. Systemic and pulmonary vascular resistance, arterial HCO3- concentration, base excess, and cardiac index were calculated. After baseline measurements were taken, morphine (0.1 mg/kg of body weight) in 5 ml of isotonic saline solution, morphine and xylazine (0.1 mg of morphine and 0.02 mg of xylazine/kg) in 5 ml of isotonic saline solution, or 5 ml of isotonic saline solution was injected into the lumbosacral epidural space. Data were recorded at 5, 15, 30, 45, 60, 75, 90, 105, and 120 minutes after epidural injection. Statistical analysis included ANOVA for repeated measures. Significance was set at P < 0.05. None of the measured variables was significantly different among the 3 treatments at any time. Results of the study indicated that epidural administration of morphine or morphine and xylazine is not associated with significant cardiovascular side effects during isoflurane-maintained anesthesia in dogs. PMID:7785829

  10. Extended-release morphine sulfate in treatment of severe acute and chronic pain

    PubMed Central

    Balch, Robert J; Trescot, Andrea

    2010-01-01

    Morphine is the archetypal opioid analgesic. Because it is a short-acting opioid, its use has been limited to the management of acute pain. The development of extended-release formulations have resulted in the increased utilization of morphine in chronic pain conditions. This review documents the history of morphine use in pain treatment, and describes the metabolism, pharmacodynamics, formulations, and efficacy of the currently available extended-release morphine medications. PMID:21197323

  11. Principles of Tablet Computing for Educators

    ERIC Educational Resources Information Center

    Katzan, Harry, Jr.

    2015-01-01

    In the study of modern technology for the 21st century, one of the most popular subjects is tablet computing. Tablet computers are now used in business, government, education, and the personal lives of practically everyone--at least, it seems that way. As of October 2013, Apple has sold 170 million iPads. The success of tablets is enormous and has…

  12. Touch Screen Tablets and Emergent Literacy

    ERIC Educational Resources Information Center

    Neumann, Michelle M.; Neumann, David L.

    2014-01-01

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

  13. Scaffolding Equals Success in Teaching Tablet PCs

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  14. Mathematics Instruction and the Tablet PC

    ERIC Educational Resources Information Center

    Fister, K. Renee; McCarthy, Maeve L.

    2008-01-01

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

  15. Species-specific lipophilicity of morphine antagonists.

    PubMed

    Mazák, Károly; Hosztafi, Sándor; Noszál, Béla

    2015-10-12

    Complete sets of microscopic acid-base and partition equilibrium constants were experimentally determined for therapeutically important morphine derivatives, including the widely used antagonists naloxone and naltrexone. The acid-base microequilibria were characterized by combining pH-potentiometry and deductive methods using synthesized auxiliary compounds. Microscopic protonation equilibria show that approximately three times as many zwitterionic microspecies than non-charged ones exist in oxymorphone and naltrexone solutions. On the other hand, the non-charged microspecies is the dominant one in the case of naloxone, although its concentration is only 1.34 times higher than that of its zwitterionic protonation isomer. Partition coefficients of the individual microspecies were determined by a combination of experimentally measured distribution constants and deductive methods. The contribution ratio of the non-charged versus zwitterionic species to the overall lipophilicity is quantified and depicted in terms of species-specific lipophilicities over the entire pH range for each compound. Our lipophilicity values allowed the molecular interpretation of the classical pharmacologic observation that naloxone has a faster onset for antagonist activity, and a concomitant shorter duration of action. PMID:26122463

  16. Effect of morphine on sympathetic nerve activity in humans

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

  17. Effect of linalool on morphine tolerance and dependence in mice.

    PubMed

    Hosseinzadeh, Hossein; Imenshahidi, Mohsen; Hosseini, Mohammadreza; Razavi, Bibi Marjan

    2012-09-01

    Linalool, a terpene alcohol, has been shown to interact with the opioid system and N-methyl-D-aspartate (NMDA) receptor. Therefore, the effect of linalool on morphine dependence and tolerance was studied. Dependence and tolerance were induced in mice using subcutaneous morphine injections, three times a day (50, 50 and 75 mg/kg /day) for 3 days. To evaluate the effect of agents on the induction of morphine dependence and tolerance, linalool (50, 75 and 100 mg/kg), clonidine (positive control), alpha-2 receptor agonist, (0.1 mg/kg), memantine, NMDA receptor antagonist (positive control), (30 mg/kg) and saline were injected intraperitoneally three times a day for 3 days. To determine the expression of morphine dependence and tolerance, all compounds were injected once intraperitoneally on the day of experiment. The effect of linalool and other agents on dependence were evaluated by counting the number of jumps (induced by naloxone 5 mg/kg). The tolerance was evaluated by the tail-flick test. The results showed that linalool in the induction and expression phase increased the nociception threshold. Linalool (48% and 95.6% at doses 75 and 100 mg/kg, respectively), clonidine and memantine reduced the severity of withdrawal signs in the induction and expression phases. This study indicated that linalool has a significant effect on morphine tolerance and dependence. This effect may be mediated partially through the inhibition of NMDA receptors. PMID:22318903

  18. Role for mTOR Signaling and Neuronal Activity in Morphine-Induced Adaptations in Ventral

    E-print Network

    Cheer, Joseph F.

    Neuron Article Role for mTOR Signaling and Neuronal Activity in Morphine-Induced Adaptations of chronic morphine-induced adapta- tions in ventral tegmental area (VTA) dopamine neurons, which increase the excitability of the cells but decrease dopamine output to target regions. Chronic morphine

  19. Synthesis of (-)-Morphine Douglass F. Taber,* Timothy D. Neubert, and Arnold L. Rheingold

    E-print Network

    Taber, Douglass

    Synthesis of (-)-Morphine Douglass F. Taber,* Timothy D. Neubert, and Arnold L. Rheingold, 2002 Morphine (1) is the principal alkaloid of opium, derived from PapaVer somniferum L., or P. album Mill, PapaVeraceae.1 Mor- phine is also found in normal brain, blood, and liver tissue.2 The morphine

  20. Cellular/Molecular Morphine Increases Brain Levels of Ferritin Heavy Chain

    E-print Network

    Meucci, Olimpia

    Cellular/Molecular Morphine Increases Brain Levels of Ferritin Heavy Chain Leading to Inhibition4. Reduced coupling of CXCR4 to G-proteins was found in the brain of morphine-treated rats of cortical neurons with morphine or the selective -opioid agonist DAMGO (D-Ala2-N- Me-Phe4 -glycol5

  1. Ontogeny of NMDA receptor-mediated morphine tolerance in the postnatal rat

    E-print Network

    Barr, Gordon A.

    Ontogeny of NMDA receptor-mediated morphine tolerance in the postnatal rat Hongbo Zhua,1 , Gordon A of morphine tolerance in adult rats. But NMDA receptors undergo dramatic change during the first few weeks antagonists MK-801 and dextromethorphan on the development of morphine tolerance in 7-, 14-, and 21-day

  2. Contribution of the Periaqueductal Gray to the Suppression of Pain Affect Produced by Administration of Morphine

    E-print Network

    Borszcz, George S.

    by Administration of Morphine Into the Intralaminar Thalamus of Rat Elizabeth M. Munn, Steven E. Harte, Alexander. Administration of morphine into nPf results in pref- erential suppression of the affective reaction to noxious the antinociceptive action of morphine injected into nPf was evaluated. Vocalizations that occur after tail shock

  3. Suppression of morphine withdrawal syndrome by interleukin-2 and its gene

    E-print Network

    Tian, Weidong

    Suppression of morphine withdrawal syndrome by interleukin-2 and its gene Jinfa Gu,1,2 MingzhongDNA3-IL-2 (8 mg DNA) had a similar e¡ect as 1Â104 IU rIL-2 protein on inhibition of morphine withdrawal; Intrathecal injection; Morphine withdrawal syndrome INTRODUCTION Many experiments have indicated the existence

  4. The role of AMPA and metabotropic glutamate receptors on morphine withdrawal in infant rats

    E-print Network

    Barr, Gordon A.

    The role of AMPA and metabotropic glutamate receptors on morphine withdrawal in infant rats Hongbo not be comparable to those in the adult. Indeed, NMDA receptor antagonists do not block morphine tolerance in the present studies to test the effect of drugs acting on AMPA and group II mGlu receptors on morphine

  5. Inhibition of Morphine Withdrawal by the NMDA Receptor Antagonist MK-801 in Rat

    E-print Network

    Barr, Gordon A.

    Inhibition of Morphine Withdrawal by the NMDA Receptor Antagonist MK-801 in Rat Is Age morphine dependence; preweaning; MK-801; age-dependent; with- drawal ABSTRACT This study investigated the effects of the NMDA receptor antagonist MK-801 on the development of morphine dependence in 7-, 14

  6. Intrathecal Morphine Attenuates Recovery of Function after a Spinal Cord Injury

    E-print Network

    Grau, James

    Intrathecal Morphine Attenuates Recovery of Function after a Spinal Cord Injury Michelle A. Hook work has shown that a high dose (20 mg=kg) of systemic morphine, required to produce significant and increases lesion size. Moreover, a single dose of systemic morphine in the early stage of injury (24 h post

  7. Analgesic efficacy of ketorolac and morphine in neonatal rats Anju Guptaa

    E-print Network

    Barr, Gordon A.

    Analgesic efficacy of ketorolac and morphine in neonatal rats Anju Guptaa , Jainxin Chengb a blinded, controlled study comparing the effects of ketorolac and morphine in neonatal rats using the formalin model. Animals were given intraperitoneal (ip) injections of ketorolac or morphine at 3 or 21 days

  8. Sex chromosome complement affects nociception in tests of acute and chronic exposure to morphine in mice

    E-print Network

    Sandini, Giulio

    Sex chromosome complement affects nociception in tests of acute and chronic exposure to morphine chromosomes. In Experiment 1 (hotplate test of acute morphine analgesia), XX mice of both gonadal sexes had significantly shorter hotplate baseline latencies prior to morphine than XY mice. In Experiment 2 (test

  9. Morphine and Heroin Differentially Modulate In Vivo Hippocampal LTP in Opiate-Dependent Rat

    E-print Network

    Tian, Weidong

    Morphine and Heroin Differentially Modulate In Vivo Hippocampal LTP in Opiate-Dependent Rat Guobin to corresponding drugs. Here, we further demonstrated that during opiates withdrawal, the re-exposure of morphine in heroin-dependent rats, but heroin could not restore the reduced LTP, in morphine-dependent rats

  10. Morphine Withdrawal Increases Glutamate Uptake and Surface Expression of Glutamate Transporter GLT1 at

    E-print Network

    Tian, Weidong

    Morphine Withdrawal Increases Glutamate Uptake and Surface Expression of Glutamate Transporter GLT1 in hippocampal synaptosomes was significantly increased (by 70% in chronic morphine-treated rats) during. Moreover, the increase in glutamate uptake was reproduced in cultured neurons during morphine withdrawal

  11. J Mol Cell Cardiol 29, 711720 (1997) Distinct Components of Morphine Effects

    E-print Network

    Vogel, Zvi

    1997-01-01

    J Mol Cell Cardiol 29, 711­720 (1997) Distinct Components of Morphine Effects on Cardiac Myocytes, Y. HASIN AND Y. EILAM. Distinct Components of Morphine Effects on Cardiac Myocytes are Mediated by the and Opioid Receptors. Journal of Molecular and Cellular Cardiology (1997) 29, 711­720. Morphine exerts direct

  12. Neurotrophin-4 is required for tolerance to morphine in the mouse Desmond J. Smitha,1

    E-print Network

    Smith, Desmond J.

    Neurotrophin-4 is required for tolerance to morphine in the mouse Desmond J. Smitha,1 , Tarek A) display substantially reduced tolerance to morphine compared to wild-type. However, there were no deficits Ltd. Keywords: Addiction; Morphine; Opiates; Neurotrophin-4; Sensitization; Tolerance; Withdrawal Drug

  13. Persistent Pain Maintains Morphine-Seeking Behavior after Morphine Withdrawal through Reduced MeCP2 Repression of Glua1 in Rat Central Amygdala

    PubMed Central

    Hou, Yuan-Yuan; Cai, You-Qing

    2015-01-01

    As long-term opioids are increasingly used for control of chronic pain, how pain affects the rewarding effect of opioids and hence risk of prescription opioid misuse and abuse remains a healthcare concern and a challenging issue in current pain management. In this study, using a rat model of morphine self-administration, we investigated the molecular mechanisms underlying the impact of pain on operant behavior of morphine intake and morphine seeking before and after morphine withdrawal. We found that rats with persistent pain consumed a similar amount of daily morphine to that in control rats without pain, but maintained their level-pressing behavior of morphine seeking after abstinence of morphine at 0.2 mg/kg, whereas this behavior was gradually diminished in control rats. In the central nucleus of amygdala (CeA), a limbic structure critically involved in the affective dimension of pain, proteins of GluA1 subunits of glutamate AMPA receptors were upregulated during morphine withdrawal, and viral knockdown of CeA GluA1 eliminated the morphine-seeking behavior in withdrawn rats of the pain group. Chromatin immunoprecipitation analysis revealed that the methyl CpG-binding protein 2 (MeCP2) was enriched in the promoter region of Gria1 encoding GluA1 and this enrichment was significantly attenuated in withdrawn rats of the pain group. Furthermore, viral overexpression of CeA MeCP2 repressed the GluA1 level and eliminated the maintenance of morphine-seeking behavior after morphine withdrawal. These results suggest direct MeCp2 repression of GluA1 function as a likely mechanism for morphine-seeking behavior maintained by long-lasting affective pain after morphine withdrawal. PMID:25716866

  14. Metronidazole Oral

    MedlinePLUS

    Metronidazole comes as a tablet to take by mouth. It is usually taken two or three times ... vomiting diarrhea upset stomach loss of appetite dry mouth; sharp, unpleasant metallic taste dark or reddish-brown ...

  15. Pharmacokinetics of nortilidine and naloxone after administration of tilidine/naloxone solution or tilidine/naloxone sustained release tablets.

    PubMed

    Brennscheidt, U; Seiler, K U; Thomann, P

    2000-11-01

    Valoron N is a compound which consists of the prodrug tilidine (CAS 20380-58-9), from which the active metabolite nortilidine is formed by demethylation in the liver, and the opiate antagonist naloxone (CAS 465-65-6), which prevents the abuse of the analgesic by opiate dependents. The pharmacokinetics of nortilidine and naloxone were studied in 18 male healthy subjects after oral application of tilidine/naloxone solution or tilidine/naloxone retard tablets, respectively. The following report gives the results on investigations of a) dose linearity after application of 25 mg, 50 mg and 100 mg Valoron N solution, b) dose equivalence of Valoron N solution (4 x 50 mg tilidine) and Valoron N retard tablets (2 x 100 mg tilidine) under steady state conditions, and c) the equivalence of different dose strengths of Valoron N retard tablets (50 mg, 100 mg, 200 mg tilidine/tablet). The results obtained in these studies demonstrate a dose linear kinetic for nortilidine after the application of 25 mg to 100 mg tilidine. Furthermore, there is dose equivalence between the tilidine/naloxone solution and tilidine/naloxone retard tablets, which permits the replacing of the solution with the retard tablets. Because of the equivalence of different dose strengths of Valoron N tablets, patients are able to exchange low dosed Valoron N retard tablets for higher-dosed ones (50 mg, 100 mg and 200 mg tilidine/tablet), if necessary. With their constant release of tilidine and the possibility for individual dosage, the retard tablets are efficient analgesics that improve pain therapy considerably for patients with chronic pain. PMID:11148857

  16. Quaternary naltrexone reverses radiogenic and morphine-induced locomotor hyperactivity

    SciTech Connect

    Mickley, G.A.; Stevens, K.E.; Galbraith, J.A.; White, G.A.; Gibbs, G.L.

    1984-04-01

    The present study attempted to determine the relative role of the peripheral and central nervous system in the production of morphine-induced or radiation-induced locomotor hyperactivity of the mouse. Toward this end, we used a quaternary derivative of an opiate antagonist (naltrexone methobromide), which presumably does not cross the blood-brain barrier. Quaternary naltrexone was used to challenge the stereotypic locomotor response observed in these mice after either an i.p. injection of morphine or exposure to 1500 rads /sup 60/Co. The quaternary derivative of naltrexone reversed the locomotor hyperactivity normally observed in the C57BL/6J mouse after an injection of morphine. It also significantly attenuated radiation-induced locomotion. The data reported here support the hypothesis of endorphin involvement in radiation-induced and radiogenic behaviors. However, these conclusions are contingent upon further research which more fully evaluates naltrexone methobromide's capacity to cross the blood-brain barrier.

  17. Oral Herpes

    MedlinePLUS

    ... Dental and Craniofacial Research (NIDCR) Improving the Nation's Oral Health National Institutes of Health Español Staff Directory A– ... Index Search Text size: Website Contents NIDCR Home Oral Health Diseases and Conditions Gum Disease TMJ Disorders Oral ...

  18. [Effect of taixian tablet on hamster buccal pouch carcinogenesis].

    PubMed

    Duan, K; Zheng, G; Li, B

    1998-05-01

    Eighty syrian hamsters were divided into 4 equal groups. The right buccal pouches of hamsters in group I and group II were painted three times weekly with 0.5% DMBA dissolved in acetone, but the hamsters in group I received 0.45 g Taixian tablet daily by mouth. The animals in group III only received 0.45 g Taixian tablet daily and group IV was control group. After 9, 12 weeks, animals were killed with their pouches excised, and tumors were counted and measured. The results showed; 1. Comparing with group II, the malignant rate of group I was lower after 9 weeks and the tumor volume was smaller after 12 weeks (P < 0.01); 2. It was found histologically many inflammatory cells locating in the epithelial layer and lamina propria of group I after 9 weeks, while only a few inflammatory cells in group II. The high differentiated squamous cell carcinoma could be seen in group I and group II after 12 weeks, but no abnormal changes in cervical lymphnodes and organs (lung, liver, spleen, et al) of all animals in 4 groups. It suggests that Taixian tablet can restrain the development of oral carcinogenesis. PMID:12214411

  19. Prolonged morphine treatment alters ? opioid receptor post-internalization trafficking

    PubMed Central

    Ong, E W; Xue, L; Olmstead, M C; Cahill, C M

    2015-01-01

    BACKGROUND AND PURPOSE The ? opioid receptor (DOP receptor) undergoes internalization both constitutively and in response to agonists. Previous work has shown that DOP receptors traffic from intracellular compartments to neuronal cell membranes following prolonged morphine treatment. Here, we examined the effects of prolonged morphine treatment on the post-internalization trafficking of DOP receptors. EXPERIMENTAL APPROACH Using primary cultures of dorsal root ganglia neurons, we measured the co-localization of endogenous DOP receptors with post-endocytic compartments following both prolonged and acute agonist treatments. KEY RESULTS A departure from the constitutive trafficking pathway was observed following acute DOP receptor agonist-induced internalization by deltorphin II. That is, the DOP receptor underwent distinct agonist-induced post-endocytic sorting. Following prolonged morphine treatment, constitutive DOP receptor trafficking was augmented. SNC80 following prolonged morphine treatment also caused non-constitutive DOP receptor agonist-induced post-endocytic sorting. The ? opioid receptor (MOP receptor) agonist DAMGO induced DOP receptor internalization and trafficking following prolonged morphine treatment. Finally, all of the alterations to DOP receptor trafficking induced by both DOP and MOP receptor agonists were inhibited or absent when those agonists were co-administered with a DOP receptor antagonist, SDM-25N. CONCLUSIONS AND IMPLICATIONS The results support the hypothesis that prolonged morphine treatment induces the formation of MOP–DOP receptor interactions and subsequent augmentation of the available cell surface DOP receptors, at least some of which are in the form of a MOP/DOP receptor species. The pharmacology and trafficking of this species appear to be unique compared to those of its individual constituents. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24819092

  20. Oral Myiasis

    PubMed Central

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

    2015-01-01

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

  1. Interaction of prenatal stress and morphine alters prolactin and seizure in rat pups.

    PubMed

    Saboory, Ehsan; Ebrahimi, Loghman; Roshan-Milani, Shiva; Hashemi, Paria

    2015-10-01

    Prenatal exposure to stress and morphine has complicated effects on epileptic seizure. In the present study, effect of prenatal forced-swim stress and morphine co-administration on pentylenetetrazol (PTZ) induced epileptic behaviors and prolactin blood level (PBL) was investigated in rat offspring. Pregnant Wistar rats were divided to four groups of control-saline, control-morphine, stressed-saline and stressed-morphine. In the stressed group, pregnant rats were placed in 25°C water on gestation days 17, 18 and 19 (GD17, GD18 and GD19) for 30 min. In the morphine/saline group, pregnant rats received morphine (10, 12 and 15 mg/kg, IP, on GD17, GD18 and GD19, respectively) or saline (1 ml, IP). In the morphine/saline-stressed group, the rats received morphine or saline and then exposed to stress. On postnatal days 6 and 15 (P6 and P15), blood samples were obtained and PBL was determined. At P15 and P25, the rest of the pups was injected with PTZ to induce seizure. Then, epileptic behaviors of each rat were observed individually. Latency of first convulsion decreased in control-morphine and stressed-saline groups while increased in stressed-morphine rats compared to control-saline group on P15 (P=0.04). Number of tonic-clonic seizures significantly increased in control-morphine and stressed-saline rats compared to control-saline group at P15 (P=0.02). PBL increased in stressed-saline, control-morphine and stress-morphine groups compared to control-saline rats. It can be concluded that prenatal exposure of rats to forced-swim stress and morphine changed their susceptibility to PTZ-induced seizure and PBL during infancy and prepubertal period. Co-administration of morphine attenuated effect of stress on epileptic behaviors. PMID:26056076

  2. Pre-Emptive Morphine Analgesia Attenuates the Long-Term Consequences of Neonatal Inflammation in Male and Female Rats

    E-print Network

    Murphy, Anne Z.

    Pre-Emptive Morphine Analgesia Attenuates the Long-Term Consequences of Neonatal Inflammation-emptive morphine attenuates these negative consequences. At P0, pups received an injection of morphine sulfate (MS-emptive morphine significantly attenuated neonatal injury-induced hypoalgesia in adolescence and adulthood

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  5. Feasibility of double-blind clinical trials with oral diacetylmorphine: a randomized controlled phase II study in an inpatient setting.

    PubMed

    Colom Farran, Joan; Casas, Miguel; Pérez de Los Cobos, José; Del Río, Miquel; Roncero, Carlos; Castells, Xavier; Valero, Sergi; Eiroa-Orosa, Francisco José; Batlle, Francisca; Trujols, Joan

    2012-01-01

    The aim of this study was to evaluate the feasibility of conducting double-blind controlled randomized clinical trials using twice-a-day immediate-release oral diacetylmorphine (DAM) in heroin-dependent patients, by means of measuring the capacity of oral DAM to block opiate withdrawal and clinicians' ability to distinguish it from morphine and methadone. This was a randomized, phase II, double-blind, multicenter pilot study comparing immediate-release oral DAM, slow-release oral morphine and oral methadone administered twice a day during 10 days. Forty-five heroin-dependent patients were randomly assigned to these three treatment groups in an inpatient regime. Patients were stabilized with a mean of 350 mg (SD = 193) of immediate-release oral DAM, 108 mg (SD = 46.2) of slow-release oral morphine and 40 mg (SD = 17.9) of methadone. No statistically significant differences were found between any studied medication in clinical outcome. Neither patients nor clinicians were able to identify the administered medication. This study shows the feasibility of double-blind clinical trials using b.i.d. immediate-release oral DAM allowing further phase III clinical trials in the process of introducing oral DAM as a medication for heroin-dependent patients not responding to standard maintenance treatments. PMID:22854605

  6. Chronic SIV and morphine treatment increases heat shock protein 5 expression at the synapse.

    PubMed

    Pendyala, Gurudutt; Periyasamy, Palsamy; Callen, Shannon; Fox, Howard S; Lisco, Steven J; Buch, Shilpa J

    2015-10-01

    The abuse of opiates such as morphine in synergy with HIV infection accelerates neurocognitive impairments and neuropathology in the CNS of HIV-infected subjects, collectively referred to as HAND. To identify potential pathogenic markers associated with HIV and morphine in perturbing the synaptic architecture, we performed quantitative mass spectrometry proteomics on purified synaptosomes isolated from the caudate of two groups of rhesus macaques chronically infected with SIV differing by one regimen-morphine treatment. The upregulation of heat shock 70-kDa protein 5 in the SIV?+?morphine group points to increased cellular stress during SIV/morphine interaction thus leading to CNS dysfunction. PMID:26037114

  7. Bioavailability of ibuprofen from matrix mini-tablets based on a mixture of starch and microcrystalline wax.

    PubMed

    De Brabander, C; Vervaet, C; Görtz, J P; Remon, J P; Berlo, J A

    2000-11-01

    The bioavailability of ibuprofen from matrix mini-tablets based on microcrystalline wax and a starch derivative was tested. An oral dose of 300 mg of ibuprofen was administered to healthy volunteers (n=8) in a randomized cross-over study design either as a commercial matrix formulation (Ibu-Slow 600) or as mini-tablets (filled into hard gelatin capsules). The mini-tablets consisted of 60% ibuprofen, 15% Paracera M (wax), 22.5% DDWM (starch) and 2.5% triacetin (lubricant). t50% of the in vitro release was 4.5 and 5 h for the mini-tablet and Ibu-slow formulations, respectively. Both formulations behaved in vivo as sustained-release formulation; their HVDt50%Cmax value was determined at 5.6 and 5.1 h for the mini-tablet and Ibu-slow formulations, respectively. A significantly higher value of Cmax was seen for the mini-tablet formulation, resulting in a relative bioavailability of 116 +/- 22.6% compared to the Ibu-slow matrix. These data demonstrate that the experimental mini-tablets can be used to formulate sustained-release dosage forms. PMID:11203270

  8. Terbutaline slow-release tablets in children with asthma. A comparison with t.i.d. beta 2-agonist therapy.

    PubMed

    Croner, S; Gustafsson, M; Kjellman, N I; Säwedal, L

    1986-07-01

    The effects of 5 mg slow-release terbutaline sulphate tablets (Bricanyl Depot) given twice daily were compared with those of ordinary oral beta 2-agonist treatment given three times daily. The study was open, randomized and cross-over and was carried out over 8 weeks in 18 children with bronchial asthma. Compared with ordinary medication, the slow-release tablets obtained higher morning expiratory peak flow values and an improvement in the asthma symptoms during the night and during exercise (P less than 0.05). No differences were found in side effects in spite of a higher total daily dose during the period with terbutaline slow-release tablets. The slow-release tablets were preferred by 15 of 18 children and their families when the effects, side effects and dosage were evaluated. PMID:2876658

  9. Morphine with adjuvant ketamine versus higher dose of morphine alone for acute pain: a meta-analysis

    PubMed Central

    Ding, Xibing; Jin, Shuqing; Niu, Xiaoyin; Wang, Tingting; Zhao, Xiang; Ren, Hao; Tong, Yao; Li, Quan

    2014-01-01

    Purpose: Ketamine is currently the N-methyl-D-aspartate receptor channel blocker in clinical use. Morphine in pain management is usually limited by adverse effect such as nausea and vomiting. Adjuvant treatment with ketamine may be value in giving better analgesia with fewer adverse effects. The purpose of this meta-analysis was to evaluate the differences when patients received morphine with adjuvant ketamine (MK) compared with higher dose of morphine (MO) for acute pain. Methods: The PubMed, EMBASE and the Cochrane Library databases were searched (Last search performed on July 1, 2014) by two reviewers independently. Data were extracted independently by the same two individuals who searched the studies. Results: A total of 7 trials involving 492 patients were included in the current analysis. We found pain scores were lower in the MK group compared to the MO group [MD 2.19, 95% CI (1.24, 3.13) P<0.00001]. And more patients in the MO required diclofenac [OR 1.97, 95% CI (1.06, 3.67) P=0.03]. Furthermore, morphine plus ketamine can reduced post-operative nausea and vomiting (PONV) [OR 3.71, 95% CI (2.37, 5.80) P<0.00001]. Importantly, the wakefulness scores for the MK group were consistently and significantly better than those for the MO group [MD -1.53, 95% CI (-2.67, -0.40) P=0.008]. Conclusion: The use of ketamine plus 1/4~2/3 the dose of morphine is better than higher dose of morphine alone in reducing pain scores, and rescuing analgesic requirement. It also improved PONV and wakefulness. PMID:25356103

  10. Accuracy of tablet splitting: Comparison study between hand splitting and tablet cutter

    PubMed Central

    Habib, Walid A.; Alanizi, Abdulaziz S.; Abdelhamid, Magdi M.; Alanizi, Fars K.

    2013-01-01

    Background Tablet splitting is often used in pharmacy practice to adjust the administered doses. It is also used as a method of reducing medication costs. Objective To investigate the accuracy of tablet splitting by comparing hand splitting vs. a tablet cutter for a low dose drug tablet. Methods Salbutamol tablets (4 mg) were chosen as low dose tablets. A randomly selected equal number of tablets were split by hand and a tablet cutter, and the remaining tablets were kept whole. Weight variation and drug content were analysed for salbutamol in 0.1 N HCl using a validated spectrophotometric method. The percentages by which each whole tablet’s or half-tablet’s drug content and weight difference from sample mean values were compared with USP specification ranges for drug content. The %RSD was also calculated in order to determine whether the drugs met USP specification for %RSD. The tablets and half tablets were scanned using electron microscopy to show any visual differences arising from splitting. Results 27.5% of samples differed from sample mean values by a percentage that fell outside of USP specification for weight, of which 15% from the tablet cutter and 25% from those split by hand fell outside the specifications. All whole tablets and half tablets met the USP specifications for drug content but the variation of content between the two halves reached 21.3% of total content in case of hand splitting, and 7.13% only for the tablet cutter. The %RSDs for drug content and weight met the USP specification for whole salbutamol tablets and the half tablets which were split by tablet cutter. The halves which were split by hand fell outside the specification for %RSD (drug content = 6.43%, weight = 8.33%). The differences were visually clear in the electron microscope scans. Conclusion Drug content variation in half-tablets appeared to be attributable to weight variation occurring during the splitting process. This could have serious clinical consequences for medications with a narrow therapeutic-toxic range. On the basis of our results, we recommend to avoid tablet splitting whenever possible or the use of an accurate tablet splitting device when splitting cannot be avoided. PMID:25473334

  11. Morphine/Codeine Ratio, a Key in Investigating a Case of Doping

    PubMed Central

    Seif-Barghi, Tohid; Moghadam, Navid; Kobarfard, Farzad

    2015-01-01

    Introduction: Consumption of codeine can lead to positive urine test for morphine in athletes. Morphine is classified as a prohibited doping drug while Codeine is not. Morphine/codeine ratio is used in forensic medicine to distinguish the consumption of codeine from abuse of morphine and other narcotics. Case Presentation: We present an athlete with positive urine test for morphine with a history of consumption of codeine. The disciplinary committee came to conclusion that the athlete had not consumed morphine and did not violate doping code based on morphine/codeine ratio. Conclusions: Analysis of codeine to morphine metabolism rate is needed when we are using morphine/codeine ratio to rule out abuse of narcotics. WADA should consider analysis for the CYP2D6 alleles (main metabolizer of codeine) in case of including morphine/codeine ratio in future prohibited list. The possibility of ultra-rapid CYP2D6 cannot be ruled out in certain results of morphine/codeine near the cut point. PMID:26715976

  12. Single-dose evaluation of safety, tolerability and pharmacokinetics of newly formulated hydromorphone immediate-release and hydrophilic matrix extended-release tablets in healthy Japanese subjects without co-administration of an opioid antagonist.

    PubMed

    Toyama, Kaoru; Uchida, Naoki; Ishizuka, Hitoshi; Sambe, Takehiko; Kobayashi, Shinichi

    2015-09-01

    This single dose, open-label study investigated the safety, tolerability and pharmacokinetics of single oral doses of newly formulated immediate-release (IR) and hydrophilic matrix extended-release (ER) hydromorphone tablets in healthy Japanese subjects without co-administration of an opioid antagonist under fasting and fed conditions. Plasma and urinary concentrations of hydromorphone and metabolites were measured by liquid-chromatography tandem mass-spectroscopy. Following administration of the ER tablet, plasma concentrations of hydromorphone slowly increased with a median tmax of 5.0?h and the Cmax decreased to 37% of the IR tablet, while the AUC0-inf was comparable with that of the IR tablet when administered at the same dose. The degree of fluctuation in the plasma concentration for the ER tablet was much lower than that of the IR tablet and certain levels of plasma concentrations were maintained after 24?h of ER dosing. The AUC0-inf and Cmax increased with food for both IR and ER tablets. The AUC0-inf of hydromorphone-3-glucoside was one-tenth of that of hydromorphone-3-glucuronide. A single oral administration of the hydromorphone tablets would be well-tolerated in healthy Japanese subjects despite a lack of co-administration of an opioid antagonist and the newly developed ER hydromorphone tablets may have the appropriate PK characteristics for once-daily dosing. PMID:25807927

  13. Role of dorsal hippocampal orexin-1 receptors in memory restoration induced by morphine sensitization phenomenon.

    PubMed

    Alijanpour, S; Tirgar, F; Zarrindast, M-R

    2016-01-15

    The present study was examined the blockade of CA1 orexin-1 receptors (OX1Rs) of the dorsal hippocampus in the induction or expression phase on morphine sensitization-induced memory restoration using the Morris water maze (MWM) apparatus. Results showed that pre-training administration of morphine (5mg/kg, s.c.) increases escape latency and traveled distance, while does not alter swimming speed. This supports the impairing effect of morphine on the spatial memory acquisition in male adult rats. Also, in the retrieval session (probe trial) this treatment decreased the time spent in the target quadrant. Moreover, morphine-induced sensitization (15 or 20mg/kg, s.c.; once daily for 3days and followed by 5days no drug treatment) restored the memory acquisition/retrieval deficit which had been induced by pre-training administration of morphine (5mg/kg, s.c.). Intra-CA1 microinjection of subthreshold doses of SB-334867 (OX1Rs antagonist; 10, 20 and 40nmol/rat), 5min before morphine (20mg/kg/day×3days, s.c.; induction phase for morphine sensitization) did not alter restoration of memory acquisition/retrieval produced by the morphine sensitization phenomenon. In contrast, microinjection of subthreshold doses of SB-334867 (10, 20 and 40nmol/rat) into the CA1 region in the training session, 5min prior to morphine (5mg/kg, s.c.; expression phase for morphine sensitization) blocked the spatial memory acquisition/retrieval in morphine-sensitized rats. In conclusion, these findings show that morphine sensitization reverses morphine-induced amnesia. Furthermore, the blockade of CA1 OX1Rs in the expression phase, but not in the induction phase, disrupts memory restoration induced by morphine sensitization. PMID:26592714

  14. The effects of serotonin/norepinephrine reuptake inhibitors and serotonin receptor agonist on morphine analgesia and tolerance in rats.

    PubMed

    Ozdemir, Ercan; Gursoy, Sinan; Bagcivan, Ihsan

    2012-07-01

    Several studies have demonstrated that serotonergic and noradrenergic systems have important roles in morphine analgesia and tolerance. However, the exact mechanism underlying the development of morphine tolerance is not fully understood. The aim of this study was to investigate the possible role of serotonin/norepinephrine reuptake inhibitors (amitriptyline, venlafaxine) and serotonin receptor (5-HT(1A) and 5-HT(1B/1D)) agonist (dihydroergotamine) in morphine analgesia and tolerance in rats. To constitute morphine tolerance, animals received morphine (50 mg/kg; s.c.) once daily for 3 days. After the last dose of morphine was injected on day 4, morphine tolerance was evaluated. The analgesic effects of amitriptyline (20 mg/kg; i.p.), venlafaxine (20 mg/kg; s.c.), dihydroergotamine (100 ?g/kg; i.v.) and morphine (5 mg/kg) were considered at 15- to 30-min intervals (0, 15, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests. In this study, the data obtained suggested that amitriptyline and venlafaxine significantly increased the analgesic effect of morphine and attenuated the expression of morphine tolerance. However, dihydroergotamine significantly increased the analgesic effect of morphine but did not reduce the expression of morphine tolerance. In conclusion, we determined that co-administration of morphine with amitriptyline and venlafaxine increased the analgesic effects of morphine and attenuated the morphine analgesic tolerance. PMID:22544464

  15. Morphine-augmented cholescintigraphy in the diagnosis of acute cholecystitis

    SciTech Connect

    Kim, E.E.; Pjura, G.; Lowry, P.; Nguyen, M.; Pollack, M.

    1986-12-01

    Cholescintigraphy is a sensitive procedure for diagnosing or excluding acute cholecystitis. However, when rapid diagnosis is critical, the requirement for delayed images (4 hr or more after injection) to minimize the false-positive rate diminishes its utility. We prospectively evaluated 40 cholescintigraphic examinations that did not visualize the gallbladder 1 hr after injection of 99mTc diisopropyliminodiacetic acid. These examinations were then augmented by administration of IV morphine, followed by an additional 30 min of imaging. After the morphine, 18 of these examinations demonstrated visualization of the gallbladder; none subsequently required surgical exploration. Of the remaining 22, who demonstrated persistent nonvisualization of the gallbladder post-morphine, 11 were explored surgically and found to be abnormal. The 11 others were treated medically. Low-dose morphine administered when the gallbladder fails to visualize after 1 hr is a useful adjunct to conventional cholescintigraphy because it reduces the time required to obtain a diagnostic result and decreases the number of false-positive results.

  16. Use of morphine in cholescintigraphy for obstructive cholecystitis

    SciTech Connect

    Kim, E.E.; Nguyen, M.; Pjura, G.; Pollack, M.; Gobuty, A.

    1985-05-01

    Non-visualization of the gallbladder (GB) during the first hour of cholescintigraphy is observed in cystic duct obstruction (e.g. in acute cholecystitis) but may also occur in chronic cholecystitis, hepatocellular disease, alcoholism and prolonged total parenteral nutrition. Low dose morphine is shown to improve the specificity of the diagnosis of acute cholecystitis (from 85% to 100%) with no loss in sensitivity (98%) at a small cost in terms of additional study time. The authors reviewed 27 selected cholescintigraphic examinations augmented by intravenous (IV) morphine (0.04 mg/Kg). Of the 16 cases with persistent nonvisualization of the GB, ultrasound revealed gallstones in 5 cases, sludge in 4, acalculous cholecystitis in 3, one distended GB, one contracted GB and 2 normal GB's. Of the 4 patients taken to surgery, one with gallstones and one with acalculous cholecystitis were confirmed to have acute cholecystitis while another with gallstones had chronic cholecystitis and the final patient, who was sonographically normal, presented a single common duct stone. The authors conclude that the use of IV morphine is an effective adjunct to cholescintigraphy in the evaluation of gallbladder disease, especially when visualization post morphine rules out acute cholecystitis.

  17. Morphine stimulates nitric oxide release in human mitochondria.

    PubMed

    Stefano, George B; Mantione, Kirk J; Capellan, Lismary; Casares, Federico M; Challenger, Sean; Ramin, Rohina; Samuel, Joshua M; Snyder, Christopher; Kream, Richard M

    2015-10-01

    The expression of morphine by plants, invertebrate, and vertebrate cells and organ systems, strongly indicates a high level of evolutionary conservation of morphine and related morphinan alkaloids as required for life. The prototype catecholamine, dopamine, serves as an essential chemical intermediate in morphine biosynthesis, both in plants and animals. We surmise that, before the emergence of specialized plant and animal cells/organ systems, primordial multi-potential cell types required selective mechanisms to limit their responsiveness to environmental cues. Accordingly, cellular systems that emerged with the potential for recruitment of the free radical gas nitric oxide (NO) as a multi-faceted autocrine/paracrine signaling molecule, were provided with extremely positive evolutionary advantages. Endogenous morphinergic signaling, in concert with NO-coupled signaling systems, has evolved as an autocrine/paracrine regulator of metabolic homeostasis, energy metabolism, mitochondrial respiration and energy production. Basic physiological processes involving morphinergic/NO-coupled regulation of mitochondrial function, with special emphasis on the cardiovascular system, are critical to all organismic survival. Key to this concept may be the phenomenon of mitochondrial enslavement in eukaryotic evolution via endogenous morphine. PMID:26350413

  18. Site and mechanism of morphine tolerance in the gastrointestinal tract

    PubMed Central

    AKBARALI, H. I.; INKISAR, A.; DEWEY, W. L.

    2015-01-01

    Opioid-induced constipation is a major clinical problem. The effects of morphine, and other narcotics, on the gastrointestinal tract persist over long-term use thus limiting the clinical benefit of these excellent pain relievers. The effects of opioids in the gut, including morphine, are largely mediated by the ?-opioid receptors at the soma and nerve terminals of enteric neurons. Recent studies demonstrate that regional differences exist in both acute and chronic morphine along the gastrointestinal tract. While tolerance develops to the analgesic effects and upper gastrointestinal motility upon repeated morphine administration, tolerance does not develop in the colon with chronic opioids resulting in persistent constipation. Here, we review the mechanisms by which tolerance develops in the small but not the large intestine. The regional differences lie in the signaling and regulation of the ?opioid receptor in the various segments of the gastrointestinal tract. The differential role of ?-arrestin2 in tolerance development between central and enteric neurons defines the potential for therapeutic approaches in developing ligands with analgesic properties and minimal constipating effects. PMID:25257923

  19. [Oral dosage forms for children: acceptability and palatability].

    PubMed

    Kojima, Jun

    2015-01-01

    Children generally reject taking medicine which does not have a favorable shape, taste, flavor, etc. However, if a child who needs to take a medicine, rejects taking it, he might never recover from his condition. When a child is unable to take medicine orally, it is intravenously administered, and he and his caregivers then may experience stress. Syrups and suspensions are considered as favorable types of dosage forms in which to orally administer medicine to infants and children. However, they may have disadvantages such as solubility, a bad taste, portability problems or required refrigerator storage. World Health Organization (WHO) currently favors that infants and children be treated with oral solid medicines. New oral solid tablets, such as a mini-tablet, instead of liquid medicines are proposed for this group, however, there are a few reports that mini-tablets are suitable for infants and children. Palatability is one of the main elements of patient acceptability of an oral pediatric medicine. Palatability is defined as the overall appreciation of an oral medicinal product in relation to its smell, taste, aftertaste and feeling in the mouth. Design of the formulation of an oral pediatric medicine should be considered together with its palatability. PMID:25747220

  20. Influence of fentanyl and morphine on intestinal circulation

    SciTech Connect

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-06-01

    The influence of fentanyl and morphine on the intestinal circulation was evaluated in an isolated loop preparation in 37 dogs anesthetized with pentobarbital intravenously. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mm Hg. A mixture of /sup 86/Rb and 9-micron spheres labeled with /sup 141/Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A strong correlation was found between the clearances of rubidium and microspheres (r = 0.97, P less than 0.0001), suggesting that the shunting of 9-micron spheres through the intestines reflects the shunting of blood through nonnutritive vessels. Intravenous fentanyl decreased oxygen uptake (O/sub 2/up), and vascular resistance (VR), and increased blood flow (BF), rubidium and microsphere clearances (Cl-Rb, Cl-Sph, respectively), and permeability--surface area product (PS) in a dose-related fashion. Intravenous morphine in a dose of 1 mg X kg-1 increased Cl-Rb (nutritive BF) without changes in total (nutritive and nonnutritive) BF. This increase in nutritive BF is probably related to morphine-induced histamine release. Morphine in a dose of 5 mg X kg-1 was accompanied by vasoconstriction that was completely abolished by alpha-adrenoceptor blockade. The data suggest that morphine-induced intestinal vasoconstriction is mediated via a release of epinephrine, apparently from the adrenal medulla. It is concluded that changes in the intestinal circulation during anesthesia with narcotics might play a certain role in the cardiovascular homeostasis during anesthesia and surgery. An increase in oxygen content in portal venous blood, resulting from a decrease in intestinal oxygen uptake, should facilitate hepatic oxygenation.

  1. Formulation of a modified-release pregabalin tablet using hot-melt coating with glyceryl behenate.

    PubMed

    Jeong, Kyu Ho; Woo, Hye Seung; Kim, Chae Jin; Lee, Kyung Hwa; Jeon, Jun Young; Lee, Sang Young; Kang, Jae-Hoon; Lee, Sangkil; Choi, Young Wook

    2015-11-10

    A modified-release (MR) tablet of the anti-anxiety drug pregabalin (PRE) was prepared by hot-melt coating PRE with glyceryl behenate (GB) as a release retardant and compressing to form a matrix with microcrystalline cellulose (MCC) as a hydrophilic diluent. GB-coated PRE had a size in the range of 177-290?m with good to acceptable flowability. Tablet hardness decreased slightly as GB content increased. PRE release from the tablet matrices was successfully modified by altering the ratio of MCC and GB, and it was found that dissolution- or diffusion-controlled release depended on the amount of GB used. Drug release was pH-independent. An accelerated stability test on the most promising MR tablet at 40°C and 75% relative humidity for 6 months showed no significant changes in PRE content, and the occurrence of total impurities-including PRE-lactam-was within acceptable limits. After oral administration of the selected MR tablet or a commercial IR capsule (Lyrica) to healthy human volunteers, pharmacokinetic parameters including Tmax, Cmax, AUC0-24, and T1/2 were compared. The confidence interval of AUC0-24 was within the adequate range, but that of Cmax was inadequate. This study demonstrated the potential use of GB for PRE-containing MR formulations. PMID:26315121

  2. Dissolution of theophylline from film-coated slow release mini-tablets in various dissolution media.

    PubMed

    Fassihi, A R; Munday, D L

    1989-06-01

    The dissolution of an experimental formulation of film-coated slow release theophylline mini-tablets has been investigated using the USP paddle apparatus in test media at pH 1.2 (hydrochloric acid), pH 5.4 and 7.4 (phosphate buffers) at 37 degrees C. Monitoring of in-vitro theophylline release over 12 h, under identical hydrodynamic conditions, showed that the dissolution rate at pH 1.2 is substantially greater (95% of total drug content released in less than 10 h) than that in phosphate buffers. The maximum release after 12 h was approximately 20 and 30% of total drug content of the tablet at pH 5.4 and 7.4, respectively. However, in vivo bioavailability after oral administration of tablets to rabbits corresponded to over 95% of total drug, compared with the same dose administered intravenously. The retarded drug release during in-vitro dissolution in phosphate buffer was attributed to a possible interaction of phosphate ions with theophylline molecules at the tablet core-coat interface. These findings indicate that both rate and extent of theophylline release from the slow release coated mini-tablets are highly sensitive to phosphate buffers. The data also emphasize the usefulness of an animal model for assessment of in-vivo drug release and subsequent absorption, during the development of modified release dosage forms. PMID:2570830

  3. Formulation and in-vitro evaluation of floating bilayer tablet of lisinopril maleate and metoprolol tartrate.

    PubMed

    Ijaz, Hira; Qureshi, Junaid; Danish, Zeeshan; Zaman, Muhammad; Abdel-Daim, Mohamed; Hanif, Muhammad; Waheed, Imran; Mohammad, Imran Shair

    2015-11-01

    The purpose of this study was to introduce the technology for the development of rate-controlled oral drug delivery system to overcome various physiological problems. Several approaches are being used for the purpose of increasing the gastric retentive time, including floating drug delivery system. Gastric floating lisinopril maleate and metoprolol tartrate bilayer tablets were formulated by direct compression method using the sodium starch glycolate, crosscarmellose sodium for IR layer. Eudragit L100, pectin, acacia as sustained release polymers in different ratios for SR metoprolol tartrate layer and sodium bicarbonate, citric acid as gas generating agents for the floating extended release layer. The floating bilayer tablets of lisinopril maleate and metoprolol tartrate were designed to overcome the various problems associated with conventional oral dosage form. Floating tablets were evaluated for floating lag time, drug contents and in-vitro dissolution profile and different kinetic release models were applied. It was clear that the different ratios of polymers affected the drug release and floating time. L2 and M4 showed good drug release profile and floating behavior. The linear regression and model fitting showed that all formulation followed Higuchi model of drug release model except M4 that followed zero order kinetic. From the study it is evident that a promising controlled release by floating bilyer tablets of lisinopril maleate and metoprolol tartrate can be developed successfully. PMID:26639495

  4. 21 CFR 520.1696d - Penicillin V tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  5. 21 CFR 520.1696d - Penicillin V tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  6. 21 CFR 520.1696d - Penicillin V potassium tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...2010-04-01 false Penicillin V potassium tablets. 520.1696d Section...DRUGS § 520.1696d Penicillin V potassium tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125...

  7. 21 CFR 520.1696d - Penicillin V potassium tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...2011-04-01 false Penicillin V potassium tablets. 520.1696d Section...DRUGS § 520.1696d Penicillin V potassium tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125...

  8. 21 CFR 520.1696d - Penicillin V potassium tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...2012-04-01 false Penicillin V potassium tablets. 520.1696d Section...DRUGS § 520.1696d Penicillin V potassium tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125...

  9. 21 CFR 520.1284 - Sodium liothyronine tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...2013-04-01 2013-04-01 false Sodium liothyronine tablets. 520.1284 Section...DOSAGE FORM NEW ANIMAL DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of...

  10. 21 CFR 520.1284 - Sodium liothyronine tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...2011-04-01 2011-04-01 false Sodium liothyronine tablets. 520.1284 Section...DOSAGE FORM NEW ANIMAL DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of...

  11. 21 CFR 520.1284 - Sodium liothyronine tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...2014-04-01 2014-04-01 false Sodium liothyronine tablets. 520.1284 Section...DOSAGE FORM NEW ANIMAL DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of...

  12. 21 CFR 520.1284 - Sodium liothyronine tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...2010-04-01 2010-04-01 false Sodium liothyronine tablets. 520.1284 Section...DOSAGE FORM NEW ANIMAL DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of...

  13. 21 CFR 520.1284 - Sodium liothyronine tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...2012-04-01 2012-04-01 false Sodium liothyronine tablets. 520.1284 Section...DOSAGE FORM NEW ANIMAL DRUGS § 520.1284 Sodium liothyronine tablets. (a) Specifications. Sodium liothyronine tablets consist of...

  14. Memory impairment and reduced exploratory behavior in mice after administration of systemic morphine.

    PubMed

    Kitanaka, Junichi; Kitanaka, Nobue; Hall, F Scott; Fujii, Mei; Goto, Akiko; Kanda, Yusuke; Koizumi, Akira; Kuroiwa, Hirotoshi; Mibayashi, Satoko; Muranishi, Yumi; Otaki, Soichiro; Sumikawa, Minako; Tanaka, Koh-Ichi; Nishiyama, Nobuyoshi; Uhl, George R; Takemura, Motohiko

    2015-01-01

    In the present study, the effects of morphine were examined on tests of spatial memory, object exploration, locomotion, and anxiety in male ICR mice. Administration of morphine (15 or 30 mg/kg, intraperitoneally (i.p.)) induced a significant decrease in Y-maze alternations compared to saline vehicle-treated mice. The reduced Y-maze alternations induced by morphine were completely blocked by naloxone (15 mg/kg) or ?-funaltrexamine (5 mg/kg) but not by norbinaltorphimine (5 mg/kg) or naltrindole (5 mg/kg), suggesting that the morphine-induced spatial memory impairment was mediated predominantly by ?-opioid receptors (MOPs). Significant spatial memory retrieval impairments were observed in the Morris water maze (MWM) in mice treated with morphine (15 mg/kg) or scopolamine (1 mg/kg), but not with naloxone or morphine plus naloxone. Reduced exploratory time was observed in mice after administration of morphine (15 mg/kg), in a novel-object exploration test, without any changes in locomotor activity. No anxiolytic-like behavior was observed in morphine-treated mice in the elevated plus maze. A significant reduction in buried marbles was observed in morphine-treated mice measured in the marble-burying test, which was blocked by naloxone. These observations suggest that morphine induces impairments in spatial short-term memory and retrieval, and reduces exploratory behavior, but that these effects are not because of overall changes in locomotion or anxiety. PMID:25987850

  15. Myoelectric activity of the small intestine during morphine dependence and withdrawal in rats

    SciTech Connect

    Kuperman, D.A.; Sninsky, C.A.; Lynch, D.F.

    1987-04-01

    The authors investigated (1) the effect of morphine dependence on the migrating myoelectric complex (MMC) of the small intestine, (2) whether bacterial overgrowth developed in morphine-dependent rats, and (3) the effect of naloxone and methylbromide naltrexone, a peripheral opioid antagonist, on the MMC in morphine-naive and morphine-dependent rats. They also evaluated intestinal motility during naloxone-induced withdrawal in animals pretreated with clonidine. Intestinal myoelectric activity was monitored by four indwelling electrodes in unanesthetized, fasted rats. D-(/sup 14/C)xylose breath tests were performed before and after morphine-pellet implantation to evaluate the presence of bacterial overgrowth of the small intestine. Naloxone had no effect on myoelectric activity of the small intestine in morphine-naive rats. Cycling activity fronts were present in morphine-dependent animals, but there was a significant prolongation of activity front periodicity and slowing of the propagation velocity. No significant increase in /sup 14/CO/sub 2/ excretion was noted in the morphine-dependent rats. They conclude from their studies that (1) myoelectric activity of the small intestine develops incomplete tolerance to morphine; (2) bacterial overgrowth is not a feature of morphine dependence in the rat; (3) alterations of intestinal myoelectric activity are a component of the opiate withdrawal syndrome, and they appear at least partially mediated by a peripheral mechanism that can be suppressed by an ..cap alpha../sub 2/-adrenergic agonist.

  16. Memory Impairment and Reduced Exploratory Behavior in Mice after Administration of Systemic Morphine

    PubMed Central

    Kitanaka, Junichi; Kitanaka, Nobue; Hall, F Scott; Fujii, Mei; Goto, Akiko; Kanda, Yusuke; Koizumi, Akira; Kuroiwa, Hirotoshi; Mibayashi, Satoko; Muranishi, Yumi; Otaki, Soichiro; Sumikawa, Minako; Tanaka, Koh-ichi; Nishiyama, Nobuyoshi; Uhl, George R; Takemura, Motohiko

    2015-01-01

    In the present study, the effects of morphine were examined on tests of spatial memory, object exploration, locomotion, and anxiety in male ICR mice. Administration of morphine (15 or 30 mg/kg, intraperitoneally (i.p.)) induced a significant decrease in Y-maze alternations compared to saline vehicle-treated mice. The reduced Y-maze alternations induced by morphine were completely blocked by naloxone (15 mg/kg) or ?-funaltrexamine (5 mg/kg) but not by norbinaltorphimine (5 mg/kg) or naltrindole (5 mg/kg), suggesting that the morphine-induced spatial memory impairment was mediated predominantly by ?-opioid receptors (MOPs). Significant spatial memory retrieval impairments were observed in the Morris water maze (MWM) in mice treated with morphine (15 mg/kg) or scopolamine (1 mg/kg), but not with naloxone or morphine plus naloxone. Reduced exploratory time was observed in mice after administration of morphine (15 mg/kg), in a novel-object exploration test, without any changes in locomotor activity. No anxiolytic-like behavior was observed in morphine-treated mice in the elevated plus maze. A significant reduction in buried marbles was observed in morphine-treated mice measured in the marble-burying test, which was blocked by naloxone. These observations suggest that morphine induces impairments in spatial short-term memory and retrieval, and reduces exploratory behavior, but that these effects are not because of overall changes in locomotion or anxiety. PMID:25987850

  17. Efficacy and Safety of Ropivacaine Addition to Intrathecal Morphine for Pain Management in Intractable Cancer

    PubMed Central

    Huang, Ying; Li, Xihan; Zhu, Tong; Lin, Jian; Tao, Gaojian

    2015-01-01

    Objective. Although intrathecal drug infusion has been commonly adopted for terminal cancer pain relief, its adverse effects have made many clinicians reluctant to employ it for intractable cancer pain. The objective of this study is to compare the efficacy and security of an intrathecal continuous infusion of morphine and ropivacaine versus intrathecal morphine alone for cancer pain. Methods. Thirty-six cancer patients received either a continuous morphine (n = 19) or morphine and ropivacaine (n = 17) infusion using an intrathecal catheter through a subcutaneous port. Numerical Rating Scale (NRS) scores and the Barthel Index were analyzed. Adverse effects and complications on postoperative days 1, 3, 7, and 15 were also analyzed. Results. All patients experienced pain relief. Compared to those who received morphine alone, patients receiving morphine and ropivacaine had significantly lower postoperative morphine requirements and higher Barthel Index scores on the 15th postsurgical day (P < 0.05). Patients receiving morphine and ropivacaine had lower NRS scores than patients receiving morphine alone on postoperative days 1, 3, 7, and 15 (P < 0.05). Negative postsurgical effects were similar in both groups. Conclusions. Morphine and ropivacaine administration through intrathecal access ports is efficacious and safe and significantly improves quality of life. PMID:26556955

  18. BiP, an endoplasmic reticulum chaperone, modulates the development of morphine antinociceptive tolerance

    PubMed Central

    Dobashi, Tamae; Tanabe, Serabi; Jin, Hisayo; Mimura, Naoya; Yamamoto, Tatsuo; Nishino, Takashi; Aoe, Tomohiko

    2010-01-01

    Abstract Morphine is a potent analgesic, but the molecular mechanism for tolerance formation after repeated use is not fully understood. Binding immunoglobulin protein (BiP) is an endoplasmic reticulum (ER) chaperone that is central to ER function. We examined knock-in mice expressing a mutant BiP with the retrieval sequence deleted in order to elucidate physiological processes that are sensitive to BiP functions. We tested the thermal antinociceptive effect of morphine in heterozygous mutant BiP mice in a hot plate test. Paw withdrawal latencies before and after a single administration of morphine were not significantly different between the wild-type and mutant BiP mice. Repeated morphine administration caused the development of morphine tolerance in the wild-type mice. The activation of glycogen synthase kinase 3b (GSK-3b) was associated with morphine tolerance, because an inhibitor of GSK-3? prevented it. On the other hand, the mutant BiP mice showed less morphine tolerance, and the activation of GSK-3b was suppressed in their brain. These results suggest that BiP may play an important role in the development of morphine tolerance. Furthermore, we found that a chemical chaperone which improves ER protein folding capacity also attenuated the development of morphine tolerance in wild-type mice, suggesting a possible clinical application of chemical chaperones in preventing morphine tolerance. PMID:19818092

  19. 21 CFR 201.306 - Potassium salt preparations intended for oral ingestion by man.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...2014-04-01 2014-04-01 false Potassium salt preparations intended for oral ingestion...Specific Drug Products § 201.306 Potassium salt preparations intended for oral ingestion...marketing of coated tablets containing potassium chloride or other potassium salts...

  20. 21 CFR 201.306 - Potassium salt preparations intended for oral ingestion by man.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...2010-04-01 2010-04-01 false Potassium salt preparations intended for oral ingestion...Specific Drug Products § 201.306 Potassium salt preparations intended for oral ingestion...marketing of coated tablets containing potassium chloride or other potassium salts...

  1. 21 CFR 201.306 - Potassium salt preparations intended for oral ingestion by man.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...2012-04-01 2012-04-01 false Potassium salt preparations intended for oral ingestion...Specific Drug Products § 201.306 Potassium salt preparations intended for oral ingestion...marketing of coated tablets containing potassium chloride or other potassium salts...

  2. 21 CFR 201.306 - Potassium salt preparations intended for oral ingestion by man.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...2011-04-01 2011-04-01 false Potassium salt preparations intended for oral ingestion...Specific Drug Products § 201.306 Potassium salt preparations intended for oral ingestion...marketing of coated tablets containing potassium chloride or other potassium salts...

  3. 21 CFR 201.306 - Potassium salt preparations intended for oral ingestion by man.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...2013-04-01 2013-04-01 false Potassium salt preparations intended for oral ingestion...Specific Drug Products § 201.306 Potassium salt preparations intended for oral ingestion...marketing of coated tablets containing potassium chloride or other potassium salts...

  4. Content uniformity of potent drugs in tablets.

    PubMed

    Orr, N A; Sallam, E A

    1978-12-01

    The type of distribution of low dosage drugs that occurs in batches of commercially available tablets has been examined. The uniformity of content of ethinyloestradiol tablets 10 micrograms B.P. from different sources, assessed by single tablet assay showed that three batches exhibited some positive skewness and one marked positive skewness. At the high level of dilution required, the mixing theory indicates that particles of drug must be very fine if acceptable content uniformity is to be obtained. Cohesion of particles impairs the efficiency of the mixing process. It is shown theoretically that unless the drug is dispersed into its component particles the shape of the distribution curve for the content of drug per tablet, in a batch of tablets, will be positively skewed. The relation between the tensile strength of the powdered drug and the degree of skewness of the drug content is also discussed. A positively skewed distribution for tablets containing a small amount of potent drug is unacceptable because this can lead to the presence of relatively large doses of drug in a single tablet. Where one unexpectedly high result occurs in the quality control of the content uniformity of tablets containing potent drugs it is suggested that sufficient single tablet assays be performed to allow the shape of the distribution curve to be assessed. A test for skewness should be included in compendial standards. PMID:32236

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

    PubMed

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

    2010-09-01

    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

  6. The effect of chitosan on the stability and morphological parameters of tablets with Epilobium parviflorum Schreb. extract.

    PubMed

    Marczy?ski, Zbigniew; Bodek, Kazimiera Henryka

    2007-01-01

    The study is a continuation of research on manufacturing oral solid drug form containing extract from Epilobium parviflorum Schreb. This study aims at investigating the usefulness of selected high-molecular substances with particular consideration of chitosan (Ch), silicified microcrystalline cellulose (Prosolv) and croscarmellose sodium (Vivasol) as a carrier of E. parviflorum Schreb. extract in oral solid drug form in the process of direct tableting. In one series the alternative technological process (with initial granulation) was applied. The polymer carriers of extract were selected so as to obtain shorter disintegration time in relation to the earlier published studies and stability after longer time of storage. The effect of chitosan was estimated on selected morphological parameters of practical relevance during storage. The obtained results allow to state that the applied high-molecular adjuvant substances proved to be useful in adequate proportions in the production of tablets from dry extract from Epilobium parviflorum Schreb. through direct pressing of the tablet mass. The tablet properties in all series were in accordance with obligatory standards also after longer time of storage (12-month). The tablets formed from E. parviflorum Schreb. extract with chitosan can be included into preparations of sustained release time of the biologically active substances. PMID:18251200

  7. Memantine and dizocilpine interactions with antinociceptive or discriminative stimulus effects of morphine in rats after acute or chronic treatment with morphine

    PubMed Central

    Chen, Yukun; Evola, Marianne

    2013-01-01

    Rationale Memantine is a N-methyl-d-aspartic acid receptor (NMDAR) channel blocker that binds to dizocilpine sites and appears well tolerated during chronic use. Published studies suggest NMDAR antagonists prevent development of tolerance to effects of morphine by blocking NMDAR hyperactivation. Objectives We sought to compare effects of memantine to those of the more frequently studied dizocilpine and to evaluate memantine as a potential adjunct to modify tolerance to mu-opioid receptor agonists. Methods Sprague–Dawley rats were trained to discriminate morphine (3.2 mg/kg) and saline under fixed ratio 15 schedules of food delivery. Potency and maximal stimulus or rate-altering effects of cumulative doses of morphine were examined 30 min after pretreatment with dizocilpine (0.032–0.1 mg/kg) or memantine (5–10 mg/kg) and after chronic treatment with combinations of dizocilpine or memantine and morphine, 10 mg/kg twice daily, for 6 to 14 days. Effects of dizocilpine or memantine on morphine antinociception were examined in a 55 °C water tail-withdrawal assay with drug treatments parallel to those in discrimination studies. Results Acutely, memantine attenuated while dizocilpine potentiated the stimulus and antinociceptive effects of morphine. Neither chronic dizocilpine nor memantine blocked tolerance to the stimulus effects of morphine. In contrast, combined-treatment with dizocilpine (0.1 mg/kg) blocked tolerance to antinociceptive effects of lower (0.1?3.2 mg/kg) but not higher doses of morphine, whereas memantine did not block tolerance. Conclusions Memantine and dizocilpine interacted differently with morphine, possibly due to different NMDAR binding profiles. The lack of memantine-induced changes in morphine tolerance suggests memantine may not be a useful adjunct in chronic pain management. PMID:22864944

  8. Morphine and methadone pre-exposures differently modify brain regional Fos protein expression and locomotor activity responses to morphine challenge in the rat.

    PubMed

    Taracha, Ewa; Chrapusta, Stanis?aw J; Lehner, Ma?gorzata; Skórzewska, Anna; Maciejak, Piotr; Szyndler, Janusz; P?a?nik, Adam

    2008-09-01

    Methadone is commonly used in substitution therapy of heroin addicts; hence, its potential for modifying reactions to opiates is of clinical importance. We compared the effects of repeated daily and every-other-day pre-exposure of rats to s.c. morphine and methadone on locomotor activity and CNS neuronal activation (as assessed by Fos immunohistochemistry) responses to s.c. morphine challenge given 2 weeks after the completion of the pretreatment. The challenge revealed behavioral sensitization after daily morphine pretreatment only. Dorsomedial striatum and basolateral amygdaloid nucleus showed robust morphine-induced Fos protein induction that was unaffected by the pretreatments tested. Centrolateral striatum, shell and core of the nucleus accumbens, paraventricular thalamic nucleus and some layers of motor and somatosensory cortices showed but negligible Fos protein induction in drug-naive rats; this response was markedly enhanced by morphine pretreatment only, which effect might be related to the emergence of opiate addiction. Minor Fos responses to morphine were also found in layers IV and VI of the somatosensory cortex and layer VI of the insular cortex of the drug-naïve rats; these responses were significantly enhanced both by morphine and methadone pretreatment. The similarity of methadone and morphine pretreatments' effects in the latter cortical regions might be relevant to the ability of methadone to alleviate signs of abstinence syndrome and craving in heroin addicts. In summary, this study revealed differing and relatively long-lasting effects of prolonged administration of morphine and methadone on the profile of behavioral and CNS neuronal activation responses to morphine challenge in the rat. PMID:18485622

  9. Modulation of ethanol-intake by morphine: Evidence for a central site of action

    SciTech Connect

    Wild, K.D.; Reid, L.D. )

    1990-01-01

    Previous studies have shown that subcutaneous administration of low doses of morphine increase, while subcutaneous naloxone decreases, ethanol-intake in rats. However, the site of action of morphine modulation of ethanol-intake remains unclear. In an attempt to elucidate this issue, seven graded doses of morphine were given intracerebroventricularly to rats 15 min prior to an opportunity to consume water and sweetened alcoholic beverage for 2 hr. Two lower doses of intracerebroventricular morphine reliably increased ethanol-intake, while higher doses decreased intake of water. Preference ratios were reliably increased by morphine doses of 1 {mu}g and higher. The present data provide support for a central site of morphine modulation of ethanol-intake.

  10. Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, part I.

    PubMed

    Armstrong, Scott C; Cozza, Kelly L

    2003-01-01

    Pharmacokinetic drug-drug interactions with morphine, hydromorphone, and oxymorphone are reviewed in this column. Morphine is a naturally occurring opiate that is metabolized chiefly through glucuronidation by uridine diphosphate glucuronosyl transferase (UGT) enzymes in the liver. These enzymes produce an active analgesic metabolite and a potentially toxic metabolite. In vivo drug-drug interaction studies with morphine are few, but they do suggest that inhibition or induction of UGT enzymes could alter morphine and its metabolite levels. These interactions could change analgesic efficacy. Hydromorphone and oxymorphone, close synthetic derivatives of morphine, are also metabolized primarily by UGT enzymes. Hydromorphone may have a toxic metabolite similar to morphine. In vivo drug-drug interaction studies with hydromorphone and oxymorphone have not been done, so it is difficult to make conclusions with these drugs. PMID:12618536

  11. Oral Ulcerations

    E-print Network

    Fetterolf, Brandon; Zabella, Alexandra; Strote, Jared

    2015-01-01

    of Emergency Medicine Fetterolf et al. Oral UlcerationsOral Ulcerations Brandon Fetterolf, DO* Alexandra Zaballa, BS † Jared Strote, MD, MS ‡ * Madigan Army Medical Center, Department of Emergency Medicine,

  12. Mitochondrial events responsible for morphine's cardioprotection against ischemia/reperfusion injury.

    PubMed

    He, Haiyan; Huh, Jin; Wang, Huihua; Kang, Yi; Lou, Jianshi; Xu, Zhelong

    2016-01-01

    Morphine may induce cardioprotection by targeting mitochondria, but little is known about the exact mitochondrial events that mediate morphine's protection. We aimed to address the role of the mitochondrial Src tyrosine kinase in morphine's protection. Isolated rat hearts were subjected to 30min ischemia and 2h of reperfusion. Morphine was given before the onset of ischemia. Infarct size and troponin I release were measured to evaluate cardiac injury. Oxidative stress was evaluated by measuring mitochondrial protein carbonylation and mitochondrial ROS generation. HL-1 cells were subjected to simulated ischemia/reperfusion and LDH release and mitochondrial membrane potential (??m) were measured. Morphine reduced infarct size as well as cardiac troponin I release which were aborted by the selective Src tyrosine kinase inhibitors PP2 and Src-I1. Morphine also attenuated LDH release and prevented a loss of ??m at reperfusion in a Src tyrosine kinase dependent manner in HL-1 cells. However, morphine failed to reduce LDH release in HL-1 cells transfected with Src siRNA. Morphine increased mitochondrial Src phosphorylation at reperfusion and this was abrogated by PP2. Morphine attenuated mitochondrial protein carbonylation and mitochondrial superoxide generation at reperfusion through Src tyrosine kinase. The inhibitory effect of morphine on the mitochondrial complex I activity was reversed by PP2. These data suggest that morphine induces cardioprotection by preventing mitochondrial oxidative stress through mitochondrial Src tyrosine kinase. Inhibition of mitochondrial complex I at reperfusion by Src tyrosine kinase may account for the prevention of mitochondrial oxidative stress by morphine. PMID:26631580

  13. Morphine formation from ethylmorphine: implications for drugs-of-abuse testing in urine.

    PubMed

    Popa, C; Beck, O; Brodin, K

    1998-01-01

    In drugs-of-abuse testing, opiates constitute a delicate and controversial task because morphine may occur in urine for several reasons. Ethylmorphine (EtM), which is used as an antitussive drug in many countries, is metabolically converted to morphine. The present study was performed in order to document intra- and interindividual differences in morphine formation after single-dose intake of EtM at two different doses (25 and 50 mg). The urinary excretion of opiates was measured during 48 h with EMIT and gas chromatography-mass spectrometry in 10 healthy volunteers. The mean values of totally recovered EtM and morphine in hydrolyzed urine during 48 h were 42 and 47% of the given dose at high and low dose level, respectively. The ratio between total recovered morphine and EtM ranged from 19 to 131% with a mean value of 48%. The rate of positive outcome in the EMIT opiate-screening assay was 100% during the first 24 h for both doses, and it was still high (> or = 67%) in the 24-48 h time interval. It was found that the decline in urinary EtM is more rapid than for morphine, which leads to an increasing morphine/EtM ratio in urine over time. THe mean value of the morphine/EtM ratio was found to be greater than 1 during the 12-24 h interval and finally increased to greater than 10. There was an intra-individual concordance in morphine/EtM ratio between doses, but there was marked interindividual variation. Morphine/EtM ratios that were greater than 1 were only seen when the concentration of morphine was below 300 micrograms/mmol creatinine. Our results demonstrate that morphine is formed from EtM at a high and variable rate and may be present in urine in concentrations greater than those of EtM even shortly after drug intake. PMID:9547411

  14. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... this chapter. (c) Conditions of use(1) Amount. Adult pigeons: 1 tablet (10 milligrams); newly weaned pigeons: 1/2 tablet (5 milligrams). (2) Indications for use. For treating trichomoniasis (canker) in ornamental and homing pigeons. (3) Limitations. Not for use in pigeons intended for human food. Consult...

  15. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... this chapter. (c) Conditions of use—(1) Amount. Adult pigeons: 1 tablet (10 milligrams); newly weaned pigeons: 1/2 tablet (5 milligrams). (2) Indications for use. For treating trichomoniasis (canker) in ornamental and homing pigeons. (3) Limitations. Not for use in pigeons intended for human food. Consult...

  16. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... this chapter. (c) Conditions of use—(1) Amount. Adult pigeons: 1 tablet (10 milligrams); newly weaned pigeons: 1/2 tablet (5 milligrams). (2) Indications for use. For treating trichomoniasis (canker) in ornamental and homing pigeons. (3) Limitations. Not for use in pigeons intended for human food. Consult...

  17. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... this chapter. (c) Conditions of use—(1) Amount. Adult pigeons: 1 tablet (10 milligrams); newly weaned pigeons: 1/2 tablet (5 milligrams). (2) Indications for use. For treating trichomoniasis (canker) in ornamental and homing pigeons. (3) Limitations. Not for use in pigeons intended for human food. Consult...

  18. 21 CFR 520.312 - Carnidazole tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... this chapter. (c) Conditions of use—(1) Amount. Adult pigeons: 1 tablet (10 milligrams); newly weaned pigeons: 1/2 tablet (5 milligrams). (2) Indications for use. For treating trichomoniasis (canker) in ornamental and homing pigeons. (3) Limitations. Not for use in pigeons intended for human food. Consult...

  19. Enhancing Student Performance Using Tablet Computers

    ERIC Educational Resources Information Center

    Enriquez, Amelito G.

    2010-01-01

    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…

  20. Tablet PCs: A Physical Educator's New Clipboard

    ERIC Educational Resources Information Center

    Nye, Susan B.

    2010-01-01

    Computers in education have come a long way from the abacus of 5,000 years ago to the desktop and laptop computers of today. Computers have transformed the educational environment, and with each new iteration of smaller and more powerful machines come additional advantages for teaching practices. The Tablet PC is one. Tablet PCs are fully…

  1. Putting Tablet PCs to the Test

    ERIC Educational Resources Information Center

    Amirian, Susan

    2004-01-01

    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…

  2. 21 CFR 520.2088 - Roxarsone tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... period. Withdraw 5 days before slaughter. Use as sole source of organic arsenic. (ii) Growing chickens—(a.... Withdraw 5 days before slaughter. Use as sole source of organic arsenic. (b)(1) Specifications. Each tablet... slaughter. Use as sole source of organic arsenic. (ii) (c)(1) Specifications. Each tablet contains...

  3. 21 CFR 520.2088 - Roxarsone tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... period. Withdraw 5 days before slaughter. Use as sole source of organic arsenic. (ii) Growing chickens—(a.... Withdraw 5 days before slaughter. Use as sole source of organic arsenic. (b)(1) Specifications. Each tablet... slaughter. Use as sole source of organic arsenic. (ii) (c)(1) Specifications. Each tablet contains...

  4. Effect of metamizol on morphine pharmacokinetics and pharmacodynamics after acute and subchronic administration in arthritic rats.

    PubMed

    Domínguez-Ramírez, Adriana Miriam; Cortés-Arroyo, Alma Rosa; Y de la Peña, Marcela Hurtado; López, José Raúl Medina; López-Muñoz, Francisco Javier

    2010-10-25

    The aim of the present study was to investigate whether metamizol alters the pharmacokinetics of morphine and to determine the relationship between morphine plasma levels and antinociceptive effect produced after co-administration of drugs under acute and subchronic treatments using the pain-induced functional impairment model in rat (PIFIR model). Administration of morphine+metamizol under acute treatment produced a significantly higher antinociceptive effect than that obtained with morphine alone (P<0.05). This effect remained unaltered after subchronic treatments for 6 and 12 days. In addition, after the simultaneous administration of the drugs in a single dose, a pharmacokinetic interaction was found, which significantly (P<0.001) increased maximum plasma concentration (C(max)), concentration at 4h (C(4h)), partial areas under the plasma concentration-time curve from zero to 4h (AUC(0-4)) and from zero to 24h (AUC(0-24)). Moreover, whereas plasma concentration of morphine markedly decreased up to 4h (C(4h)) after subchronic administration of the opioid, multiple dosing of the morphine+metamizol combination produced an accumulation of the drug in plasma (P<0.001). The increase observed in morphine plasma levels after co-administration of metamizol may be explained by a possible enzymatic inhibition of the glucuronosyl-transferase system involved in the metabolism of morphine. This study reveals both a pharmacodynamic and a pharmacokinetic interaction between morphine and metamizol, leading to an increased antinociceptive effect and a delay in tolerance development. PMID:20655302

  5. Acute food deprivation reverses morphine-induced locomotion deficits in M5 muscarinic receptor knockout mice.

    PubMed

    Steidl, Stephan; Lee, Esther; Wasserman, David; Yeomans, John S

    2013-09-01

    Lesions of the pedunculopontine tegmental nucleus (PPT), one of two sources of cholinergic input to the ventral tegmental area (VTA), block conditioned place preference (CPP) for morphine in drug-naïve rats. M5 muscarinic cholinergic receptors, expressed by midbrain dopamine neurons, are critical for the ability of morphine to increase nucleus accumbens dopamine levels and locomotion, and for morphine CPP. This suggests that M5-mediated PPT cholinergic inputs to VTA dopamine neurons critically contribute to morphine-induced dopamine activation, reward and locomotion. In the current study we tested whether food deprivation, which reduces PPT contribution to morphine CPP in rats, could also reduce M5 contributions to morphine-induced locomotion in mice. Acute 18-h food deprivation reversed the phenotypic differences usually seen between non-deprived wild-type and M5 knockout mice. That is, food deprivation increased morphine-induced locomotion in M5 knockout mice but reduced morphine-induced locomotion in wild-type mice. Food deprivation increased saline-induced locomotion equally in wild-type and M5 knockout mice. Based on these findings, we suggest that food deprivation reduces the contribution of M5-mediated PPT cholinergic inputs to the VTA in morphine-induced locomotion and increases the contribution of a PPT-independent pathway. The contributions of cholinergic, dopaminergic and GABAergic neurons to the effects of acute food deprivation are discussed. PMID:23742799

  6. Morphine- and CaMKII-dependent enhancement of GIRK channel signaling in hippocampal neurons.

    PubMed

    Nassirpour, Rounak; Bahima, Laia; Lalive, Arnaud L; Lüscher, Christian; Luján, Rafael; Slesinger, Paul A

    2010-10-01

    G-protein-gated inwardly rectifying potassium (GIRK) channels, which help control neuronal excitability, are important for the response to drugs of abuse. Here, we describe a novel pathway for morphine-dependent enhancement of GIRK channel signaling in hippocampal neurons. Morphine treatment for ?20 h increased the colocalization of GIRK2 with PSD95, a dendritic spine marker. Western blot analysis and quantitative immunoelectron microscopy revealed an increase in GIRK2 protein and targeting to dendritic spines. In vivo administration of morphine also produced an upregulation of GIRK2 protein in the hippocampus. The mechanism engaged by morphine required elevated intracellular Ca(2+) and was insensitive to pertussis toxin, implicating opioid receptors that may couple to Gq G-proteins. Met-enkephalin, but not the ?-selective (DAMGO) and ?-selective (DPDPE) opioid receptor agonists, mimicked the effect of morphine, suggesting involvement of a heterodimeric opioid receptor complex. Peptide (KN-93) inhibition of CaMKII prevented the morphine-dependent change in GIRK localization, whereas expression of a constitutively activated form of CaMKII mimicked the effects of morphine. Coincident with an increase in GIRK2 surface expression, functional analyses revealed that morphine treatment increased the size of serotonin-activated GIRK currents and Ba(2+)-sensitive basal K(+) currents in neurons. These results demonstrate plasticity in neuronal GIRK signaling that may contribute to the abusive effects of morphine. PMID:20926668

  7. CXCR4 signaling mediates morphine-induced tactile hyperalgesia.

    PubMed

    Wilson, Natalie M; Jung, Hosung; Ripsch, Matthew S; Miller, Richard J; White, Fletcher A

    2011-03-01

    Morphine and related compounds are the first line of therapy in the treatment of moderate to severe pain. Over time, individuals taking opioids can develop an increasing sensitivity to noxious stimuli, even evolving into a painful response to previously non-noxious stimuli (opioid-induced hyperalgesia; OIH). The mechanism underlying OIH is not well understood although complex intracellular neural mechanisms, including opioid receptor desensitization and down-regulation, are believed to be major mechanisms underlying OIH. However, OIH may also be associated with changes in gene expression. A growing body of evidence suggests that cellular exposure to mu agonists upregulate chemokines/receptors and recent work from our laboratory implicates chemokine upregulation in a variety of neuropathic pain behaviors. Here we characterized the degree to which chemokines/receptors signaling is increased in primary afferent neurons of the dorsal root ganglion (DRG) following chronic morphine sulfate treatment and correlated these changes with tactile hyperalgesic behavior in rodents. We demonstrate that mRNA expression of the chemokine, stromal-derived factor-1 (SDF1/CXCL12) is upregulated following morphine treatment in sensory neurons of the rat. The release of SDF1 was found to be constitutive when compared with the activity dependent release of the C-C chemokine, monocyte chemoattractant protein-1 (MCP1/CCL2) in a line of F11 neuroblastoma-sensory neuron hybrid cells. We further determined that there is pronounced CXCR4 expression in satellite glial cells and following morphine treatment, increased functional CXCR4 expression in sensory neurons of the DRG. Moreover, intraperitoneal administration of the specific CXCR4 antagonist, AMD3100, completely reversed OIH in the rat. Taken together; the data suggest that opioid-induced SDF1/CXCR4 signaling is central to the development of long lasting OIH and that receptor antagonists represent a promising novel approach to the management of the side effects associated with the use of opioids for chronic pain management. PMID:21193025

  8. Analgesic Effects of Paracetamol and Morphine After Elective Laparotomy Surgeries

    PubMed Central

    Alimian, Mahzad; Pournajafian, Alireza; Kholdebarin, Alireza; Ghodraty, Mohammadreza; Rokhtabnak, Faranak; Yazdkhasti, Payman

    2014-01-01

    Background: Opioids have been traditionally used for postoperative pain control, but they have some unpleasant side effects such as respiratory depression or nausea. Some other analgesic drugs like non-steroidal anti-inflammatory drugs (NSAIDs) are also being used for pain management due to their fewer side effects. Objectives: The aim of our study was to compare the analgesic effects of paracetamol, an intravenous non-opioid analgesic and morphine infusion after elective laparotomy surgeries. Patients and Methods: This randomized clinical study was performed on 157 ASA (American Society of Anesthesiology) I-II patients, who were scheduled for elective laparotomy. These patients were managed by general anesthesia with TIVA technique in both groups and 150 patients were analyzed. Paracetamol (4 g/24 hours) in group 1 and morphine (20 mg/24 hours) in group 2 were administered by infusion pump after surgery. Postoperative pain evaluation was performed by visual analog scale (VAS) during several hours postoperatively. Meperidine was administered for patients complaining of pain with VAS > 3 and repeated if essential. Total doses of infused analgesics, were recorded following the surgery and compared. Analysis was performed on the basis of VAS findings and meperidine consumption. Results: There were no differences in demographic data between two groups. Significant difference in pain score was found between the two groups, in the first eight hours following operation (P value = 0.00), but not after 12 hours (P = 0.14) .The total dose of rescue drug (meperidine) and number of doses injected showed a meaningful difference between the two groups (P = 0.00). Also nausea, vomiting and itching showed a significant difference between the two groups and patients in morphine group, experienced higher levels of them. Conclusions: Paracetamol is not enough for postoperative pain relief in the first eight hour postoperatively, but it can reduce postoperative opioid need and is efficient enough for pain management as morphine after the first eight hours following surgery. PMID:24829880

  9. Comparison of the hydrolysis rates of morphine-3-glucuronide and morphine-6-glucuronide with acid and beta-glucuronidase.

    PubMed

    Romberg, R W; Lee, L

    1995-01-01

    The acid and enzymatic hydrolysis rates for two morphine metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), were compared. Urine fortified with M3G or M6G was hydrolyzed in a boiling water bath or with beta-glucuronidases. Optimal temperatures for beta-glucuronidases were 60 degrees C for Helix pomatia and abalone and 50 degrees C for Escherichia coli. A 3-h incubation with 1,000-1,500 Fishman units of enzyme gave complete hydrolysis of M3G. The enzymatic hydrolysis rate of M6G was approximately 25% of the hydrolysis rate of M3G and required 24 h for completion. The acid hydrolysis rate of M6G was slower than M3G and required a 0.5-h incubation with a 1:1 mixture of concentrated HCl in a boiling water bath for completion. For comparison, the acid hydrolysis rate of codeine conjugates was found to be similar to the rate of M6G, but the enzymatic rate of codeine conjugates appeared slower than the rate of M6G. PMID:7564293

  10. Laboratory analysis of remotely collected oral fluid specimens for opiates by immunoassay.

    PubMed

    Niedbala, R S; Kardos, K; Waga, J; Fritch, D; Yeager, L; Doddamane, S; Schoener, E

    2001-01-01

    The performance characteristics of a method for detecting opiates (morphine, codeine, heroin, and 6-acetylmorphine [6-AM]) in oral fluid specimens were examined and compared with methods for urine specimens. The oral fluid was easily obtained using a simple device that collects between 1 and 1.5 mL of fluid for laboratory analysis. Simultaneously collected specimens from 60 known opiate abusers from a drug-treatment center were first tested using an immunoassay cutoff of 10 ng/mL in oral fluids and 2,000 ng/mL in urine. Using a second aliquot, opiate confirmation in urine was performed by gas chromatography-mass spectrometry (GC-MS) and in oral fluids by GC-MS-MS. The combined immunoassay and GC-MS-MS procedures were completed with less than 250 pL of oral fluid. Opiates identified in oral fluid specimens from heroin users included morphine, codeine, heroin, and 6-AM. The immunoassay was tested for precision, stability, and the effects of potential cross-reactants. The results yielded 93.6% agreement between oral fluid and urine, suggesting that oral fluid may be a reliable matrix for opiate detection. PMID:11499883

  11. The reliability of tablet computers in depicting maxillofacial radiographic landmarks

    PubMed Central

    Mahdian, Mina; Sheth, Sonam; Chandhoke, Taranpreet K; Gopalakrishna, Aadarsh; Potluri, Anitha; Yadav, Sumit

    2015-01-01

    Purpose This study was performed to evaluate the reliability of the identification of anatomical landmarks in panoramic and lateral cephalometric radiographs on a standard medical grade picture archiving communication system (PACS) monitor and a tablet computer (iPad 5). Materials and Methods A total of 1000 radiographs, including 500 panoramic and 500 lateral cephalometric radiographs, were retrieved from the de-identified dataset of the archive of the Section of Oral and Maxillofacial Radiology of the University Of Connecticut School Of Dental Medicine. Major radiographic anatomical landmarks were independently reviewed by two examiners on both displays. The examiners initially reviewed ten panoramic and ten lateral cephalometric radiographs using each imaging system, in order to verify interoperator agreement in landmark identification. The images were scored on a four-point scale reflecting the diagnostic image quality and exposure level of the images. Results Statistical analysis showed no significant difference between the two displays regarding the visibility and clarity of the landmarks in either the panoramic or cephalometric radiographs. Conclusion Tablet computers can reliably show anatomical landmarks in panoramic and lateral cephalometric radiographs. PMID:26389060

  12. Effects of Intrathecal ?-Opioid Receptor Agonist on Morphine-Induced Itch and Antinociception in Mice.

    PubMed

    Sakakihara, Manabu; Imamachi, Noritaka; Saito, Yoji

    2016-01-01

    The ?-opioid receptor (MOR) agonist-induced itch is a significant issue associated with analgesic therapies. Research suggested that systemically administered ?-opioid receptor (KOR) agonists inhibit intrathecal morphine-induced itch in primates. However, serious adverse effects induced by systemically administered KOR agonists may restrict their usefulness in humans. We investigated the effects of intrathecal KOR agonists on intrathecal morphine-mediated itch and antinociception in mice.Mice received intrathecal injections of one of the following drugs: morphine (0.1-1.0 nmol), the selective KOR agonist TRK-820 100 pmol, the combination of morphine 0.3 nmol + TRK-820 (10-100 pmol), and 5 ?L of saline. One hour after intraperitoneal administration of the selective KOR antagonist nor-binaltorphimine 1.0 ?mol, the effect of TRK-820 100 pmol on intrathecal morphine 0.3 nmol-induced scratching was tested. Total numbers of scratches after intrathecal injection were analyzed. After observing scratching behavior, sedation level was evaluated subjectively. Nociceptive threshold was determined by tail immersion test with intrathecal injections of the following agents: morphine (0.1-1.0 nmol), TRK-820 (10-100 pmol), morphine 0.1 nmol + TRK-820 10 pmol, and 5 ?L of saline.Intrathecal TRK-820 dose-dependently inhibited intrathecal morphine-induced scratching compared with that in the saline group. Intraperitoneal nor-binaltorphimine completely inhibited the antiscratching effect of intrathecal TRK-820 100 pmol. The combination of morphine 0.3 nmol and TRK-820 did not alter the sedation score compared with that in the morphine 0.3 nmol group. Morphine 0.1 nmol + TRK-820 10 pmol significantly produced greater thermal antinociceptive effects than morphine 0.1 nmol.We demonstrated that intrathecal KOR agonists exert antipruritic effects on intrathecal morphine-induced itch without affecting sedation. The combination of intrathecal morphine and intrathecal KOR agonists produces more potent antinociceptive effects against a thermal stimulus compared with morphine alone. PMID:26587674

  13. Intrathecal rapamycin attenuates morphine-induced analgesic tolerance and hyperalgesia in rats with neuropathic pain

    PubMed Central

    Xu, Ji-Tian; Sun, Linlin; Lutz, Brianna Marie; Bekker, Alex; Tao, Yuan-Xiang

    2015-01-01

    Repeated and long-term administration of opioids is often accompanied by the initiation of opioid-induced analgesic tolerance and hyperalgesia in chronic pain patients. Our previous studies showed that repeated intrathecal morphine injection activated the mammalian target of rapamycin complex 1 (mTORC1) in spinal dorsal horn neurons and that blocking this activation prevented the initiation of morphine-induced tolerance and hyperalgesia in healthy rats. However, whether spinal mTORC1 is required for morphine-induced tolerance and hyperalgesia under neuropathic pain conditions remains elusive. We here observed the effect of intrathecal infusion of rapamycin, a specific mTORC1 inhibitor, on morphine-induced tolerance and hyperalgesia in a neuropathic pain model in rats induced by the fifth lumbar spinal nerve ligation (SNL). Continuous intrathecal infusion of morphine for one week starting on day 8 post-SNL led to morphine tolerance demonstrated by morphine-induced reduction in maximal possible analgesic effect (MPAE) to tail heat stimuli and ipsilateral paw withdrawal threshold (PWT) to mechanical stimuli in SNL rats. Such reduction was attenuated by co-infusion of rapamycin. Co-infusion of rapamycin also blocked morphine tolerance demonstrated by attenuation of morphine-induced reduction in MPAE in sham rats and morphine-induced hyperalgesia demonstrated by the reverse of morphine-induced reduction in PWT on both sides of sham rats and on the contralateral side of SNL rats. The results suggest that mTORC1 inhibitors could serve as promising medications for use as adjuvants with opioids in clinical neuropathic pain management. PMID:26339682

  14. Terahertz Technology: A Boon to Tablet Analysis

    PubMed Central

    Wagh, M. P.; Sonawane, Y. H.; Joshi, O. U.

    2009-01-01

    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. PMID:20490288

  15. Development and optimization of carvedilol orodispersible tablets: enhancement of pharmacokinetic parameters in rabbits

    PubMed Central

    Aljimaee, Yazeed HM; El-Helw, Abdel-Rahim M; Ahmed, Osama AA; El-Say, Khalid M

    2015-01-01

    Background Carvedilol (CVD) is used for the treatment of essential hypertension, heart failure, and systolic dysfunction after myocardial infarction. Due to its lower aqueous solubility and extensive first-pass metabolism, the absolute bioavailability of CVD does not exceed 30%. To overcome these drawbacks, the objective of this work was to improve the solubility and onset of action of CVD through complexation with hydroxypropyl-?-cyclodextrin and formulation of the prepared complex as orodispersible tablets (ODTs). Methods Compatibility among CVD and all tablet excipients using differential scanning calorimetry and Fourier transform infrared spectroscopy, complexation of CVD with different polymers, and determination of the solubility of CVD in the prepared complexes were first determined. A Box-Behnken design (BBD) was used to study the effect of tablet formulation variables on the characteristics of the prepared tablets and to optimize preparation conditions. According to BBD design, 15 formulations of CVD-ODTs were prepared by direct compression and then evaluated for their quality attributes. The relative pharmacokinetic parameters of the optimized CVD-ODTs were compared with those of the marketed CVD tablet. A single dose, equivalent to 2.5 mg/kg CVD, was administered orally to New Zealand white rabbits using a double-blind, randomized, crossover design. Results The solubility of CVD was improved from 7.32 to 22.92 mg/mL after complexation with hydroxypropyl-?-cyclodextrin at a molar ratio of 1:2 (CVD to cyclodextrin). The formulated CVD-ODTs showed satisfactory results concerning tablet hardness (5.35 kg/cm2), disintegration time (18 seconds), and maximum amount of CVD released (99.72%). The pharmacokinetic data for the optimized CVD-ODT showed a significant (P<0.05) increase in maximum plasma concentration from 363.667 to 496.4 ng/mL, and a shortening of the time taken to reach maximum plasma concentration to 2 hours in comparison with the marketed tablet. Conclusion The optimized CVD-ODTs showed improved oral absorption of CVD and a subsequent acceleration of clinical effect, which is favored for hypertensive and cardiac patients. PMID:25834396

  16. 49 CFR 40.139 - On what basis does the MRO verify test results for codeine and morphine?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... codeine and morphine? 40.139 Section 40.139 Transportation Office of the Secretary of Transportation... Verification Process § 40.139 On what basis does the MRO verify test results for codeine and morphine? As the MRO, you must proceed as follows when you receive a laboratory confirmed positive morphine or...

  17. 49 CFR 40.139 - On what basis does the MRO verify test results for codeine and morphine?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... codeine and morphine? 40.139 Section 40.139 Transportation Office of the Secretary of Transportation... Verification Process § 40.139 On what basis does the MRO verify test results for codeine and morphine? As the MRO, you must proceed as follows when you receive a laboratory confirmed positive morphine or...

  18. Inhibition of SNAP-25 Phosphorylation at Ser187 Involved in Chronic Morphine-induced Down-regulation of

    E-print Network

    Tian, Weidong

    Inhibition of SNAP-25 Phosphorylation at Ser187 Is Involved in Chronic Morphine-induced Down release, was found to be dramatically regu- lated in hippocampus after chronic morphine treat- ment, which with morphine-induced inhibition of PKC activity. Moreover, the level of ternary complex of SNARE pro- teins

  19. Brain Research, 368 (1986) 170-173 The effect of analgesic doses of morphine on regional cerebral

    E-print Network

    Stryker, Michael

    1986-01-01

    170 BRE 21422 Brain Research, 368 (1986) 170-173 Elsevier The effect of analgesic doses of morphine: morphine - analgesia - regional cerebral metabolism - ['4C]2-deoxyglucose autoradiography - pain The effect of morphine on regional cerebral glucose metabolism was measured in rats using high resolution (14C]2

  20. Optimization of Carboxymethyl-Xyloglucan-Based Tramadol Matrix Tablets Using Simplex Centroid Mixture Design

    PubMed Central

    Madgulkar, Ashwini R.; Bhalekar, Mangesh R.; Padalkar, Rahul R.; Shaikh, Mohseen Y.

    2013-01-01

    The aim was to determine the release-modifying effect of carboxymethyl xyloglucan for oral drug delivery. Sustained release matrix tablets of tramadol HCl were prepared by wet granulation method using carboxymethyl xyloglucan as matrix forming polymer. HPMC K100M was used in a small amount to control the burst effect which is most commonly seen with natural hydrophilic polymers. A simplex centroid design with three independent variables and two dependent variables was employed to systematically optimize drug release profile. Carboxymethyl xyloglucan (X1), HPMC K100M (X2), and dicalcium phosphate (X3) were taken as independent variables. The dependent variables selected were percent of drug release at 2nd hour (Y1) and at 8th hour (Y2). Response surface plots were developed, and optimum formulations were selected on the basis of desirability. The formulated tablets showed anomalous release mechanism and followed matrix drug release kinetics, resulting in regulated and complete release from the tablets within 8 to 10 hours. The polymer carboxymethyl xyloglucan and HPMC K100M had significant effect on drug release from the tablet (P > 0.05). Polynomial mathematical models, generated for various response variables using multiple regression analysis, were found to be statistically significant (P > 0.05). The statistical models developed for optimization were found to be valid. PMID:26555977

  1. [Oral formulation of choice for children].

    PubMed

    Lajoinie, A; Henin, E; Kassai, B

    2015-08-01

    Selecting the most appropriate oral formulation is very challenging when developing medicines for children and in routine practice. Research in pediatric pharmacology has focused on oral drug formulation, determining whether the active pharmaceutical ingredient can be successfully delivered to children. Pediatric expert committees (EMA, EuFPI) recommend that children's medicines be safe, well tolerated, easy to use (palatable and requiring minimal handling), transportable, easily produced, cost effective, commercially viable, with a minimal impact on children's life-style. Oral liquid drug formulations (OLFs: solutions, syrups, suspensions) are historically considered as the most appropriate oral formulation for children, since they are easy to swallow for younger infants and palatable for children. However, OLFs present numerous disadvantages, such as low stability, potentially toxic excipients for children, and low transportability. In the long-term, dose volume and frequency of administration might lead to non-compliance. Multiple preparation steps and volume calculations are also among risk factors for medicine errors in children. An alternative to OLFs is the conventional solid oral dosage form (OSF), such as tablets and capsules. These offer the advantages of greater stability, easy dose selection, improved transportability, and ease of storage. They also allow the modification of drug pharmacokinetic parameters, minimizing administration frequency. Finally, OSFs are less costly than OLFs, since they are easier to develop, manufacture, transport, store, and deliver. Controlled study results suggest that the use of OSFs in children would be associated with greater acceptability by children, greater preference on the part of caregivers, and higher drug compliance than OLFs. Recent controlled studies, confirming that OSFs with an acceptable size for children (mini-tablets), should shift the current paradigm of OLFs as the reference for children's oral medicine. We lack evidence on OSF acceptability in children and its influence on drug compliance, particularly with appropriate-size OSFs for children. Further investigation on oral formulation should investigate the utilisation of OSFs in young children. Few OSFs are licensed for children under 6 years of age. PMID:26141805

  2. A Conjugate Vaccine Attenuates Morphine- and Heroin-Induced Behavior in Rats

    PubMed Central

    Li, Qian-Qian; Sun, Cheng-Yu; Luo, Yi-Xiao; Xue, Yan-Xue; Meng, Shi-Qiu; Xu, Ling-Zhi; Chen, Na; Deng, Jia-Hui; Zhai, Hai-Feng; Kosten, Thomas R.; Shi, Jie

    2015-01-01

    Background: Currently approved medications for opioid addiction have shown clinical efficacy, but undesired side effects, dependence induced by the medications themselves, and low treatment compliance necessitate the need for novel therapies. Methods: A novel morphine-keyhole limpet hemocyanin conjugate vaccine was synthesized with 6-glutarylmorphine as the hapten and a lengthened linker of 6 carbon atoms. The titer and specificity of the triggered antibody were assessed by enzyme-linked immunosorbent assay. The effects of the vaccine on the morphine-induced elevation of dopamine levels in the nucleus accumbens were determined by high-performance liquid chromatography. The effects of the vaccine on morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin self-administration were also assessed. Results: After subcutaneous administration in rats, the vaccine triggered a high antibody titer, with comparable specificity for morphine, 6-acetylmorphine, and heroin, but no interaction with dissimilar therapeutic opioid compounds, including buprenorphine, naloxone, and nalorphine, was observed. The vaccine significantly prevented the elevation of dopamine levels in the nucleus accumbens induced by a single morphine challenge. Moreover, the vaccine prevented the expression of morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin seeking, suggesting its potential for preventing relapse. Conclusion: These results demonstrate that active immunization with the present vaccine induces a robust morphine/heroin-specific antibody response in rats and attenuates the behavioral effects of morphine and heroin. PMID:25522425

  3. In vivo morphine treatment synergistically increases LPS-induced caspase activity in immune organs

    PubMed Central

    Olin, Michael; Lee, Brian; Roy, Sabita; Molitor, Thomas

    2013-01-01

    Apoptosis is an important mechanism for the elimination of infected cells, which would normally serve as hosts for further pathogen replication. Apoptosis is initiated through complex pathways involving a family of cysteine proteases known as caspases. The detection of apoptosis is essential for understanding the long-term health effects inflicted by the therapeutic use of opiate drugs such as morphine for pain treatment following major trauma or disease and abusive use of such drugs in addiction. Common practices of apoptosis detection involve the removal of tissues, which subsequently induce spontaneous apoptosis unrelated to the actual effects of the opioid drug exposure. The objective of this study was to develop an in vivo detection method for assessing morphine’s ability to directly induce apoptosis, and in the combination of morphine following an inflammatory response induced by lipopolysaccharide (LPS). Mice were administered saline, morphine, LPS, or a combination of morphine and LPS. Prior to sacrifice, mice were injected with a poly-caspase-specific apoptosis detection probe, to detect internal caspase activity in vivo. Administration of morphine alone did not directly induce apoptosis. However, morphine significantly enhanced the LPS induced apoptosis in splenocyte and bone marrow cells as well as in spleen, liver, and thymus tissues. The use of a poly-caspase detection probe methodology, to label apoptotic cells in vivo, provides a powerful quantitative tool for the in vivo analysis of caspase activity. PMID:20390371

  4. Pharmacokinetics of Morphine and Its Metabolites in Infants and Young Children After Congenital Heart Surgery.

    PubMed

    Elkomy, Mohammed H; Drover, David R; Glotzbach, Kristi L; Galinkin, Jeffery L; Frymoyer, Adam; Su, Felice; Hammer, Gregory B

    2016-01-01

    The objective of this study was to characterize morphine glucuronidation in infants and children following cardiac surgery for possible treatment individualization in this population. Twenty children aged 3 days to 6 years, admitted to the cardiovascular intensive care unit after congenital heart surgery, received an intravenous (IV) loading dose of morphine (0.15 mg/kg) followed by subsequent intermittent IV bolus doses based on a validated pain scale. Plasma samples were collected over 6 h after the loading dose and randomly after follow-up doses to measure morphine and its major metabolite concentrations. A population pharmacokinetic model was developed with the non-linear mixed effects software NONMEM. Parent disposition was adequately described by a linear two-compartment model. Effect of growth (size and maturation) on morphine parameters was accounted for by allometric body weight-based models. An intermediate compartment with Emax model best characterized glucuronide concentrations. Glomerular filtration rate was identified as a significant predictor of glucuronide formation time delay and maximum concentrations. Clearance of morphine in children with congenital heart disease is comparable to that reported in children without cardiac abnormalities of similar age. Children 1-6 months of age need higher morphine doses per kilogram to achieve an area under concentration-time curve comparable to that in older children. Pediatric patients with renal failure receiving morphine therapy are at increased risk of developing opioid toxicity due to accumulation of morphine metabolites. PMID:26349564

  5. Differential response to morphine of the oligomeric state of ?-opioid in the presence of ?-opioid receptors.

    PubMed

    Golebiewska, Urszula; Johnston, Jennifer M; Devi, Lakshmi; Filizola, Marta; Scarlata, Suzanne

    2011-04-12

    Prolonged morphine treatment induces extensive desensitization of the ?-opioid receptor (?OR) which is the G-protein-coupled receptor that primarily mediates the cellular response to morphine. To date, the molecular mechanism underlying this process is unknown. Here, we have used live cell fluorescence imaging to investigate whether prolonged morphine treatment affects the physical environment of ?OR, or its coupling with G-proteins, in two neuronal cell lines. We find that chronic morphine treatment does not change the amount of enhanced yellow fluorescence protein (eYFP)-tagged ?OR on the plasma membrane, and only slightly decreases its association with G-protein subunits. Additionally, morphine treatment does not have a detectable effect on the diffusion coefficient of eYFP-?OR. However, in the presence of another family member, the ?-opioid receptor (?OR), prolonged morphine exposure results in a significant increase in the diffusion rate of ?OR. Number and brightness measurements suggest that ?OR exists primarily as a dimer that will oligomerize with ?OR into tetramers, and morphine promotes the dissociation of these tetramers. To provide a plausible structural context to these data, we used homology modeling techniques to generate putative configurations of ?OR-?OR tetramers. Overall, our studies provide a possible rationale for morphine sensitivity. PMID:21361347

  6. Radiolabeling of morphine with (131)i and its biodistribution in rats.

    PubMed

    Enginar, Hüseyin; Unak, Perihan; Yurt-Lambrecht, Fatma; Biber-Müftüler, Fazilet Z; Seyito?lu, Beyza; Yurt, Ayfer; Yolcular, Seniha; Medine, Ilker; Bulduk, Ibrahim

    2010-08-01

    This study was conducted to determine the possible radiopharmaceutical potential of morphin labeled with (131)I. Morphine was extracted from dry capsules of the opium poppy (Papaver somniferum L.), purified by high-performance liquid chromatography, and characterized with nuclear magnetic resonance and infrared spectroscopy. The purified compound was labeled with (131)I. Male Albino Wistar rats (18) were used for receptor blockage and unblockage biodistribution studies. Tissue distribution studies showed that radiolabeled morphine had higher uptake in lung, liver, small intestines, large intestines, and stomach than the other tissues. The highest uptake of radiolabeled compounds in rats' brain was found to be in the midbrain and hypothalamus. After receptor blockage with morphine, uptake of (131)I-morphine decreased in the lungs, liver, kidney, testis, prostate, spinal cord, cerebellum, hippocampus, striatum, and temporal cortex with respect to receptor unblockage studies of rats. This study concludes that the labeling yield of (131)I-morphine was high, high amount of (131)I-morphine was found in the hypothalamus, and (131)I-morphine has enough stability for diagnostic scanning. PMID:20707720

  7. Stereospecific effects of morphine on plasma opioid peptide levels and nociception in dogs

    SciTech Connect

    Adams, M.L.; Morris, D.L.; Dewey, W.L.

    1986-03-05

    ..beta..-endorphin, (met)enkephalin, and (leu)enkephalin were quantitated in canine plasma by radioimmunoassay (RIA) after extraction of the peptides on Sep Pak C18 cartridges. Plasma samples were taken one hour after a 10 mg/kg s.c. injection of (-)-morphine SO/sub 4/ or (+)-morphine HBr. Antinociception, measured by a dog tail-flick test, and morphine-induced emesis, salivation, diarrhea, and ataxia were quantitated before sampling. Control levels for each dog were taken one week earlier at the same time of day after saline injections. Antinociception, morphine signs, and opioid peptide levels in plasma were significantly increased by (-)-morphine. Antinociception increased from zero to 83.54 +/- 11.0%. The number of morphine signs increased from zero to 2.9 +/- 0.28 per dog. ..beta..-endorphin levels increased from 44.52 +/- 4.25 to 90.6 +/- 7.38 pg/ml; (met)enkephalin levels increased from 253.56 +/- 22.04 to 497.1 +/- 58.12 pg/ml; (leu)-enkephalin increased from 141.65 +/- 12.9 to 313.24 +/- 35.95 pg/ml. None of these effects were observed in the dogs that received (+)-morphine. The conclude that morphine stereospecifically inhibits nociception, induces observable signs, and increases plasma opioid peptide levels in dogs.

  8. Study on the interaction of morphine chloride with deoxyribonucleic acid by fluorescence method

    NASA Astrophysics Data System (ADS)

    Li, J. F.; Dong, C.

    2009-01-01

    The mode and mechanism of the interaction of morphine chloride, an important alkaloid compound to calf thymus deoxyribonucleic acid (ct DNA) was investigated from absorption and fluorescence titration techniques. Hypochromic effect was founded in the absorption spectra of morphine when concentration of DNA increased. The decreased fluorescence study revealed non-cooperative binding of the morphine to DNA with an affinity of 3.94 × 10 3 M -1, and the stoichiometry of binding was characterized to be about one morphine molecule per nucleotide. Stern-Volmer plots at different temperatures proved that the quenching mechanism was static. Ferrocyanide quenching study showed that the magnitude of KSV of the bound morphine was lower than that of the free one. In addition, it was found that ionic strength could affect the binding of morphine and DNA. Fluorescence polarization and denatured DNA studies also applied strong evidences that morphine molecule was partially intercalated between every alternate base pairs of ct DNA. As observed from above experiments, intercalation was well supported as the binding mode of morphine and ct DNA.

  9. Role of Medial Prefrontal Cortex Narp in the Extinction of Morphine Conditioned Place Preference

    ERIC Educational Resources Information Center

    Blouin, Ashley M.; Han, Sungho; Pearce, Anne M.; Cheng, KaiLun; Lee, JongAh J.; Johnson, Alexander W.; Wang, Chuansong; During, Matthew J.; Holland, Peter C.; Shaham, Yavin; Baraban, Jay M.; Reti, Irving M.

    2013-01-01

    Narp knockout (KO) mice demonstrate an impaired extinction of morphine conditioned place preference (CPP). Because the medial prefrontal cortex (mPFC) has been implicated in extinction learning, we tested whether Narp cells in this region play a role in the extinction of morphine CPP. We found that intracranial injections of adenoassociated virus…

  10. Distinct interactions of cannabidiol and morphine in three nociceptive behavioral models in mice.

    PubMed

    Neelakantan, Harshini; Tallarida, Ronald J; Reichenbach, Zachary W; Tuma, Ronald F; Ward, Sara J; Walker, Ellen A

    2015-04-01

    Cannabinoid and opioid agonists can display overlapping behavioral effects and the combination of these agonists is known to produce enhanced antinociception in several rodent models of acute and chronic pain. The present study investigated the antinociceptive effects of the nonpsychoactive cannabinoid, cannabidiol (CBD) and the µ-opioid agonist morphine, both alone and in combination, using three behavioral models in mice, to test the hypothesis that combinations of morphine and CBD would produce synergistic effects. The effects of morphine, CBD, and morphine/CBD combinations were assessed in the following assays: (a) acetic acid-stimulated stretching; (b) acetic acid-decreased operant responding for palatable food; and (c) hot plate thermal nociception. Morphine alone produced antinociceptive effects in all three models of acute nociception, whereas CBD alone produced antinociception only in the acetic acid-stimulated stretching assay. The nature of the interactions between morphine and CBD combinations were assessed quantitatively based on the principle of dose equivalence. Combinations of CBD and morphine produced synergistic effects in reversing acetic acid-stimulated stretching behavior, but subadditive effects in the hot plate thermal nociceptive assay and the acetic acid-decreased operant responding for palatable food assay. These results suggest that distinct mechanisms of action underlie the interactions between CBD and morphine in the three different behavioral assays and that the choice of appropriate combination therapies for the treatment of acute pain conditions may depend on the underlying pain type and stimulus modality. PMID:25485642

  11. Brain cholinergic involvement during the rapid development of tolerance to morphine

    NASA Technical Reports Server (NTRS)

    Wahba, Z. Z.; Oriaku, E. T.; Soliman, S. F. A.

    1987-01-01

    The effect of repeated administration of morphine on the activities of the cholinergic enzymes, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), in specific brain regions were studied in rats treated with 10 mg/kg morphine for one or two days. Repeated administration of morphine was associated with a decline in the degree of analgesia produced and with a significant increase of AChE activity of the medulla oblongata. A single injection of morphine resulted in a significant decline in ChAT activity in the hypothalamus, cerebellum, and medulla oblongata regions. After two consecutive injections, no decline in ChAT was observed in these regions, while in the cerebral cortex the second administration elicited a significant decline. The results suggest that the development of tolerance to morphine may be mediated through changes in ChAT activity and lend support to the involvement of the central cholinergic system in narcotic tolerance.

  12. The development of tolerance to intrathecal morphine in rat models of visceral and cutaneous pain.

    PubMed

    Ness, T J; Follett, K A

    1998-05-22

    The development of tolerance to intrathecal morphine was studied in rats chronically implanted with intrathecal catheters connected to osmotic minipumps. Measures of cutaneous nociception were the hot plate (HP) and tail flick (TF) tests. Measures of visceral nociception were visceromotor (VM) responses to ramped colorectal distension (CRD) and cardiovascular (CV) responses to phasic colorectal distension. Tolerance to a continuous infusion of 6 or 20 nmol/h of morphine sulfate developed over 6 days. A significant reduction in the dose-dependent effects of intrathecal morphine in the TF and HP tests and VM and CV responses to CRD occurred in rats receiving continuous infusions of morphine. The development of tolerance to intrathecal morphine was similar in both cutaneous and visceral models. PMID:9665657

  13. Effects of dronabinol on morphine-induced dopamine-related behavioral effects in animals.

    PubMed

    Mori, Tomohisa; Shibasaki, Masahiro; Abe, Minako; Udagawa, Yuya; Suzuki, Tsutomu

    2012-11-01

    The present study examined the effects of dronabinol, a United States FDA-approved synthetic cannabinoid receptor agonist, on morphine (a prototypic ?-opioid receptor agonist)-induced dopamine-related behaviors in animals. Dronabinol suppressed the rewarding effects of morphine in rats and its emetic effects in ferrets. Furthermore, the morphine-induced increase in dopamine release from the nucleus accumbens was significantly attenuated by dronabinol, which indicated that the suppressive effects of dronabinol on morphine-induced behaviors are at least in part mediated by regulation of the dopaminergic system. Since cannabinoid receptor agonists have been shown to enhance the antinociceptive effects of morphine, the use of dronabinol as an adjuvant could be useful for preventing the adverse effects of ?-opioid receptor agonists when used to control pain. PMID:22807156

  14. Nano and Microparticulate Chitosan Based System for Formulation of Carvedilol Rapid Melt Tablet

    PubMed Central

    Patil, Ravindra; Pande, Vishal; Sonawane, Raju

    2015-01-01

    Purpose: In the present study rapid melt tablets (RMT’s) of carvedilol were prepared by using ionotropic-gelated chitosan nanoparticles using a spray-drying method. Carvedilol is beta-adrenergic antagonist and its oral bioavailability is about 25-35% because of first pass metabolism. Methods: The spray-dried microparticles were formulated into RMT’s using a wet granulation process. The Formulation and optimization of carvedilol loaded RMTs using nano and microparticulate chitosan based system (NMCS) was done by using 32 factorial designs. Results: Drug entrapment efficiency of about 64.9 % (w/w) and loading capacity of 14.44% (w/w) were achieved for the microparticles, which were ranged from 1 ?m to 4 ?m in diameter. Results of disintegration tests showed that the formulated RMTs could be completely dissolved within 40 seconds. Dissolution studies suggested that Carvedilol is released more slowly from tablets made using the microencapsulation process compared with tablets containing Carvedilol that is free or in the form of nanoparticles. Conclusion: Results shown that the development of new RMTs designed with crosslinked microparticle might be a rational way to overcome the unwanted taste of conventional RMTs and the side effects related to Carvedilol intrinsic characteristics. The development of Carvedilol NMCS using ludiflash as RMTs could be used as a promising approach for improving the solubility and oral bioavailability of water insoluble drug. PMID:26236654

  15. Changes in key constituents of clonally propagated Artemisia annua L. during preparation of compressed leaf tablets for possible therapeutic use

    PubMed Central

    Weathers, Pamela J.; Towler, Melissa J.

    2014-01-01

    Artemisia annua L., long used as a tea infusion in traditional Chinese medicine, produces artemisinin. Although artemisinin is currently used as artemisinin-based combination therapy (ACT) against malaria, oral consumption of dried leaves from the plant showed efficacy and will be less costly than ACT. Many compounds in the plant have some antimalarial activity. Unknown, however, is how these plant components change as leaves are processed into tablets for oral consumption. Here we compared extracts from fresh and dried leaf biomass with compressed leaf tablets of A. annua. Using GC-MS, nineteen endogenous compounds, including artemisinin and several of its pathway metabolites, nine flavonoids, three monoterpenes, a coumarin, and two phenolic acids, were identified and quantified from solvent extracts to determine how levels of these compounds changed during processing. Results showed that compared to dried leaves, artemisinin, arteannuin B, artemisinic acid, chlorogenic acid, scopoletin, chrysoplenetin, and quercetin increased or remained stable with powdering and compression into tablets. Dihydroartemisinic acid, monoterpenes, and chrysoplenol-D decreased with tablet formation. Five target compounds were not detectable in any of the extracts of this cultivar. In contrast to the individually measured aglycone flavonoids, using the AlCl3 method, total flavonoids increased nearly fivefold during the tablet formation. To our knowledge this is the first study documenting changes that occurred in processing dried leaves of A. annua into tablets. These results will improve our understanding of the potential use of not only this medicinal herb, but also others to afford better quality control of intact plant material for therapeutic use. PMID:25228784

  16. Effects of ultra-low doses of morphine, naloxone and ethanol on morphine state-dependent memory of passive avoidance in mice.

    PubMed

    Tayebi Meybodi, K; Vakili Zarch, A; Zarrindast, M R; Djahanguiri, B

    2005-05-01

    This experiment examined and compared the effects of pre-test administration of morphine, naloxone and ethanol, at doses in the range of milligram/kg to those of nanogram/kg, on morphine state-dependent learning in a step-down passive avoidance task in mice. Morphine (5 mg/kg) administered before training impaired retention tested 24 hours later, but when the same dose of morphine was also administered before the test, the retention was significantly restored. Pre-training administration of 10 or 20 ng/kg (i.p.) of morphine had no effect, but when co-administered with the same drug at 5 mg/kg (s.c.), it prevented significantly the memory recall improvement after the administration of morphine (5 mg/kg, s.c.) alone. In a parallel experiment, naloxone (5 mg/kg) prevented the memory recall improvement by morphine. However, the effects of naloxone at doses in the range of ng/kg were opposite to those of milligram doses of the same drug. Pre-test administration of ethanol (1 mg/kg) improved memory recall and mimicked the effects of pre-test morphine administration. At doses in the nanogram range, the effects of ethanol were opposite those of mg/kg of the drug. A review of the literature indicates that, for several drugs and chemicals, the effects of nanogram doses are the opposite of the effects of milligrams, because different doses have different sites as well as mechanisms of actions. In conclusion, from the above results one may suggest that, in determination of the dose-response of at least some drugs, the study of the effects of doses much lower than two orders of magnitude of the minimum effective dose are warranted. PMID:15864068

  17. Photoaffinity labeling of rat liver microsomal morphine UDP-glucuronosyltransferase by ( sup 3 H)flunitrazepam

    SciTech Connect

    Thomassin, J.; Tephly, T.R. )

    1990-09-01

    Benzodiazepines have been shown to competitively inhibit morphine glucuronidation in rat and human hepatic microsomes. Flunitrazepam exerted a potent competitive inhibition of rat hepatic morphine UDP-glucuronosyltransferase (UDPGT) activity (Ki = 130 microM). It has no effect on the activity of p-nitrophenol, 17 beta-hydroxysteroid, 3 alpha-hydroxysteroid, or 4-hydroxybiphenyl UDPGTs. Because flunitrazepam is an effective photoaffinity label for benzodiazepine receptors, studied were performed in solubilized rat hepatic microsomes and with partially purified preparations of morphine UDPGT to determine the enhancement of flunitrazepam inhibition and binding to morphine UDPGT promoted by exposure to UV light. Under UV light, flunitrazepam inhibition was markedly enhanced. UV light exposure also led to a marked increase in binding of (3H)flunitrazepam to microsomal protein, which was protected substantially by preincubation with morphine. Testosterone, androsterone, and UDP-glucuronic acid did not protect against UV-enhanced flunitrazepam binding, and morphine did not reverse flunitrazepam binding once binding had occurred. As morphine UDPGT was purified, a good correlation was found between the increases in specific activity of morphine UDPGT and flunitrazepam binding to protein. Chromatofocusing chromatography showed that flunitrazepam bound only to fractions containing active morphine UDPGT, and no binding to 4-hydroxybiphenyl UDPGT was observed. Fluorography of a sodium dodecyl sulfate-polyacrylamide electrophoresis gel of solubilized hepatic microsomes that had been treated with (3H) flunitrazepam under UV light revealed a band with a monomeric molecular weight between 54,000 and 58,000. This monomeric molecular weight compares favorably with the reported monomeric molecular weight of homogeneous morphine UDPGT (56,000).

  18. Role of C-fibers in pain and morphine induced analgesia/hyperalgesia in rats

    PubMed Central

    Alizadeh, Zahra; Behnam-Rassouli, Morteza; Hosseini, Shirin

    2014-01-01

    Background Usual dosage of morphine (10 mg/kg) induces analgesia and ultra-low dose (ULD) of morphine (1 µg/kg); hyperalgesia, and C-fibers are also bearing µ-opioid receptors; here the importance of C-fibers on pain and morphine induced analgesia/hyperalgesia is questioned and investigated using pain evaluation methods and infant capsaicin treating for C-fibers lesioning. Methods Wistar male rats (200-250 grams) were assigned to three categories i.e. control, sham (receiving neonatal capsaicin vehicle) and c-lesion (receiving neonatal capsaicin), each one with three groups (n=7). They were injected intraperitoneally with single dosage of saline, 10 mg/kg or 1 µg/kg morphine, respectively. Thermal pain threshold was evaluated using the tail flick test before and 30 minutes after the injections. Chemical pain was assessed using the formalin test (FT) 30 minutes after the administrations. Results Results indicated that thermal (P < 0.001) and chemical pains in both neurogenic and inflammatory phases of FT (P < 0.05) were reduced in C-lesion animals. In the C-normal and C-lesion animals, 10 mg/kg morphine exerted analgesia both in thermal (P < 0.001) and two phases of FT (P < 0.01), but it was more potent in C-lesion animals (P < 0.05). Although ULD of morphine in C-normal animals produced hyperalgesic effect in thermal and chemical pains (P < 0.001), in C-lesion animals, it produced analgesia (P < 0.05) at the neurogenic phase of FT. Conclusion Results can raise the C-fibers involvement for a significant portion of nociceptive transmission, because C-lesioning potentiated morphine induced analgesia and eliminated ULD of morphine induced hyperalgesia. Therefore C and A? fibers can be involved in morphine analgesia; while, just C-fibers are possibly responsible for only presynaptically hyperalgesic/excitatory action of ULD in morphine. PMID:24800043

  19. The interaction of adenosine and morphine on pentylenetetrazole-induced seizure threshold in mice.

    PubMed

    Moezi, Leila; Akbarian, Reyhane; Niknahad, Hossein; Shafaroodi, Hamed

    2013-09-01

    Adenosine agonists or low doses of morphine exert anti-convulsant effects in different models of seizures. On the other hand, a tight interaction has been reported between morphine and adenosine in various paradigms. This study investigated the effect of the interaction of adenosine and morphine on seizure susceptibility in the intravenous mouse model of pentylenetetrazole (PTZ)-induced clonic seizures. The researchers used acute systemic administration of morphine, N(6)-cyclohexyladenosine (CHA) (a selective A1 receptor agonist), naltrexone (an opioid receptor antagonist) and 8-Cyclopentyl-1,3-dimethylxanthine (8-CPT) (a selective A1 receptor antagonist). Acute administration of morphine (0.25, 0.5 and 1 mg/kg) or CHA (0.25, 0.5, 1, 2 and 4 mg/kg) raised the threshold of seizures induced by PTZ. Non-effective dose of 8-CPT (2 mg/kg) inhibited the anticonvulsant effects of CHA (0.5 and 1 mg/kg). Combination of sub-effective doses of morphine (0.125 mg/kg) and CHA (0.125 mg/kg) increased clonic seizure latency showing the additive effect of morphine and CHA. The enhanced latency induced by combination of low doses of morphine and CHA completely reversed by 8-CPT (2 mg/kg) or naltrexone (1 mg/kg). Moreover, 8-CPT (2 mg/kg) inhibited anticonvulsant effects of morphine (0.25 and 0.5 mg/kg) and naltrexone (1 mg/kg) inhibited anticonvulsant effects of CHA (0.25, 0.5 and 1 mg/kg). Combination of low doses of 8-CPT (1 mg/kg) and naltrexone (0.5 mg/kg) inhibited the anticonvulsant effect of CHA (0.5 and 1 mg/kg). In conclusion, adenosine and morphine exhibit an additive effect on the enhancement of the pentylenetetrazole-induced seizure threshold in mice, probably through A1 or ? receptors. PMID:23624288

  20. Morphine dependence in single enteric neurons from the mouse colon requires deletion of ??arrestin2

    PubMed Central

    Smith, Tricia H.; Ngwainmbi, Joy; Hashimoto, Atsushi; Dewey, William L.; Akbarali, Hamid I.

    2014-01-01

    Abstract Chronic administration of morphine results in the development of tolerance to the analgesic effects and to inhibition of upper gastrointestinal motility but not to colonic motility, resulting in persistent constipation. In this study we examined the effect of chronic morphine in myenteric neurons from the adult mouse colon. Similar to the ileum, distinct neuronal populations exhibiting afterhyperpolarization (AHP)?positive and AHP?negative neurons were identified in the colon. Acute morphine (3 ?M) decreased the number of action potentials, and increased the threshold for action potential generation indicative of reduced excitability in AHP?positive neurons. In neurons from the ileum of mice that were rendered antinociceptive tolerant by morphine?pellet implantation for 5 days, the opioid antagonist naloxone precipitated withdrawal as evidenced by increased neuronal excitability. Overnight incubation of ileum neurons with morphine also resulted in enhanced excitability to naloxone. Colonic neurons exposed to long?term morphine, remained unresponsive to naloxone suggesting that precipitated withdrawal does not occur in colonic neurons. However, morphine?treated colonic neurons from ??arrestin2 knockout mice demonstrated increased excitability upon treatment with naloxone as assessed by change in rheobase, number of action potentials and input resistance. These data suggest that similar to the ileum, acute exposure to morphine in colonic neurons results in reduced excitability due to inhibition of sodium currents. However, unlike the ileum, dependence to chronic exposure of morphine develops in colonic neurons from the ??arrestin2 knockout mice. These studies corroborate the in?vivo findings of the differential role of neuronal ??arrestin2 in the development of morphine tolerance/dependence in the ileum and colon. PMID:25194025

  1. Characterization of norfloxacine release from tablet coated with a new pH-sensitive polymer, P-4135F.

    PubMed

    Hu, Z; Shimokawa, T; Ohno, T; Kimura, G; Mawatari, S S; Kamitsuna, M; Yoshikawa, Y; Masuda, S; Takada, K

    1999-01-01

    A new pH-sensitive polymer, P-4135F, was evaluated as a colon delivery device for norfloxacine (NFLX) which is used for the therapy of patients with Vero toxin-producing Escherichia coli gastroenteritis. P-4135F has a dissolution threshold pH of 7.2 which is higher than the conventional pH-sensitive polymers, Eudragit S100 and L100. To compare the dissolution site of P-4135F coated tablets with other enteric polymer coatings, mini-tablets containing sodium fluorescein (FL) as a model drug were prepared by coating them with the three polymers. After oral administration of FL mini-tablets to rats, the first-appearance time, Ti, of FL into the systemic circulation was measured. The Tis were 0.7+/-0.2 h for Eudragit L100, 1.8+/-0.4 h for S100 and 2.0+/-0.3 h for P-4135F. Direct inspection of the dissolution process of the FL mini-tablets after oral administration to rats was performed by abdominal incision studies. All of the coated FL mini-tablets started to dissolve in the rat ileum. The dissolution sites were identified to be proximal to the ileocecal junction for P-4135F, at the middle part of the ileum for Eudragit S100 and at the proximal part of the ileum for Eudragit L100. NFLX tablets with different membrane thicknesses of P-4135F were prepared and were orally administered to beagle dogs. The colon delivery efficiency was evaluated by measuring the Ti of NFLX into the systemic circulation. The mean Tis were 1.33+/-0.33 h for 56.8+/-0.5 microm membranes, 3.75+/-0.25 h for 64.6+/-0.7 microm membranes, 4.00+/-1.00 h for 70.5+/-0.5 microm membranes and 3.00+/-1.00 h for 74.9+/-0.4 microm membranes. By comparing the Ti, 4.33+/-0.33 h, obtained after oral administration of NFLX in a pressure-controlled colon delivery capsule, and the colon arrival time, 3.5+/-0.3 h, determined by a sulfasalazine test in beagle dogs. P-4135F coated NFLX tablets appeared to dissolve and disintegrate before reaching the colon. Studies using rats and beagle dogs have suggested that P-4135F dissolves in the lower part of the small intestine, i.e., the ileum. These studies also suggest that this new polymer will be useful for the delivery of NFLX to the lower part of the small intestine. PMID:10680978

  2. Therapeutic suggestion has not effect on postoperative morphine requirements.

    PubMed

    van der Laan, W H; van Leeuwen, B L; Sebel, P S; Winograd, E; Baumann, P; Bonke, B

    1996-01-01

    This study was designed to confirm the effect of therapeutic intraoperative auditory suggestion on recovery from anesthesia, to establish the effect of preoperative suggestion, and to assess implicit memory for intraoperative information using an indirect memory task. Sixty consenting unpremedicated patients scheduled for elective gynecologic surgery were randomly divided into three equal groups: Group 1 received a tape of therapeutic suggestions preoperatively, and the story of Robinson Crusoe intraoperatively; Group 2 heard the story of Peter Pan preoperatively and therapeutic suggestions intraoperatively; Group 3 heard the Crusoe story preoperatively and the Peter Pan story intraoperatively. A standardized anesthetic technique was used with fentanyl, propofol, isoflurane, and nitrous oxide. After surgery, all patients received patient-controlled analgesia (PCA) with a standardized regimen. In the 24 h postsurgery, morphine use was recorded every 6 h and at 24 h an indirect memory test (free association) was used to test for memory of the stories. Anxiety scores were measured before surgery and at 6 and 24 h postsurgery. There were no significant differences between groups for postoperative morphine use, pain or nausea scores, anxiety scores, or days spent in hospital after surgery. Seven of 20 patients who heard the Pan story intraoperative gave a positive association with the word "Hook," whereas 2 of 20 who did not hear the story gave such an association. Indirect memory for the Pan story was established using confidence interval (CI) analysis. (The 95% CI for difference in proportion did not include zero). No indirect memory for the Crusoe story could be demonstrated. This study did not confirm previous work which suggested that positive therapeutic auditory suggestions, played intraoperatively, reduced PCA morphine requirements. In contrast, a positive implicit memory effect was found for a story presented intraoperatively. PMID:8712392

  3. Pharmaceutical tablet compaction : product and process design

    E-print Network

    Pore, Mridula

    2009-01-01

    This thesis explores how tablet performance is affected by microstructure, and how microstructure can be controlled by selection of excipients and compaction parameters. A systematic strategy for formulation and process ...

  4. Dell recommends Windows. Dell Venue 7 tablet

    E-print Network

    Azad, Abdul-Majeed

    * Super Sale Shop. Save. Enjoy the rewards.* Join Dell Advantage for free and get 10% back in rewards tablet* . Take advantage of this student offer with the purchase of a PC for $699.99 or more. Shop your

  5. Onsite Wastewater Treatment Systems: Tablet Chlorination 

    E-print Network

    Lesikar, Bruce J.

    2008-10-23

    Wastewater that is sprayed onto lawns must first be disinfected to prevent odors and remove disease-causing organisms. This publication explains how tablet chlorinators disinfect wastewater and gives tips on how to maintain them....

  6. Long-term Morphine-treated Rats are more Sensitive to Antinociceptive Effect of Diclofenac than the Morphine-naive rats

    PubMed Central

    Akbari, Esmaeil; Mirzaei, Ebrahim; Shahabi Majd, Naghi

    2013-01-01

    This study investigates the effectiveness of the antinociceptive effects of diclofenac, an NSAID, on the nociceptive behavior of morphine-treated rats on formalin test. Rats were treated with morphine-containing drinking water for twenty one days, which induced morphine dependence. The antinociceptive effects of 8, 16, and 32 mg/kg doses of diclofenac were then evaluated and compared with distilled water in a formalin-based model of pain. Diclofenac potentiated pain suppression in morphine-dependent rats during the interphase of the formalin test and reduced the pain score during phase II. The post-test analysis revealed that both 16 mg/kg (p < 0.0001) and 32 mg/kg (p < 0.0001) doses of diclofenac had a significant effect on the interphase, while 8 mg/kg (p < 0.05), 16 mg/kg (p < 0.05), and 32 mg/kg (p < 0.01) doses of diclofenac significantly affected phase II. In contrast, the antinociceptive effects of diclofenac on morphine-naïve rats were observed during phase II only with the a 32 mg/kg dose (p < 0.05). In general, these results suggest that the long-term use of morphine in rats increases their sensitivity to the antinociceptive effects of diclofenac. Furthermore, the results support the existence of a non-opioid-dependent mechanism of pain suppression during the interphase of formalin test. PMID:24250586

  7. Electronic acquisition of OSCE performance using tablets

    PubMed Central

    Hochlehnert, Achim; Schultz, Jobst-Hendrik; Möltner, Andreas; T?mb?l, Sevgi; Brass, Konstantin; Jünger, Jana

    2015-01-01

    Background: Objective Structured Clinical Examinations (OSCEs) often involve a considerable amount of resources in terms of materials and organization since the scores are often recorded on paper. Computer-assisted administration is an alternative with which the need for material resources can be reduced. In particular, the use of tablets seems sensible because these are easy to transport and flexible to use. Aim: User acceptance concerning the use of tablets during OSCEs has not yet been extensively investigated. The aim of this study was to evaluate tablet-based OSCEs from the perspective of the user (examiner) and the student examinee. Method: For two OSCEs in Internal Medicine at the University of Heidelberg, user acceptance was analyzed regarding tablet-based administration (satisfaction with functionality) and the subjective amount of effort as perceived by the examiners. Standardized questionnaires and semi-standardized interviews were conducted (complete survey of all participating examiners). In addition, for one OSCE, the subjective evaluation of this mode of assessment was gathered from a random sample of participating students in semi-standardized interviews. Results: Overall, the examiners were very satisfied with using tablets during the assessment. The subjective amount of effort to use the tablet was found on average to be “hardly difficult”. The examiners identified the advantages of this mode of administration as being in particular the ease of use and low rate of error. During the interviews of the examinees, acceptance for the use of tablets during the assessment was also detected. Discussion: Overall, it was found that the use of tablets during OSCEs was well accepted by both examiners and examinees. We expect that this mode of assessment also offers advantages regarding assessment documentation, use of resources, and rate of error in comparison with paper-based assessments; all of these aspects should be followed up on in further studies. PMID:26483854

  8. Formulation and optimization of potassium iodide tablets.

    PubMed

    Al-Achi, Antoine; Patel, Binit

    2015-01-01

    The use of potassium iodide (KI) as a protective agent against accidental radioactive exposure is well established. In this study, we aimed to prepare a KI tablet formulation using a direct compression method. We utilized Design of Experiment (DoE)/mixture design to define the best formulation with predetermined physical qualities as to its dissolution, hardness, assay, disintegration, and angle of repose. Based on the results from the DoE, the formulation had the following components (%w/w): Avicel 48.70%, silicon dioxide 0.27%, stearic acid (1.00%), magnesium stearate 2.45%, and dicalcium phosphate 18.69%, in addition to potassium iodide 28.89% (130 mg/tablet). This formulation was scaled-up using two tablet presses, a single-punch press and a rotary mini tablet press. The final scaled-up formulation was subjected to a variety of quality control tests, including photo-stability testing. The results indicate that potassium iodide tablets prepared by a rotary mini tablet press had good pharmaceutical characteristics and a shelf-life of 25 days when stored at room temperature protected from light. PMID:25685048

  9. A comparison of the clinical and bronchodilating effects of plain and slow-release tablets of terbutaline at steady state.

    PubMed

    Pauwels, R; Elinck, W; Lamont, H; van der Straeten, M; Ljungholm, K

    1986-02-01

    The clinical efficacy, the bronchodilating effect and the side effects of two oral forms of terbutaline were compared in a double-blind, cross-over study involving ten patients with chronic reversible airways obstruction. The administration of plain-tablets, containing 2.5 mg terbutaline sulphate, three times daily at 6 h intervals was compared to the administration of slow-release (SR) tablets, containing 5 mg terbutaline sulphate, every 12 h. Each course of treatment lasted for 7 days. Treatment with SR-tablets resulted in significantly higher lung function values in the morning (PEFR at home and FEV1 at the lung function laboratory on day 7). There were no significant differences between the two forms with regard to symptom score, extra use of rimiterol aerosol, heart rate or blood pressure. The plasma terbutaline concentration in the morning of the seventh treatment day was significantly higher during SR-tablet treatment. The plasma terbutaline concentration curve showed a smaller peak/trough ratio for the SR-tablets. PMID:3513810

  10. Gastroretentive pulsatile release tablets of lercanidipine HCl: development, statistical optimization, and in vitro and in vivo evaluation.

    PubMed

    Reddy, Gagganapalli Santhoshi; Nayak, Usha Yogendra; Deshpande, Praful Balavant; Mutalik, Srinivas

    2014-01-01

    The present study was aimed at the development of gastroretentive floating pulsatile release tablets (FPRTs) of lercanidipine HCl to enhance the bioavailability and treat early morning surge in blood pressure. Immediate release core tablets containing lercanidipine HCl were prepared and optimized core tablets were compression-coated using buoyant layer containing polyethylene oxide (PEO) WSR coagulant, sodium bicarbonate, and directly compressible lactose. FPRTs were evaluated for various in vitro physicochemical parameters, drug-excipient compatibility, buoyancy, swelling, and release studies. The optimized FPRTs were tested in vivo in New Zealand white rabbits for buoyancy and pharmacokinetics. DoE optimization of data revealed FPRTs containing PEO (20%?w/w) with coat weight 480?mg were promising systems exhibiting good floating behavior and lag time in drug release. Abdominal X-ray imaging of rabbits after oral administration of the tablets, confirmed the floating behavior and lag time. A quadratic model was suggested for release at 7th and 12th?h and a linear model was suggested for release lag time. The FPRT formulation improved pharmacokinetic parameters compared to immediate release tablet formulation in terms of extent of absorption in rabbits. As the formulation showed delay in drug release both in vitro and in vivo, nighttime administration could be beneficial to reduce the cardiovascular complications due to early morning surge in blood pressure. PMID:25525619

  11. Preparation and evaluation of once-daily sustained-release coated tablets of tolterodine-L-tartrate.

    PubMed

    Pradhan, Roshan; Kim, Yong-Il; Chang, Sun Woo; Kim, Jong Oh

    2014-01-01

    In this study, once-daily, sustained-release matrix tablets of tolterodine l-tartrate (TOL) for treatment of overactive bladder (OAB) were prepared by direct compression using various amounts of hydrophilic polymers such as HPMC 2910 and HPMC 2208 along with other tablet excipients; the tablets were then coated. In vitro dissolution studies were carried out under different pH conditions. The dissolution data were fitted into zero-order, first-order, Higuchi and Korsemeyer-Peppas models to identify the pharmacokinetics and mechanism of drug release. Among the four formulations (F1-F4), the dissolution profiles of formulation F2 were most similar to the marketed product with similarity and difference factors of 70.25 and 1.59 respectively. Furthermore, pharmacokinetic studies were carried out in healthy human volunteers after oral administration of the prepared TOL sustained-release matrix-coated tablet and the marketed product. The results revealed that the pharmacokinetic parameters of AUC, Cmax, Tmax, t1/2, Kel, and MRT of TOL for the developed formulation (F2) were not significantly different from that for the marketed product, suggesting that they were bioequivalent. Therefore, the developed sustained-release tablet formulation of TOL could be an alternative dosage form to the SR capsule for treatment of OAB. PMID:24184032

  12. The effects of a permanent and selective depletion of brain catecholamines on the antinociceptive action of morphine.

    PubMed

    Slater, P; Blundell, C

    1978-12-01

    6-Hydroxydopamine was given to newborn mice. After 60 days their brains were deficient in noradrenaline and dopamine while morphine's antinociceptive action was reduced. 6-Hydroxydopa was administered to adult mice. This depleted brain noradrenaline and reduced morphine's antinociceptive action. Newborn rats received 6-hydroxydopa. After 60 days morphine's antinociceptive action was potentiated, brain noradrenaline was reduced while dopamine had increased. Adult rats were treated with 6-hydroxydopa. This reduced brain noradrenaline but did not affect morphine's antinociceptive action. Guanethidine, which depletes noradrenaline in the peripheral nervous sytem, was given to newborn animals of both species. It had no effect on morphine's antinociceptive action. It is concluded that in the mouse the antinociceptive action of morphine relies in part on normal brain noradrenaline function and dopamine is not directly involved. In the rat morphine's action is affected by neurotoxic drugs which alter brain dopamine function. PMID:740050

  13. Formulation, development, and performance evaluation of metoclopramide HCl oro-dispersible sustained release tablet.

    PubMed

    Kasliwal, Nikhil; Negi, Jeetendra Singh; Jugran, Vandana; Jain, Rahul

    2011-10-01

    The present study was undertaken to develop and evaluate an oro-dispersible, sustained release tablet of metoclopramide HCl. The technology was comprised of developing sustained release microparticles, and compression of resultant microspheres into a fast dispersible tablet by direct compression. The microspheres of metoclopramide HCl were prepared by an emulsification-solvent evaporation method using ethylcellulose as the matrix polymer. The prepared microspheres were evaluated for morphology, particle size, entrapment efficiency, and in vitro drug release characteristics. Scanning electron microscopy demonstrated spherical particles with a mean diameter of 81.27 ± 5.87 ?m and the drug encapsulation efficiency was found to be 70.15 ± 3.06%. The process and formulation variables such as rotation speed, polymer concentration, and drug concentration influenced the drug encapsulation efficiency and in vitro drug release. Optimized microspheres were compressed into tablets which were comprised of metoclopramide HCl microspheres, 53% (w/v) of D-mannitol granules, 7% (w/w) of Polyplasdone XL 10, and 0.5% (w/w) of calcium stearate. The tablets demonstrated a hardness of 59 ± 3 N, friability of 0.21% and disintegration time of 27 ± 3 sec. The formulations were subjected to stability studies as per ICH guidelines and were found to be stable after a 6 month study. In vivo experiments conducted in rats demonstrated that a constant level of metoclopramide HCl in plasma could be maintained for up to 20 h at a suitable concentration for antiemetic activity. An appropriate combination of excipients made it possible to obtain orally disintegrating sustained release tablets of metoclopramide HCl using simple and conventional techniques. PMID:22076769

  14. Hippocampal Long-Term Potentiation Is Disrupted during Expression and Extinction But Is Restored after Reinstatement of Morphine Place Preference

    PubMed Central

    Portugal, George S.; Al-Hasani, Ream; Fakira, Amanda K.; Gonzalez -Romero, Jose L.; Melyan, Zare; McCall, Jordan G.

    2014-01-01

    Learned associations between environmental cues and morphine use play an important role in the maintenance and/or relapse of opioid addiction. Although previous studies suggest that context-dependent morphine treatment alters glutamatergic transmission and synaptic plasticity in the hippocampus, their role in morphine conditioned place preference (CPP) and reinstatement remains unknown. We investigated changes in synaptic plasticity and NMDAR expression in the hippocampus after the expression, extinction, and reinstatement of morphine CPP. Here we report that morphine CPP is associated with increased basal synaptic transmission, impaired hippocampal long-term potentiation (LTP), and increased synaptic expression of the NR1 and NR2b NMDAR subunits. Changes in synaptic plasticity, synaptic NR1 and NR2b expression, and morphine CPP were absent when morphine was not paired with a specific context. Furthermore, hippocampal LTP was impaired and synaptic NR2b expression was increased after extinction of morphine CPP, indicating that these alterations in plasticity may be involved in the mechanisms underlying the learning of drug–environment associations. After extinction of morphine CPP, a priming dose of morphine was sufficient to reinstate morphine CPP and was associated with LTP that was indistinguishable from saline control groups. In contrast, morphine CPP extinguished mice that received a saline priming dose did not show CPP and had disrupted hippocampal LTP. Finally, we found that reinstatement of morphine CPP was prevented by the selective blockade of the NR2b subunit in the hippocampus. Together, these data suggest that alterations in synaptic plasticity and glutamatergic transmission play an important role in the reinstatement of morphine CPP. PMID:24403152

  15. Retrieval of morphine-associated context induces cFos in dentate gyrus neurons

    PubMed Central

    Rivera, Phillip D.; Raghavan, Ramya K.; Yun, Sanghee; Latchney, Sarah E.; McGovern, Mary-Katherin; García, Emily F.; Birnbaum, Shari G.; Eisch, Amelia J.

    2015-01-01

    Addiction has been proposed to emerge from associations between the drug and the reward-associated contexts. This associative learning has a cellular correlate, as there are more cFos+ neurons in the hippocampal dentate gyrus (DG) after psychostimulant conditioned place preference (CPP) vs. saline controls. However, it is unknown whether morphine CPP leads to a similar DG activation, or whether DG activation is due to locomotion, handling, pharmacological effects, or – as data from contextual fear learning suggests – exposure to the drug-associated context. To explore this, we employed an unbiased, counterbalanced, and shortened CPP design that led to place preference, more DG cFos+ cells, and yet decreased locomotion. Next, mice underwent morphine CPP but were then sequestered into the morphine-paired (conditioned stimulus+ [CS+]) or saline-paired (CS?) context on test day. Morphine-paired mice sequestered to CS+ had ~30% more DG cFos+ cells than saline-paired mice. Furthermore, Bregma analysis revealed morphine-paired mice had more cFos+ cells in CS+ compared to CS? controls. Notably, there was no significant difference in DG cFos+ cell number after handling alone or after receiving morphine in home cage. Thus, retrieval of morphine-associated context is accompanied by activation of hippocampal DG granule cell neurons. PMID:25424867

  16. Morphine Biosynthesis in Opium Poppy Involves Two Cell Types: Sieve Elements and Laticifers[W][OPEN

    PubMed Central

    Onoyovwe, Akpevwe; Hagel, Jillian M.; Chen, Xue; Khan, Morgan F.; Schriemer, David C.; Facchini, Peter J.

    2013-01-01

    Immunofluorescence labeling and shotgun proteomics were used to establish the cell type–specific localization of morphine biosynthesis in opium poppy (Papaver somniferum). Polyclonal antibodies for each of six enzymes involved in converting (R)-reticuline to morphine detected corresponding antigens in sieve elements of the phloem, as described previously for all upstream enzymes transforming (S)-norcoclaurine to (S)-reticuline. Validated shotgun proteomics performed on whole-stem and latex total protein extracts generated 2031 and 830 distinct protein families, respectively. Proteins corresponding to nine morphine biosynthetic enzymes were represented in the whole stem, whereas only four of the final five pathway enzymes were detected in the latex. Salutaridine synthase was detected in the whole stem, but not in the latex subproteome. The final three enzymes converting thebaine to morphine were among the most abundant active latex proteins despite a limited occurrence in laticifers suggested by immunofluorescence labeling. Multiple charge isoforms of two key O-demethylases in the latex were revealed by two-dimensional immunoblot analysis. Salutaridine biosynthesis appears to occur only in sieve elements, whereas conversion of thebaine to morphine is predominant in adjacent laticifers, which contain morphine-rich latex. Complementary use of immunofluorescence labeling and shotgun proteomics has substantially resolved the cellular localization of morphine biosynthesis in opium poppy. PMID:24104569

  17. Morphine-induced enhancement in the granulocyte response to thioglycollate administration in the rat.

    PubMed

    Fecho, Karamarie; Lysle, Donald T

    2002-12-01

    The present study determined the pharmacological effects of acute morphine treatment on the granulocyte phase of the peritoneal inflammatory response to thioglycollate (TG) in rats. Dual-color flow cytometry using anti-CD11b/c-PE mAb in combination with HIS48-FITC mAb allowed for the determination of morphine's effects on 4 inflammatory cell subsets: CD11b/c(+)HIS48med granulocytes; CD11b/c(hi)HIS48neg/lo activated macrophages; CD11b/c(-)HIS48(-) lymphocytes; and CD11b/c(+)HIS48hi cells (a monocyte/macrophage and granulocyte subset). Morphine produced a dose-dependent increase in a select subset of inflammatory peritoneal cells, the CD11b/c(+)HIS48med granulocytes. The effect of morphine was time-dependent, with significant effects first apparent at 4 hr after TG, but the administration of morphine 1 hr before or simultaneously with TG produced a similar increase in CD11b/c(+)HIS48med granulocytes. Naltrexone completely antagonized the morphine-induced increase in CD11b/c(+)HIS48med granulocytes. Collectively, these studies show that a single administration of morphine produces a time-dependent, dose-dependent, opioid receptor-mediated enhancement in the peritoneal granulocyte response to TG. PMID:12546135

  18. Ineffective Doses of Dexmedetomidine Potentiates the Antinociception Induced by Morphine and Fentanyl in Acute Pain Model

    PubMed Central

    Unal, Mumin; Gursoy, Sinan; Altun, Ahmet; Duger, Cevdet; Kol, Iclal Ozdemir; Kaygusuz, Kenan; Bagcivan, Ihsan

    2013-01-01

    The aim of this study was to evaluate the synergistic potentiation effect of ineffective doses of dexmedetomidine on antinociception induced by morphine and fentanyl in acute pain model in rats. Seventy albino Wistar rats were separated into 7 groups. Data for the control and sham groups were recorded. The ineffective dose of dexmedetomidine was investigated and found to be 3 µ g/kg. Each group was administered the following medications: 3 mg/kg morphine (intraperitoneal) to Group 3, 5 µg/kg fentanyl (intraperitoneal) to Group 4, dexmedetomidine 3 µ g/kg (subcutaneously) to Group 5, dexmedetomidine 3 µg/kg (subcutaneous)+3 mg/kg morphine (intraperitoneal) to Group 6 and finally 3 µg/kg dexmedetomidine (subcutaneous)+5 µg/kg fentanyl (intraperitoneal) to Group 7. Just before the application and 15, 30, 60, 90 and 120 min after the administration of medication, two measurements of tail flick (TF) and hot plate (HP) tests were performed. The averages of the measurements were recorded. TF and HP latencies were the main outcomes. The analgesic effect of the combinations with dexmedetomidine+morphine (Group 6) and dexmedetomidine+fentanyl (Group 7), compared to the analgesic effect of morphine alone and fentanyl alone was significantly higher at 15, 30, 60 and 90 minutes after administration. In this study, dexmedetomidine in ineffective doses, when combined with morphine and fentanyl, potentiates the effects of both morphine and fentanyl. PMID:24227942

  19. Morphine Modulates Interleukin-4- or Breast Cancer Cell-induced Pro-metastatic Activation of Macrophages

    PubMed Central

    Khabbazi, Samira; Goumon, Yannick; Parat, Marie-Odile

    2015-01-01

    Interactions between cancer cells and stromal cells in the tumour microenvironment play a key role in the control of invasiveness, metastasis and angiogenesis. Macrophages display a range of activation states in specific pathological contexts and alternatively activated (M2) macrophages can promote tumour aggressiveness. Opioids are able to modulate tumour growth and metastasis. We tested whether morphine modulates the activation of macrophages induced by (i) interleukin-4 (IL-4), the prototypical M2 polarization-inducing cytokine, or (ii) coculture with breast cancer cells. We showed that IL-4 causes increased MMP-9 production and expression of the alternative activation markers arginase-1 and MRC-1. Morphine prevented IL-4-induced increase in MMP-9 in a naloxone- and methylnaltrexone-reversible fashion. Morphine also prevented IL-4-elicited alternative activation of RAW264.7 macrophages. Expression of MMP-9 and arginase-1 were increased when RAW264.7 were subjected to paracrine activation by 4T1 cells, and this effect was prevented by morphine via an opioid receptor-mediated mechanism. Morphine further decreased 4T1 breast cancer cell invasion elicited by co-culture with RAW264.7. Reduction of MMP-9 expression and alternative activation of macrophages by morphine was confirmed using mouse bone marrow-derived macrophages. Taken together, our results indicate that morphine may modulate tumour aggressiveness by regulating macrophage protease production and M2 polarization within the tumour microenvironment. PMID:26078009

  20. Enhancement of the contact hypersensitivity reaction by acute morphine administration at the elicitation phase.

    PubMed

    Nelson, C J; How, T; Lysle, D T

    1999-11-01

    The present study investigated the effects of morphine on the irritant contact sensitivity (ICS) and contact hypersensitivity (CHS) reaction. ICS was induced by croton oil application on the pinnae of naïve rats. Morphine injected prior to croton oil application did not affect the ICS response when assessed by measurements of pinnae thickness. CHS was induced by applying the antigen 2,4-dinitro-1-fluorobenzene (DNFB) to the pinnae of rats sensitized to DNFB. Rats received an injection of morphine prior to either initial antigen exposure (sensitization) or antigen reexposure (challenge). Morphine prior to challenge, but not sensitization, resulted in a pronounced enhancement of the CHS response as measured by pinna thickness. Quantitative PCR also showed increased IFN-gamma mRNA levels in the inflamed tissue of morphine-treated rats. Naltrexone blocked the morphine-induced enhancement of the CHS response. The differential effects of morphine suggest that opioids have a more pronounced effect on in vivo immune responses that involve immunological memory. PMID:10527694

  1. Morphine has latent deleterious effects on the ventilatory responses to a hypoxic-hypercapnic challenge

    PubMed Central

    May, Walter J.; Henderson, Fraser; Gruber, Ryan B.; Discala, Joseph F.; Young, Alex P.; Bates, James N.; Palmer, Lisa A.; Lewis, Stephen J.

    2014-01-01

    This study explored the concept that morphine has latent deleterious actions on the ventilatory control systems that respond to a hypoxic-hypercapnic challenge. In this study, we examined the ventilatory responses elicited by hypoxic-hypercapnic challenge in conscious rats at a time when the effects of morphine (10 mg/kg) on arterial blood-gas chemistry and minute ventilation had subsided. Morphine induced pronounced changes in arterial blood-gas chemistry (e.g., an increase in pCO2, decreases in pO2 and sO2) and decreases in minute ventilation. Despite the complete resolution of the morphine-induced changes in arterial blood-gas chemistry and minute ventilation and almost complete resolution of the effects on peak inspiratory flow and peak expiratory flow, subsequent exposure to hypoxic-hypercapnic challenge elicited markedly blunted increases in minute ventilation and in peak inspiratory and expiratory flows. These findings demonstrate that (1) the changes in arterial blood-gas chemistry elicited by morphine parallel changes in minute ventilation rather than PIF and PEF, and (2) morphine has latent untoward effects on the ventilatory responses to hypoxic-hypercapnic challenge. These novel findings raise the possibility that patients deemed to have recovered from the acute ventilatory depressant effects of morphine may still be susceptible to the latent effects of this opioid analgesic. The mechanisms underlying these latent effects remain to be elucidated. PMID:25045592

  2. Neuroprotection of donepezil against morphine-induced apoptosis is mediated through Toll-like receptors.

    PubMed

    Shafie, Alireza; Moradi, Farshid; Izadpanah, Esmael; Mokarizadeh, Aram; Moloudi, Mohammad Raman; Nikzaban, Mehrnoush; Hassanzadeh, Kambiz

    2015-10-01

    Previously, we had shown that donepezil provides anti-apoptotic effects associated with the prevention of morphine tolerance to the analgesic effect. In this regard, the present study aimed to evaluate the molecular mechanisms involved in this effect considering the possible role of Toll-like receptor (TLR) 2,4, and the balance between pre-apoptotic and anti-apoptotic Bcl family proteins. To this end, male Wistar rats received daily morphine in combination with either normal saline or donepezil (0.5, 1, or 1.5mg/kg, ip). The analgesic effect was assessed by the plantar test apparatus. The latency was recorded when the animal responded to the light stimulus. On the 15th day, when no significant difference was observed between morphine and saline groups in terms of analgesia, the frontal cortex and lumbar spinal cord of the animals were dissected. Then, TLR2 and 4, Bcl2, and Bax mRNA fold changes were calculated using Real-time PCR method. The results indicated no significant analgesic effect in the morphine group compared with the saline treated animals after 15 days of injection, while daily co-administration of donepezil with morphine preserved significant analgesia. Moreover, Quantitative PCR showed that morphine significantly increased TLRs and Bax gene expressions and decreased the anti-apoptotic Bcl2. In contrast, donepezil prevented these morphine induced changes in the mentioned gene expressions. Taken together, the results suggest that the neuroprotective effects of donepezil in attenuating morphine-induced tolerance and apoptosis are mediated by preventing morphine-induced changes in TLR2 and 4 gene expressions. PMID:26172079

  3. Nigella sativa extract affects conditioned place preference induced by morphine in rats

    PubMed Central

    Anvari, Milad; Seddigh, Atefeh; Shafei, Mohammad Naser; Rakhshandeh, Hassan; Talebi, Amir Hossein; Tahani, Mohammad Reza; Saeedjalali, S. Mohsen; Hosseini, Mahmoud

    2012-01-01

    Objective: Neuroprotective, antioxidant, anticonvulsant, and analgesic effects of Nigella sativa (NS) have been previously shown. The interaction of NS with opioid system has also been reported. In the present study, the effects of NS hydro-alcoholic extract on the acquisition and expression of morphine-induced conditioned place preference (CPP) in rats were evaluated. Materials and Methods: CPP was induced by injection of morphine (5 mg/kg, i.p.) on three consecutive days in compartment A of the CPP apparatus. Injection of NS extract (200 and 400 mg/kg, i.p.) 60 min before morphine administration on the conditioning days and 60 min before the post-conditioning phase was done for the evaluation of acquisition and expression effects, respectively. Conditioning effect of NS extract was also evaluated by injection of extract (200 or 400 mg/kg, i.p.) in the conditioning phase, instead of morphine in different groups. The difference in time which the animals spent in compartment A on the day before conditioning and the days after conditioning was determined and compared between groups. Results: The time spent by the rats in compartment A in the morphine group was greater than that in the saline group (P < 0.01). Both doses of NS extract decreased acquisition of morphine-induced CPP (P < 0.01 and P < 0.001), but had no significant effect on the expression of morphine CPP. Higher dose of the extract (400 mg) showed a significant conditioning effect which was comparable to the effect of morphine. Conclusion: The results of the present study showed that the hydro-alcoholic extract of NS has conditioning effect. It also decreased acquisition, but had no significant effect on the expression of morphine CPP. PMID:24167332

  4. Age- and Strain- Dependent Influences of Morphine on Mouse Social Investigation Behavior

    PubMed Central

    Kennedy, Bruce C.; Panksepp, Jules B.; Wong, Jenny C.; Krause, Emily J.; Lahvis, Garet P.

    2011-01-01

    Opioid-coded neural circuits play a substantial role in how individuals respond to drugs of abuse, and most individuals begin using such drugs during adolescence and within a social context. Several studies indicate that adolescent mice exhibit a heightened sensitivity to the effects of morphine, the prototypical opiate drug, when compared with adults, but it is unclear whether these developmental differences are related to aspects of motivated behavior. Moreover, exposure to opioids within the rodent brain can alter the expression of social behavior, yet little is known about whether this relationship changes as a function of development or genetic variation. In this study, we conducted a series of experiments to characterize the relationship between genetic background, adolescent development and morphine-induced changes in mouse social investigation (SI). At two time-points during adolescent development (postnatal day [PD] 25 and 45), social interactions of test mice of the gregarious C57BL/6J (B6) strain were more tolerant to the suppressive effects of morphine (ED50 = 0.97 and 2.17 mg/kg morphine, respectively) than test mice from the less social BALB/cJ (BALB) strain (ED50 = 0.61 and 0.91 mg/kg morphine, respectively). By contrast, this strain-dependent difference was not evident among adult mice on PD 90 (ED50 = 1.07 and 1.41 mg/kg morphine for BALB and B6 mice, respectively). An additional experiment demonstrated that the ability of morphine to alter social responsiveness was not directly related to drug-induced changes in locomotor behavior. Finally, administration of morphine to stimulus mice on PD 25 reduced social interaction of test mice only when individuals were from the B6 genetic background. Overall, these results indicate that alterations in endogenous opioid systems are related to changes in SI that occur during adolescence and that morphine administration may mimic the rewarding nature of SI. PMID:21358324

  5. Morphine modifies the cingulate-operculum network underlying painful rectal evoked potentials.

    PubMed

    Lelic, D; Olesen, A E; Gregersen, H; Dahan, A; Kolesnikov, Y; Drewes, A M

    2014-02-01

    The effect of opioids on brain networks underlying rectal evoked potentials (EPs) has never been investigated. This study utilized brain source connectivity to explore whether morphine induced changes in brain networks underlying painful rectal EPs would reflect changes in pain scores due to morphine. Twenty healthy volunteers were included in this placebo-controlled cross-over study. Sensory and pain thresholds to electrically induced rectal stimulation were taken before (baseline) and 70 min after placebo/morphine (30 mg) administration. The stimulation intensity required to evoke moderate pain at baseline was employed for EPs. The pain score of this stimulation intensity was recorded again 70 min after placebo/morphine administration. 62-channel EPs were recorded for both arms. Amplitudes and latencies were analysed and brain source connectivity analysis was done. Changes in any of the parameters describing EPs were correlated to changes in subjective pain ratings. Morphine increased sensory and pain thresholds by 28.8% and 27.5% (P ? 0.02). The pain score corresponding to moderate pain at baseline was attenuated in both placebo and morphine arms by 14.5% and 37.5% (P < 0.05). There was a 33.9% reduction in EP amplitudes due to placebo (P < 0.05), whereas EP amplitudes remained stable due to morphine. A dominating cingulate-operculum network to rectal pain was seen. Cingulate source shifted anteriorly in the morphine arm (P < 0.001) and this shift was positively correlated to the change in the pain score (r = 0.6, P < 0.05). These findings indicate that visceral pain relief due to morphine is associated with reorganization within cingulate cortex, which may be used as a biomarker of opioid effects. PMID:24184388

  6. Nitric oxide in central amygdala potentiates expression of conditioned withdrawal induced by morphine

    PubMed Central

    Karami, Manizheh; Rahimpour, Mahnaz; Karimi, Sara; Sahraei, Hedayat

    2014-01-01

    Objective: The aim of this study was to evaluate if nitric oxide (NO) in the central amygdala (CeA) is involved in the expression of withdrawal aspects induced by morphine. Materials and Methods: Male Wistar rats (weighing 200-250 g) were bilaterally cannulated in the CeA and conditioned to morphine using an unbiased paradigm. Morphine (2.5-10 mg/kg) was subcutaneously injected once a day throughout the conditioning phase of the procedure. This phase also included 3-saline paired sessions. Naloxone (0.1-0.4 mg/kg, intraperitoneally [i.p.]), an antagonist of opioid receptors, was administered i.p. 10 min prior to testing of morphine-induced withdrawal features. The NO precursor, L-arginine (0.3-3 ?g/rat) was intra-CeA injected prior to testing of naloxone response. To evaluate the involvement of NO system an inhibitor of NO synthase (NOS), NG-nitro-L-arginine methyl ester (L-NAME) (0.3-3 ?g/rat), was injected ahead of L-arginine. Control group received saline solely instead of drug. As a complementary study, the activation of NOS was studied by nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d). Results: Morphine induced a significant increase in wet dog shaking and grooming behaviors compared with controls. Injection of naloxone pre-testing of morphine response significantly reversed the response to morphine. However, pre-microinjection of L-arginine intra-CeA recovered the response to morphine. Injection of L-NAME intra-CeA ahead of L-arginine though had no effect behaviorally, but, inhibited the NOS which has been evidenced by NADPH-d. Conclusion: The present study shows that NO in the CeA potentiates the expression of conditioned withdrawal induced by morphine paired with naloxone. PMID:24550586

  7. Intra-accumbal CB1 receptor blockade reduced extinction and reinstatement of morphine.

    PubMed

    Khaleghzadeh-Ahangar, Hossein; Haghparast, Abbas

    2015-10-01

    The limbic dopaminergic reward system is the main target of morphine-like drugs which begins from the ventral tegmental area (VTA) and sends its dopaminergic projections to the nucleus accumbens (NAc), amygdala, hippocampus and prefrontal cortex. Cannabinoid receptors exist in afferent neurons from these areas to the NAc and can modulate glutamate synaptic transmission in the NAc. Cannabinoids can interact with the opiate system in reward-related behaviors; nevertheless these systems' interaction in extinction duration and reinstatement has not been shown. In the present study, the effects of bilateral intra-accumbal administration of AM251, a CB1 receptor antagonist, on the duration of the extinction phase and reinstatement to morphine were investigated by conditioned place preference (CPP) paradigm. Forty eight adult male albino Wistar rats were used. Bilateral intra-accumbal administration of AM251 (15, 45 and 90?M/0.5?l DMSO per side) was performed. Subcutaneous administration of morphine (5mg/kg) in three consecutive days was used to induce CPP. The results showed that administration of the maximal dose of AM251 during the extinction period significantly reduces duration of extinction and reinstatement to morphine. Administration of the middle dose during the extinction period significantly attenuated reinstatement to morphine. A single microinjection of the middle dose just before the reinstatement phase significantly attenuated reinstatement to morphine only, while bilateral intra-accumbal administration of neither the lowest dose nor the vehicle (DMSO) had any effects. These results for the first time indicated that CB1 receptors within the NAc are involved in the maintenance of morphine rewarding properties, and morphine seeking behaviors in extinguished morphine-induced CPP rats. PMID:26057574

  8. Functionally Selective Signaling for Morphine and Fentanyl Antinociception and Tolerance Mediated by the Rat Periaqueductal Gray

    PubMed Central

    Morgan, Michael M.; Reid, Rachel A.; Saville, Kimber A.

    2014-01-01

    Functionally selective signaling appears to contribute to the variability in mechanisms that underlie tolerance to the antinociceptive effects of opioids. The present study tested this hypothesis by examining the contribution of G protein-coupled receptor kinase (GRK)/Protein kinase C (PKC) and C-Jun N-terminal kinase (JNK) activation on both the expression and development of tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray of the rat. Microinjection of morphine or fentanyl into the periaqueductal gray produced a dose-dependent increase in hot plate latency. Microinjection of the non-specific GRK/PKC inhibitor Ro 32-0432 into the periaqueductal gray to block mu-opioid receptor phosphorylation enhanced the antinociceptive effect of morphine but had no effect on fentanyl antinociception. Microinjection of the JNK inhibitor SP600125 had no effect on morphine or fentanyl antinociception, but blocked the expression of tolerance to repeated morphine microinjections. In contrast, a microinjection of Ro 32-0432 blocked the expression of fentanyl, but not morphine tolerance. Repeated microinjections of Ro 32-0432 blocked the development of morphine tolerance and inhibited fentanyl antinociception whether rats were tolerant or not. Repeated microinjections of SP600125 into the periaqueductal gray blocked the development of tolerance to both morphine and fentanyl microinjections. These data demonstrate that the signaling molecules that contribute to tolerance vary depending on the opioid and methodology used to assess tolerance (expression vs. development of tolerance). This signaling difference is especially clear for the expression of tolerance in which JNK contributes to morphine tolerance and GRK/PKC contributes to fentanyl tolerance. PMID:25503060

  9. Differential involvement of dopamine D1 receptors in morphine- and lithium-conditioned saccharin avoidance.

    PubMed

    Fenu, Sandro; Rivas, Emilia; Di Chiara, Gaetano

    2009-01-01

    Conditioned saccharin avoidance (CSA) can be produced when either lithium chloride (LiCl) or a reinforcing drug, such as morphine, is administered following exposure to the taste of saccharin. In this study we investigated the involvement of dopamine (DA) transmission in the acquisition of morphine and LiCl-CSA. CSA was evaluated in a two-bottle choice paradigm with two conditioning pairings between saccharin and morphine or LiCl as unconditioned stimulus (US). Morphine hydrochloride (7.5 mg/kg s.c.) or LiCl (40 mg/kg i.p.), administered 45 and 120' respectively after saccharin-drinking session, induced strong CSA. The DA D(1) receptor antagonist, SCH 39166 (0.1 mg/kg s.c.), impaired morphine-CSA if administered 15' and, to a lesser extent, 30' but not 45' before the drug (i.e immediately after saccharin drinking). In contrast SCH 39166 reduced LiCl-CSA when administered 45' before the drug and even more so when administered 105' before LiCl i.e. immediately after saccharin drinking. Therefore SCH 39166 impaired morphine-CSA when given shortly before the drug, while it impaired LiCl-CSA when given shortly after saccharin. Raclopride, a specific antagonist of D(2) receptors, failed to affect LiCl- and morphine-CSA. These results are consistent with the idea that DA, acting on D(1) receptors, plays a differential role in morphine- and LiCl-CSA. In LiCl-CSA DA is necessary for the processing (consolidation) of the short-term memory trace of the saccharin taste to be associated with the lithium-induced aversive state, while in morphine CSA contributes to mediate the appetitive properties of the drug. PMID:18790704

  10. Effect of repeated compaction of tablets on tablet properties and work of compaction using an instrumented laboratory tablet press.

    PubMed

    Gamlen, Michael John Desmond; Martini, Luigi G; Al Obaidy, Kais G

    2015-01-01

    The repeated compaction of Avicel PH101, dicalcium phosphate dihydrate (DCP) powder, 50:50 DCP/Avicel PH101 and Starch 1500 was studied using an instrumented laboratory tablet press which measures upper punch force, punch displacement and ejection force and operates using a V-shaped compression profile. The measurement of work compaction was demonstrated, and the test materials were ranked in order of compaction behaviour Avicel PH101?>?DCP/Avicel PH101?>?Starch?>?DCP. The behaviour of the DCP/Avicel PH101 mixture was distinctly non-linear compared with the pure components. Repeated compaction and precompression had no effect on the tensile fracture strength of Avicel PH101 tablets, although small effects on friability and disintegration time were seen. Repeated compaction and precompression reduced the tensile strength and the increased disintegration time of the DCP tablets, but improved the strength and friability of Starch 1500 tablets. Based on the data reported, routine laboratory measurement of tablet work of compaction may have potential as a critical quality attribute of a powder blend for compression. The instrumented press was suitable for student use with minimal supervisor input. PMID:24171692

  11. Ampicillin Oral

    MedlinePLUS

    ... capsule, liquid, and pediatric drops to take by mouth. It is usually taken every 6 hours (four ... blood thinners') such as warfarin (Coumadin), atenolol (Tenormin), oral contraceptives, probenecid (Benemid), rifampin, sulfasalazine, and vitamins.tell ...

  12. Oral Cancer

    MedlinePLUS

    ... swallowing A lump in your neck An earache Oral cancer treatments may include surgery, radiation therapy or chemotherapy. Some patients have a combination of treatments. NIH: National Cancer Institute

  13. Oral Cancer

    MedlinePLUS

    ... oral cancer during regular checkups. Speech-language pathologists (SLPs) also make note of unusual or abnormal growths ... examinations and provide referrals to appropriate medical professionals. SLPs are important members of the cancer team. They ...

  14. Inhibition of Morphine Tolerance and Dependence by the NMDA Receptor Antagonist MK-801

    NASA Astrophysics Data System (ADS)

    Trujillo, Keith A.; Akil, Huda

    1991-01-01

    The N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor is an important mediator of several forms of neural and behavioral plasticity. The present studies examined whether NMDA receptors might be involved in the development of opiate tolerance and dependence, two examples of behavioral plasticity. The noncompetitive NMDA receptor antagonist MK-801 attenuated the development of tolerance to the analgesic effect of morphine without affecting acute morphine analgesia. In addition, MK-801 attenuated the development of morphine dependence as assessed by naloxone-precipitated withdrawal. These results suggest that NMDA receptors may be important in the development of opiate tolerance and dependence.

  15. Postoperative analgesia after paediatric orchidopexy: evaluation of a bupivacaine-morphine mixture.

    PubMed

    Wolf, A R; Hughes, D; Wade, A; Mather, S J; Prys-Roberts, C

    1990-04-01

    The value of combining morphine with bupivacaine for caudal analgesia was investigated. Thirty children, undergoing orchidopexy, received a caudal block of 0.125% bupivacaine with or without morphine 0.05 mg kg-1. Analgesia, side-effects, ventilatory frequency and oxygen saturation (SaO2) were recorded after operation. None of the 15 patients receiving the bupivacaine-morphine mixture required post-operative opioids, whereas eight of 15 patients receiving bupivacaine alone needed additional opioid analgesia. The incidence of side effects after surgery was similar for the two groups and there was no detectable difference in ventilatory frequency or SaO2. PMID:1970738

  16. Formulation and Evaluation of Fixed-Dose Combination of Bilayer Gastroretentive Matrix Tablet Containing Atorvastatin as Fast-Release and Atenolol as Sustained-Release

    PubMed Central

    Dey, Sanjay; Chattopadhyay, Sankha; Mazumder, Bhaskar

    2014-01-01

    The objective of the present study was to develop bilayer tablets of atorvastatin and atenolol that are characterized by initial fast-release of atorvastatin in the stomach and comply with the release requirements of sustained-release of atenolol. An amorphous, solvent evaporation inclusion complex of atorvastatin with ?-cyclodextrin, present in 1?:?3 (drug/cyclodextrin) molar ratio, was employed in the fast-release layer to enhance the dissolution of atorvastatin. Xanthan gum and guar gum were integrated in the sustained-release layer. Bilayer tablets composed of sustained-release layer (10% w/w of xanthan gum and guar gum) and fast-release layer [1?:?3 (drug/cyclodextrin)] showed the desired release profile. The atorvastatin contained in the fast-release layer showed an initial fast-release of more than 60% of its drug content within 2?h, followed by sustained release of the atenolol for a period of 12?h. The pharmacokinetic study illustrated that the fast absorption and increased oral bioavailability of atorvastatin as well as therapeutic concentration of atenolol in blood were made available through adoption of formulation strategy of bilayer tablets. It can be concluded that the bilayer tablets of atorvastatin and atenolol can be successfully employed for the treatment of hypertension and hypercholesterolemia together through oral administration of single tablet. PMID:24527446

  17. 21 CFR 520.62 - Aminopentamide hydrogen sulphate tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...2013-04-01 false Aminopentamide hydrogen sulphate tablets. 520.62 Section...ANIMAL DRUGS § 520.62 Aminopentamide hydrogen sulphate tablets. (a) Chemical name...Dimethylamino)-2,2-diphenylvaleramide hydrogen sulfate. (b) Specifications....

  18. 21 CFR 520.62 - Aminopentamide hydrogen sulphate tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...2012-04-01 false Aminopentamide hydrogen sulphate tablets. 520.62 Section...ANIMAL DRUGS § 520.62 Aminopentamide hydrogen sulphate tablets. (a) Chemical name...Dimethylamino)-2,2-diphenylvaleramide hydrogen sulfate. (b) Specifications....

  19. 21 CFR 520.62 - Aminopentamide hydrogen sulphate tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...2014-04-01 false Aminopentamide hydrogen sulphate tablets. 520.62 Section...ANIMAL DRUGS § 520.62 Aminopentamide hydrogen sulphate tablets. (a) Chemical name...Dimethylamino)-2,2-diphenylvaleramide hydrogen sulfate. (b) Specifications....

  20. 21 CFR 520.62 - Aminopentamide hydrogen sulphate tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...2011-04-01 false Aminopentamide hydrogen sulphate tablets. 520.62 Section...ANIMAL DRUGS § 520.62 Aminopentamide hydrogen sulphate tablets. (a) Chemical name...Dimethylamino)-2,2-diphenylvaleramide hydrogen sulfate. (b) Specifications....

  1. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...2013-04-01 false Methylprednisolone, aspirin tablets. 520.1409 Section 520... § 520.1409 Methylprednisolone, aspirin tablets. (a) Specifications. ...methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No....

  2. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...2014-04-01 false Methylprednisolone, aspirin tablets. 520.1409 Section 520... § 520.1409 Methylprednisolone, aspirin tablets. (a) Specifications. ...methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No....

  3. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...2011-04-01 false Methylprednisolone, aspirin tablets. 520.1409 Section 520... § 520.1409 Methylprednisolone, aspirin tablets. (a) Specifications. ...methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No....

  4. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...2012-04-01 false Methylprednisolone, aspirin tablets. 520.1409 Section 520... § 520.1409 Methylprednisolone, aspirin tablets. (a) Specifications. ...methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No....

  5. 21 CFR 520.62 - Aminopentamide hydrogen sulphate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...2010-04-01 false Aminopentamide hydrogen sulphate tablets. 520.62 Section...ANIMAL DRUGS § 520.62 Aminopentamide hydrogen sulphate tablets. (a) Chemical name...Dimethylamino)-2,2-diphenylvaleramide hydrogen sulfate. (b) Specifications....

  6. SANCTUARY : asymmetric interfaces for game-based tablet learning

    E-print Network

    Haas, Jason M. (Jason Matthew)

    2013-01-01

    This thesis describes the production of Sanctuary, a multiplayer learning game to be played on two tablet computers. Sanctuary's principle innovation is the splitting of the user interface onto two tablets, separating ...

  7. 21 CFR 529.400 - Chlorhexidine tablets and suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Chlorhexidine tablets and suspension. (a) Specification. Each tablet and each 28-milliliter syringe of... water; or infuse one syringe of suspension into the uterus.1 (2) Indications for use. For prevention...

  8. Astronomy Learning Activities for Tablets

    NASA Astrophysics Data System (ADS)

    Pilachowski, Catherine A.; Morris, Frank

    2015-08-01

    Four web-based tools allow students to manipulate astronomical data to learn concepts in astronomy. The tools are HTML5, CSS3, Javascript-based applications that provide access to the content on iPad and Android tablets. The first tool “Three Color” allows students to combine monochrome astronomical images taken through different color filters or in different wavelength regions into a single color image. The second tool “Star Clusters” allows students to compare images of stars in clusters with a pre-defined template of colors and sizes in order to produce color-magnitude diagrams to determine cluster ages. The third tool adapts Travis Rector’s “NovaSearch” to allow students to examine images of the central regions of the Andromeda Galaxy to find novae. After students find a nova, they are able to measure the time over which the nova fades away. A fourth tool, Proper Pair, allows students to interact with Hipparcos data to evaluate close double stars are physical binaries or chance superpositions. Further information and access to these web-based tools are available at www.astro.indiana.edu/ala/.

  9. Comparative stability of repackaged metoprolol tartrate tablets.

    PubMed

    Yang, Yongsheng; Gupta, Abhay; Carlin, Alan S; Faustino, Patrick J; Lyon, Robbe C; Ellison, Christopher D; Rothman, Barry; Khan, Mansoor A

    2010-01-29

    The stability of metoprolol tartrate tablets packaged in original high density polyethylene containers and repackaged in USP Class A unit-dose blister packs was investigated. Studies were conducted at 25 degrees C/60% relative humidity (RH) for 52 weeks and at 40 degrees C/75% RH for 13 weeks. The potency, dissolution, water content, loss on drying and hardness of the drug products were analyzed. Results indicated no differences in the stability between the tablets in both packages stored under 25 degrees C/60% RH. No difference in potency was found in both packages under either condition. However, a significant weight increase due to moisture uptake was observed for the repackaged tablets stored under 40 degrees C/75% RH. The weight increase was accompanied by a decrease in tablet hardness (6.5-0 kp) and a increase in dissolution rate (51-92%) in 5 min. Near-infrared (NIR) chemical imaging also monitored moisture uptake of the tablet non-invasively through the package. The observed changes in product stability may adversely affect the products bioavailability profile, even though the potency of the active drug remained within USP specification range of 90-110%. Study results suggest product quality can be negatively impacted even when using USP Class A repackaging materials. PMID:19879937

  10. Oleuropein, chief constituent of olive leaf extract, prevents the development of morphine antinociceptive tolerance through inhibition of morphine-induced L-type calcium channel overexpression.

    PubMed

    Zare, Leila; Esmaeili-Mahani, Saeed; Abbasnejad, Mehdi; Rasoulian, Bahram; Sheibani, Vahid; Sahraei, Hedayat; Kaeidi, Ayat

    2012-11-01

    It has been shown that blockade of L-type calcium channels could abolish the development of opioid-induced antinociceptive tolerance. Here, the antitolerant effects of olive leaf extract (OLE) and its main component, oleuropein, which have a calcium channel blocker property were determined. Adult male Wistar rats were injected with morphine (20?mg/kg, i.p.) for 8?days to induce antinociceptive tolerance. Then OLE (50-200?mg/kg i.g.) and oleuropein (1-10?mg/kg?i.p.) were injected concomitantly with morphine. The tail-flick test was used to assess the nociceptive threshold. The dorsal half of the lumbar spinal cord was assayed for the expression of L-type calcium channel using semiquantitative RT-PCR. The results showed that OLE (200?mg/kg) completely prevented morphine tolerance development. In addition, oleuropein in dose of 10?mg/kg, but not in 5?mg/kg, prevented the development of morphine antinociceptive tolerance. In addition, a significant increase in the mRNA levels of calcium channel (43.9%) was observed in the lumbar spinal cord of tolerant animals, which was reversed by effective of dose OLE. In conclusion, the results indicate that olive leaf extract has a potential antitolerant property against the chronic usage of morphine and that its main component, oleuropein, is responsible for such effect. PMID:22422486

  11. Preemptive morphine analgesia attenuates the long-term consequences of neonatal inflammation in male and female rats.

    PubMed

    Laprairie, Jamie L; Johns, Malcolm E; Murphy, Anne Z

    2008-12-01

    Despite mounting evidence on the importance of pain management in preterm infants, clinical use of analgesics in this population is limited. Our previous studies have shown that neonatal inflammation results in long-term alterations in adult somatosensory thresholds, characterized by decreased baseline nociceptive sensitivity, and enhanced hyperalgesia after a subsequent inflammatory insult. The present studies were conducted to determine whether preemptive morphine attenuates these negative consequences. At P0, pups received an injection of morphine sulfate before an intraplantar injection of 1% carrageenan. Control pups received either saline (SAL) followed by intraplantar carrageenan, morphine sulfate followed by intraplantar SAL, or SAL followed by intraplantar SAL. Preemptive morphine significantly attenuated neonatal injury-induced hypoalgesia in adolescence and adulthood. Similarly, morphine pretreated animals displayed significantly less hyperalgesia and recovered faster from a subsequent inflammatory insult compared with controls. Neonatal morphine had no significant effect on morphine analgesia in adulthood. Interestingly, neonatally injured animals that did not receive morphine displayed a significant rightward shift in the morphine dose-response curve in the absence of peripheral inflammation. Together, these results demonstrate that preemptive morphine significantly attenuates the long-term behavioral impact of neonatal inflammatory injury. PMID:18679159

  12. Periadolescent Male but not Female Rats have Higher Motor Activity in Response to Morphine than do Adult Rats

    PubMed Central

    White, David A.; Michaels, Clifford C.; Holtzman, Stephen G.

    2008-01-01

    Little has been done to investigate the effects of opioid exposure during adolescence. Therefore, our first objective was to determine behavioral differences in response to acutely administered morphine (e.g., antinociception and locomotion) between periadolescent and adult male and female rats. Our second objective was to determine the impact of age of morphine exposure on sensitivity to morphine-induced locomotion later in life. For the acute morphine studies, antinociceptive responses (using tail-flick and hot plate latencies) were assessed using cumulative morphine dosing (0.5–12 mg/kg) followed by a time course after the last morphine injection (up to 4 hr), and dose-response curves for motor activity (2 h test) were determined following saline and morphine (0.1–3.0 mg/kg) administration. For the long-term study, periadolescent and adult rats were given one of four treatment regimens (saline or one, three, or five days of morphine; 5.0 mg/kg, 2X/day). Changes in locomotor activity in response to saline or morphine (0.1–3.0 mg/kg) were determined one month later. A number of age- and sex-related behavioral differences were observed: basal differences in behavior were assay-dependent; however, male periadolescent rats were generally more sensitive to acute morphine-induced motor stimulation, while both male and female periadolescent rats tended to be less sensitive to morphine-induced antinociception. Lastly, following morphine exposure, activity was dependent on age of treatment and treatment regimen, with the greatest effects in five-day periadolescent-treated animals. These findings demonstrate that the sensitivity of periadolescent rats to the acute and protracted effects of morphine is different from that of adult rats. PMID:18206219

  13. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c)...

  14. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c)...

  15. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c)...

  16. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c)...

  17. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c)...

  18. PRINT | ONLINE | MOBILE | TABLET | EVENTS THE AGE Media Kit 2015

    E-print Network

    Peters, Richard

    Total Audience: Print & Computer/Tablet/Mobile Web/App/PDF (net). Income(HH) Age 3,226,000 44% 56PRINT | ONLINE | MOBILE | TABLET | EVENTS MediaKit 2015 #12;THE AGE Media Kit 2015 2 PRINT | ONLINE | MOBILE | TABLET | EVENTS VISION Since its first publication on October 17, 1854, The Age has been serving

  19. 21 CFR 520.1696d - Penicillin V potassium tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Penicillin V potassium tablets. 520.1696d Section... Penicillin V potassium tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125 milligrams (200,000 units) or 250 milligrams (400,000 units) of penicillin V. (b) Sponsors....

  20. 21 CFR 520.1696d - Penicillin V potassium tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Penicillin V potassium tablets. 520.1696d Section... Penicillin V potassium tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125 milligrams (200,000 units) or 250 milligrams (400,000 units) of penicillin V. (b) Sponsors....

  1. 21 CFR 520.1446 - Milbemcyin oxime and lufenuron tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... oxime and lufenuron tablets. (a) Specifications—(1) Tablets containing: 2.3 milligrams (mg) milbemycin oxime and 46 mg lufenuron, 5.75 mg milbemycin oxime and 115 mg lufenuron, 11.5 mg milbemycin oxime and 230 mg lufenuron, or 23 mg milbemycin oxime and 460 mg lufenuron. (2) Flavored tablets containing:...

  2. 21 CFR 520.1446 - Milbemcyin oxime and lufenuron tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... oxime and lufenuron tablets. (a) Specifications—(1) Tablets containing: 2.3 milligrams (mg) milbemycin oxime and 46 mg lufenuron, 5.75 mg milbemycin oxime and 115 mg lufenuron, 11.5 mg milbemycin oxime and 230 mg lufenuron, or 23 mg milbemycin oxime and 460 mg lufenuron. (2) Flavored tablets containing:...

  3. 21 CFR 520.1446 - Milbemcyin oxime and lufenuron tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... oxime and lufenuron tablets. (a) Specifications—(1) Tablets containing: 2.3 milligrams (mg) milbemycin oxime and 46 mg lufenuron, 5.75 mg milbemycin oxime and 115 mg lufenuron, 11.5 mg milbemycin oxime and 230 mg lufenuron, or 23 mg milbemycin oxime and 460 mg lufenuron. (2) Flavored tablets containing:...

  4. Kinetic spectrophotometric method for the determination of morphine in biological samples

    NASA Astrophysics Data System (ADS)

    Sheibani, A.; Shishehbore, M. Reza; Mirparizi, E.

    2010-10-01

    In this paper a simple, selective and inexpensive kinetic method was developed for the determination of morphine based on its inhibitory effect on the Janus green-bromate system in sulfuric acid media. The reaction was monitored spectrophotometrically at 618 nm by a fixed time method. The effect of different parameters such as concentration of reactants and temperature on the rate of reaction was investigated and optimum conditions were obtained. The calibration curve was linear in the concentration range 0.07-7.98 mg L -1 of morphine, and detection limit of the method was 3.0 × 10 -2 mg L -1. The relative standard deviation for five determinations of 3.74 mg L -1 of morphine was 0.57%. Finally, the proposed method was successfully applied to the determination of morphine in human urine and serum as real samples.

  5. Effects of chronic cadmium exposure on the conditioned reinforcing properties of morphine and fentanyl in rats 

    E-print Network

    Miller, Dennis K

    1997-01-01

    Chronic exposure to the toxicant cadmium has been shown to produce an attenuation in behavior properties of drugs of abuse. The experiments presented examined the effects of cadmium on the conditioned reinforcing properties of morphine and fentanyl...

  6. THE EFFECTS OF REPEATED MORPHINE EXPOSURE ON METABOTROPIC GLUTAMATE RECEPTOR ACTIVITY IN ADOLESCENT MICE 

    E-print Network

    Seloff, Katelyn Elizabeth

    2013-02-04

    Adolescent mice exhibit marked changes in D2/D3 dopamine receptor activity following administration of certain opioids. Thus, the present study examined whether repeated exposure to morphine would also modulate the activity of metabotropic glutamate...

  7. Blood pH and brain uptake of /sup 14/C-morphine

    SciTech Connect

    Schulman, D.S.; Kaufman, J.J.; Eisenstein, M.M.; Rapoport, S.I.

    1984-11-01

    /sup 14/C-Morphine was injected iv in control awake rats or in rats subjected to metabolic alkalosis or acidosis. Ten minutes later, radioactivity was determined within each of seven brain regions, after correction was made for intravascular tracer. In each region, parenchymal radioactivity was correlated positively and significantly (P less than 0.05) with arterial blood pH. Brain radioactivity was twofold to threefold greater in alkalotic rats (mean pH . 7.62) than in acidotic rats (mean pH . 7.16). The results are consistent with the pH-partition hypothesis for drug entry into the brain and indicate that morphine uptake can be increased by elevating the fraction of lipid-soluble uncharged morphine base in blood, by means of alkalosis. The observations may account for an exaggerated morphine-induced analgesia in alkalotic patients.

  8. Morphine-induced suppression of conditioned stimulus intake: Effects of stimulus type and insular cortex lesions

    PubMed Central

    Lin, Jian-You; Roman, Christopher; Reilly, Steve

    2009-01-01

    Intake of an unconditionally preferred taste stimulus (e.g., saccharin) is reduced by contingent administration of a drug of abuse (e.g., morphine). We examined the influence of insular cortex (IC) lesions on morphine-induced suppression of an olfactory cue and two taste stimuli with different levels of perceived innate reward value. Two major findings emerged from this study. First, morphine suppressed intake of an aqueous odor as well as each taste stimulus in neurologically intact rats. Second, IC lesions disrupted morphine-induced suppression of the taste stimuli but not the aqueous odor cue. These results indicate that the perceived innate reward value of the CS is not a factor that governs drug-induced intake suppression. PMID:19631620

  9. Effect of diazepam and midazolam on the antinociceptive effect of morphine, metamizol and indomethacin in mice.

    PubMed

    Pakulska, W; Czarnecka, E

    2001-01-01

    The influence of midazolam and diazepam on antinociceptive effect of morphine (10 mg/kg), metamizol (500 mg/kg) and indomethacin (10 mg/kg) was investigated in a mouse model using the tail-flick and hot-plate tests. All drugs were injected intraperitoneally. Benzodiazepines were administered to mice 30 min before applying the analgesic drugs. Measurement of nociception was performed within 2 h after benzodiazepine administration. Diazepam at doses of 0.25 mg/kg and 2.5 mg/kg injected with morphine was found to decrease the antinociceptive effect of morphine. Similarly, diazepam decreased the antinociceptive effect of metamizol (only in the tail-flick test) and indomethacin. Midazolam used at doses of 1.25 mg/kg and 2.5 mg/kg decreased the antinociceptive effect of morphine, metamizol (only in the tail-flick test) and indomethacin. PMID:11210678

  10. Antinociceptive interactions of opioid delta receptor agonists with morphine in mice: supra- and sub-additivity.

    PubMed

    Horan, P; Tallarida, R J; Haaseth, R C; Matsunaga, T O; Hruby, V J; Porreca, F

    1992-01-01

    In this study, the antinociceptive interactions of fixed ratio combinations of intracerebroventricularly (i.c.v.) given morphine and subantinociceptive doses of the delta agonists, [D-Pen2, D-Pen5]enkephalin (DPDPE), [D-Ala2, Glu4]deltorphin (DELT) or [Met5]enkephalin (MET) were examined using the mouse warm water tail flick test. When morphine was coadministered with DPDPE or DELT in a 4:1 and 9:1 mixture, respectively, a synergistic antinociceptive effect was observed. In contrast, when morphine was coadministered with MET in a 1:2 fixed ratio mixture, a subadditive interaction occurred. These results demonstrate both positive and negative modulatory interactions of delta agonists with morphine in an antinociceptive endpoint and that these interactions can be either supra- or subadditive. The data support the concept of a functional interaction between opioid mu and delta receptors and a potential regulatory role for the endogenous ligands of the opioid delta receptor. PMID:1315897

  11. Brain receptors for thyrotropin releasing hormone in morphine tolerant-dependent rats

    SciTech Connect

    Bhargava, H.N.; Das, S.

    1986-03-01

    The effect of chronic treatment of rats with morphine and its subsequent withdrawal on the brain receptors for thyrotropin releasing hormone (TRH) labeled with /sup 3/H-(3MeHis/sup 2/)TRH (MeTRH). Male Sprague Dawley rats were implanted with 4 morphine pellets (each containing 75 mg morphine base) during a 3-day period. Placebo pellet implanted rats served as controls. Both tolerance to and dependence on morphine developed as a result of this procedure. For characterization of brain TRH receptors, the animals were sacrificed 72 h after the implantation of first pellet. In another set of animals the pellets were removed and were sacrificed 24 h later. The binding of /sup 3/H-MeTRH to membranes prepared from brain without the cerebellum was determined. /sup 3/H-MeTRH bound to brain membranes prepared from placebo pellet implanted rats at a single high affinity site with a B/sub max/ value of 33.50 +/- 0.97 fmol/mg protein and a K/sub d/ of 5.18 +/- 0.21 nM. Implantation of morphine pellets did not alter the B/sub max/ value of /sup 3/H-MeTRH but decreased the K/sub d/ value significantly. Abrupt or naloxone precipitated withdrawal of morphine did not alter B/sub max/ or the K/sub d/ values. The binding of /sup 3/H-MeTRH to brain areas was also determined. The results suggest that the development of tolerance to morphine is associated with enhanced sensitivity of brain TRH receptors, however abrupt withdrawal of morphine does not change the characteristics of brain TRH receptors.

  12. Pharmacokinetics of morphine and oxycodone following intravenous administration in elderly patients

    PubMed Central

    Villesen, Hanne H; Banning, Anne-Marie; Petersen, Rasmus H; Weinelt, Sebatian; Poulsen, Jesper B; Hansen, Steen H; Christrup, Lona L

    2007-01-01

    Background An increased and prolonged duration of pain relief after morphine administration has been found in elderly patients. Whether this is due to alterations in pharmacokinetics, receptor binding profile or other factors remains unsolved. The aims were to elucidate the pharmacokinetics after intravenous administration of morphine and oxycodone in elderly patients older than 70 years. Methods A randomized non-blinded study with 16 patients aged older than 70 years scheduled for elective hip replacement receiving morphine or oxycodone 0.05 mg/kg as an IV infusion over 15 minutes. Results A 2-compartment pharmacokinetic model best described the disposition of morphine and oxycodone. The estimated elimination half-lives for morphine and oxycodone were (mean ± SD) 2.7 ± 3.6 (range 0.8–11.6) and 3.1 ± 1.3 (range 1.1–4.8) hr, respectively. Volume of distribution at steady state was estimated to be 243 ± 256 and 277 ± 187 L, and clearance to be 1748 ± 623 and 1206 ± 546 ml/min for morphine and oxycodone, respectively. Conclusion The increased and prolonged duration of pain relief after morphine administration seen in some elderly patients cannot, based on these findings, be ascribed to changes in the pharmacokinetic parameters between elderly and younger patients. Similar for oxycodone, no changes in the pharmacokinetic could be found when comparing the parameters found in elderly patients with those from younger healthy volunteers. A great variability within the individual pharmacokinetic parameters was seen for both drugs. Therefore, we recommend that treatment with morphine and oxycodone in elderly patients is initiated very conservatively and is titrated slowly to effect. PMID:18473019

  13. Morphine modulates mouse hippocampal progenitor cell lineages by upregulating miR-181a level.

    PubMed

    Xu, Chi; Zhang, Yue; Zheng, Hui; Loh, Horace H; Law, Ping-Yee

    2014-11-01

    The mechanism by which addictive drugs such as morphine regulate adult neurogenesis remains elusive. We now demonstrate that morphine can regulate neurogenesis by control of miR-181a and subsequent hippocampal neural progenitor cell (hNPC) lineages. In the presence of morphine, hNPCs preferentially differentiated into astrocytes, an effect blocked by the specific ?-opioid receptor antagonist, Cys(2)-Tyr(3)-Orn(5)-Pen(7)-amide. This effect was mediated by the Prox1/Notch1 pathway as demonstrated by an increase in Notch1 level in the morphine- but not fentanyl-treated hNPCs and blocked by overexpression of Notch1 siRNA. Overexpression of Prox1 siRNA upregulated Notch1 level and potentiated the morphine-induced lineage changes. Prox1 transcript level was regulated by direct interaction between miR-181a and its 3'-UTR sequence. In vitro and in vivo treatment with morphine resulted in an increase in miR-181a level in hNPCs and mouse hippocampi, respectively. Overexpression of miR-181a mimics reduced Prox1 levels, increased Notch1 levels, and enhanced hNPCs differentiation into astrocytes. Meanwhile, overexpression of the miR-181a inhibitor raised Prox1 levels, decreased Notch1 levels, and subsequently blocked the morphine-induced lineage changes. Thus, by modulating Prox1/Notch1 activities via miR-181a, morphine influences the fate of differentiating hNPCs differentiation and therefore the ultimate quantities of mature neurons and astrocytes. PMID:24964978

  14. Role of nitric oxide in the induction and expression of morphine tolerance and dependence in mice.

    PubMed Central

    Dambisya, Y. M.; Lee, T. L.

    1996-01-01

    1. The possible involvement of nitric oxide (NO) in the induction and expression of morphine tolerance and dependence was studied in mice. A two-day repeated injection regimen was used to induce morphine tolerance and dependence. Tolerance was assessed by the tail flick test and physical dependence by naloxone challenge, on the third day. 2. Two days pretreatment with L-arginine (20 mg kg-1, twice daily) or D-NG-nitro arginine methyl ester (D-NAME, 20 mg kg-1, twice daily) alone had no effect on subsequent morphine antinociception. L-NG-monomethyl arginine (L-NMMA, 10 mg kg-1, twice daily) for two days led to a slight increase (not statistically significant) in morphine antinociception; while L-NG-nitro arginine methyl ester (L-NAME, 10 mg kg-1, twice daily) for two days led to attenuation of morphine analgesia. None of the animals treated with these drugs alone showed signs characteristic of the opioid withdrawal syndrome upon naloxone challenge. 3. Induction phase L-arginine slowed the development of opioid tolerance and physical dependence, while L-NAME and L-NMMA led to a higher degree of tolerance but had no effect on the development of physical dependence. 4. L-Arginine and D-NAME had no effect on the expression of morphine tolerance and physical dependence. Expression phase L-NAME and L-NMMA, on the other hand, attenuated morphine tolerance and reduced the incidence of withdrawal signs. 5. NO may, therefore, play a role in both phases of morphine tolerance and dependence: elevation of NO levels during the induction phase delays the development of opioid tolerance/dependence, while inhibition of NO synthase accelerates the development of tolerance. Inhibition of NO attenuates the expression of both tolerance and physical dependence. PMID:8851510

  15. Attenuation of morphine-induced behavioral changes in rodents by D- and L-glucose.

    PubMed

    Talley, C P; Arankowsky-Sandoval, G; McCarty, R; Gold, P E

    1999-01-01

    Administration of d-glucose enhances learning and memory in several tasks and also attenuates memory impairments and other behavioral effects of several drugs, including morphine. The present experiment compared the effects of peripherally administered d-glucose with those of l-glucose, a stereoisomer of d-glucose that is not metabolized and does not readily cross the blood-brain barrier. Like d-glucose, though at somewhat different doses, peripherally administered l-glucose attenuated morphine-induced deficits in spontaneous alternation performance in rats and mice and attenuated morphine-induced hyperactivity in mice. l-Glucose did not raise circulating levels of plasma d-glucose, suggesting that the effects of l-glucose are not secondary to increased availability of d-glucose. Using direct injections of d- and l-glucose and morphine into the medial septum of rats, the findings indicate that d-glucose but not l-glucose attenuated morphine-induced deficits in spontaneous alternation performance; indeed, intraseptal injections of l-glucose alone impaired spontaneous alternation performance. These findings suggest that peripheral l-glucose antagonizes morphine-induced behavioral effects by a peripheral signaling mechanism, one distinct from the mechanisms that mediate at least some of the effects of d-glucose on brain function. PMID:9889073

  16. Morphine enhances the release of /sup 3/H-purines from rat brain cerebral cortical prisms

    SciTech Connect

    Wu, P.H.; Phillis, J.W.; Yuen, H.

    1982-10-01

    In vitro experiments have shown that /sup 3/H-purines can be released from /sup 3/H-adenosine preloaded rat brain cortical prisms by a KCl-evoked depolarization. The KCl-evoked release of /sup 3/H-purines is dependent on the concentration of KCl present in the superfusate. At concentrations of 10(-7) approximately 10(-5)M morphine did not influence the basal release of /sup 3/H-purines from the prisms, although it enhanced the KCl-evoked release of /sup 3/H-purines. The enhancement of KCl-evoked /sup 3/H-purine release by morphine was concentration-dependent and was antagonized by naloxone, suggesting the involvement of opiate receptors. Uptake studies with rat brain cerebral cortical synaptosomes show that morphine is a very weak inhibitor of adenosine uptake. Comparisons with dipyridamole, a potent inhibitor of adenosine uptake, suggest that this low level of inhibition of the uptake did not contribute significantly to the release of /sup 3/H-purine by morphine seen in our experiments. It is therefore suggested that morphine enhances KCl-evoked /sup 3/H-purine release by an interaction with opiate receptors and that the resultant increase in extracellular purine (adenosine) levels may account for some of the actions of morphine.

  17. Spinal cord thyrotropin releasing hormone receptors of morphine tolerant-dependent and abstinent rats

    SciTech Connect

    Rahmani, N.H.; Gulati, A.; Bhargava, H.N. )

    1990-07-01

    The effect of chronic administration of morphine and its withdrawal on the binding of 3H-(3-MeHis2)thyrotropin releasing hormone (3H-MeTRH) to membranes of the spinal cord of the rat was determined. Male Sprague-Dawley rats were implanted with either 6 placebo or 6 morphine pellets (each containing 75-mg morphine base) during a 7-day period. Two sets of animals were used. In one, the pellets were left intact at the time of sacrificing (tolerant-dependent) and in the other, the pellets were removed 16 hours prior to sacrificing (abstinent rats). In placebo-pellet-implanted rats, 3H-MeTRH bound to the spinal cord membranes at a single high affinity binding site with a Bmax of 21.3 +/- 1.6 fmol/mg protein, and an apparent dissociation constant Kd of 4.7 +/- 0.8 nM. In morphine tolerant-dependent or abstinent rats, the binding constants of 3H-MeTRH to spinal cord membranes were unaffected. Previous studies from this laboratory indicate that TRH can inhibit morphine tolerance-dependence and abstinence processes without modifying brain TRH receptors. Together with the present results, it appears that the inhibitory effect of TRH on morphine tolerance-dependence and abstinence is probably not mediated via central TRH receptors but may be due to its interaction with other neurotransmitter systems.

  18. Proteomic analysis of rat prefrontal cortex in three phases of morphine-induced conditioned place preference.

    PubMed

    Yang, Liu; Sun, Zhong Sheng; Zhu, Yong-ping

    2007-06-01

    Morphological alterations of synapse are found after morphine administration, suggesting that regulation of synaptic plasticity may be one of the mechanisms of neuroadaptation in addiction. However, the molecular basis underlying the abnormal synapse morphological and physiological changes in the morphine-induced dependence, withdraw, and relapse is not well understood. As prefrontal cortex (PFC) is one of the most important brain regions, which provides executive control over drug use and is severely impaired in many addicts, systematic analysis of the biochemical and molecular alteration of synaptic fraction of PFC in morphine-induced neuroadaptation is necessary. In this study, differential protein expression profiling of synaptic fraction of rat PFC based on morphine-induced conditioned place preference (CPP) model was performed with two-dimensional gel electrophoresis (2-DE). Our results showed that a total of 80 proteins were differentially expressed by 2-DE analysis during three phases of CPP assay. Of them, 58 were further identified by mass spectrometry. These proteins were classified into multiple categories, such as energy metabolism, signal transduction, synaptic transmission, cytoskeletal proteins, chaperones, and local synaptic protein synthetic machinery according to their biological functions. Our study provides a global view of synaptic-related molecular networking in PFC under morphine-induced dependence, withdraw, and relapse, indicative of a concerted biological process in neuroadaptation under chronic morphine exposure. PMID:17444669

  19. Sex differences in morphine-induced behavioral sensitization and social behaviors in ICR mice.

    PubMed

    Zhan, Bo; Ma, Hong-Yuan; Wang, Jian-Li; Liu, Chao-Bao

    2015-03-18

    Gender and genetic strain are two prominent variants that influence drug abuse. Although certain sex-related behavioral responses have been previously characterized in ICR mice, little is known about the effects of sex on morphine-induced behavioral responses in this outbred strain. Therefore, in this study, we investigated the sex differences of morphine-induced locomotion, anxiety-like and social behaviors in ICR mice. After morphine or saline exposure for four consecutive days (twice daily), increased locomotion, more time spent in the central area, as well as attenuated rearing and self-grooming behaviors were found in morphine-treated females in an open field; no differences were found in locomotion and the time spent in the central area between male and female controls. When interacting with the same-sex individuals, female controls were engaged in more social investigation, following, body contacting and self-grooming behaviors than controls; morphine exposure reduced contacting and self-grooming behaviors in females; in contrast, these effects were not found in males. These results indicate that female ICR mice are more prosocial and are more susceptible to morphine exposure than males. PMID:25855229

  20. Interactive Effects of Morphine on HIV Infection: Role in HIV-Associated Neurocognitive Disorder

    PubMed Central

    Reddy, Pichili Vijaya Bhaskar; Pilakka-Kanthikeel, Sudheesh; Saxena, Shailendra K.; Saiyed, Zainulabedin; Nair, Madhavan P. N.

    2012-01-01

    HIV epidemic continues to be a severe public health problem and concern within USA and across the globe with about 33 million people infected with HIV. The frequency of drug abuse among HIV infected patients is rapidly increasing and is another major issue since injection drug users are at a greater risk of developing HIV associated neurocognitive dysfunctions compared to non-drug users infected with HIV. Brain is a major target for many of the recreational drugs and HIV. Evidences suggest that opiate drug abuse is a risk factor in HIV infection, neural dysfunction and progression to AIDS. The information available on the role of morphine as a cofactor in the neuropathogenesis of HIV is scanty. This review summarizes the results that help in understanding the role of morphine use in HIV infection and neural dysfunction. Studies show that morphine enhances HIV-1 infection by suppressing IL-8, downregulating chemokines with reciprocal upregulation of HIV coreceptors. Morphine also activates MAPK signaling and downregulates cAMP response element-binding protein (CREB). Better understanding on the role of morphine in HIV infection and mechanisms through which morphine mediates its effects may help in devising novel therapeutic strategies against HIV-1 infection in opiate using HIV-infected population. PMID:22666564

  1. Contributions of spinal d-amino acid oxidase to chronic morphine-induced hyperalgesia.

    PubMed

    Ma, Shuai; Li, Xin-Yan; Gong, Nian; Wang, Yong-Xiang

    2015-12-10

    Spinal d-amino acid oxidase (DAAO) is an FAD-dependent peroxisomal flavoenzyme which mediates the conversion of neutral and polar d-amino acids (including d-serine) to the corresponding ?-keto acids, and simultaneously produces hydrogen peroxide and ammonia. This study has aimed to explore the potential contributions of spinal DAAO and its mediated hydrogen peroxide/d-serine metabolism to the development of morphine-induced hyperalgesia. Bi-daily subcutaneous injections of morphine to mice over 7 days induced thermal hyperalgesia as measured by both the hot-plate and tail-immersion tests, and spinal astroglial activation with increased spinal gene expression of DAAO, glial fibrillary acidic protein (GFAP) and pro-inflammatory cytokines (interleukin-1? (IL-1?), interleukin-6 (IL-6) and tumor necrosis factor-? (TNF-?)). Subcutaneous injections of the potent DAAO inhibitor CBIO (5-chloro-benzo[d]isoxazol-3-ol) prevented and reversed the chronic morphine-induced hyperalgesia. CBIO also inhibited both astrocyte activation and the expression of pro-inflammatory cytokines. Intrathecal injection of the hydrogen peroxide scavenger PBN (phenyl-N-tert-butylnitrone) and of catalase completely reversed established morphine hyperalgesia, whereas subcutaneous injections of exogenous d-serine failed to alter chronic morphine-induced hyperalgesia. These results provided evidence that spinal DAAO and its subsequent production of hydrogen peroxide rather than the d-serine metabolism contributed to the development of morphine-induced hyperalgesia. PMID:25850373

  2. Morphine Produces Immunosuppressive Effects in Nonhuman Primates at the Proteomic and Cellular Levels*

    PubMed Central

    Brown, Joseph N.; Ortiz, Gabriel M.; Angel, Thomas E.; Jacobs, Jon M.; Gritsenko, Marina; Chan, Eric Y.; Purdy, David E.; Murnane, Robert D.; Larsen, Kay; Palermo, Robert E.; Shukla, Anil K.; Clauss, Theresa R.; Katze, Michael G.; McCune, Joseph M.; Smith, Richard D.

    2012-01-01

    Morphine has long been known to have immunosuppressive properties in vivo, but the molecular and immunologic changes induced by it are incompletely understood. To explore how these changes interact with lentiviral infections in vivo, animals from two nonhuman primate species (African green monkeys and pigtailed macaques) were provided morphine and studied using a systems biology approach. Biological specimens were obtained from multiple sources (e.g. lymph node, colon, cerebrospinal fluid, and peripheral blood) before and after the administration of morphine (titrated up to a maximum dose of 5 mg/kg over a period of 20 days). Cellular immune, plasma cytokine, and proteome changes were measured and morphine-induced changes in these parameters were assessed on an interorgan, interindividual, and interspecies basis. In both species, morphine was associated with decreased levels of Ki-67+ T-cell activation but with only minimal changes in overall T-cell counts, neutrophil counts, and NK cell counts. Although changes in T-cell maturation were observed, these varied across the various tissue/fluid compartments studied. Proteomic analysis revealed a morphine-induced suppressive effect in lymph nodes, with decreased abundance of protein mediators involved in the functional categories of energy metabolism, signaling, and maintenance of cell structure. These findings have direct relevance for understanding the impact of heroin addiction and the opioids used to treat addiction as well as on the potential interplay between opioid abuse and the immunological response to an infective agent. PMID:22580588

  3. Rewarding effects of ethanol combined with low doses of morphine through dopamine D1 receptors.

    PubMed

    Ise, Yuya; Mori, Tomohisa; Katayama, Shirou; Nagase, Hiroshi; Suzuki, Tsutomu

    2013-01-01

    This study investigated whether ethanol combined with low doses of morphine produces rewarding effects in rats. Ethanol (0.075-1.2 g/kg, intraperitoneal [i.p.]) alone did not induce place preference. A moderate dose (1 mg/kg, s.c.), but not a low dose (0.1 mg/kg), of morphine induced a significant place preference. The combination of ethanol (0.075-0.6 g/kg, i.p.) and 0.1 mg/kg of morphine, as well as low doses of morphine (0.03-0.1 mg/kg, subcutaneous [s.c.]) combined with ethanol (0.3 g/kg, i.p.), induced a significant place preference. The combined effect of ethanol and morphine was significantly attenuated by naloxone (0.3 mg/kg, s.c.), naltrindole (1.0 mg/kg, s.c.), or long-term administration of the dopamine D1 receptor antagonist SCH23390 (1.0 mg/kg/day, s.c.). These results suggest that the rewarding effect induced by ethanol and a low dose of morphine is mediated by activation of the central opioidergic and dopaminergic systems through dopamine D1 receptors. PMID:23470804

  4. Morphine has latent deleterious effects on the ventilatory responses to a hypoxic challenge

    PubMed Central

    May, Walter J.; Gruber, Ryan B.; Discala, Joseph F.; Puskovic, Veljko; Henderson, Fraser; Palmer, Lisa A.; Lewis, Stephen J.

    2014-01-01

    The aim of this study was to determine whether morphine depresses the ventilatory responses elicited by a hypoxic challenge (10% O2, 90% N2) in conscious rats at a time when the effects of morphine on arterial blood gas (ABG) chemistry, Alveolar-arterial (A-a) gradient and minute ventilation (VM) had completely subsided. In vehicle-treated rats, each episode of hypoxia stimulated ventilatory function and the responses generally subsided during each normoxic period. Morphine (5 mg/kg, i.v.) induced an array of depressant effects on ABG chemistry, A-a gradient and VM (via decreases in tidal volume). Despite resolution of these morphine-induced effects, the first episode of hypoxia elicited substantially smaller increases in VM than in vehicle-treated rats, due mainly to smaller increases in frequency of breathing. The pattern of ventilatory responses during subsequent episodes of hypoxia and normoxia changed substantially in morphine-treated rats. It is evident that morphine has latent deleterious effects on ventilatory responses elicited by hypoxic challenge. PMID:25045593

  5. Morphine produces immunosuppressive effects in nonhuman primates at the proteomic and cellular levels.

    PubMed

    Brown, Joseph N; Ortiz, Gabriel M; Angel, Thomas E; Jacobs, Jon M; Gritsenko, Marina; Chan, Eric Y; Purdy, David E; Murnane, Robert D; Larsen, Kay; Palermo, Robert E; Shukla, Anil K; Clauss, Theresa R; Katze, Michael G; McCune, Joseph M; Smith, Richard D

    2012-09-01

    Morphine has long been known to have immunosuppressive properties in vivo, but the molecular and immunologic changes induced by it are incompletely understood. To explore how these changes interact with lentiviral infections in vivo, animals from two nonhuman primate species (African green monkeys and pigtailed macaques) were provided morphine and studied using a systems biology approach. Biological specimens were obtained from multiple sources (e.g. lymph node, colon, cerebrospinal fluid, and peripheral blood) before and after the administration of morphine (titrated up to a maximum dose of 5 mg/kg over a period of 20 days). Cellular immune, plasma cytokine, and proteome changes were measured and morphine-induced changes in these parameters were assessed on an interorgan, interindividual, and interspecies basis. In both species, morphine was associated with decreased levels of Ki-67(+) T-cell activation but with only minimal changes in overall T-cell counts, neutrophil counts, and NK cell counts. Although changes in T-cell maturation were observed, these varied across the various tissue/fluid compartments studied. Proteomic analysis revealed a morphine-induced suppressive effect in lymph nodes, with decreased abundance of protein mediators involved in the functional categories of energy metabolism, signaling, and maintenance of cell structure. These findings have direct relevance for understanding the impact of heroin addiction and the opioids used to treat addiction as well as on the potential interplay between opioid abuse and the immunological response to an infective agent. PMID:22580588

  6. Effect of the Combination of CI-988 and Morphine on Neuropathic Pain after Spinal Cord Injury in Rats

    PubMed Central

    Kim, Youngkyung; Hahm, Suk-Chan

    2015-01-01

    Cholecystokinin is known to be involved in the modulation of nociception and to reduce the efficacy of morphine analgesia. This study investigated the effects of intrathecal administration of morphine and the cholecystokinin type B antagonist CI-988 on below-level neuropathic pain after spinal cord injury in rats. We also examined the interaction of morphine and CI-988 in the antinociceptive effect. Both morphine and CI-988 given individually increased the paw withdrawal threshold to mechanical stimulation in a dose-dependent manner. The combination of ineffective doses of intrathecally administered CI-988 and morphine produced significant analgesic effects and the combination of effective doses resulted in analgesic effects that were greater than the sum of the individual effects of each drug. Thus, morphine showed a synergistic interaction with CI-988 for analgesia of central neuropathic pain. PMID:25729274

  7. The Effect of Morphine on Regional Cerebral Blood Flow Measured by 99mTc-ECD SPECT in Dogs

    PubMed Central

    Adriaens, Antita; Peremans, Kathelijne; Waelbers, Tim; Vandermeulen, Eva; Croubels, Siska; Duchateau, Luc; Dobbeleir, André; Audenaert, Kurt; Eersels, Jos; Vermeire, Simon; De Spiegeleer, Bart; Polis, Ingeborgh

    2014-01-01

    To gain insights into the working mechanism of morphine, regional cerebral blood flow (rCBF) patterns after morphine administration were assessed in dogs. In a randomized cross-over experimental study, rCBF was estimated with 99mTc-Ethylcysteinate Dimer single photon emission computed tomography in 8 dogs at baseline, at 30 minutes and at 120 minutes after a single bolus of morphine. Perfusion indices (PI) in the frontal, parietal, temporal and occipital cortex and in the subcortical and cerebellar region were calculated. PI was significantly decreased 30 min after morphine compared to baseline in the right frontal cortex. The left parietal cortex and subcortical region showed a significantly increased PI 30 min after morphine compared to baseline. No significant differences were noted for the other regions or at other time points. In conclusion, a single bolus of morphine generated a changing rCBF pattern at different time points. PMID:25295733

  8. Formulation of orodispersible tablets of ondansetron HCl: investigations using glycine-chitosan mixture as superdisintegrant.

    PubMed

    Goel, Honey; Vora, Nishant; Tiwary, Ashok K; Rana, Vikas

    2009-05-01

    The objective of this investigation was to prepare orodispersible tablets (ODTs) of ondansetron HCl using a direct compression method. A combination of glycine and chitosan was used as a disintegrating system and these tablets were compared for mechanical strength and disintegration time with those containing superdisintegrants. The Plackett-Burman screening design was used to screen the independent variables [concentration of glycine (X(1)), concentration of chitosan (X(2)), concentration of ondansetron HCl (X(3)) and tablet crushing strength (X(4))] which were found to actively influence the dependent variables [disintegration time in the oral cavity (DT), wetting time (WT), and water absorption ratio (WAR)]. Further, a central composite design was used to formulate additional ODTs of ondansetron HCl for estimating response in the extended spherical domain. The regression analysis (performed using Statistica-7.0) of quadratic fit revealed that DT or WT and WAR were 99% and 98% correlated with active factors (X(1), X(2) or X(3)), respectively. The data showed that disintegration time of optimized ondansetron HCl ODTs was not significantly different (p<0.05) from ODTs prepared using Croscarmellose sodium or Crospovidone. PMID:19420882

  9. A Single-Dose Intra-Articular Morphine plus Bupivacaine versus Morphine Alone following Knee Arthroscopy: A Systematic Review and Meta-Analysis

    PubMed Central

    Wang, Yi-lun; Li, Yu-sheng; Wei, Jie; Li, Hui; Yang, Tuo; Yang, Tu-bao; Lei, Guang-hua

    2015-01-01

    Objectives The purpose of this study was to compare the efficacy and safety of a single-dose intra-articular morphine plus bupivacaine versus morphine alone in patients undergoing arthroscopic knee surgery. Methods Randomized controlled trials comparing a combination of morphine and bupivacaine with morphine alone injected intra-articularly in the management of pain after knee arthrocopic surgery were retrieved (up to August 10, 2014) from MEDLINE, the Cochrane Library and Embase databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95% confidence intervals (CIs) were calculated using RevMan statistical software. Results Thirteen randomized controlled trials were included. Statistically significant differences were observed with regard to the VAS values during the immediate period (0-2h) (WMD -1.16; 95% CI -2.01 to -0.31; p = 0.007) and the time to first request for rescue analgesia (WMD = 2.05; 95% CI 0.19 to 3.92; p = 0.03). However, there was no significant difference in the VAS pain score during the early period (2-6h) (WMD -0.36; 95% CI -1.13 to 0.41; p = 0.35), the late period (6-48h) (WMD 0.11; 95% CI -0.40 to 0.63; p = 0.67), and the number of patients requiring supplementary analgesia (RR = 0.78; 95% CI 0.57 to 1.05; p = 0.10). In addition, systematic review showed that intra-articular morphine plus bupivacaine would not increase the incidence of adverse effects compared with morphine alone. Conclusion The present study suggested that the administration of single-dose intra-articular morphine plus bupivacaine provided better pain relief during the immediate period (0-2h), and lengthened the time interval before the first request for analgesic rescue without increasing the short-term side effects when compared with morphine alone. Level of Evidence Level I, meta-analysis of Level I studies. PMID:26474401

  10. Compressibility of tableting materials and properties of tablets with glyceryl behenate.

    PubMed

    Mužíková, Jitka; Muchová, Sandra; Komersová, Alena; Locha?, Václav

    2015-03-01

    The paper studies the compressibility of directly compressible tableting materials with dry binders, spray-dried lactose and microcrystalline cellulose, and glyceryl dibehenate at various concentrations. Compressibility was evaluated by means of the energy profile of compression and tensile strength of tablets. Release rate of the active ingredient, salicylic acid, from the tablets was also examined. In the case of microcrystalline cellulose, a higher concentration of glyceryl dibehenate increased the strength of tablets, while this did not occur in the case of spray-dried lactose. Increasing concentration of glyceryl dibehenate prolonged the release of salicylic acid; however, no statistically significant difference was found compared to the type of the dry binder used. PMID:25781708

  11. Optimization of Fast Dissolving Etoricoxib Tablets Prepared by Sublimation Technique

    PubMed Central

    Patel, D. M.; Patel, M. M.

    2008-01-01

    The purpose of this investigation was to develop fast dissolving tablets of etoricoxib. Granules containing etoricoxib, menthol, crospovidone, aspartame and mannitol were prepared by wet granulation technique. Menthol was sublimed from the granules by exposing the granules to vacuum. The porous granules were then compressed in to tablets. Alternatively, tablets were first prepared and later exposed to vacuum. The tablets were evaluated for percentage friability and disintegration time. A 32 full factorial design was applied to investigate the combined effect of 2 formulation variables: amount of menthol and crospovidone. The results of multiple regression analysis indicated that for obtaining fast dissolving tablets; optimum amount of menthol and higher percentage of crospovidone should be used. A surface response plots are also presented to graphically represent the effect of the independent variables on the percentage friability and disintegration time. The validity of a generated mathematical model was tested by preparing a checkpoint batch. Sublimation of menthol from tablets resulted in rapid disintegration as compared with the tablets prepared from granules that were exposed to vacuum. The optimized tablet formulation was compared with conventional marketed tablets for percentage drug dissolved in 30 min (Q30) and dissolution efficiency after 30 min (DE30). From the results, it was concluded that fast dissolving tablets with improved etoricoxib dissolution could be prepared by sublimation of tablets containing suitable subliming agent. PMID:20390084

  12. Stability of high-dose morphine chloride injection upon heat sterilization: comparison of UV-spectroscopy and HPLC.

    PubMed

    Steger, P J; Martinelli, E F; Mühlebach, S F

    1996-04-01

    The stability of a preservative-free morphine chloride solution for intravenous or intrathecal use manufactured at a concentration of 40 mg/ml, near the solubility limit in water, was studied. The influence of heat and oxygen on morphine content was measured with and without autoclaving, and after additional thermal and oxidative stress. The morphine injection was stable during steam sterilization at 121 degrees C for up to 180 min if the solution was adjusted to a pH of 3.2 and if oxygen was eliminated by saturating the solution and flushing the vial with nitrogen before sealing. By adding an oxidizing agent (200 microliters H2O2 3% per 20 ml vial) before 15 min of sterilization, a decomposition of approximately 20% of morphine resulted when compared to oxygen-free control samples (P < 0.01, n = 3) High-performance liquid chromatography with UV detection (HPLC) and direct UV spectroscopy (UV) (the latter available in most hospital pharmacies for analytical purposes) were compared for specificity, precision and appropriateness for content and stability assessment of morphine solutions. UV could only be used for quantification of undecomposed morphine. Morphine degradation products of stressed solutions interfered with the direct UV assay of morphine at 286 nm, whereas these interfering components were separated by the ion-pair reversed-phase HPLC used. The results demonstrate that even in the absence of stabilizers, morphine chloride solutions may safely be sterilized for 15 min at 121 degrees C. The HPLC method was shown to be sufficiently sensitive and specific for quality control and stability assessment of morphine preparations, and, therefore, appropriate for the validation of the manufacture of morphine injection solutions in hospital pharmacies, where morphine solutions are manufactured in special strengths and volumes for individual patients' needs. PMID:8809642

  13. Ultra-low dose naloxone upregulates interleukin-10 expression and suppresses neuroinflammation in morphine-tolerant rat spinal cords.

    PubMed

    Lin, Shinn-Long; Tsai, Ru-Yin; Tai, Yueh-Hua; Cherng, Chen-Hwen; Wu, Ching-Tang; Yeh, Chun-Chang; Wong, Chih-Shung

    2010-02-11

    Co-infusion of ultra-low dose naloxone and morphine attenuates morphine tolerance through the prevention of mu opioid receptor-Gs protein coupling. We previously demonstrated that chronic intrathecal infusion of morphine leads to tolerance and spinal neuroinflammation. The aim of present study was to examine the possible mechanisms by which ultra-low dose naloxone modulates spinal neuroinflammation, particularly the role of anti-inflammatory cytokine interleukin 10 (IL-10). Morphine tolerance was induced in male Wistar rats by intrathecal infusion of morphine (15 microg/h) for 5 days, and co-infusion of naloxone (15 pg/h) was used to evaluate the impact on spinal cytokine expression. Recombinant rat IL-10 (rrIL-10) or anti-rat IL-10 antibody was injected to elucidate the effect of IL-10 on morphine tolerance. Our results showed that co-infusion of naloxone (15 pg/h) with morphine not only attenuated tolerance, shifting the AD(50) from 89.2 to 11.7 microg but also inhibited the increased expression of pro-inflammatory cytokine (TNF-alpha, IL-1beta, and IL-6) caused by chronic intrathecal morphine infusion. The increase of IL-10 protein and mRNA were 1.5- and 3-fold, respectively, compared to that in morphine-infused rat spinal cords. A combination of daily rrIL-10 (1 microg) injection with morphine infusion produced, in a less potent, preservative antinociception and inhibited pro-inflammatory cytokine production compared to ultra-low dose naloxone co-infusion, and the effect of ultra-low dose naloxone co-infusion was inhibited by daily intrathecal anti-rat IL-10 antibody injection. These results demonstrate that IL-10 contributes to the attenuation of pro-inflammatory cytokine expression caused by ultra-low dose naloxone/morphine co-infusion and thus the attenuation of morphine tolerance. PMID:19799935

  14. Compressed mini-tablets as a biphasic delivery system.

    PubMed

    Lopes, Carla M; Lobo, José Manuel Sousa; Pinto, João F; Costa, Paulo

    2006-10-12

    Compressed mini-tablets systems are presented as a biphasic delivery system designed for zero-order sustained drug release. The outer layer that fills the void spaces between the mini-tablets was formulated to release the drug in a very short time (fast release), while the mini-tablets provided a prolonged release. Different composition (HPMC or EC) and number (10 or 21) of mini-tablets were used to obtain different drug release rates. The in vitro performance of these systems showed the desired biphasic behaviour: the drug contained in the fast releasing phase (powder enrobing the mini-tablets) dissolved within the first 2 min, whereas the drug contained in the mini-tablets was released at different rates, depending up on formulation. Based on the release kinetic parameters calculated, it can be concluded that mini-tablets containing HPMC were particularly suitable approaching to zero-order (constant) release over 8h time periods. PMID:16828999

  15. Oral Cancer Screening

    MedlinePLUS

    ... Oral Cavity and Oropharyngeal Cancer Screening Research Oral Cavity and Oropharyngeal Cancer Screening (PDQ®) What is screening? ... are called diagnostic tests . General Information About Oral Cavity and Oropharyngeal Cancer Key Points Oral cancer is ...

  16. Oral Cancer Prevention

    MedlinePLUS

    ... Oral Cavity and Oropharyngeal Cancer Screening Research Oral Cavity and Oropharyngeal Cancer Prevention (PDQ®) What is prevention? ... and How to Quit General Information About Oral Cavity and Oropharyngeal Cancer Key Points Oral cavity cancer ...

  17. Oral Health

    MedlinePLUS

    ... mouth A lump, rough spot, or other change Pain, tenderness, or numbness anywhere in the mouth or on the lips Problems chewing, swallowing, speaking, or moving the jaw or tongue A change in the way the teeth fit together Thrush. Thrush is also called oral ...

  18. Morphine administration during low ovarian hormone stage results in transient over expression of fear memories in females

    PubMed Central

    Perez-Torres, Emily M.; Ramos-Ortolaza, Dinah L.; Morales, Roberto; Santini, Edwin; Rios-Ruiz, Efrain J.; Torres-Reveron, Annelyn

    2015-01-01

    Acute exposure to morphine after a traumatic event reduces trauma related symptoms in humans and conditioned fear expression in male rats. We aimed to determine whether acute administration of morphine alters consolidation of fear learning and extinction. Male and female rats in proestrus and metaestrus (high and low ovarian hormones respectively) underwent fear conditioning and received saline or morphine (2.5 mg/kg s.c.). The next day they underwent extinction. Results showed increased freezing during extinction only in the morphine metaestrus group while morphine did not affect males or proestrus females. Recall of extinction was similar on all groups. On a second experiment, a subset of rats conditioned during metaestrus was administered morphine prior to extinction producing no effects. We then measured mu opioid receptor (MOR) expression in the amygdala and periaqueductal gray (PAG) at the end of extinction (day 2). In males and proestrus females, morphine caused an increase in MOR in the amygdala but no in the PAG. In metaestrus females, morphine did not change MOR expression in either structure. These data suggests that ovarian hormones may interact with MORs in the amygdala to transiently alter memory consolidation. Morphine given after trauma to females with low ovarian hormones might increase the recall of fear responses, making recovery harder. PMID:26052274

  19. Fatty acid amide hydrolase inhibitor URB597 prevented tolerance and cognitive deficits induced by chronic morphine administration in rats.

    PubMed

    Hasanein, Parisa; Ghafari-Vahed, Masumeh

    2016-02-01

    Inhibitors of the endocannabinoid metabolic enzyme fatty acid amide hydrolase exert therapeutic effects, but might also be associated with some of the adverse effects of cannabis. However, at least one fatty acid amide hydrolase inhibitor, URB597, has beneficial effects without signs of abuse or dependence. Although previous investigations have evaluated URB597-morphine interactions, the effects of URB597 on morphine tolerance and cognition deficits have not been studied previously. Rats were rendered tolerant to or dependent on morphine by an injection of morphine (10?mg/kg, subcutaneous) twice daily, respectively, for 7 or 10 days. URB597 (1?mg/kg, intraperitoneal) was administered before morphine. The tail-flick and passive avoidance learning tests were used to evaluate tolerance and cognition. Chronic morphine injection led to significant tolerance to the antinociceptive effect on days 5 and 7. URB597 completely prevented the development of morphine tolerance. URB597 also enhanced memory acquisition in the passive avoidance learning test, and although morphine impaired memory, URB597 alleviated this effect. These data show that URB597 protects against tolerance and memory deficits in chronic usage of morphine and suggests URB597 as a promising candidate for the treatment of adverse effects of opioids. PMID:26274041

  20. Morphine administration during low ovarian hormone stage results in transient over expression of fear memories in females.

    PubMed

    Perez-Torres, Emily M; Ramos-Ortolaza, Dinah L; Morales, Roberto; Santini, Edwin; Rios-Ruiz, Efrain J; Torres-Reveron, Annelyn

    2015-01-01

    Acute exposure to morphine after a traumatic event reduces trauma related symptoms in humans and conditioned fear expression in male rats. We aimed to determine whether acute administration of morphine alters consolidation of fear learning and extinction. Male and female rats in proestrus and metaestrus (high and low ovarian hormones respectively) underwent fear conditioning and received saline or morphine (2.5 mg/kg s.c.). The next day they underwent extinction. Results showed increased freezing during extinction only in the morphine metaestrus group while morphine did not affect males or proestrus females. Recall of extinction was similar on all groups. On a second experiment, a subset of rats conditioned during metaestrus was administered morphine prior to extinction producing no effects. We then measured mu opioid receptor (MOR) expression in the amygdala and periaqueductal gray (PAG) at the end of extinction (day 2). In males and proestrus females, morphine caused an increase in MOR in the amygdala but no in the PAG. In metaestrus females, morphine did not change MOR expression in either structure. These data suggests that ovarian hormones may interact with MORs in the amygdala to transiently alter memory consolidation. Morphine given after trauma to females with low ovarian hormones might increase the recall of fear responses, making recovery harder. PMID:26052274