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Sample records for oral morphine tablets

  1. Comparative pharmacokinetics of two modified-release oral morphine formulations (Reliadol® and Kapanol®) and an immediate-release morphine tablet (Morfin 'DAK') in healthy volunteers

    DEFF Research Database (Denmark)

    Bochner, F.; Somogyi, A.A.; Danz, C.

    1999-01-01

    , its metabolites morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G), after ingestion of Reliadol® (2 x 30 mg capsules) compared with Kapanolo (3 x 20 mg) [Glaxo Wellcome Australia Ltd] and an immediate-release morphine tablet (Morfin 'DAK', 30 mg; Nycomed Denmark A/S). Design and Setting...

  2. Human Abuse Potential of an Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate (Morphine-ADER Injection-Molded Tablets) vs Extended-Release Morphine Administered Intranasally in Nondependent Recreational Opioid Users.

    Science.gov (United States)

    Webster, Lynn R; Smith, Michael D; Lawler, John; Lindhardt, Karsten; Dayno, Jeffrey M

    2017-09-01

    To compare the relative human abuse potential after insufflation of manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine ER tablets. A randomized, double-blind, double-dummy, active- and placebo-controlled five-way crossover study was performed with adult volunteers who were experienced, nondependent, recreational opioid users. After intranasal (IN) administration of manipulated high-volume (HV) morphine-ADER-IMT (60 mg), participants were randomized (1:1:1:1) to receive IN manipulated low-volume (LV) morphine ER (60 mg), IN manipulated LV morphine-ADER-IMT, intact oral morphine-ADER-IMT (60 mg), and placebo in crossover fashion. Pharmacodynamic and pharmacokinetic assessments included peak effect of drug liking (E max ; primary endpoint) using drug liking visual analog scale (VAS) score, E max using overall drug liking, and take drug again (TDA) VASs scores, and mean abuse quotient (AQ), a pharmacokinetic parameter associated with drug liking. Forty-six participants completed the study. After insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT, drug liking E max was significantly lower ( P  <   0.0001) compared with IN morphine ER. Overall drug liking and TDA E max values were significantly lower ( P  <   0.0001) after insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT compared with IN morphine ER. Mean AQ was lower after insufflation of HV (9.2) and LV (2.3) morphine-ADER-IMT or ingestion of oral morphine-ADER-IMT (5.5) compared with insufflation of LV morphine ER (37.2). All drug liking, take drug again, and abuse quotient endpoints support a significantly lower abuse potential with insufflation of manipulated morphine-ADER-IMT compared with manipulated and insufflated non-AD ER morphine. © 2016 American Academy of Pain Medicine.

  3. Morphine

    African Journals Online (AJOL)

    'it's a bad drug it can kill and even its side effect(s) are very dangerous'. ... the use of oral morphine in the palliative care management of HIV/AIDS and .... State Medical Boards definition of addiction as 'psychological dependence on the use of ...

  4. Premedication with oral Dextromethorphan reduces intra-operative Morphine requirement

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    R Talakoub

    2005-09-01

    Full Text Available Background: Intra-operative pain has adverse effects on hemodynamic parameters. Due to complications of opioids for pain relief, using non-opioids medication is preferred. The purpose of this study was to investigate the effect of oral dextrometorphan premedication on intra-operative Morphine requirement. Methods: After approval of the Ethics committee and informed consent, 40 adult patients who stand in American Society of Anesthesiologists Physical Status I and II, under general anesthesia for elective laparatomy were selected and classified in two equal groups randomly. In group A, oral dextromethorphan (60mg was administered at 10 PM and 6 AM preoperatively. In group B, placebo (dextrose was administered. After induction of general anesthesia and before skin incision, intravenous morphine (0.01 mg/kg was administered. During surgery, when systolic blood pressure or heart rate was increased more than 20% of the preoperative baseline, 0.01 mg/kg morphine was administered. At the end of surgery, the totally prescribed morphine (mg/kg and maximal increase in systolic, diastolic, mean arterial blood pressure and heart rate relative to the baseline values were calculated and statistically compared with student’s t-test. Results: The mean dose of administered morphine during surgery was significantly less in group A than group B (P<0.0001. Also, Maximal increase in systolic, diastolic and mean arterial blood pressure was significantly less in group A (p<0.003, p<0.004, p<0.0001, respectively. There was no significant difference in maximal heart rate increase between two groups (p<0.114. Conclusion: Oral dextromethorphan premedication may decrease intra-operative morphine requirement and reduce maximal increase in systolic and mean arterial blood pressure during surgery. Key words: Dextromethorphan, Morphine, Intra-operative, Premedication Hemodynamic

  5. Optimized furosemide taste masked orally disintegrating tablets

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    Mohamed Abbas Ibrahim

    2017-11-01

    Full Text Available Optimized orally disintegrating tablets (ODTs containing furosemide (FUR were prepared by direct compression method. Two factors, three levels (32 full factorial design was used to optimize the effect of taste masking agent (Eudragit E100; X1 and superdisintegarant; croscarmellose sodium (CCS; X2 on tablet properties. A composite was prepared by mixing ethanolic solution of FUR and Eudragit E100 with mannitol prior to mixing with other tablet ingredients. The prepared ODTs were characterized for their FUR content, hardness, friability and wetting time. The optimized ODT formulation (F1 was evaluated in term of palatability parameters and the in vivo disintegration. The manufactured ODTs were complying with the pharmacopeia guidelines regarding hardness, friability, weight variation and content. Eudragit E100 had a very slightly enhancing effect on tablets disintegration. However, the effects of both Eudragit E100 (X1 and CCS (X2 on ODTs disintegration time (Y1 were insignificant (p > 0.05. Moreover, X1 exhibited antagonistic effect on the dissolution after 5 and 30 min (D5 and D30, respectively, but only its effect on D30 is significant (p = 0.0004. Furthermore, the optimized ODTs formula showed good to acceptable taste in term of palatability, and in vivo disintegration time of this formula was about 10 s.

  6. Pharmacokinetics of morphine-6-glucuronide following oral administration in healthy volunteers

    DEFF Research Database (Denmark)

    Villesen, Hanne H.; Kristensen, Kim; Hansen, Steen Honoré

    2007-01-01

    After oral administration, morphine-6-glucuronide (M6G) displays an atypical absorption profile with two peak plasma concentrations. A proposed explanation is that M6G is hydrolysed to morphine in the colon, which is then absorbed and subsequently undergoes metabolism in the liver to morphine-3-g......-glucuronide (M3G) and M6G. The aims of this study were to confirm and elucidate the biphasic absorption profile as well as clarify the conversion of M6G to morphine after a single oral administration of M6G in healthy volunteers....

  7. Formulation studies for mirtazapine orally disintegrating tablets.

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    Yıldız, Simay; Aytekin, Eren; Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

    2016-01-01

    Orally disintegrating tablets (ODTs) recently have gained much attention to fulfill the needs for pediatric, geriatric, and psychiatric patients with dysphagia. Aim of this study was to develop new ODT formulations containing mirtazapine, an antidepressant drug molecule having bitter taste, by using simple and inexpensive preparation methods such as coacervation, direct compression and to compare their characteristics with those of reference product (Remereon SolTab). Coacervation method was chosen for taste masking of mirtazapine. In vitro characterization studies such as diameter and thickness, weight variation, tablet hardness, tablet friability and disintegration time were performed on tablet formulations. Wetting time and in vitro dissolution tests of developed ODTs also studied using 900 mL 0.1 N HCl medium, 900 mL pH 6.8 phosphate buffer or 900 mL pH 4.5 acetate buffer at 37 ± 0.2 °C as dissolution medium. Ratio of Eudragit® E-100 was chosen as 6% (w/w) since the dissolution profile of A1 (6% Eudragit® E-100) was found closer to the reference product than A2 (4% Eudragit® E-100) and A3 (8% Eudragit® E-100). Group D, E and F formulations were presented better results in terms of disintegration time. Dissolution results indicated that Group E and F formulations showed optimum properties in all three dissolution media. Formulations D1, D4, D5, E3, E4, F1 and F5 found suitable as ODT formulations due to their favorable disintegration times and dissolution profiles. Developed mirtazapine ODTs were found promising in terms of showing the similar characteristics to the original formulation.

  8. [Formulation optimization of panax notoginsenoside orally fast disintegration tablets].

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    Wang, Zhi; Wei, Li; Chen, Ting

    2008-07-01

    To optimize the formulation of panax notoginsenoside orally fast disintegrating tablets. Mannitol, microcrystalline cellulose (PH 102) and lactose 80 were used as diluent. A polynomial regression algorithm was used to evaluate the relationship between the controlling factor, compacting pressure and diluent ratio, and disintegration time, tensile strength of tablets. Optimum formulation and process parameters could be determined by contrast the contour plot of tensile strength to that of disintegration time. The disintegration time and tensile strength of panax notoginsenoside oral disintegrating tablets were good, and the taste was satisfactory. Panax notoginsenoside oral disintegrating tablets achieve the goal of design and this method can be fairly used in formulation screening.

  9. Oral Morphine Use in South India: A Population-Based Study

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    M.R. Rajagopal

    2017-12-01

    Full Text Available Purpose: Access to opioids for pain control is recognized as an urgent issue in low- and middle-income countries. Here we report temporal and regional trends in morphine use in Kerala, India. Methods: Oral morphine use data for the State of Kerala (2012 to 2015 was used to describe temporal trends, regional variation, and provider characteristics. Total morphine use was calculated for each district of Kerala to derive an annual per capita use rate (milligrams per capita. Each provider was classified as government, private, nongovernment organization (NGO, or NGO partnership. Results: Oral morphine use for Kerala was 1.32 mg/capita and increased over the study period 27% (from 1.23 mg/capita to 1.56 mg/capita. There was substantial variation in morphine use across districts (range, 0.49 mg/capita to 2.97 mg/capita; six-fold difference. This variation increased over time (19-fold difference in 2015. In 2015, 31% of morphine providers (51 of 167 were government institutions; they delivered 48% of total morphine in Kerala. Corresponding data for other providers are private institutions, 23% of centers and 13% of morphine; NGOs, 41% of centers and 34% of morphine; and NGO partnerships, 5% of centers and 4% of morphine. From 2012 to 2015, the total number of centers increased by 35%, from 124 to 167. Conclusion: Oral morphine use has increased over time in Kerala but remains substantially lower than estimated need. There is significant geographic variation of use. Efforts are needed to improve palliative care in Kerala and to reduce regional disparities in access to opioids.

  10. Oral Morphine Use in South India: A Population-Based Study.

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    Rajagopal, M R; Karim, Safiya; Booth, Christopher M

    2017-12-01

    Purpose Access to opioids for pain control is recognized as an urgent issue in low- and middle-income countries. Here we report temporal and regional trends in morphine use in Kerala, India. Methods Oral morphine use data for the State of Kerala (2012 to 2015) was used to describe temporal trends, regional variation, and provider characteristics. Total morphine use was calculated for each district of Kerala to derive an annual per capita use rate (milligrams per capita). Each provider was classified as government, private, nongovernment organization (NGO), or NGO partnership. Results Oral morphine use for Kerala was 1.32 mg/capita and increased over the study period 27% (from 1.23 mg/capita to 1.56 mg/capita). There was substantial variation in morphine use across districts (range, 0.49 mg/capita to 2.97 mg/capita; six-fold difference). This variation increased over time (19-fold difference in 2015). In 2015, 31% of morphine providers (51 of 167) were government institutions; they delivered 48% of total morphine in Kerala. Corresponding data for other providers are private institutions, 23% of centers and 13% of morphine; NGOs, 41% of centers and 34% of morphine; and NGO partnerships, 5% of centers and 4% of morphine. From 2012 to 2015, the total number of centers increased by 35%, from 124 to 167. Conclusion Oral morphine use has increased over time in Kerala but remains substantially lower than estimated need. There is significant geographic variation of use. Efforts are needed to improve palliative care in Kerala and to reduce regional disparities in access to opioids.

  11. Dissolution testing of orally disintegrating tablets.

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

    2012-07-01

    For industrially manufactured pharmaceutical dosage forms, product quality tests and performance tests are required to ascertain the quality of the final product. Current compendial requirements specify a disintegration and/or a dissolution test to check the quality of oral solid dosage forms. These requirements led to a number of compendial monographs for individual products and, at times, the results obtained may not be reflective of the dosage form performance. Although a general product performance test is desirable for orally disintegrating tablets (ODTs), the complexity of the release controlling mechanisms and short time-frame of release make such tests difficult to establish. For conventional oral solid dosage forms (COSDFs), disintegration is often considered to be the prerequisite for subsequent dissolution. Hence, disintegration testing is usually insufficient to judge product performance of COSDFs. Given the very fast disintegration of ODTs, the relationship between disintegration and dissolution is worthy of closer scrutiny. This article reviews the current status of dissolution testing of ODTs to establish the product quality standards. Based on experimental results, it appears that it may be feasible to rely on the dissolution test without a need for disintegration studies for selected ODTs on the market. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  12. Delay discounting of oral morphine and sweetened juice rewards in dependent and non-dependent rats.

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    Harvey-Lewis, Colin; Perdrizet, Johnna; Franklin, Keith B J

    2014-07-01

    Opioid-dependent humans are reported to show accelerated delay discounting of opioid rewards when compared to monetary rewards. It has been suggested that this may reflect a difference in discounting of consumable and non-consumable goods not specific to dependent individuals. Here, we evaluate the discounting of similar morphine and non-morphine oral rewards in dependent and non-dependent rats We first tested the analgesic and rewarding effects of our morphine solution. In a second experiment, we assigned rats randomly to either dependent or non-dependent groups that, 30 min after daily testing, received 30 mg/kg subcutaneous dose of morphine, or saline, respectively. Delay discounting of drug-free reward was examined prior to initiation of the dosing regimen. We tested discounting of the morphine reward in half the rats and retested the discounting of the drug-free reward in the other half. All tests were run 22.5 h after the daily maintenance dose. Rats preferred the morphine cocktail to the drug-free solution and consumed enough to induce significant analgesia. The control quinine solution did not produce these effects. Dependent rats discounted morphine rewards more rapidly than before dependence and when compared to discounting drug-free rewards. In non-dependent rats both reward types were discounted similarly. These results show that morphine dependence increases impulsiveness specifically towards a drug reward while morphine experience without dependence does not.

  13. Ginger Orally Disintegrating Tablets to Improve Swallowing in Older People.

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    Hirata, Ayumu; Funato, Hiroki; Nakai, Megumi; Iizuka, Michiro; Abe, Noriaki; Yagi, Yusuke; Shiraishi, Hisashi; Jobu, Kohei; Yokota, Junko; Hirose, Kahori; Hyodo, Masamitsu; Miyamura, Mitsuhiko

    2016-01-01

    We previously prepared and pharmaceutically evaluated ginger orally disintegrating (OD) tablets, optimized the base formulation, and carried out a clinical trial in healthy adults in their 20 s and 50s to measure their effect on salivary substance P (SP) level and improved swallowing function. In this study, we conducted clinical trials using the ginger OD tablets in older people to clinically evaluate the improvements in swallowing function resulting from the functional components of the tablet. The ginger OD tablets were prepared by mixing the excipients with the same amount of mannitol and sucrose to a concentration of 1% ginger. Eighteen healthy older adult volunteers aged 63 to 90 were included in the swallowing function test. Saliva was collected before and 15 min after administration of the placebo and ginger OD tablets. Swallowing endoscopy was performed by an otolaryngologist before administration and 15 min after administration of the ginger OD tablets. A scoring method was used to evaluate the endoscopic swallowing. Fifteen minutes after taking the ginger OD tablets, the salivary SP amount was significantly higher than prior to ingestion or after taking the placebo (pginger OD tablets. Our findings showed that the ginger OD tablets increased the salivary SP amount and improved swallowing function in older people with appreciably reduced swallowing function.

  14. Oral Morphine Consumption Reduces Lens Development in Rat Embryos

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    Hossein Bahadoran

    2012-07-01

    Full Text Available Objective: Consumption of morphine, during pregnancy, in addition to inducing defects in the mother’s nervous system function, caused defects or delays in the formation and evolution of embryonic visual system. In the present study, changes in lens development was assessed in embryos exposed in utero to morphine. Material and Methods: Female Wistar rats (250-300 g were mated with male rats and pregnancy was determined by sperm observation in vaginal smear. This day was considered as embryonic day zero (E0. The females were then divided randomly into the experimental and the control groups. The control group received tap water and the experimental group received morphine (0.05 mg/ml in their water. On embryonic day 13 ( E13, blood samples were collected from the retro-orbital sinus of all animals for plasma corticosterone detection. On embryonic day 17(E17, the animals were killed by an overdose of chloroform and the embryos were taken out surgically. The embryos were fixed in 10% formalin for 30 days. At this time, the head of the embryos were removed for tissue processing and Hematoxylin- Eosin (H&E staining. The samples were evaluated using light microscope and MOTIC software. Results: Our data indicated that plasma corticosterone level was dramatically increased and the lens was thinner in the experimental group. (Although the proliferation of lens cells increased in the experiment group but that lens had delay in removing the proliferated and elongation cells with abnormal density in the lateral part of the lens in compare with control group. I have no idea what the authors are stating here. Moreover, the opening of the eyelids was delayed in the off springs of the mothers who received morphine. Conclusions: This study showed that morphine consumption during pregnancy leads to defects in fetal visual system development, particularly in the lens, and eyelids.

  15. BIOWAIVER STUDY OF ORAL TABLETTED ETHYLCELLULOSE ...

    African Journals Online (AJOL)

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    classification of drugs on the basis of their solubility and permeability. ..... velocity of drug release was slower from tablets with low polymer ... when the drug solubility is high, (b) loading dose in the polymeric matrix is large and (c) lack of.

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

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    Mostafa Sarvizadeh

    2015-01-01

    Conclusions: Topical morphine is more effective and more satisfactory to patients than the magic mouthwash in reducing severity of cancer treatment-induced oral mucositis. More studies with larger sample size and longer follow-up are required in this regard.

  17. Orally Disintegrating Tablets: A Review | Hirani | Tropical Journal of ...

    African Journals Online (AJOL)

    Drug delivery systems are becoming increasingly sophisticated as pharmaceutical scientists acquire a better understanding of the physicochemical and biochemical parameters pertinent to their performance. Over the past three decades, orally disintegrating tablets (ODTs) have gained considerable attention as a preferred ...

  18. Preparation and evaluation of diclofenac sodium orally disintegrating tablets

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    Iancu Valeriu

    2016-06-01

    Full Text Available Orally disintegrating tablets (ODTs are dosage forms which disintegrate in mouth within seconds without need of water. This type of quality in dosage form can be attained by addition of different varieties of excipients. Pharmaburst™ 500 is a co-processed excipient system which allows rapid disintegration and low adhesion to punches. The aim of the present study was to develop and evaluate 25 mg diclofenac sodium ODTs (orodispersible tablets batches by direct compression method at different compression forces 10 kN (F1 and 20 kN (F2 and directly compressible excipients used in different ratio (Avicel PH 102, magnesium stearate and coprocessed excipient Pharmaburst™ 500, 70% and 80% w/w. The obtained batches were analyzed for appearance, tablet thickness, uniformity of weight, hardness, friability, disintegration time, and non-compendial methods (wetting time. Co-processed Pharmaburst™ 500 excipient 70% used for sodium diclofenac ODT obtaining determined good results for quality control tests evaluation.

  19. The Effects of Preoperative Oral Pregabalin and Perioperative Intravenous Lidocaine Infusion on Postoperative Morphine Requirement in Patients Undergoing Laparatomy

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    Senniye Ulgen Zengin

    2015-01-01

    Full Text Available 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.

  20. Formulation and evaluation of orally disintegrating clopidogrel tablets

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    Gamal Mohamed Mahrous

    Full Text Available ABSTRACT Recent advances in drug delivery systems have aimed to achieve better patient compliance. One of these advances is the formulation of orally disintegrating tablets (ODTs that dissolve instantaneously, releasing drugs within a few seconds without the need of water. The main objective of this paper was to prepare and develop ODTs of clopidogrel. The ODTs were prepared by direct compression. The effect of three superdisintegrants, namely crospovidone, croscarmellose sodium, and sodium starch glycolate, using three different disintegration times on the dissolution rate was investigated. The prepared tablets were evaluated for hardness, friability, disintegration time and in vitro drug release. Furthermore, the interaction of clopidogrel with the formulation excipients was studied using differential scanning calorimetry (DSC. DSC studies revealed that there were no interactions between the drug and the excipients used. All tablets had hardness values in the range 4.0-5.2 kp and friability lower than 1%. The weight and drug content uniformity of all formulations was within official limits according to BP. In vitro drug release studies of the ODTs showed that more than 90% of the drug was released within ten minutes. A palatability test in human volunteers showed acceptable taste and mouth feel. Thus, the obtained results conclusively demonstrated successful rapid disintegration of the formulated tablets and acceptable palatability.

  1. Disintegration of chemotherapy tablets for oral administration in patients with swallowing difficulties.

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    Siden, Rivka; Wolf, Matthew

    2013-06-01

    The administration of oral chemotherapeutic drugs can be problematic in patients with swallowing difficulties. Inability to swallow solid dosage forms can compromise compliance and may lead to poor clinical outcome. The current technique of tablet crushing to aid in administration is considered an unsafe practice. By developing a technique to disintegrate tablets in an oral syringe, the risk associated with tablet crushing can be avoided. The purpose of this study was to determine the feasibility of using disintegration in an oral syringe for the administration of oral chemotherapeutic tablets. Eight commonly used oral chemotherapeutic drugs were tested. Tablets were placed in an oral syringe and allowed to disintegrate in tap water. Various volumes and temperatures were tested to identify which combination allows for complete disintegration of the tablet in the shortest amount of time. The oral syringe disintegration method was considered feasible if disintegration occurred in ≤15 min and in ≤20 mL of water and the dispersion passed through an oral syringe tip. The following tablets were shown to disintegrate within 15 min and in disintegration test. Disintegrating oral chemotherapeutic tablets in a syringe provides a closed system to administer hazardous drugs and allows for the safe administration of oral chemotherapeutic drugs in a tablet form to patients with swallowing difficulties.

  2. Pharmacokinetics of Oral and Intravenous Paracetamol (Acetaminophen) When Co-Administered with Intravenous Morphine in Healthy Adult Subjects.

    Science.gov (United States)

    Raffa, Robert B; Pawasauskas, Jayne; Pergolizzi, Joseph V; Lu, Luke; Chen, Yin; Wu, Sutan; Jarrett, Brant; Fain, Randi; Hill, Lawrence; Devarakonda, Krishna

    2018-03-01

    Several features favor paracetamol (acetaminophen) administration by the intravenous rather than the oral route in the postoperative setting. This study compared the pharmacokinetics and bioavailability of oral and intravenous paracetamol when given with or without an opioid, morphine. In this randomized, single-blind, parallel, repeat-dose study in healthy adults, subjects received four repeat doses of oral or intravenous 1000 mg paracetamol at 6-h intervals, and morphine infusions (0.125 mg/kg) at the 2nd and 3rd intervals. Comparisons of plasma pharmacokinetic profiles were conducted before, during, and after opioid co-administrations. Twenty-two subjects were included in the pharmacokinetic analysis. Observed paracetamol peak concentration (C max ) and area under the plasma concentration-time curve over the dosing interval (AUC 0-6 ) were reduced when oral paracetamol was co-administered with morphine (reduced from 11.6 to 7.25 µg/mL and from 31.00 to 25.51 µg·h/mL, respectively), followed by an abruptly increased C max and AUC 0-6 upon discontinuation of morphine (to 13.5 µg/mL and 52.38 µg·h/mL, respectively). There was also a significantly prolonged mean time to peak plasma concentration (T max ) after the 4th dose of oral paracetamol (2.84 h) compared to the 1st dose (1.48 h). However, pharmacokinetic parameters of paracetamol were not impacted when intravenous paracetamol was co-administered with morphine. Morphine co-administration significantly impacted the pharmacokinetics of oral but not intravenous paracetamol. The abrupt release of accumulated paracetamol at the end of morphine-mediated gastrointestinal inhibition following oral but not intravenous administration of paracetamol suggests that intravenous paracetamol provides a better option for the management of postoperative pain. CLINICALTRIALS. NCT02848729.

  3. Oral morphine versus ibuprofen administered at home for postoperative orthopedic pain in children: a randomized controlled trial.

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    Poonai, Naveen; Datoo, Natasha; Ali, Samina; Cashin, Megan; Drendel, Amy L; Zhu, Rongbo; Lepore, Natasha; Greff, Michael; Rieder, Michael; Bartley, Debra

    2017-10-10

    Oral morphine for postoperative pain after minor pediatric surgery, while increasingly popular, is not supported by evidence. We evaluated whether oral morphine was superior to ibuprofen for at-home management of children's postoperative pain. We conducted a randomized superiority trial comparing oral morphine (0.5 mg/kg) with ibuprofen (10 mg/kg) in children 5 to 17 years of age who had undergone minor outpatient orthopedic surgery (June 2013 to September 2016). Participants took up to 8 doses of the intervention drug every 6 hours as needed for pain at home. The primary outcome was pain, according to the Faces Pain Scale - Revised, for the first dose. Secondary outcomes included additional analgesic requirements, adverse effects, unplanned health care visits and pain scores for doses 2 to 8. We analyzed data for 77 participants in each of the morphine and ibuprofen groups. Both interventions decreased pain scores with no difference in efficacy. The median difference in pain score before and after the first dose of medication was 1 (interquartile range 0-1) for both morphine and ibuprofen ( p = 0.2). For doses 2 to 8, the median differences in pain score before and after the dose were not significantly different between groups. Significantly more participants taking morphine reported adverse effects (45/65 [69%] v. 26/67 [39%], p ibuprofen groups, respectively; p = 0.003). Morphine was not superior to ibuprofen, and both drugs decreased pain with no apparent difference in efficacy. Morphine was associated with significantly more adverse effects, which suggests that ibuprofen is a better first-line option after minor surgery. ClinicalTrials.gov, no. NCT01686802. © 2017 Canadian Medical Association or its licensors.

  4. Development of a new disintegration method for orally disintegrating tablets.

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    Kakutani, Ryo; Muro, Hiroyuki; Makino, Tadashi

    2010-07-01

    Recently, the focus has been on the importance of assessing the oral disintegrative properties of orally disintegrating tablets (ODTs). In particular, in the development stages and the quality control field of ODT products, a physical assessment method which easily measures oral disintegrative properties is desired. For this reason, we developed a new disintegration test method (Kyoto-model disintegration method or KYO method), which is useful to predict the oral disintegrative properties of an ODT easily, and examined the availability of the method. In the KYO method, ODT samples were classified in terms of their water permeability, and a moderate water volume was decided. Subsequently, the disintegrative properties were assessed with the newly proposed method. For 25 commercial prescription ODTs used as samples, a good correlation was shown between the results of a human sensory test by five healthy male volunteers and the results using the KYO method. Furthermore, the KYO method could evaluate time-dependent changes in ODT samples. On the other hand, no correlation was observed between the Japanese Pharmacopeia disintegration test and the human sensory test. These results suggested that the KYO method reflected the disintegration nature of the ODTs in the oral cavity, and could easily be applied to development stages and the quality control field of ODT products.

  5. Rectal absorption of morphine from controlled release suppositories

    NARCIS (Netherlands)

    Moolenaar, Frits; Meyler, Pim; Frijlink, Erik; Jauw, Tjoe Hang; Visser, Jan; Proost, Johannes

    1995-01-01

    The absorption profiles and bioavailability of morphine in human volunteers (n = 13) were described after oral administration of MS Contin tablets and rectal administration of a newly developed controlled release suppository. By manipulating the viscosity of fatty suppository base an entirely

  6. Preoperative oral dextromethorphan does not reduce pain or morphine consumption after open cholecystectomy

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    Mahmoodzadeh Hossein

    2009-01-01

    Full Text Available Background: Dextromethorphan, the D-isomer of the codeine analog levorphanol, is a weak, noncompetitive N-Methyl-D-Aspartate (NMDA receptor antagonist. It has been suggested that NMDA receptor antagonists induce preemptive analgesia when administered before tissue injury occurs, thus decreasing the subsequent sensation of pain. Materials and Methods: The study was conducted in the Dr. Ali Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran, between February 2005 and December 2006. In this study, 72 patients scheduled for elective cholesyctectomy were randomized into three groups to receive either oral dextromethorphan 45 mg (Group D45 = 24, dextromethorphan 90 mg (Group D90 = 24, or placebo (Group C, n = 24, as premedication, 120 minutes before surgery. A visual analog scale (VAS for pain of each patient was measured at arrival in the ward and six and 24 hours after surgery. Results: The demographic characteristics of patients, ASA physical status class, duration of surgery, and the basal VAS pain score were similar in the two groups. There was no significant difference in the mean of the VAS pain scores measured over time or morphine consumption among the three groups. Conclusion: Dextromethorphan 45 mg and 90 mg, administrated orally, two hours before surgery, had no effect on postoperative morphine requirement and pain intensity.

  7. Oral misoprostol versus dinoprostone vaginal tablets for labor induction

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    Khaled Ibrahim Abu El aish

    2013-06-01

    Full Text Available Background: Induction of labour is common in obstetric practice. We conducted this study to find the appropriate and safe drug for labour induction and to compare the safety and efficacy of oral misoprostol and vaginal dinoprostone for labour induction. Methods: In a provisional, prospective and cross-sectional study, one hundred and fifty five singleton cephalic presentation full term pregnancies with medical or obstetric indication for labour induction were allocated in two groups. First group received oral 50 micrograms for nulliparas and low parity group (1-4, and 25micrograms for grand multiparas (≥ 5 misoprostol orally every 6 hours to a maximum of four doses daily. In the second group vaginal tablets of dinoprostone 3mg then 1.5mg for nulliparas and 1.5mg for low parity and grand multiparas groups were inserted in the posterior fornix, every 8 hours. Primary outcome measures were: induction success, induction-delivery interval and number of used doses. Secondary outcome measures included: maternal side effects, caesarean section rate, mode of delivery and neonatal outcome. Data was collected from patient case notes and analyzed using software SPSS (version 13.0 and p-value < 0.05 was used as statistical significance of differences. Results: In our study there were no significant differences in baseline parameters in the two groups nor in the indications for labor induction except misoprostol was used in premature rupture of membrane. Induction of labor succeeded in 123 (79.35% women without other interventions from other methods (80.26%misoprostol group versus 78.5% dinoprostone p=0.492. It was observed that there were no significant differences between the two groups in final outcomes nor in obstetrical complications. There was no significance in differences between misoprostol and dinoprostone groups in induction-delivery interval (15.2 ± 14.5 hours versus 16.4 ± 11.3 hours p=0.6 resp.. Conclusions: This study demonstrated that oral

  8. Development and evaluation of ofloxacin orally disintegrating tablets

    Directory of Open Access Journals (Sweden)

    Badrinath Pralhadrao Mohite

    2012-06-01

    Full Text Available Bitter taste of ofloxacin, a broad spectrum bactericidal agent, is masked and orally disintegrating tablets were formulated. The bitter taste is masked by forming complex between drug and weak cation exchange resins, Tulsion 335 and Indion 204. Effect of pH and drug:resin ratio on the drug loading was studied. Maximum drug loading was observed at pH 6. Ratio of 1:2 of drug:resin masked almost complete bitterness of ofloxacin. Formation of complexes was confirmed by IR spectroscopy. Physical characterization of taste masked complexes was carried out. Present work envisages the taste masking of ofloxacin and development of orally disintegrating tablets. The effect of pH and resin quantities on drug loading were studied to find the optimum conditions of drug loading for complete taste masking. Effect of superdisintegrants like sodium starch glycolate, croscarmellose sodium and polyplasdone XL at varying level on physical parameters of compressed tablets was also assessed. The formulations containing 5 % w/w polyplasdone XL showed about 90 % of drug release within 5 minutes. No significant differences were observed in the physical parameters of resinates as well as tablets prepared from Tulsion 335 and Indion 204.O gosto amargo de ofloxacina, agente bactericida de largo espectro, é mascarado e formularam-se comprimidos dispersíveis. O sabor amargo é mascarado pela formação de complexo entre o fármaco e resinas de troca catiônica fraca, Tulsion 335 e Indion 204. Efeito do pH e da proporção fármaco: resina sobre a carga de fármaco foi estudada. Carga de fármaco máxima foi observada em pH 6. Proporção 1:2 do fármaco: resina mascarou quase completamente o gosto amargo de ofloxacina. A formação de complexos foi confirmada por espectroscopia no IV. Caracterização física dos complexos de sabor mascarado foi realizada. O presente trabalho preconiza o mascaramento do gosto de ofloxacina e desenvolvimento decomprimidos por via oral, se

  9. [Effect of Food Thickeners on the Disintegration, Dissolution, and Drug Activity of Rapid Oral-disintegrating Tablets].

    Science.gov (United States)

    Tomita, Takashi; Kohda, Yukinao; Kudo, Kenzo

    2018-01-01

     For patients with dysphagia in medical facilities and nursing homes, food thickeners are routinely used to aid the ingestion of medicines such as tablets. However, some types of thickeners affect the disintegration and dissolution of tablets, such as rapidly-disintegrating magnesium oxide tablets and donepezil hydrochloride orally disintegrating tablets. Additionally, delayed disintegration and dissolution of tablets affect a drug's efficacy. As an example, with Voglibose orally disintegrating tablets, marked differences are observed in changes in glucose levels during glucose tolerance testing. When using food thickeners to aid tablet ingestion, it is therefore necessary to select a product that has little effect on drug disintegration, dissolution, and activity.

  10. Long-term high-dose oral morphine in phantom limb pain with no addiction risk

    Directory of Open Access Journals (Sweden)

    Vinod Kumar

    2015-01-01

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

  11. Enhanced oral bioavailability of felodipine by novel solid self-microemulsifying tablets.

    Science.gov (United States)

    Jing, Boyu; Wang, Zhiyuan; Yang, Rui; Zheng, Xia; Zhao, Jia; Tang, Si; He, Zhonggui

    2016-01-01

    The novel self-microemulsifying (SME) tablets were developed to enhance the oral bioavailability of a poor water-soluble drug felodipine (FDP). Firstly, FDP was dissolved in the optimized liquid self-microemusifying drug delivery systems (SMEDDS) containing Miglyol® 812, Cremophor® RH 40, Tween 80 and Transcutol® P, and the mixture was solidified with porous silicon dioxide and crospovidone as adsorbents. Then after combining the solidified powders with other excipients, the solid SME tablets were prepared by wet granulation-compression method. The prepared tablets possessed satisfactory characterization; the droplet size of the SME tablets following self-emulsification in water was nearly equivalent to the liquid SMEDDS (68.4 ± 14.0 and 64.4 ± 12.0 nm); differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) analysis demonstrated that FDP in SME tablets had undergone a polymorphism transition from a crystal form to an amorphous state, which was further confirmed by transmission electron microscopy (TEM). A similar dissolution performance of SME tablets and liquid SMEDDS was also obtained under the sink condition (85% within 10 min), both significantly higher than commercial tablets. The oral bioavailability was evaluated for the SME tablets, liquid SMEDDS and commercial conventional tablets in the fasted beagle dogs. The AUC of FDP from the SME tablets was about 2-fold greater than that of conventional tablets, but no significant difference was found when compared with the liquid SMEDDS. Accordingly, these preliminary results suggest that this formulation approach offers a useful large-scale producing method to prepare the solid SME tablets from the liquid SMEDDS for oral bioavailability equivalent enhancement of poorly soluble FDP.

  12. Oral Delivery of Probiotics in Poultry Using pH-Sensitive Tablets.

    Science.gov (United States)

    Jiang, Tao; Li, Hui-Shan; Han, Geon Goo; Singh, Bijay; Kang, Sang-Kee; Bok, Jin-Duck; Kim, Dae-Duk; Hong, Zhong-Shan; Choi, Yun-Jaie; Cho, Chong-Su

    2017-04-28

    As alternatives to antibiotics in livestocks, probiotics have been used, although most of them in the form of liquid or semisolid formulations, which show low cell viability after oral administration. Therefore, suitable dry dosage forms should be developed for livestocks to protect probiotics against the low pH in the stomach such that the products have higher probiotics survivability. Here, in order to develop a dry dosage forms of probiotics for poultry, we used hydroxypropyl methylcellulose phthalate 55 (HPMCP 55) as a tablet-forming matrix to develop probiotics in a tablet form for poultry. Here, we made three different kinds of probiotics-loaded tablet under different compression forces and investigated their characteristics based on their survivability, morphology, disintegration time, and kinetics in simulated gastrointestinal fluid. The results indicated that the probiotics formulated in the tablets displayed higher survival rates in acidic gastric conditions than probiotics in solution. Rapid release of the probiotics from the tablets occurred in simulated intestinal fluid because of fast swelling of the tablets in neutral pH. As a matrix of tablet, HPMCP 55 provided good viability of probiotics after 6 months under refrigeration. Moreover, after oral administration of probiotics-loaded tablets to chicken, more viable probiotics were observed, than with solution type, through several digestive areas of chicken by the tablets.

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

    Science.gov (United States)

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

    2009-12-01

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

  14. Design and Evaluation of an Oral Floating Matrix Tablet of ...

    African Journals Online (AJOL)

    Purpose: To develop floating matrix tablets of salbutamol sulphate using ethyl cellulose and acrycoat S-100 as polymers, and sodium bicarbonate, citric acid and tartaric acid as gas generating agents. Methods: Twenty four formulations were prepared and segregated into four major categories, A to D. The floating tablets ...

  15. Oral controlled release drug delivery system and Characterization of oral tablets; A review

    Directory of Open Access Journals (Sweden)

    Muhammad Zaman

    2016-01-01

    Full Text Available Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes diffusion controlled drug delivery systems; dissolution controlled drug delivery systems, osmotically controlled drug delivery systems, ion-exchange controlled drug delivery systems, hydrodynamically balanced systems, multi-Particulate drug delivery systems and microencapsulated drug delivery system. The systems are formulated using different natural, semi-synthetic and synthetic polymers. The purpose of the review is to provide information about the orally controlled drug delivery system, polymers which are used to formulate these systems and characterizations of one of the most convenient dosage form which is the tablets

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

    Science.gov (United States)

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

    2012-11-01

    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.

  17. Evaluation of disintegration properties of orally rapidly disintegrating tablets using a novel disintegration tester.

    Science.gov (United States)

    Kondo, Keita; Niwa, Toshiyuki; Danjo, Kazumi

    2012-01-01

    This report describes a new disintegration tester that can determine not only the disintegration time of orally rapidly disintegrating tablets (ODT), but also the disintegration behavior and mechanism. Using the tester, the disintegration properties of the tablets prepared in a previous study were examined. The purpose of this study is to confirm the utility of the tester as an instrument for evaluating the disintegration properties of ODT and determine relations among time, behavior and mechanism of the disintegration. Results demonstrated that in vitro disintegration time in the tester is similar to that in the commercial disintegration tester for ODT and is highly correlated with oral disintegration time. Observations of disintegration process revealed that a difference in disintegration behavior between tablets compressed at 50-75 MPa and 100 MPa; the disintegration behavior of the tablets were designated immediate disintegrating type and gradual disintegrating type, respectively. The dynamic swelling profile and water absorption profile indicated that the disintegration mechanism of the tablets involved wicking action induced by swelling of the disintegrant; the disintegration time was closely related to the initial rates of swelling and water absorption. Furthermore, the mechanism of water absorption of tablets compressed at 50-75 MPa and 100 MPa shows anomalous diffusion and case-II transport, respectively. The shift in this mechanism is consistent with differences in disintegration time and behavior between the tablets. These findings suggest that information on disintegration properties obtained by our tester is useful for understanding of disintegration phenomena of ODT.

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

    International Nuclear Information System (INIS)

    Desai, Samixa; Poddar, Aditi; Sawant, Krutika

    2016-01-01

    The present investigation was aimed towards developing a beta-cyclodextrin (β-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 β-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 60 min 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 ± 1.52 s 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 β-CD–ESL SD-ODT could provide faster onset of action and higher bioavailability, which would be beneficial in case of epileptic seizures. - Highlights: • β-cyclodextrin–eslicarbazepine acetate complex developed with enhanced solubility. • Formulated Orally disintegrating tablets (ODT) disintegrated within 30 s. • Bioavailability from ODT was 2 times higher than marketed tablets. • Onset of action for ODT was also faster than marketed tablets. • Formulated ODT would aid epileptic patients incapable of swallowing tablets.

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

    Energy Technology Data Exchange (ETDEWEB)

    Desai, Samixa; Poddar, Aditi; Sawant, Krutika, E-mail: dr_krutikasawant@yahoo.co.in

    2016-01-01

    The present investigation was aimed towards developing a beta-cyclodextrin (β-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 β-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 60 min 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 ± 1.52 s 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 β-CD–ESL SD-ODT could provide faster onset of action and higher bioavailability, which would be beneficial in case of epileptic seizures. - Highlights: • β-cyclodextrin–eslicarbazepine acetate complex developed with enhanced solubility. • Formulated Orally disintegrating tablets (ODT) disintegrated within 30 s. • Bioavailability from ODT was 2 times higher than marketed tablets. • Onset of action for ODT was also faster than marketed tablets. • Formulated ODT would aid epileptic patients incapable of swallowing tablets.

  20. Mechanistic Population Pharmacokinetics of Morphine in Neonates With Abstinence Syndrome After Oral Administration of Diluted Tincture of Opium.

    Science.gov (United States)

    Liu, Tao; Lewis, Tamorah; Gauda, Estelle; Gobburu, Jogarao; Ivaturi, Vijay

    2016-08-01

    Conducting and analyzing clinical trials in vulnerable neonates are extremely challenging. The aim of this analysis is to develop a morphine population pharmacokinetics (PK) model using data collected during a randomized control trial in neonates with abstinence syndrome (NAS). A 3-compartment morphine structural PK model after intravenous (IV) administration from previously published work was utilized as prior, whereas an allometric scaling method with physiological consideration was used to extrapolate a PK profile from adults to pediatrics. The absorption rate constant and bioavailability were estimated in NAS after oral administration of diluted tincture of opium (DTO). Goodness-of-fit plots along with normalized prediction distribution error and bootstrap method were performed for model evaluation. We successfully extrapolated the PK profile from adults to pediatrics after IV administration. The estimated first-order absorption rate constant and bioavailability were 0.751 hour(-1) and 48.5%, respectively. Model evaluations showed that the model can accurately and precisely describe the observed data. The population pharmacokinetic model we derived for morphine after oral administration of DTO is reasonable and acceptable; therefore, it can be used to describe the PK and guide future studies. The integration of the previous population PK knowledge as prior information successfully overcomes the logistic and practical issue in vulnerable neonate population. © 2016, The American College of Clinical Pharmacology.

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

    Science.gov (United States)

    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

  2. A comparison of detomidine in combination with saline, morphine or methadone in horses submitted to experimental oral stimuli

    Directory of Open Access Journals (Sweden)

    Rafael Costa Guilhen

    2015-12-01

    Full Text Available This study aimed to compare the sedative and cardiopulmonary effects of detomidine in combination with saline, morphine or methadone and to determine whether the addition of these opioids increases the degree of sedation in horses submitted to experimental oral stimuli. In a blinded, randomized, experimental study, six adult mares were evaluated using a crossover design with at least 15 days between trials: 10?g/kg detomidine in combination with saline (D/SAL, 0.1mg/kg morphine (D/ MORPH or 0.1mg/kg methadone (D/METH. The degree of sedation, response to oral stimuli and cardiopulmonary parameters were monitored for 120 minutes. Parametric data were analyzed using the ANOVA and Tukey’s tests, and non- parametric data were analyzed with the Kruskal-Wallis and Friedman’s tests with the post-Dunn test (P<0.05. The degree of sedation was significantly greater for the D/SAL than for the D/MORPH and D/METH treatments at 30 min. The horses´ responses to the oral stimuli decreased significantly following all treatments at 5 and 30 min from baseline values. The heart rate, respiratory rate, arterial pH and blood gas variables were all similar among the treatment groups. Mean arterial blood pressure was significantly higher in the D/MORPH group when compared with the D/SAL group between 75 and 120 min. It was concluded that all treatments provided sedative effects with mild cardiopulmonary changes. However the addition of morphine or methadone to detomidine did not improve the degree of sedation in horses submitted to experimental oral stimuli.

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

    Science.gov (United States)

    Moghimipour, Eskandar; Aghel, Nasrin; Adelpour, Akram

    2012-01-01

    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. 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. 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. 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. 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.

  4. Quantitative evaluation of the disintegration of orally rapid disintegrating tablets by X-ray computed tomography.

    Science.gov (United States)

    Otsuka, Makoto; Yamanaka, Azusa; Uchino, Tomohiro; Otsuka, Kuniko; Sadamoto, Kiyomi; Ohshima, Hiroyuki

    2012-01-01

    To measure the rapid disintegration of Oral Disintegrating Tablets (ODT), a new test (XCT) was developed using X-ray computing tomography (X-ray CT). Placebo ODT, rapid disintegration candy (RDC) and Gaster®-D-Tablets (GAS) were used as model samples. All these ODTs were used to measure oral disintegration time (DT) in distilled water at 37±2°C by XCT. DTs were affected by the width of mesh screens, and degree to which the tablet holder vibrated from air bubbles. An in-vivo tablet disintegration test was performed for RDC using 11 volunteers. DT by the in-vivo method was significantly longer than that using the conventional tester. The experimental conditions for XCT such as the width of the mesh screen and degree of vibration were adjusted to be consistent with human DT values. Since DTs by the XCT method were almost the same as the human data, this method was able to quantitatively evaluate the rapid disintegration of ODT under the same conditions as inside the oral cavity. The DTs of four commercially available ODTs were comparatively evaluated by the XCT method, conventional tablet disintegration test and in-vivo method.

  5. Lyophilized mucoadhesive-dendrimer enclosed matrix tablet for extended oral delivery of albendazole.

    Science.gov (United States)

    Mansuri, Shakir; Kesharwani, Prashant; Tekade, Rakesh Kumar; Jain, Narendra Kumar

    2016-05-01

    Dendrimers are multifunctional carriers widely employed for delivering drugs in a variety of disease conditions including HIV/AIDS and cancer. Albendazole (ABZ) is a commonly used anthelmintic drug in human as well as veterinary medicine. In this investigation, ABZ was formulated as a "muco-dendrimer" based sustained released tablet. The mucoadhesive complex was synthesized by anchoring chitosan to fifth generation PPI dendrimer (Muco-PPI) and characterized by UV, FTIR, (1)H NMR spectroscopy and electron microscopy. ABZ was entrapped inside Muco-PPI followed by lyophilization and tableting as matrix tablet. A half-life (t1/2) of 8.06±0.15, 8.17±0.47, 11.04±0.73, 11.49±0.92, 12.52±1.04 and 16.9±1.18h was noted for ABZ (free drug), conventional ABZ tablet (F1), conventional ABZ matrix tablet (F2), PPI-ABZ complex, PPI-ABZ matrix tablet (F3) and Muco-PPI-ABZ matrix tablet (F4), respectively. Thus the novel mucoadhesive-PPI based formulation of ABZ (F4) increased the t1/2 of ABZ significantly by almost twofold as compared to the administration of free drug. The in vivo drug release data showed that the Muco-PPI based formulations have a significantly higher Cmax (2.40±0.02μg/mL) compared with orally administered free ABZ (0.19±0.07μg/mL) as well as conventional tablet (0.20±0.05μg/mL). In addition, the Muco-PPI-ABZ matrix tablet displayed increased mean residence time (MRT) and is therefore a potential candidate to appreciably improve the pharmacokinetic profile of ABZ. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Prediction of oral disintegration time of fast disintegrating tablets using texture analyzer and computational optimization.

    Science.gov (United States)

    Szakonyi, G; Zelkó, R

    2013-05-20

    One of the promising approaches to predict in vivo disintegration time of orally disintegrating tablets (ODT) is the use of texture analyzer instrument. Once the method is able to provide good in vitro in vivo correlation (IVIVC) in the case of different tablets, it might be able to predict the oral disintegration time of similar products. However, there are many tablet parameters that influence the in vivo and the in vitro disintegration time of ODT products. Therefore, the measured in vitro and in vivo disintegration times can occasionally differ, even if they coincide in most cases of the investigated products and the in vivo disintegration times may also change if the aimed patient group is suffering from a special illness. If the method is no longer able to provide good IVIVC, then the modification of a single instrumental parameter may not be successful and the in vitro method must be re-set in a complex manner in order to provide satisfactory results. In the present experiment, an optimization process was developed based on texture analysis measurements using five different tablets in order to predict their in vivo disintegration times, and the optimized texture analysis method was evaluated using independent tablets. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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 pre- and post-compression characteristics. The prepared OD-mini-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.

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

    Directory of Open Access Journals (Sweden)

    El-Say Khalid M.

    2015-12-01

    Full Text Available 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.

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

    Science.gov (United States)

    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, δ and β 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 β-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. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Taste-masking assessment of orally disintegrating tablets and lyophilisates with cetirizine dihydrochloride microparticles

    Directory of Open Access Journals (Sweden)

    Aleksandra Amelian

    2017-12-01

    Full Text Available Orally disintegrating tablets and oral lyophilisates are novel attractive dosage forms that disintegrate or dissolve in the buccal cavity within seconds without necessity of drinking. The major limitation in designing of these dosage forms is unpleasant taste of the drug substance. Cetirizine dihydrochloride is a H1-antihistamine substance indicated for the treatment of allergy. It is characterized by extremely bitter taste, therefore in order to deliver cetirizine dihydrochloride using orodispersible formulations, effective taste-masking is required. The aim of this study was to investigate whether microparticles containing cetirizine dihydrochloride could be successfully used to formulate orally disintegrating tablets by direct compression method and oral lyophilisates by freeze-drying process. Taste masking of cetirizine dihydrochloride was achieved by the spray-drying technique using Eudragit® E PO as the drug agent carrier. Based on the preliminary studies, optimal compositions of microparticles, tablets and lyophilisates were chosen. Obtained dosage forms were characterized for drug content, disintegration time and mechanical properties. In order to determine whether the microparticles subjected to direct compression and freeze-drying process effectively mask the bitter taste of cetirizine dihydrochloride, the in vivo and in vitro evaluation was performed. The results showed that designed formulates with microparticles containing cetirizine dihydrochloride were characterized by appropriate mechanical properties, uniformity of weight and thickness, short disintegration time, and the uniform content of the drug substance. Taste-masking assessment performed by three independent methods (e-tongue evaluation, human test panel and the in vitro drug release revealed that microparticles with Eudragit® E PO are effective taste – masking carriers of cetirizine dihydrochloride and might be used to formulate orally disintegrating tablets and oral

  11. Improved anticoagulant effect of fucosylated chondroitin sulfate orally administered as gastro-resistant tablets.

    Science.gov (United States)

    Fonseca, Roberto J C; Sucupira, Isabela D; Oliveira, Stephan Nicollas M C G; Santos, Gustavo R C; Mourão, Paulo A S

    2017-04-03

    Fucosylated chondroitin sulfate (FucCS) is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of unique branches of sulfated fucose. Although this glycosaminoglycan exerts an antithrombotic effect following oral administration, high doses are necessary to achieve the maximum effect. The diminished activity of FucCS following oral administration is likely due to its degradation in the gastrointestinal tract and its limited ability to cross the intestinal cell membranes. The latter aspect is particularly difficult to overcome. However, gastro-resistant tablet formulation may help limit the degradation of FucCS in the gastrointestinal tract. In the present work, we found that the oral administration of FucCS as gastro-resistant tablets produces a more potent and prolonged anticoagulant effect compared with its administration as an aqueous solution, with no significant changes in the bleeding tendency or arterial blood pressure. Experiments using animal models of arterial thrombosis initiated by endothelial injury demonstrated that FucCS delivered as gastro-protective tablets produced a potent antithrombotic effect, whereas its aqueous solution was ineffective. However, there was no significant difference between the effects of FucCS delivered as gastro-resistant tablets or as aqueous solution in a venous thrombosis model, likely due to the high dose of thromboplastin used. New oral anticoagulants tested in these experimental models for comparison showed significantly increased bleeding tendencies. Our study provides a framework for developing effective oral anticoagulants based on sulfated polysaccharides from marine organisms. The present results suggest that FucCS is a promising oral anticoagulant.

  12. User of ordered mixtures to obtain high dose homogeneity in mini-tablets : studies of orally disintegrating systems for children

    OpenAIRE

    Løding, Fredrik Sandberg

    2011-01-01

    Studies have shown that homogeneity is higher in ordered mixtures compared to random mixtures. Based on this ordered mixtures should be particularly suitable for the preparation of mini-tablets. The overall aim of the study was to compare the homogeneity of ordered mixtures prepared using different particle size of carrier particles, and test their suitability for preparation of mini-tablets. The mini-tablets are intended for use as orally disintegrating systems (ODT) for children...

  13. Comparison of the efficacy of fluconazole tablet and oral nystatin ...

    African Journals Online (AJOL)

    Background: Oral candidiasis is the most common HIV/AIDs related complication. It limits patients from feeding and interferes with the intake of HAART, as the patients find it difficult to swallow food and their medications. It leads to poor adherence, poor feeding, depression, loss of man hours, deterioration of patient's state of ...

  14. Development and Evaluation of Orally Disintegrating Tablets of ...

    African Journals Online (AJOL)

    designed and manufactured by direct compression method, using microcrystalline (Avicel PH-102), mannitol ... batch (FOB-01) reflected the successful development of new formulation of orally disintegrating ... investigate the product variables that influence product quality. .... thickness was high but was within limits of ± 5 %.

  15. PHARMACOKINETICS OF DICLOFENAC SODIUM AND PAPAVERINE HYDROCHLORIDE AFTER ORAL ADMINISTRATION OF TABLETS TO RABBITS.

    Science.gov (United States)

    Kasperek, Regina; Zimmer, Łukasz; Jawień, Wojciech; Poleszak, Ewa

    2015-01-01

    Non-compartmental pharmacokinetic analysis of diclofenac sodium (DIC) and papaverine hydrochloride (PAP) after oral administration of composed tablets to rabbits was developed. HPLC method for determination of DIC and PAP in rabbit plasma was developed and validated. Chromatographic separation of DIC, PAP and the IS was achieved on a Zorbax SB C18 5-µm column (150 mm x 4.6 mm) using methanol-water (55:45, v/v) as mobile phase at a flow rate of 0.8 mL/min. Pharmacokinetic analysis showed that oral administration of a tablet composed of DIC and PAP do not change the pharmacokinetic parameters such as MRT, MAT, Cl and bioavailability of the active substances compared with single administration of DIC and PAP after single dose.

  16. Weight loss during therapy with olanzapine orally disintegrating tablets: two case reports.

    Science.gov (United States)

    Kozumplik, Oliver; Uzun, Suzana; Jakovljević, Miro

    2009-03-01

    The aim of this article is to report weight loss in patients with schizophrenia after switching from olanzapine standard oral tablet (SOT) to olanzapine orally disintegrating tablets (ODT). In the first case report, the patient was switched to olanzapine ODT in daily dosage of 20 mg, while in the second case report, the patient was switched to olanzapine ODT in daily dosage of 15 mg, and weight loss was similar (14 kg vs. 15 kg). Switching patients from olanzapine SOT to olanzapine ODT treatment resulted in significant weight loss that was maintained during 12 months in both case reports. Further controlled clinical investigations are necessary to evaluate change in weight during treatment with olanzapine ODT, and to improve our understanding of this change.

  17. Treatment of the acute sickle cell vaso-occlusive crisis in the Emergency Department: a Brazilian method of switching from intravenous to oral morphine.

    Science.gov (United States)

    Campos, Jessica; Lobo, Clarisse; Queiroz, Ana Maria Mach; do Nascimento, Emilia Matos; Lima, Carlos Bernardo; Cardoso, Gilberto; Ballas, Samir K

    2014-07-01

    Describe the treatment of patients with vaso-occlusive crises (VOC) in a Brazilian emergency department (ED) and the successful switch from intravenous to oral morphine. We analyzed records of 315 patients with sickle cell disease using two different protocols for pain: one in March 2010 prescribing intravenous morphine every 4 h throughout their stay, and another in March 2011 and 2012 prescribing one initial dose of intravenous morphine followed by equianalgesic doses of oral morphine every 4 h. Patients were triaged into three groups: mild, moderate, and severe VOC. The mild group was treated within 1 h after triage, the moderate within 30 min and the severe was treated immediately. Patients whose pain was not relieved within 6 h after the first dose of morphine were transferred into a different holding area of the ED where they continued to receive the same treatment for 48 h after which they were hospitalized if still in pain. The number of patients who stayed <24 h in the ED increased significantly from 63 in 2010 to 87 in 2012, and the number of admissions decreased from 26 in 2010 to 10 in 2012. The incidence of acute chest syndrome decreased from 8.5% in 2010 to 1.9% in 2012. Patients treated with oral morphine stayed a shorter time in the ED, had more pain relief, were admitted less frequently, and had less acute chest syndrome. These differences may be due to environmental, cultural, psychological, and pharmacogenetic factors. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Oral sustained release tablets of zidovudine using binary blends of natural and synthetic polymers.

    Science.gov (United States)

    Emeje, Martins; Olaleye, Olajide; Isimi, Christiana; Fortunak, Joseph; Byrn, Stephen; Kunle, Olobayo; Ofoefule, Sabinus

    2010-01-01

    Oral sustained release matrix tablets of zidovudine (ZDV) were prepared using different types, proportions and blends of carbopol 71G (C71) and a plant gum obtained from Abelmoschus esculentus (AEG). The effect of various formulation factors like polymer proportion, polymer type and pH of the dissolution medium on the in vitro release of the drug was studied, using the half change technique, in 900 ml of dissolution medium, at 100 rpm. Release kinetics were analyzed using Zero-order, Higuchi's square-root and Ritger-Peppas' empirical equations. In vitro release performance as revealed by the time taken for 70% of the drug to be released (t70%), showed that the release rate decreased with increase in polymer proportion. Matrix tablets containing 10 and 20% AEG were found to exhibit immediate-release characteristics. Matrix tablets containing 30% AEG showed t70% value of 204 min and extended the release up to 5 h, while matrix tablets containing 30% carbopol showed t70% value of 234 min and extended the release up to 6 h. Three blends of AEG and C71 at the ratio of 1:2, 2:1 and 1:3 showed t70% values of 132, 312 and 102 min respectively and extended the release up to 8 h. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets followed Fickian and anomalous release. Drug release from matrix tablets of zidovudine containing blends of AEG and C71 demonstrates the advantage of blending a natural and synthetic polymer over single polymer use.

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

    Science.gov (United States)

    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.

  20. Relative bioavailability of diclofenac potassium from softgel capsule versus powder for oral solution and immediate-release tablet formulation.

    Science.gov (United States)

    Bende, Girish; Biswal, Shibadas; Bhad, Prafulla; Chen, Yuming; Salunke, Atish; Winter, Serge; Wagner, Robert; Sunkara, Gangadhar

    2016-01-01

    The oral bioavailability of diclofenac potassium 50 mg administered as a soft gelatin capsule (softgel capsule), powder for oral solution (oral solution), and tablet was evaluated in a randomized, open-label, 3-period, 6-sequence crossover study in healthy adults. Plasma diclofenac concentrations were measured using a validated liquid chromatography-mass spectrometry/mass spectrometry method, and pharmacokinetic analysis was performed by noncompartmental methods. The median time to achieve peak plasma concentrations of diclofenac was 0.5, 0.25, and 0.75 hours with the softgel capsule, oral solution, and tablet formulations, respectively. The geometric mean ratio and associated 90%CI for AUCinf, and Cmax of the softgel capsule formulation relative to the oral solution formulation were 0.97 (0.95-1.00) and 0.85 (0.76-0.95), respectively. The geometric mean ratio and associated 90%CI for AUCinf and Cmax of the softgel capsule formulation relative to the tablet formulation were 1.04 (1.00-1.08) and 1.67 (1.43-1.96), respectively. In conclusion, the exposure (AUC) of diclofenac with the new diclofenac potassium softgel capsule formulation was comparable to that of the existing oral solution and tablet formulations. The peak plasma concentration of diclofenac from the new softgel capsule was 67% higher than the existing tablet formulation, whereas it was 15% lower in comparison with the oral solution formulation. © 2015, The American College of Clinical Pharmacology.

  1. Research studies on in vitro and ex vivo yield of the miconazole nitrate from oral biomucoadhesive tablets.

    Science.gov (United States)

    Birsan, Magdalena; Cojocaru, Ileana; Scutariu, Mihaela Monica; Popovici, Iuliana

    2014-01-01

    Among the various routes of drug administration, the oral mucosa is perhaps the most often preferred by patients and medical staff. However, oral administration of drugs has disadvantages, which may limit or prevent oral administration of some drugs, especially peptides and proteins, little when they are inserted in special administration systems for the colon. The disaggregation of some oral biomucoadhesive tablets and the in vitro yield of the miconazole nitrate was evaluated and in parallel with this, the evaluation of the in vivo yield of the antifungal from the pharmaceutical form. Thus, for a clear determination of the oral mucobioadhesive tablets' disintegration with miconazole nitrate, it was necessary to implement a method to simulate the conditions of the oral cavity at a flow of solution (artificial saliva) similar to that of the human one. miconazole nitrate. The determination of disintegration time according to method A (FRX); the disaggregation of oral biomucoadhesive tablets with miconazole nitrate by means of simulation methods of in vitro conditions; the quantitative determination of the miconazole nitrate by means of HPLC method, after the in vitro dissolution test; the study of miconazole nitrate's yield in dynamic condition from biomucoadhesive tablets in the presence of artificial saliva (AFNOR). The yield profile of the miconazole nitrate in the disintegration solutions by means of classical method from FR X, by HPLC dosage was researched. The release of miconazole nitrate from the oral mucobioadhesive tablets was determined, that varies in time, depending on the type and relation of matrix forming polymers; a low yield speed of the miconazole nitrate from the tablets was determined; the yield profile of miconazole nitrate in disintegration solutions by means of the new suggested method was researched. The release of miconazole nitrate from the formulated biomucoadhesive tablets is of swelling and erosion.

  2. Expedited Development of Diphenhydramine Orally Disintegrating Tablet through Integrated Crystal and Particle Engineering.

    Science.gov (United States)

    Wang, Chenguang; Hu, Shenye; Sun, Changquan Calvin

    2017-10-02

    A palatable direct compression (DC) orally disintegrating tablet (ODT) product of a bitter drug, diphenhydramine (DPH), was developed using an integrated crystal and particle engineering approach. A DPH salt with a sweetener, acesulfame (Acs), DPH-Acs, was synthesized and its solid state properties were comprehensively characterized. Tablet formulation composition and compaction parameters were optimized by employing material sparing techniques. In vivo disintegration time, bitterness, and grittiness of the final ODT product, were evaluated by a taste panel. Physical stability of the ODT tablets was assessed to identify appropriate storage conditions. Phase-pure DPH-Acs exhibited significantly better tabletability and palatability than DPH-HCl. A DC formulation was designed and optimized to obtain a new ODT product with good manufacturability and excellent product characteristics, including fast in vivo disintegration, and acceptable bitterness and grittiness. A new ODT product of DPH with excellent pharmaceutical properties was successfully developed using 15 g of DPH and in two months. This example shows that integrated crystal and particle engineering is an effective approach for developing high quality ODT products using the DC process.

  3. A new modified wetting test and an alternative disintegration test for orally disintegrating tablets.

    Science.gov (United States)

    Hooper, Patrick; Lasher, Jason; Alexander, Kenneth S; Baki, Gabriella

    2016-02-20

    Industrial manufacturing of solid oral dosage forms require quality tests, such as friability, hardness, and disintegration. The United States Pharmacopeia (USP) disintegration test uses 900mL of water. However, recent studies of orally disintegrating tablets (ODTs) have shown that this volume does not accurately portray the oral environment. In our study, various tests were conducted with a more moderate amount of water that accurately resembles the oral environment. A simulated wetting test was performed to calculate the water absorption ratio. Results showed that wetting was comparable to disintegration. Although the wetting test worked for most types of ODTs, it had limitations that produced inaccurate results. This led to the use of a modified shaking water bath test. This test was found to work for all types of ODT products and was not subject to the limitations of the wetting test. The shake test could provide disintegration times rather than water permeation times; however, it could not be used to calculate the water absorption ratio. A strong correlation was observed between the standardized shake test and the USP disintegration times for the tablets. This shake test could be used during the development stages and quality tests for ODTs with relative ease. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Morphine metabolites

    DEFF Research Database (Denmark)

    Christrup, Lona Louring

    1997-01-01

    , morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are the major metabolites of morphine. The metabolism of morphine occurs not only in the liver, but may also take place in the brain and the kidneys. The glucuronides are mainly eliminated via bile and urine. Glucuronides as a rule...... are considered as highly polar metabolites unable to cross the blood-brain barrier. Although morphine glucuronidation has been demonstrated in human brain tissue, the capacity is very low compared to that of the liver, indicating that the M3G and M6G concentrations observed in the cerebrospinal fluid (CSF) after...... systemic administration reflect hepatic metabolism of morphine and that the morphine glucuronides, despite their high polarity, can penetrate into the brain. Like morphine, M6G has been shown to be relatively more selective for mu-receptors than for delta- and kappa-receptors while M3G does not appear...

  5. Comparison of intramuscular olanzapine, orally disintegrating olanzapine tablets, oral risperidone solution, and intramuscular haloperidol in the management of acute agitation in an acute care psychiatric ward in Taiwan.

    Science.gov (United States)

    Hsu, Wen-Yu; Huang, Si-Sheng; Lee, Bo-Shyan; Chiu, Nan-Ying

    2010-06-01

    The purpose of this study was to compare efficacy and safety among intramuscular olanzapine, intramuscular haloperidol, orally disintegrating olanzapine tablets, and oral risperidone solution for agitated patients with psychosis during the first 24 hours of treatment in an acute care psychiatric ward. Forty-two inpatients from an acute care psychiatric ward of a medical center in central Taiwan were enrolled. They were randomly assigned to 1 of the 4 treatment groups (10-mg intramuscular olanzapine, 10-mg olanzapine oral disintegrating tablet, 3-mg oral risperidone solution, or 7.5-mg intramuscular haloperidol). Agitation was measured by using the excited component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation-Calmness Evaluation Scale, and the Clinical Global Impression--Severity Scale during the first 24 hours. There were significant differences in the PANSS-EC total scores for the 4 intervention groups at 15, 30, 45, 60, 75, and 90 minutes after the initiation of treatment. More significant differences were found early in the treatment. In the post hoc analysis, the patients who received intramuscular olanzapine or orally disintegrating olanzapine tablets showed significantly greater improvement in PANSS-EC scores than did patients who received intramuscular haloperidol at points 15, 30, 45, 60, 75, and 90 minutes after injection. These findings suggest that intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution are as effective treatments as intramuscular haloperidol for patients with acute agitation. Intramuscular olanzapine and disintegrating olanzapine tablets are more effective than intramuscular haloperidol in the early phase of the intervention. There is no significant difference in effectiveness among intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution.

  6. Clinical disintegration time of orally disintegrating tablets clinically available in Japan in healthy volunteers.

    Science.gov (United States)

    Yoshita, Tomohiro; Uchida, Shinya; Namiki, Noriyuki

    2013-01-01

    Disintegration time is an important characteristic of orally disintegrating tablets (ODTs), and evaluation of disintegration time is a key step in formulation development, manufacturing, and clinical practice. In this study, we aimed to clarify the clinical disintegration time of ODTs that are currently used clinically, and to evaluate its correlation with the in vitro disintegration time of ODTs which was measured using Tricorptester, a newly developed disintegration testing apparatus. The clinical disintegration time of 17 ODT products was measured in healthy volunteers (n=9-10; age range, 21-28 years). A randomized single-blind trial was performed; each tablet was placed on the tongues of the participants, and it disintegrated in their oral cavities. No significant difference was observed in the clinical disintegration time of each ODT among the 3 groups to which the subjects were randomly assigned. The clinical disintegration time of the 17 ODT products was between 17.6 s and 33.8 s. The in vitro disintegration time of 26 clinically used ODT products measured using Tricorptester ranged between 4.40 s and 30.4 s. A significant positive correlation was observed between in vitro and clinical disintegration times (r=0.79; pdisintegration and that the disintegration time varied according to the product. In addition, the in vitro disintegration time of ODTs measured using Tricorptester is a good reflection of the disintegration time in the oral cavity.

  7. The efficacy and safety of clotrimazole vaginal tablet vs. oral fluconazole in treating severe vulvovaginal candidiasis.

    Science.gov (United States)

    Zhou, Xiaofang; Li, Ting; Fan, Shangrong; Zhu, Yuxia; Liu, Xiaoping; Guo, Xuedong; Liang, Yiheng

    2016-07-01

    To compare the efficacy and safety of two doses of clotrimazole vaginal tablet 500 mg with two doses of oral fluconazole 150 mg in treating severe vulvovaginal candidiasis (SVVC), 240 consecutive patients with SVVC were studied at the Department of Obstetrics and Gynaecology of Peking University Shenzhen Hospital between June 2014, and September 2015. Patients were randomly assigned in a 1 : 1 ratio to receive treatment with either two doses of clotrimazole vaginal tablet or two doses of oral fluconazole. The clinical cure rates in the clotrimazole group and the fluconazole group at days 7-14 follow-up were 88.7% (102/115) and 89.1% (98/110) respectively; the clinical cure rates at days 30-35 in the two groups were 71.9% (82/114) and 78.0% (85/109) respectively. The mycological cure rates at days 7-14 follow-up in the two groups were 78.3% (90/115) and 73.6% (81/110) respectively. The mycological cure rates of the patients at days 30-35 in the two groups were 54.4% (62/114) and 56.0% (61/109) respectively (P > 0.05). The adverse events of clotrimazole were mainly local. This study demonstrated that two doses of clotrimazole vaginal tablet 500 mg were as effective as two doses of oral fluconazole 150 mg in the treatment of patients with SVVC and could be an appropriate treatment for this disorder. © 2016 The Authors Mycoses Published by Blackwell Verlag GmbH.

  8. Oral controlled release drug delivery system and Characterization of oral tablets; A review

    OpenAIRE

    Muhammad Zaman; Junaid Qureshi; Hira Ejaz; Rai Muhammad Sarfraz; Hafeez ullah Khan; Fazal Rehman Sajid; Muhammad Shafiq ur Rehman

    2016-01-01

    Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes dif...

  9. EffenDys-Fentanyl Buccal Tablet for the Relief of Episodic Breathlessness in Patients With Advanced Cancer: A Multicenter, Open-Label, Randomized, Morphine-Controlled, Crossover, Phase II Trial.

    Science.gov (United States)

    Simon, Steffen T; Kloke, Marianne; Alt-Epping, Bernd; Gärtner, Jan; Hellmich, Martin; Hein, Rebecca; Piel, Maren; Cornely, Oliver A; Nauck, Friedemann; Voltz, Raymond

    2016-11-01

    Episodic breathlessness is a frequent and burdensome symptom in cancer patients but pharmacological treatment is limited. To determine time to onset, efficacy, feasibility, and safety of transmucosal fentanyl in comparison to immediate-release morphine for the relief of episodic breathlessness. Phase II, investigator-initiated, multicenter, open-label, randomized, morphine-controlled, crossover trial with open-label titration of fentanyl buccal tablet (FBT) in inpatients with incurable cancer. The primary outcome was time to onset of meaningful breathlessness relief. Secondary outcomes were efficacy (breathlessness intensity difference at 10 and 30 minutes; sum of breathlessness intensity difference at 15 and 60 minutes), feasibility, and safety. Study was approved by local ethics committees. Twenty-five of 1341 patients were eligible, 10 patients agreed to participate (four female, mean age 58 ± 11, mean Karnofsky score 67 ± 11). Two patients died before final visits and two patients dropped-out because of disease progression leaving six patients for analysis with 61 episodes of breathlessness. Mean time to onset was for FBT 12.7 ± 10.0 and for immediate-release morphine 23.6 ± 15.1 minutes with a mean difference of -10.9 minutes (95% CI = -24.5 to 2.7, P = 0.094). Efficacy measures were predominately in favor for FBT. Both interventions were safe. Feasibility failed because of too much study demands for a very ill patient group. The description of a faster and greater relief of episodic breathlessness by transmucosal fentanyl versus morphine justifies further evaluation by a full-powered trial. Copyright © 2016. Published by Elsevier Inc.

  10. Bioequivalence of 2 Formulations of Sildenafil Oral Soluble Film 100 mg and Sildenafil Citrate (Viagra) 100 mg Oral Tablets in Healthy Male Volunteers.

    Science.gov (United States)

    Dadey, Eric

    Sildenafil citrate tablets (VIAGRA; Pfizer Inc) have been used since 1998 as an oral therapy for the treatment of erectile dysfunction. However, in some cases, patients may have difficulty in swallowing tablets, and the need to use water to aid in the oral administration of the tablets has the potential to interrupt the sexual encounter, reduce spontaneity, and therefore decrease the quality of the experience. Two oral soluble film (OSF) formulations of sildenafil were developed using MonoSol Rx's proprietary PharmFilm technology. Both films were formulated to dissolve rapidly on the tongue, thereby releasing the drug into the oral cavity, whereupon it is swallowed without the use of water. From a patient perspective, it is anticipated that the film formulations of sildenafil citrate will provide a more compliant and discreet dosage form. The purpose of this clinical study was to compare the bioequivalence of the 2 sildenafil OSF 100 mg formulations (MonoSol Rx, LLC) with the sildenafil citrate 100 mg tablets. The design was a single-dose, randomized, open-label, 3-period, 6-sequence, 3-treatment, single-center, crossover study conducted in 18 healthy, nonsmoking male volunteers under fasting conditions, with each treatment period separated by a 7-day washout period. Plasma sildenafil concentrations were measured predose and then periodically to 24 hours after dosing. The 90% confidence intervals for plasma sildenafil AUC0-t, AUC0-∞, and Cmax for both sildenafil OSF formulations as compared with sildenafil citrate tablets were all within the 80%-125% range, indicating bioequivalence of both film formulations to sildenafil citrate tablets. Overall, the demonstrated bioequivalence coupled with the performance advantages of an OSF dosage form (ie, rapid dissolution in the mouth, can be taken without water, and can be dosed discreetly) suggest that the sildenafil OSF may provide an attractive alternative to sildenafil citrate oral tablets.

  11. Effervescent N-Acetylcysteine Tablets versus Oral Solution N-Acetylcysteine in Fasting Healthy Adults: An Open-Label, Randomized, Single-Dose, Crossover, Relative Bioavailability Study

    Directory of Open Access Journals (Sweden)

    Spencer C. Greene, MD, FACEP, FACMT

    2016-01-01

    Conclusions: Data from this study of a single dose of 11 g oral NAC demonstrated that effervescent NAC tablets and oral solution NAC met the regulatory criteria for bioequivalence in fasting healthy adult subjects. Effervescent NAC tablets appear to be a more palatable alternative for treatment of acetaminophen overdose. ClinicalTrials.gov identifier: NCT02723669.

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

    Science.gov (United States)

    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 tablet hardness of ∼ 73 N, hardness decreased with increasing mannitol content. Friability of all formulations 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.

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

    Directory of Open Access Journals (Sweden)

    Ali Al-Khattawi

    Full Text Available 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  16. Self-Nanoemulsifying Lyophilized Tablets for Flash Oral Transmucosal Delivery of Vitamin K: Development and Clinical Evaluation.

    Science.gov (United States)

    El-Say, Khalid M; Ahmed, Tarek A; Ahmed, Osama A A; Hosny, Khaled M; Abd-Allah, Fathy I

    2017-09-01

    Owing to limited solubility, vitamin K undergoes low bioavailability with large inter-individual variability after oral administration. This article aimed to prepare self-nanoemulsifying lyophilized tablets (SNELTs) for the flash oral transmucosal delivery of vitamin K. Twenty-one formulae of vitamin K self-nanoemulsifying drug delivery systems (SNEDDS) were prepared using different concentrations of vitamin K, Labrasol, and Transcutol according to mixture design. The SNEDDS was loaded on porous carriers and formulated as lyophilized tablets. The release profile and the pharmacokinetic parameters of vitamin K SNELTs were evaluated in comparison with commercial tablets and ampoules on human volunteers. Results revealed that the optimized SNEDDS showed the smallest and most stable nanoemulsion globules. SNELTs were prepared successfully and showed substantial superiority drug release compared with the commercial tablets. Interestingly, SNELTs enhanced both rate and extent of vitamin K absorption as well as relative bioavailability (169.67%) in healthy subjects compared with the commercial tablets. SNELTs revealed promising no significant difference in the area under the curve compared with the commercial intramuscular injection. SNELTs enhanced dissolution and bioavailability that expected to have the strong impact on the efficiency of vitamin K in the prophylaxis and treatment of bleeding disorders in patients with hepatic dysfunction. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  17. Evaluation of co-processed excipients used for direct compression of orally disintegrating tablets (ODT) using novel disintegration apparatus.

    Science.gov (United States)

    Brniak, Witold; Jachowicz, Renata; Krupa, Anna; Skorka, Tomasz; Niwinski, Krzysztof

    2013-01-01

    The compendial method of evaluation of orodispersible tablets (ODT) is the same disintegration test as for conventional tablets. Since it does not reflect the disintegration process in the oral cavity, alternative methods are proposed that are more related to in vivo conditions, e.g. modified dissolution paddle apparatus, texture analyzer, rotating shaft apparatus, CCD camera application, or wetting time and water absorption ratio measurement. In this study, three different co-processed excipients for direct compression of orally disintegrating tablets were compared (Ludiflash, Pharmaburst, F-Melt). The properties of the prepared tablets such as tensile strength, friability, wetting time and water absorption ratio were evaluated. Disintegration time was measured using the pharmacopoeial method and the novel apparatus constructed by the authors. The apparatus was based on the idea of Narazaki et al., however it has been modified. Magnetic resonance imaging (MRI) was applied for the analysis of the disintegration mechanism of prepared tablets. The research has shown the significant effect of excipients, compression force, temperature, volume and kind of medium on the disintegration process. The novel apparatus features better correlation of disintegration time with in vivo results (R(2) = 0.9999) than the compendial method (R(2) = 0.5788), and presents additional information on the disintegration process, e.g. swelling properties.

  18. Comparative Study Between Different Ready-Made Orally Disintegrating Platforms for the Formulation of Sumatriptan Succinate Sublingual Tablets.

    Science.gov (United States)

    Tayel, Saadya A; El Nabarawi, Mohamed A; Amin, Maha M; AbouGhaly, Mohamed H H

    2017-02-01

    Sumatriptan succinate (SS) is a selective serotonin receptor agonist used for the treatment of migraine attacks, suffering from extensive first-pass metabolism and low oral bioavailability (∼14%). The aim of this work is to compare the performance of different ready-made co-processed platforms (Pharmaburst®, Prosolv ODT®, Starlac®, Pearlitol Flash®, or Ludiflash®) in the formulation of SS sublingual orodispersible tablets (ODTs) using direct compression technique. The prepared SS ODT formulae were evaluated regarding hardness, friability, simulated wetting time, and in vitro disintegration and dissolution tests. Different mucoadhesive polymers-HPMC K4M, Carbopol®, chitosan, or Polyox®-were tested aiming to increase the residence time in the sublingual area. A pharmacokinetic study on healthy human volunteers was performed, using LC/MS/MS assay, to compare the optimum sublingual formula (Ph25/HPMC) with the conventional oral tablet Imitrex®. Results showed that tablets prepared using Pharmaburst® had significantly (p disintegration times of 17.17 and 23.50 s, respectively, with Q 5 min of 83.62%. HPMC showed a significant (p tablet Imitrex®. In conclusion, Pharmaburst® was chosen as the optimum ready-made co-processed platform that can be successfully used in the preparation of SS sublingual tablets for the rapid relief of migraine attacks.

  19. Evaluation of spray and freeze dried excipient bases containing disintegration accelerators for the formulation of metoclopramide orally disintegrating tablets

    International Nuclear Information System (INIS)

    Alanazi, Fars K.

    2007-01-01

    Orally disintegrating tablets (ODT) are gaining attractiveness over conventional tablets especially for patients having difficulty in swallowing such as pediatric, geriatric, bedridden and disable patients. ODT technologies render the tablets disintegrate in the mouth without chewing or additional water intake. So far there have been many patents for ODT, but only few publications are dealing with this dosage form. The aim of the present study was to formulate metoclopramide in ODT with sufficient mechanical strength and fast disintegration from bases prepared by both spray (SD) and freeze drying (FD) techniques. Different disintegration accelerators (DA) were utilized to prepare proper ODT using various super-disintegrants (Ac-Di-Sol, Kollidon and Sodium Starch glycolate), a volatilizing solvent (ethanol) and an amino acid (glycine). Metoclopramide, an antiemetic medication, was used a model drug in the formulated ODT. It was noted that the disintegration of ODT depends on utilization of DA in both SD and FD techniques to prepare tablet bases for ODT and so many other factors such as drying processes. The good disintegration property of the prepared tablets was related to the excellent wettability of the ingredients after being subjected to the drying processes. Results also showed that the addition of DA to the tablet bases before drying process results in lengthening of the disintegration time in comparison to their addition to the tablet bases after the drying process. Those findings be utilized for many drugs and they may be considered versatile in their applications. Also, the disintegration of the ODT in the buccal cavity may favor fast absorption via the mucus membrane in the oral cavity. (author)

  20. A Randomized Placebo-Controlled Trial of Oral Ramosetron for Prevention of Post Operative Nausea and Vomiting after Intrathecal Morphine in Patients Undergoing Gynecological Surgery.

    Science.gov (United States)

    Wangnamthip, Suratsawadee; Chinachoti, Thitima; Amornyotin, Somchai; Wongtangman, Karuna; Sukantarat, Numphung; Noitasaeng, Papiroon

    2016-05-01

    The incidence of postoperative nausea and vomiting (PONV) after intrathecal morphine is high. Ramosetron is a 5-HT₃ antagonist that has been shown to reduce PONV in general anesthesia. The objective of this study was to evaluate the efficacy of Ramosetron in preventing PONV MATERIAL AND METHOD: 165 patients undergoing elective gynecological surgery under spinal anesthesia were randomly allocated to two groups: the Ramosetron group (0.1 mg orally, n = 82), and the placebo group (oral corn starch, n = 83). The incidence of PONV severity of nausea and use of rescue antiemetic during the first 24 hour after surgery were evaluated. The incidence of PONV was significantly lower in the Ramosetron group compared with the placebo group (24.4% vs. 44.6%, number needed to treat (NNT) = 5.0). The severity of nausea was significantly lower in the Ramosetron group compared with the placebo group (20.7% vs. 39.8%, NNT = 6.0) in the 24 hour period. Oral Ramosetron 0.1 mg was more effective than placebo in PONV prevention and reduced the incidence of moderate to severe nausea after intrathecal morphine in the first 24 hour after gynecological surgery.

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

    Science.gov (United States)

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

    2014-06-05

    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. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. A dual strategy to improve psychotic patients’ compliance using sustained release quetiapine oral disintegrating tablets

    Directory of Open Access Journals (Sweden)

    Refaat Ahmed

    2016-12-01

    Full Text Available Quetiapine (QT is a short acting atypical antipsychotic drug effective in schizophrenia and bipolar disorder. This study aims at designing a novel dosage form of sustained release taste-masked QT orally disintegrating tablets (ODTs based on solid lipid micro-pellets (SLMPs. QT SLMPs were prepared using the hot melt extrusion technique and utilizing three lipid carriers: Compritol, Precirol and white beeswax either alone or in mixtures. They showed sustained QT release and a taste masking effect. The selected QT SLMP was further blended with an aqueous solution containing polyvinylpyrollidone (2.5 %, croscarmellose sodium (2 % and mannitol (50 %; it was then lyophilized into ODT in a mass ratio of 1:2, respectively. ODTs containing QT SLMPs showed: average wetting time (40.92 s, average oral disintegration time (21.49 s, average hardness (16.85 N and also imparted suitable viscosity to suspend pellets during the lyophilization process. In conclusion, lyophilization is a promising technique for the formulation of multiparticulate systems into ODTs.

  3. An oral modified-release nifedipine tablet (Adalat LA) and its appearance on double contrast barium enema

    International Nuclear Information System (INIS)

    Bleehen, Robert E.

    2000-01-01

    Adalat LA 30 mg and 60 mg tablets are widely prescribed oral modified release nifedipine preparations with a porous, non-digestible plastic tablet coating which is required in order to effect the osmotically driven slow release mechanism. These tablets may therefore be seen anywhere along the gastrointestinal tract and are passed apparently whole in the faeces. An example of the appearance within the rectum of Adalat LA 30 (Bayer) on double contrast barium enema is shown and the main features described. A review of the literature is given. Recognition of the appearances during the barium enema examination will prompt those performing the procedure to question the drug history where relevant and will reduce the incidence of false-positive reporting. Bleehen, R.E. (2000)

  4. Characterization of absorption enhancers for orally administered therapeutic peptides in tablet formulations - Applying statistical learning

    DEFF Research Database (Denmark)

    Welling, Søren Havelund

    . In the Caco-2 model all reagents are pre-dissolved, and therefore the assay cannot predict critical solubility issues and bile salt interactions in the final tablet formulation. A QSAR solubility model was built to foresee and avoid slow tablet dissolution. Due to enzyme kinetics, slow tablet dissolution...

  5. A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets

    Directory of Open Access Journals (Sweden)

    Li FQ

    2011-04-01

    Full Text Available Feng-Qian Li1, Cheng Yan2, Juan Bi1, Wei-Lin Lv3, Rui-Rui Ji3, Xu Chen1, Jia-Can Su3, Jin-Hong Hu31Department of Pharmaceutics, Shanghai Eighth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Pharmacy, Bethune International Peace Hospital, Shijiazhuang, People’s Republic of China; 3Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of ChinaAbstract: Scopolamine hydrobromide (SH-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w and loading capacity of 20% (w/w were achieved for the microparticles, which ranged from 2 µm to 8 µm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH’s intrinsic characteristics.Keywords: scopolamine hydrobromide, chitosan, nanoparticles-in-microparticles system, spray-drying, orally disintegrating tablets

  6. Morphine overdose

    Science.gov (United States)

    ... tests Chest x-ray EKG (electrocardiogram, or heart tracing) Fluids through a vein (IV) Laxative Naloxone, a ... Toxicology Data Network. Morphine. Toxnet.nlm.nih.gov Web site. toxnet.nlm.nih.gov/cgi-bin/sis/ ...

  7. A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets

    Science.gov (United States)

    Li, Feng-Qian; Yan, Cheng; Bi, Juan; Lv, Wei-Lin; Ji, Rui-Rui; Chen, Xu; Su, Jia-Can; Hu, Jin-Hong

    2011-01-01

    Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 μm to 8 μm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH’s intrinsic characteristics. PMID:21720502

  8. Development and analytical characterization of a new antiparasitic fenbendazole compound tablet and pharmacokinetic investigations after its oral administration to dogs.

    Science.gov (United States)

    Dai, Cunchun; Qu, Shaoqi; Zhang, Ruili; Zhao, Li; Li, Yuwen; Zhu, Jiajia; Wang, Chunmei; Guo, Hui; Hao, Zhihui

    2018-02-01

    The objective of this study was to prepare a new compound fenbendazole tablet containing 29.7 % fenbendazole, 1.50 % praziquantel and 0.059 % ivermectin for oral administration. The tablets were successfully prepared using mannitol as filler agent, polyvinyl polypyrrolidone as disintegrant, 5 % povidone (PVAK30) as a binder agent and magnesium stearate as lubricant. The appearance, hardness, fragility, time limit of disintegration and fenbendazole dissolution at 45 min all met the technical standards of the Ministry of Agriculture for the People's Republic of China. We used high performance liquid chromatography and electrospray-mass spectrometry for drug detection. Oral administration of 100 mg/kg fenbendazole, 5 mg/kg praziquantel and 0.2 mg/kg ivermectin using a non-compartmental model defined peak plasma concentrations (Cmax) of 495, 826, 73 ng/mL, and 218 ng/mL for the metabolite oxfendazole, respectively. The area under the curve (AUClast) values for these drugs were 4653, 1045, 1971 and 5525 h×ng/mL, respectively. This study enriches the pharmacokinetic data of compound fenbendazole tablets using dogs as a model system. The new tablet formulation was assimilated quickly and systemically and this study will be beneficial for the clinical application of parasite treatments in dogs.

  9. Comparison of efficacy of dexketoprofen versus paracetamol on postoperative pain and morphine consumption in laminectomy patients.

    Science.gov (United States)

    Kesimci, Elvin; Gümüş, Tülin; Izdeş, Seval; Sen, Pelin; Kanbak, Orhan

    2011-10-01

    The aim of this prospective randomized, double-blind study was to evaluate the analgesic efficacy and opioid-sparing effects of preemptive single dose of dexketoprofen trometamol in comparison with that of paracetamol or placebo for elective lumbar disc surgery, over a 24-hour (h) investigation period. After institutional approval and informed consent had been obtained, 75 patients scheduled for single level lumbar disc surgery were randomly allocated into three equal groups. Patients received oral dexketoprofen 25 mg (Group D), 500 mg paracetamol (Group P) or placebo tablets (Group C) 30 minutes (min) before induction of standard anesthesia. Patient-controlled analgesia was supplied postoperatively using morphine. Hemodynamics, visual analogue scale (VAS), sedation score, morphine consumption, and side effects were recorded every 15 min in the first hour and at 2, 6 and 24 h after surgery. The mean pain scores were similar among groups (p>0.05). The cumulative (SD) 24-h morphine consumption was 28.1 mg, 40.6 mg, and 43.6 mg for Groups D, P and C, respectively. The amount of morphine use at 2, 6 and 24 h was significantly lower in Group D (p0.05). The study demonstrated that preemptive dexketoprofen trometamol 25 mg is associated with a decrease of up to 35% in morphine consumption compared with placebo over the first 24 h following lumbar disc surgery; however, paracetamol 500 mg did not show the expected opioid-sparing effect comparatively.

  10. Prevalence of dental fluorosis in children taking part in an oral health programme including fluoride tablet supplements from the age of 2 years

    DEFF Research Database (Denmark)

    Eckersten, Charlotte; Pylvänen, Lena; Schröder, Ulla

    2010-01-01

    To investigate the prevalence of dental fluorosis in children who had participated in an oral health programme between the ages 2-5 years, including fluoride tablets from the age of 2 years.......To investigate the prevalence of dental fluorosis in children who had participated in an oral health programme between the ages 2-5 years, including fluoride tablets from the age of 2 years....

  11. Development of Oral Flexible Tablet (OFT) Formulation for Pediatric and Geriatric Patients: a Novel Age-Appropriate Formulation Platform.

    Science.gov (United States)

    Chandrasekaran, Prabagaran; Kandasamy, Ruckmani

    2017-08-01

    Development of palatable formulations for pediatric and geriatric patients involves various challenges. However, an innovative development with beneficial characteristics of marketed formulations in a single formulation platform was attempted. The goal of this research was to develop solid oral flexible tablets (OFTs) as a platform for pediatrics and geriatrics as oral delivery is the most convenient and widely used mode of drug administration. For this purpose, a flexible tablet formulation using cetirizine hydrochloride as model stability labile class 1 and 3 drug as per the Biopharmaceutical Classification System was developed. Betadex, Eudragit E100, and polacrilex resin were evaluated as taste masking agents. Development work focused on excipient selection, formulation processing, characterization methods, stability, and palatability testing. Formulation with a cetirizine-to-polacrilex ratio of 1:2 to 1:3 showed robust physical strength with friability of 0.1% (w/w), rapid in vitro dispersion within 30 s in 2-6 ml of water, and 0.2% of total organic and elemental impurities. Polacrilex resin formulation shows immediate drug release within 30 min in gastric media, better taste masking, and acceptable stability. Hence, it is concluded that ion exchange resins can be appropriately used to develop taste-masked, rapidly dispersible, and stable tablet formulations with tailored drug release suitable for pediatrics and geriatrics. Flexible formulations can be consumed as swallowable, orally disintegrating, chewable, and as dispersible tablets. Flexibility in dose administration would improve compliance in pediatrics and geriatrics. This drug development approach using ion exchange resins can be a platform for formulating solid oral flexible drug products with low to medium doses.

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

    Science.gov (United States)

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

    2014-10-01

    Chitosan-6-mercaptonicotinic acid (chitosan-6-MNA) is a thiolated chitosan with strong mucoadhesive properties and a pH-independent reactivity. This study aimed to evaluate the in vivo potential for the oral delivery of insulin. The comparison of the nonconjugated chitosan and chitosan-6-MNA was performed on several studies such as mucoadhesion, release, and in vivo studies. Thiolated chitosan formulations were both about 80-fold more mucoadhesive compared with unmodified ones. The thiolated chitosan tablets showed a sustained release for 5 h for the polymer of 20 kDa and 8 h for the polymer of 400 kDa. Human insulin was quantified in rats' plasma by means of ELISA specific for human insulin with no cross-reactivity with the endogenous insulin. In vivo results showed thiolation having a tremendous impact on the absorption of insulin. The absolute bioavailabilities were 0.73% for chitosan-6-MNA of 20 kDa and 0.62% for chitosan-6-MNA 400 kDa. The areas under the concentration-time curves (AUC) of chitosan-6-MNA formulations compared with unmodified chitosan were 4.8-fold improved for the polymer of 20 kDa and 21.02-fold improved for the polymer of 400 kDa. The improvement in the AUC with regard to the most promising aliphatic thiomer was up to 6.8-fold. Therefore, chitosan-6-MNA represents a promising excipient for the oral delivery of insulin. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  13. Application of water-insoluble polymers to orally disintegrating tablets treated by high-pressure carbon dioxide gas.

    Science.gov (United States)

    Ito, Yoshitaka; Maeda, Atsushi; Kondo, Hiromu; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

    2016-09-10

    The phase transition of pharmaceutical excipients that can be induced by humidifying or heating is well-known to increase the hardness of orally disintegrating tablets (ODTs). However, these conditions are not applicable to drug substances that are chemically unstable against such stressors. Here, we describe a system which enhances the hardness of tablets containing water-insoluble polymers by using high-pressure carbon dioxide (CO2). On screening of 26 polymeric excipients, aminoalkyl methacrylate copolymer E (AMCE) markedly increased tablet hardness (+155N) when maintained in a high-pressure CO2 environment. ODTs containing 10% AMCE were prepared and treatment with 4.0MPa CO2 gas at 25°C for 10min increased the hardness to +30N, whose level corresponded to heating at 70°C for 720min. In addition, we confirmed the effects of CO2 pressure, temperature, treatment time, and AMCE content on the physical properties of ODTs. Optimal pressure of CO2 gas was considered to be approximately 3.5MPa for an AMCE formula, as excessive pressure delayed the disintegration of ODTs. Combination of high-pressure CO2 gas and AMCE is a prospective approach for increasing the tablet hardness for ODTs, and can be conducted without additional heat or moisture stress using a simple apparatus. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. High-amylose sodium carboxymethyl starch matrices: development and characterization of tramadol hydrochloride sustained-release tablets for oral administration.

    Science.gov (United States)

    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.

  15. Citric Acid Suppresses the Bitter Taste of Olopatadine Hydrochloride Orally Disintegrating Tablets.

    Science.gov (United States)

    Sotoyama, Mai; Uchida, Shinya; Tanaka, Shimako; Hakamata, Akio; Odagiri, Keiichi; Inui, Naoki; Watanabe, Hiroshi; Namiki, Noriyuki

    2017-01-01

    Orally disintegrating tablets (ODTs) are formulated to disintegrate upon contact with saliva, allowing administration without water. Olopatadine hydrochloride, a second-generation antihistamine, is widely used for treating allergic rhinitis. However, it has a bitter taste; therefore, the development of taste-masked olopatadine ODTs is essential. Some studies have suggested that citric acid could suppress the bitterness of drugs. However, these experiments were performed using solutions, and the taste-masking effect of citric acid on ODTs has not been evaluated using human gustatory sensation tests. Thus, this study evaluated citric acid's taste-masking effect on olopatadine ODTs. Six types of olopatadine ODTs containing 0-10% citric acid were prepared and subjected to gustatory sensation tests that were scored using the visual analog scale. The bitterness and overall palatability of olopatadine ODTs during disintegration in the mouth and after spitting out were evaluated in 11 healthy volunteers (age: 22.8±2.2 years). The hardness of the ODTs was >50 N. Disintegration time and dissolution did not differ among the different ODTs. The results of the gustatory sensation tests suggest that citric acid could suppress the bitterness of olopatadine ODTs in a dose-dependent manner. Olopatadine ODTs with a high content of citric acid (5-10%) showed poorer overall palatability than that of those without citric acid despite the bitterness suppression. ODTs containing 2.5% citric acid, yogurt flavoring, and aspartame were the most suitable formulations since they showed low bitterness and good overall palatability. Thus, citric acid is an effective bitterness-masking option for ODTs.

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

    Science.gov (United States)

    KuKanich, K; KuKanich, B

    2015-04-01

    The purpose of this study was to determine the effect of concurrent sucralfate (tablet or suspension) on doxycycline pharmacokinetics and to determine the effects of delaying sucralfate by 2 h on doxycycline absorption. Five dogs were included in a crossover study receiving: doxycycline alone; doxycycline concurrently with sucralfate tablet; doxycycline followed 2 h by sucralfate tablet; doxycycline concurrently with sucralfate suspension; and doxycycline followed 2 h by sucralfate suspension. Doxycycline plasma concentrations were evaluated with liquid chromatography with mass spectrometry. No interaction was seen when sucralfate was administered as a tablet. Sucralfate tablet fragments were frequently observed in some dogs' feces. The area under the curve (AUC) and maximum plasma concentration (CMAX ) were significantly lower (P < 0.001) in the concurrent sucralfate suspension group (AUC 7.2 h·μg/mL, CMAX 0.43 μg/mL) than with doxycycline alone (AUC 36.0 h·μg/mL, CMAX 2.53 μg/mL) resulting in a relative bioavailability of 20%. Delaying sucralfate suspension by 2 h after doxycycline administration resulted in no difference in doxycycline absorption as compared with doxycycline administration alone with a relative bioavailability of 74%. The lack of an interaction with sucralfate tablets suggests sucralfate should be administered as a suspension rather than tablet in dogs. © 2014 John Wiley & Sons Ltd.

  17. Evaluation of the disintegration properties of commercial famotidine 20 mg orally disintegrating tablets using a simple new test and human sensory test.

    Science.gov (United States)

    Harada, Tsutomu; Narazaki, Ryuichi; Nagira, Shinsuke; Ohwaki, Takayuki; Aoki, Shigeru; Iwamoto, Kiyoshi

    2006-08-01

    The purpose of this study was to demonstrate the usefulness and broad-applicability of a simple disintegration test method for orally disintegrating tablets (ODT). Eight types of commercial famotidine 20 mg orally disintegrating tablets with different physical properties (formulation, manufacturing method, tablet weight, shape, diameter, thickness, etc.), were used. Disintegration times of these tablets were evaluated employing human sensory test, conventional disintegration test, and the new proposed disintegration test. The human sensory test was performed in 5 healthy volunteers. In the conventional disintegration test, the disintegration apparatus described in the Japanese Pharmacopeia (JP 1(st)) was used. Our proposed new test which is characterized by a rotating shaft with a low weight (10, 15 g) and rotation speed (10, 25, 50 rpm) was evaluated using tablets with and without storage under severe conditions (60 degrees C/75%RH for 1 week). The disintegration times of famotidine 20 mg orally disintegrating tablets in human sensory test varied from 9 to 32 s. In contrast, disintegration times in the conventional test were prolonged to over 300 s. Disintegration times in the new proposed test were close to those in human sensory test. Especially, when the new test was conducted with 15 or 10 g weight and 25 rpm, the slope (human sensory test vs. new proposed test) was almost 1. We were able to demonstrate that the new proposed test was useful to estimate the actual human disintegration time.

  18. Preparation of Orally Disintegrating Tablets Containing Powdered Tea Leaves with Enriched Levels of Bioactive Compounds by Means of Microwave Irradiation Technique.

    Science.gov (United States)

    Tanaka, Hironori; Iwao, Yasunori; Izumikawa, Masahiro; Sano, Syusuke; Ishida, Hitoshi; Noguchi, Shuji; Itai, Shigeru

    2016-01-01

    In the present study, a microwave treatment process has been applied to prepare orally disintegrating tablets (ODTs) containing powdered tea leaves with enriched levels of the anti-inflammatory compounds such as chafuroside A (CFA) and chafuroside B (CFB). The use of distilled water as the adsorbed and granulation solvents in this preparation process afforded tablets with a long disintegration time (more than 120 s). The CFA and CFB contents of these tablets did not also change after 4 min of microwave irradiation due to the tablet temperature, which only increased to 100°C. In contrast, the tablet temperature increased up to 140°C after 3 min of microwave irradiation when a 1.68 M Na2HPO4 solution instead of distilled water. Notably, the disintegration time of these tablets was considerably improved (less than 20 s) compared with the microwave-untreated tablets, and there were 7- and 11-fold increases in their CFA and CFB contents. In addition, the operational conditions for the preparation of the tablets were optimized by face-centered composite design based on the following criteria: tablet hardness greater than 13 N, disintegration time less than 30 s and friability less than 0.5%. The requirements translated into X1 (the amount of granulation solvent), X2 (tableting pressure) and X3 (content of the powdered tea leaves) values of 45%, 0.43 kN and 32%, respectively, and the ODTs containing powdered tea leaves prepared under these optimized conditions were found to show excellent tablet properties and contain enriched levels of CFA and CFB.

  19. Interchangeability and comparative effectiveness between generic and brand montelukast immediate release tablets after a single oral administration in healthy volunteers.

    Science.gov (United States)

    Zaid, Abdel Naser; Mousa, Ayman; Ghazal, Nadia; Bustami, Rana

    2015-01-01

    Montelukast is a leukotriene receptor antagonist. The release of leukotrienes causes narrowing and constricting in the respiratory airways. Blocking the action of these leukotrienes, montelukast can be used for the prophylaxis and treatment of chronic asthma. The aim of this study was to evaluate the interchangeability and comparative effectiveness between a generic and a brand montelukast 10 mg immediate release tablets (Broncast(®) and Singulair(®), respectively) after a single oral dose among Arab Mediterranean volunteers. An open-label, randomized two-period crossover bioequivalence design was conducted in 31 healthy male volunteers with a 1 week washout between each study period and under fasting conditions. The plasma drug concentration was assessed by using a previously validated LC MS/MS method. The ratio between the generic and brand of geometric least squares means was reported for both generic and brand products. Moreover, an in vitro dissolution study was conducted on generic and brand tablets using three different pH media, and similarity and non-similarity factors (f2 and f1) were calculated. The used bioanalytical method was found to be linear within the range 6.098-365.855 ng/mL. The correlation coefficient was close to 0.999 during the course of the study validation. Statistical comparison of the main pharmacokinetic parameters showed the inexistence of any significant difference between generic and the brand. The point estimates (ratios of geometric means) were 111.939, 111.711, and 112.169 % for AUC0-24, AUC0-∞, and Cmax, respectively. The 90 % confidence intervals (CIs) were within the pre-defined limits of 80.00-125.00 % as specified by the FDA and EMA for bioequivalence studies. F2 and f1 were higher than 50 and lower than 15, respectively in all selected pH media. Broncast(®) immediate release film coated tablets (10 mg/tablet) are bioequivalent to Singulair(®) immediate release film coated tablets (10 mg/tablet), with a

  20. A comparison of oral misoprostol and vaginal prostaglandin e2 tablets for induction of labour at term

    International Nuclear Information System (INIS)

    Munzar, Z.

    2015-01-01

    To compare the efficacy and safety of oral misoprostol with prostaglandin E2 vaginal tablets for ripening of cervix and induction of labour at term. Study Design: A non blinded, randomised, controlled trial. Place and Duration of Study: Department of Obstetrics and Gynaecology, Pakistan Air Force Hospital, Air Headquarters Islamabad from July 2005 to January 2006. Patients and Methods: Hundred pregnant women with a singleton live pregnancy, at term (37-42 weeks) with cephalic presentation were selected for induction of labour for various indications having a Bishop's score of < or =5. These women were randomly allocated to receive either 100 micro gm of misoprostol rally repeated four hourly to a maximum of four doses or a 3mg PGE2 tablet vaginally repeated six hourly to a maximum of two doses. Main outcomes measured: Cervical score before and after oral misoprostol and prostaglandin E2 vaginal tablets, vaginal birth within 24 hours of first prostaglandin dose, no of patients having failed induction, caesarean sections (all), caesarean section for fetal distress and uterine hyperstimulation with associated changes in fetal heart rate. Results: Over the period of one year 100 women were recruited for the study, 50 to the misoprostol group and 50 to the vaginal prostaglandin E2 group. There was no significant differences between the two treatment groups in the primary outcomes: improvement in bishops score in both the groups, no of patients with failed induction in both the groups misoprostol 2/50 (4%) v PGE2 3/50 (6%) , vaginal birth achieved in 24 hours (misoprostol 27/50 (54%) v PGE2 29/50 (58%), caesarean sections 14/50 (28%) v 12/50(24%) caesarean section for fetal distress 4/50((8%) v 5/50(9%); uterine hyperstimulation with fetal heart rate changes 2/50 ((4%) v none in the PGE2 group.). Neonatal outcomes were not significantly different in the two groups. Conclusion: Oral misoprostol in strength of 100 micro gm has similar efficacy to vaginal PGE2 tablets

  1. Comparison of clinical outcomes with orodispersible versus standard oral olanzapine tablets in nonadherent patients with schizophrenia or bipolar disorder.

    Science.gov (United States)

    Novick, Diego; Montgomery, William; Treuer, Tamas; Koyanagi, Ai; Aguado, Jaume; Kraemer, Susanne; Haro, Josep Maria

    2017-01-01

    Medication nonadherence is common in the treatment of patients with severe mental illness and is a frequent cause of relapse. Different formulations have been developed in an effort to improve medication adherence. The aim of this study was to explore whether there are differential clinical outcomes between two different formulations of olanzapine (orodispersible tablets [ODTs] vs standard oral tablets [SOT]) for the treatment of nonadherent patients with schizophrenia or bipolar disorder. Data for this analysis were from an observational study conducted in Europe (N=903). Adult schizophrenia and bipolar disorder patients in outpatient settings who initiated or changed to either olanzapine ODT or SOT according to physician decision within the last 45 days were eligible for enrollment. The follow-up period was 1 year. Of the 903 participants, 266 nonadherent patients (Medication Adherence Rating Scale score 0-4 at baseline) were included in the analysis. Clinical outcomes of interest were: 1) hospitalization and 2) relapse identified by the participating psychiatrist or hospitalization. An adjusted logistic regression model was fitted. Patients taking ODT had more severe illness at baseline ( P <0.001) as assessed with the Clinical Global Impression with mean (standard deviation [SD]) scores of ODT 4.63 (1.03) and SOT 4 (1.16). In the regression models adjusted for potential confounders, patients taking ODT had significantly lower odds for hospitalization (odds ratio =0.355; 95% confidence interval =0.13-0.974) and relapse or hospitalization (odds ratio =0.368; 95% confidence interval =0.183-0.739), respectively. Nonadherent patients with schizophrenia or bipolar disorder treated with the orodispersible formulation were less likely to be hospitalized or suffer relapse compared to those patients taking the standard oral coated tablets.

  2. Morphine and oxycodone in the management of cancer pain

    International Nuclear Information System (INIS)

    Kalso, E.; Vainio, A.; Rosenberg, P.H.; Mattila, M.J.; Seppaelae, T.

    1990-01-01

    Morphine and oxycodone were administered to ten patients suffering from severe cancer pain in a double-blind cross-over study. The patients titrated themselves pain-free, first intravenously, using a patient-controlled analgesia device, and then orally. Each titration phase lasted for 48 hours. Blood samples were drawn after 36 hr of each administration phase. The plasma levels of morphine, morphine-6- and morphine-3 glucuronides were determined with high performance liquid chromatography (HPLC), whereas the oxycodone samples were assayed with gas chromatography (GC). Twin samples were analyzed for plasma opioid activity with a radioreceptor assay (RRA) using 3 H-dihydromorphien and 3 H-naloxone as radioligands. Adequate analgesia was achieved with both morphine and oxycodone. About 30% more oxycodone was needed intravenously, whereas 25% less oxycodone than morphine was consumed orally. There was a good linear correlation between the morphine concentrations measured with HPLC and RRA. The mean morphine-6-glucuronide to morphine concentration ratio was 2.3 after intravenous and 4.6 after oral administration. Results from RRA indicate that oxycodone in vivo is a potent μ-agonist and that a least part of its analgesic action is mediated by active metabolites. In vitro morphine glucuronides enhanced morphine in displacing radioligands from the opioid receptors, thus suggesting their complex interactions in vivo. (author)

  3. Development and Efficacy Assessment of an Enteric Coated Porous Tablet Loaded With F4 Fimbriae for Oral Vaccination of Piglets against F4+ Escherichia coli Infections.

    Science.gov (United States)

    Srivastava, Atul; Gowda, D V; Madhunapantula, SubbaRao V; Siddaramaiah

    2016-01-01

    Enterotoxigenic Escherichia coli (ETEC) infection is one of the major causes contributing to the development of diarrhoea and mortality in new born, suckling and newly weaned piglets. To date, no preventive/treatment strategy showed promising results, which could be due to the lack of potent vaccines, and/or due to the development of resistance of ETEC to antibiotics. Therefore, in the present investigation, a novel porous sodium alginate (SA) tablet formulation loaded with F4 fimbriae antigen was developed and tested for efficacy against ETEC infections in piglet models. Precompression parameters of the powder mixes and post compression parameters of tablets have been evaluated and results were found to be satisfactory. Loading of F4 fimbrial antigens into the tablets was achieved by inducing pores in the tablets via the sublimation of camphor followed by incubation with purified F4 fimbriae. The loaded tablets have been coated with Eudragit L100 to protect the F4 fimbriae from (a) highly acidic gastric environment; (b) proteolytic cleavage by pepsin; and (c) to promote subsequent release in the intestine. Evaluation of developed F4 fimbrial tablets in a Pig model demonstrated induction of mucosal immunity, and a significant reduction of F4+ E. coli in faeces. Therefore, F4 fimbriae loaded porous tablets could be a novel oral vaccination candidate to induce mucosal and systemic immunity against ETEC infections.

  4. Pharmacokinetics of diclofenac potassium after oral administration of sachets and tablets

    Directory of Open Access Journals (Sweden)

    A Martso

    2008-01-01

    Results. There is evidence that patients tolerate both its sachets and tablets equally well, as confirmed by subjective and objective observations. There are neither marked side effects nor considerable changes in laboratory tests and in the values of vital functions. Diclofenac potassium as early-action tablets (50 and 100 mg exerts a very good analgesic effect in treating migraine since the plasma concentration of the drug peaks on an average of an hour of administration (range 0,33-2 hours and the analgesic effect developed following 60-90 min. Conclusion. By comparing the rate of absorption, it may be concluded that diclofenac potassium as sachets will produce a much rapider analgesic effect. Thus, the high solubility of diclofenac potassium and its very good absorbability (as sachets in particular make the drug a superior analgesic that has a rapid analgesic activity.

  5. Deposition of a model substance, Tc E-HIDA, in the oral cavity after administration of lozenges, chewing gum and sublingual tablets

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Davis, S.S.; Melia, C.D.

    1990-01-01

    The deposition and clearance of a model substance, Tc E-HIDA, in the oral cavity/upper oesophagus and in the stomach after administration of lozenges, chewing gum and sublingual tablets has been followed by gamma scintigraphy in a group of healthy male volunteers. Following administration...

  6. Self-Paced Segmentation of Written Words on a Touchscreen Tablet Promotes the Oral Production of Nonverbal and Minimally Verbal Children with Autism

    Science.gov (United States)

    Vernay, Frédérique; Kahina, Harma; Thierry, Marrone; Jean-Yves, Roussey

    2017-01-01

    We investigated in a pilot study the effects of various types of visual mediation (photos, written words and self-paced syllabic segmentation of written words displayed on a touchscreen tablet) that are thought to facilitate the oral production of nonverbal and minimally verbal children with autism, according to the participants' level of oral…

  7. Formulation and evaluation of a montelukast sodium orally disintegrating tablet with a similar dissolution profile as the marketed product.

    Science.gov (United States)

    Chen, Yong; Feng, Tingting; Li, Yong; Du, Bin; Weng, Weiyu

    2017-03-01

    A major challenge of orally disintegrating tablet (ODT) development is predicting its bioequivalence to its corresponding marketed product. Therefore, comparing ODT dissolution profiles to those of the corresponding marketed product is very important. The objective of this study was to develop a 5.2-mg montelukast sodium (MS) ODT with a similar dissolution profile to that of the marketed chewable tablet. Dissolution profiles were examined in different media to screen each formulation. We found that MS dissolution from ODTs in acidic medium heavily depended on manufacturing methods. All MS ODTs prepared using direct compression rapidly disintegrated in acidic medium. However, dispersed MS powders aggregated into sticky masses, resulting in slow dissolution. In contrast, MS ODTs prepared using wet granulation had much faster dissolution rates in acidic medium with no obvious aggregation. Additionally, the optimized formulation, prepared using wet granulation, displayed similar dissolution profiles to the marketed reference in all four types of media examined (f 2  >   50). The in vitro disintegration time of the optimized ODT was 9.5 ± 2.4 s, which meets FDA requirements. In conclusion, the wet granulation preparation method of MS ODTs resulted in a product with equivalent dissolution profiles as those of the marketed product.

  8. The practical approach to the evaluation of methods used to determine the disintegration time of orally disintegrating tablets (ODTs).

    Science.gov (United States)

    Brniak, Witold; Jachowicz, Renata; Pelka, Przemyslaw

    2015-09-01

    Even that orodispersible tablets (ODTs) have been successfully used in therapy for more than 20 years, there is still no compendial method of their disintegration time evaluation other than the pharmacopoeial disintegration test conducted in 800-900 mL of distilled water. Therefore, several alternative tests more relevant to in vivo conditions were described by different researchers. The aim of this study was to compare these methods and correlate them with in vivo results. Six series of ODTs were prepared by direct compression. Their mechanical properties and disintegration times were measured with pharmacopoeial and alternative methods and compared with the in vivo results. The highest correlation with oral disintegration time was found in the case of own-construction apparatus with additional weight and the employment of the method proposed by Narazaki et al. The correlation coefficients were 0.9994 (p disintegration time determination is eligible and scientifically justified.

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

    Directory of Open Access Journals (Sweden)

    Gao Feng

    2009-05-01

    Full Text Available Abstract Background Amlexanox has been developed as a 5 percent topical oral paste for the treatment of patients with recurrent aphthous stomatitis (RAS in most European countries. However, it is not yet available in China and has not been generally accepted in clinical treatment. The aim of this study was to explore the effectiveness of amlexanox oral adhesive pellicles in the treatment of minor recurrent aphthous ulcers, and compare the results with those of amlexanox oral adhesive tablets in order to analyse the difference between the two dosage forms of amlexanox. Methods We performed a randomized, blinded, placebo-controlled, parallel, multicenter clinical study. A total of 216 patients with minor recurrent aphthous ulcers (MiRAU were recruited and randomized to amlexanox pellicles or placebo pellicles. Pellicles were consecutively applied four times per day, for five days. The size and pain level of ulcers were measured and recorded on treatment days 0, 4 and 6. Finally, the results were compared with those of our previous 104 cases treated with amlexanox tablets. Results Amlexanox oral adhesive pellicles significantly reduced ulcer size (P= 0.017 for day 4, P=0.038 for day 6 and alleviated ulcer pain (P=0.021 for day 4, P=0.036 for day 6. No significant difference was observed in the treatment effectiveness between the pellicle and tablet form of amlexanox. Conclusions Amlexanox oral adhesive pellicles are as effective and safe as amlexanox oral adhesive tablets in the treatment of MiRAU for this Chinese cohort. However, pellicles seem to be more comfortable to use when compared with the dosage form of tablets. Therefore, in clinical practice, amlexanox oral adhesive pellicles may be a better choice for RAS patients. Trials registration Nederlands Trial Register NTR1727.

  10. Unusual pattern of leukoencephalopathy after morphine sulphate intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Nanan, R.; Stockhausen, H.B. von; Petersen, B. [Children' s Hospital, University of Wuerzburg (Germany); Solymosi, L.; Warmuth-Metz, M. [Department for Neuroradiology, University of Wuerzburg (Germany)

    2000-11-01

    We report a 14-year-old girl with an unusual pattern of leukoencephalopathy after intentional intoxication with morphine sulphate tablets. Toxicological analysis showed exceedingly high levels of morphine and its metabolites. MRI disclosed a leukoencephalopathy with high signal from the centrum semiovale, corpus callosum and cerebellar white matter on T2-weighted images. These findings could be only partially explained by a hypoxic-ischaemic event; neurotoxic effects must be considered in this atypical leukoencephalopathy. (orig.)

  11. Unusual pattern of leukoencephalopathy after morphine sulphate intoxication

    International Nuclear Information System (INIS)

    Nanan, R.; Stockhausen, H.B. von; Petersen, B.; Solymosi, L.; Warmuth-Metz, M.

    2000-01-01

    We report a 14-year-old girl with an unusual pattern of leukoencephalopathy after intentional intoxication with morphine sulphate tablets. Toxicological analysis showed exceedingly high levels of morphine and its metabolites. MRI disclosed a leukoencephalopathy with high signal from the centrum semiovale, corpus callosum and cerebellar white matter on T2-weighted images. These findings could be only partially explained by a hypoxic-ischaemic event; neurotoxic effects must be considered in this atypical leukoencephalopathy. (orig.)

  12. In vivo anti-psoriatic activity, biodistribution, sub-acute and sub-chronic toxicity studies of orally administered methotrexate loaded chitin nanogel in comparison with methotrexate tablet.

    Science.gov (United States)

    Panonnummal, Rajitha; Jayakumar, R; Anjaneyan, Gopikrishnan; Sabitha, M

    2018-04-15

    The anti-psoriatic efficacy of orally administered methotrexate loaded chitin nanogel (MCNG) was evaluated (two doses- 2.715 mg/kg and 5.143 mg/kg) and compared against orally administered methotrexate tablet MTX (5.143 mg/kg). MCNG at both dose levels of 2.715 mg/kg and 5.143 mg/kg exhibited significant anti-psoriatic activity which is very much comparable with MTX, caused normalization of histological features and inflammatory score associated with induced psoriasis. Biodistribution studies revealed the presence of drug in serum and in vital organs at all the three cases with highest amount in MCNG at 5.143 mg/kg dose, followed by MTX tablet and are lowest in MCNG at 2.715 mg/kg dose. MCNG at the highest dose of 5.143 mg/kg caused liver, lung and kidney toxicities on sub acute toxicity studies and MTX tablet was found to be toxic on liver and lung on sub chronic toxicity studies. MCNG 2.715 mg/kg was found to be safe on both sub acute and sub chronic administrations, suggesting that it can provide sufficient serum and tissue level of methotrexate necessary to clear psoriatic lesions, without inducing systemic toxicity and expected to be a better alternative for orally administered conventional methotrexate tablet for patients who need systemic medications for psoriasis. Copyright © 2018. Published by Elsevier B.V.

  13. Biowaiver study of oral tabletted ethylcellulose microcapsules of a BCS class I drug

    Directory of Open Access Journals (Sweden)

    Ghulam Murtaza

    2009-08-01

    Full Text Available This article describes the preparation and characterization (in vitro and in vivo of three different sustained-release salbutamol sulfate−ethylcellulose tabletted microparticles (T1, T2 and T3 and reference sustained release tablet (Ventolin 8 mg SR, GSK. In vitro characterization included dissolution study, scanning electron microscopy, UV and FTIR spectroscopy, X−ray diffractometry and thermal analysis. A validated HPLC−fluorescent detection method was adopted to conduct bioavailability studies in young healthy human volunteers. The microparticles exhibited an irregular and slightly aggregated morphology with fine rheological properties. No strong chemical interaction was found between drug and polymer. A good linear correlation (R2 = 0.9224, 0.945, 0.9363 and 0.9694 for T1, T2, T3 and reference formulations, respectively was obtained between the percent cumulative drug released (in vitro and the percent cumulative drug absorbed (in vivo data of these formulations at specific time points to develop level A in vitro−in vivo correlation. However, T2 was found closer to the reference formulation that shows a reliable prediction of the plasma concentrations obtained following a single dose of salbutamol sulfate modified release formulations.

  14. ORAL ADMINISTRATION OF EXOGENOUS LACTASE IN TABLETS FOR PATIENTS DIAGNOSED WITH LACTOSE INTOLERANCE DUE TO PRIMARY HYPOLACTASIA.

    Science.gov (United States)

    Francesconi, Carlos Fernando de Magalhães; Machado, Marta Brenner; Steinwurz, Flavio; Nones, Rodrigo Bremer; Quilici, Flávio Antonio; Catapani, Wilson Roberto; Miszputen, Sender Jankiel; Bafutto, Mauro

    2016-01-01

    Primary hypolactasia is a common condition where a reduced lactase activity in the intestinal mucosa is present. The presence of abdominal symptoms due to poor absorption of lactose, which are present in some cases, is a characteristic of lactose intolerance. Evaluate the efficacy of a product containing exogenous lactase in tablet form compared to a reference product with proven effectiveness in patients with lactose intolerance. Multicentre, randomized, parallel group, single-blind, comparative non-inferiority study. One hundred twenty-nine (129) adult lactose intolerance patients with hydrogen breath test results consistent with a diagnosis of hypolactasia were randomly assigned to receive the experimental product (Perlatte(r) - Eurofarma Laboratórios S.A.) or the reference product (Lactaid(r) - McNeilNutritionals, USA) orally (one tablet, three times per day) for 42 consecutive days. Data from 128 patients who actually received the studied treatments were analysed (66 were treated with the experimental product and 62 with the reference product). The two groups presented with similar baseline clinical and demographic data. Mean exhaled hydrogen concentration tested at 90 minutes after the last treatment (Day 42) was significantly lower in the experimental product treated group (17±18 ppm versus 34±47 ppm) in the per protocol population. The difference between the means of the two groups was -17 ppm (95% confidence interval [95% CI]: -31.03; -3.17). The upper limit of the 95% CI did not exceed the a priori non-inferiority limit (7.5 ppm). Secondary efficacy analyses confirmed that the treatments were similar (per protocol and intention to treat population). The tolerability was excellent in both groups, and there were no reports of serious adverse events related to the study treatment. The experimental product was non-inferior to the reference product, indicating that it was an effective replacement therapy for endogenous lactase in lactose intolerance

  15. ORAL ADMINISTRATION OF EXOGENOUS LACTASE IN TABLETS FOR PATIENTS DIAGNOSED WITH LACTOSE INTOLERANCE DUE TO PRIMARY HYPOLACTASIA

    Directory of Open Access Journals (Sweden)

    Carlos Fernando de Magalhães FRANCESCONI

    Full Text Available ABSTRACT Background Primary hypolactasia is a common condition where a reduced lactase activity in the intestinal mucosa is present. The presence of abdominal symptoms due to poor absorption of lactose, which are present in some cases, is a characteristic of lactose intolerance. , Objective Evaluate the efficacy of a product containing exogenous lactase in tablet form compared to a reference product with proven effectiveness in patients with lactose intolerance. Methods Multicentre, randomized, parallel group, single-blind, comparative non-inferiority study. One hundred twenty-nine (129 adult lactose intolerance patients with hydrogen breath test results consistent with a diagnosis of hypolactasia were randomly assigned to receive the experimental product (Perlatte(r - Eurofarma Laboratórios S.A. or the reference product (Lactaid(r - McNeilNutritionals, USA orally (one tablet, three times per day for 42 consecutive days. Results Data from 128 patients who actually received the studied treatments were analysed (66 were treated with the experimental product and 62 with the reference product. The two groups presented with similar baseline clinical and demographic data. Mean exhaled hydrogen concentration tested at 90 minutes after the last treatment (Day 42 was significantly lower in the experimental product treated group (17±18 ppm versus 34±47 ppm in the per protocol population. The difference between the means of the two groups was -17 ppm (95% confidence interval [95% CI]: -31.03; -3.17. The upper limit of the 95% CI did not exceed the a priori non-inferiority limit (7.5 ppm. Secondary efficacy analyses confirmed that the treatments were similar (per protocol and intention to treat population. The tolerability was excellent in both groups, and there were no reports of serious adverse events related to the study treatment. Conclusion The experimental product was non-inferior to the reference product, indicating that it was an effective

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

    Science.gov (United States)

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

    2015-02-01

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

  17. A randomised comparison of oral desmopressin lyophilisate (MELT) and tablet formulations in children and adolescents with primary nocturnal enuresis

    DEFF Research Database (Denmark)

    Lottmann, H; Froeling, F; Alloussi, S

    2007-01-01

    (MELT) vs. tablet treatment, and the efficacy, safety, compliance and ease of use associated with each formulation. In total, 221 patients aged 5-15 years who were already receiving desmopressin tablets were randomised 1 : 1 to receive desmopressin treatment in the order MELT/tablet (n = 110) or tablet....../MELT (n = 111) for 3 weeks each. Each formulation was administered in bioequivalent doses (0.2/0.4 mg tablets identical with 120/240 microg MELT). Following treatment, patients were questioned regarding treatment preference. Diary card data and 100 mm Visual Analogue Scale scores were also recorded....... RESULTS: Overall, patients preferred the MELT formulation to the tablet (56% vs. 44%; p = 0.112). This preference was age dependent (p = 0.006); patients aged

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

    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 (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. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  1. Combined Effect of Synthetic and Natural Polymers in Preparation of Cetirizine Hydrochloride Oral Disintegrating Tablets: Optimization by Central Composite Design.

    Science.gov (United States)

    Patro, Chandra Sekhar; Sahu, Prafulla Kumar

    2017-01-01

    Our aim was to employ experimental design to formulate and optimize cetirizine hydrochloride oral disintegrating tablets (ODTs) by direct compression technique, using the mutual effect of synthetic croscarmellose sodium (CCS) and natural Hibiscus rosa-sinensis mucilage (HRM) as disintegrants in the formulation. Central composite design (CCD) was applied to optimize the influence of three levels each of CCS ( X 1 ) and HRM ( X 2 ) concentrations (independent variables) for investigated responses: disintegration time (DT) ( Y 1 ), % friability ( F ) ( Y 2 ), and % cumulative drug release (DR) ( Y 3 ) (dependent variables). This face-centered second-order model's reliability was verified by the probability and adequate precision values from the analysis of variance, while the significant factor effects influencing the studied responses were identified using multiple linear regression analysis. Perturbation and response surface plots were interpreted to evaluate the responses' sensitivity towards the variables. During optimization, the concentrations of the processed factors were evaluated, and the resulting values were in good agreement with predicted estimates endorsing the validity. Spectral study by Fourier Transform Infrared Spectroscopy (FTIR) and thermograms from Differential Scanning Calorimetry (DSC) demonstrated the drug-excipients compatibility of the optimized formulation. The optimized formulation has concentrations of 9.05 mg and 16.04 mg of CCS and HRM each, respectively, and the model predicted DT of 13.271 sec, F of 0.498, and DR of 99.768%.

  2. Combined Effect of Synthetic and Natural Polymers in Preparation of Cetirizine Hydrochloride Oral Disintegrating Tablets: Optimization by Central Composite Design

    Directory of Open Access Journals (Sweden)

    Chandra Sekhar Patro

    2017-01-01

    Full Text Available Our aim was to employ experimental design to formulate and optimize cetirizine hydrochloride oral disintegrating tablets (ODTs by direct compression technique, using the mutual effect of synthetic croscarmellose sodium (CCS and natural Hibiscus rosa-sinensis mucilage (HRM as disintegrants in the formulation. Central composite design (CCD was applied to optimize the influence of three levels each of CCS (X1 and HRM (X2 concentrations (independent variables for investigated responses: disintegration time (DT (Y1, % friability (F (Y2, and % cumulative drug release (DR (Y3 (dependent variables. This face-centered second-order model’s reliability was verified by the probability and adequate precision values from the analysis of variance, while the significant factor effects influencing the studied responses were identified using multiple linear regression analysis. Perturbation and response surface plots were interpreted to evaluate the responses’ sensitivity towards the variables. During optimization, the concentrations of the processed factors were evaluated, and the resulting values were in good agreement with predicted estimates endorsing the validity. Spectral study by Fourier Transform Infrared Spectroscopy (FTIR and thermograms from Differential Scanning Calorimetry (DSC demonstrated the drug-excipients compatibility of the optimized formulation. The optimized formulation has concentrations of 9.05 mg and 16.04 mg of CCS and HRM each, respectively, and the model predicted DT of 13.271 sec, F of 0.498, and DR of 99.768%.

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

    Directory of Open Access Journals (Sweden)

    Jatinderpal Singh

    2015-01-01

    Full Text Available Present investigation deals with the preparation and evaluation of orally disintegrating tablets (ODTs of lamotrigine using β-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 β-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.

  4. Lactobacillus salivarius WB21--containing tablets for the treatment of oral malodor: a double-blind, randomized, placebo-controlled crossover trial.

    Science.gov (United States)

    Suzuki, Nao; Yoneda, Masahiro; Tanabe, Kazunari; Fujimoto, Akie; Iha, Kosaku; Seno, Kei; Yamada, Kazuhiko; Iwamoto, Tomoyuki; Masuo, Yosuke; Hirofuji, Takao

    2014-04-01

    This study evaluated the effect of probiotic intervention using lactobacilli on oral malodor. We conducted a 14-day, double-blind, placebo-controlled, randomized crossover trial of tablets containing Lactobacillus salivarius WB21 (2.0 × 10(9) colony-forming units per day) or placebo taken orally by patients with oral malodor. Organoleptic test scores significantly decreased in both the probiotic and placebo periods compared with the respective baseline scores (P < .001 and P = .002), and no difference was detected between periods. In contrast, the concentration of volatile sulfur compounds (VSCs) (P = .019) and the average probing pocket depth (P = .001) decreased significantly in the probiotic period compared with the placebo period. Bacterial quantitative analysis found significantly lower levels of ubiquitous bacteria (P = .003) and Fusobacterium nucleatum (P = .020) in the probiotic period. These results indicated that daily oral consumption of tablets containing probiotic lactobacilli could help to control oral malodor and malodor-related factors. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. An integrated, quality by design (QbD) approach for design, development and optimization of orally disintegrating tablet formulation of carbamazepine.

    Science.gov (United States)

    Mishra, Saurabh M; Rohera, Bhagwan D

    2017-11-01

    The objective of the present study was to design and develop a formulation for orally disintegrating tablets (ODTs) of carbamazepine using quality by design principles. The target product profile (TPP) and quality target product profile (QTPP) of ODTs were identified. Risk assessment was carried out by leveraging prior knowledge and experience to define the criticality of factors based on their impact by Ishikawa fishbone diagram and preliminary hazard analysis tool. Box-Behnken response surface methodology was used to study the effect of critical factors on various attributes of ODTs. The independent factors selected were compression pressure (X 1 ), concentration of sublimating agent (volatile material) (X 2 ), disintegrant concentration (X 3 ) and the responses were tablet crushing strength, tablet porosity, disintegration time, water absorption time, tablet friability and drug dissolution. ANOVA and lack of fit test illustrated that selected independent variables had significant effect on the response variables, and excellent correlation was observed between actual and predicted values. Optimization by desirability function indicated that compression pressure, X 1 (1534 lbs), ammonium bicarbonate concentration, X 2 (7.68%) and Kollidon ® CL-SF concentration, X 3 (6%) were optimum to prepare ODT formulation of carbamazepine of desired attributes complying with QTPP. Thus, in the present study, a high level of assurance was established for ODT product quality and performance.

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

    Science.gov (United States)

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

    2010-06-01

    Morphine sulfate/sequestered naltrexone hydrochloride (HCl) (MS-sNT) extended-release fixed-dose combination capsules, approved by the US Food and Drug Administration (FDA) in August 2009 for chronic moderate to severe pain, contain extended-release morphine pellets with a sequestered core of the opioid antagonist naltrexone. MS-sNT was designed so that if the product is tampered with by crushing, the naltrexone becomes bioavailable to mitigate morphine-induced subjective effects, rendering the product less attractive for tampering. The primary aim of this study was to compare the oral bioavailability of naltrexone and its metabolite 6-beta-naltrexol, derived from crushed pellets from MS-sNT capsules, to naltrexone solution. This study also assessed the relative bioavailability of morphine from crushed pellets from MS-sNT capsules and that from the whole, intact product. This single-dose, randomized-sequence, open-label, 3-period, 3-treatment crossover trial was conducted in healthy volunteers. Adults admitted to the study center underwent a 10-hour overnight fast before study drug administration. Each subject received all 3 of the following treatments, 1 per session, separated by a 14-day washout: tampered pellets (crushed for >or=2 minutes with a mortar and pestle) from a 60-mg MS-sNT capsule (60 mg morphine/2.4 mg naltrexone); 60-mg whole, intact MS-sNT capsule; and oral naltrexone HCl (2.4 mg) solution. Plasma concentrations of naltrexone and 6-beta-naltrexol were measured 0 to 168 hours after administration. Morphine pharmaco-kinetics of crushed and whole pellets were determined 0 to 72 hours after administration. The analysis of relative bioavailability was based on conventional FDA criteria for assuming bioequivalence; that is, 90% CIs for ratios of geometric means (natural logarithm [In]-transformed C(max) and AUC) fell within the range of 80% to 125%. Subjects underwent physical examinations, clinical laboratory tests, and ECG at screening and study

  7. Bioequivalence of a single 400-mg dose of imatinib 100-mg oral tablets and a 400-mg tablet in healthy adult Korean volunteers.

    Science.gov (United States)

    Lee, Hae Won; Seong, Sook Jin; Park, Sung Min; Lee, Joomi; Gwon, Mi-Ri; Kim, Hyun-Ju; Lim, Sung Mook; Lim, Mi-Sun; Kim, Woomi; Yang, Dong Heon; Yoon, Young-Ran

    2015-06-01

    Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. A new once-daily 400-mg film-coated tablet of imatinib has been developed by a pharmaceutical company in Korea. The present study was designed to assess and compare the PK parameters, bioavailability, and bioequivalence of the new imatinib 400-mg formulation (test) versus the conventional 100-mg formulation (reference) administered as a single 400-mg dose in healthy adult male volunteers. This randomized, open-label, single-dose, two-way crossover study was conducted in healthy Korean male volunteers. Eligible subjects were randomly assigned in a 1 : 1 ratio to receive 400 mg of the test (one 400-mg tablet) or reference (four 100-mg tablets) formulation, followed by a 2-week washout period and administration of the alternate formulation. Serial blood samples were collected at 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, and 72 hours after administration. Plasma imatinib concentrations were determined using liquid chromatography coupled with tandem mass spectrometry. The formulations were to be considered bioequivalent if the 90% confidence intervals (CIs) of the adjusted geometric mean ratios for Cmax, AUC(0-t), and AUC(0-∞)ž were within the predetermined range of 0.80 - 1.25. In total, 35 subjects completed the study. No serious adverse event was reported during the study. The 90% CIs of the adjusted geometric mean ratios of the test formulation to the reference formulation for C(max), AUC(0-t) and AUC(0-∞)ž of imatinib were all within the bioequivalence criteria range of 0.8 - 1.25. The test formulation of imatinib met the Korean regulatory requirements for bioequivalence. Both imatinib formulations were well-tolerated in all subjects.

  8. A novel pH-responsive interpolyelectrolyte hydrogel complex for the oral delivery of levodopa. Part II: characterization and formulation of an IPEC-based tablet matrix.

    Science.gov (United States)

    Ngwuluka, Ndidi C; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Khan, Riaz A; Pillay, Viness

    2015-03-01

    This study was undertaken in order to apply a synthesized interpolyelectrolyte complex (IPEC) of polymethacrylate and carboxymethylcellulose as a controlled release oral tablet matrix for the delivery of the model neuroactive drug levodopa. The IPEC (synthesized in Part I of this work) was characterized by techniques such as Fourier Transform Infra-Red (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC), Advanced DSC (ADSC), and Scanning Electron Microscopy (SEM). The tablet matrices were formulated and characterized for their drug delivery properties and in vitro drug release. FTIR confirmed the interaction between the two polymers. The IPEC composite generated tablet matrices with a hardness ranging from 19.152-27.590 N/mm and a matrix resilience ranging between 42 and 46%. An IPEC of polymethacrylate and carboxymethylcellulose was indeed an improvement on the inherent properties of the native polymers providing a biomaterial with the ability to release poorly soluble drugs such as levodopa at a constant rate over a prolonged period of time. © 2014 Wiley Periodicals, Inc.

  9. Buccals tablets - literature search

    OpenAIRE

    Horáček, Jan

    2007-01-01

    BUCCAL TABLETS Jan Horáček ABSTRACT My diploma thesis was aimed at summarising information about phenomena of bioadhesion in connection with administration of drugs. The work describes anatomy and physiology of oral mucosa and differencies in various parts of oral cavity. It refers about advantages and limits of administrating drugs through the oral mucosa. The part called Bioadhesion / mucoadhesion includes definition, theories, influencing factors and description of methods to determinate b...

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

    Science.gov (United States)

    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 C max 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

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

    Directory of Open Access Journals (Sweden)

    Zhaohui Ge

    2014-01-01

    Full Text Available 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 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.

  12. Long-term weight loss observed with olanzapine orally disintegrating tablets in overweight patients with chronic schizophrenia. A 1 year open-label, prospective trial.

    Science.gov (United States)

    Chawla, Bharat; Luxton-Andrew, Heather

    2008-04-01

    To investigate the long-term weight loss outcomes during usual clinical practice after switching from olanzapine standard oral tablet (SOT) to olanzapine orally disintegrating tablets (ODT). In this open-label prospective study, 26 patients with schizophrenia who were clinically stable on olanzapine SOT treatment were switched to olanzapine ODT. All other aspects of treatment remained constant. Weight was recorded at 3, 6, and 12 months. Patients incurred an average weight loss of 2.7 +/- 0.7 kg (p = 0.001) after switching patients from olanzapine SOT to olanzapine ODT at 12 months. Peak weight loss was observed at 6 months; however, significant weight loss was achieved as early as 3 months. The majority (81.9%) of patients lost weight, while 18.1% had no weight change or weight gain. Body mass index (BMI) significantly decreased by 1.0 +/- 0.3 kg/m(2) (p = 0.001). Interestingly, patients treated with higher doses of olanzapine (> or = 20 mg) incurred a greater weight loss of their body weight (5.6%), compared to those treated with lower doses (< 20 mg), who lost 1.9% of their body weight (p = 0.04). This study demonstrated that, in usual clinical practice, switching patients from olanzapine SOT to olanzapine ODT treatment resulted in significant weight loss that was maintained over 12 months. 2008 John Wiley & Sons, Ltd.

  13. Simultaneous LC-MS/MS determination of five tripterygium pyridine alkaloids in dog plasma and its application to their pharmacokinetic study after oral administration of tripterygium glycosides tablets.

    Science.gov (United States)

    Su, Meng-xiang; Song, Min; Yang, Da-song; Shi, Jin-fang; Di, Bin; Hang, Tai-jun

    2015-05-15

    A sensitive and selective liquid chromatography tandem mass spectrometric method was developed and validated for the simultaneous determination of five pyridine alkaloids contained in tripterygium glycosides tablets (triptolide, wilforine, wilforgine, wilfording and wilfortrine) in dog plasma. The analysis was carried out on a Sepax GP-Phenyl column using a mixture of methanol and 10mmol/L ammonium formate buffer solution containing 0.1% formic acid (75:25, v/v) as the mobile phase pumped at a flow-rate of 1.0mL/min. All MS data were obtained in the positive ESI mode with selective multiple reaction monitoring of ion transitions. The method was fully validated to be accurate and precise with a linear range of 0.2-1000ng/mL for triptolide and 0.05-1000ng/mL for the other four pyridine alkaloids. The intra-day and inter-day precisions (relative standard deviation, RSD, %) were within 10.6% and 14.0%, respectively, and the relative error (RE, %) were all less than 13.1%. The method was successfully applied to multi-components pharmacokinetic study of the five pyridine alkaloids in beagle dogs after a single oral administration of 3mg/kg and 30mg/kg tripterygium glycosides tablets, respectively, and a multiple oral administration of 30mg/kg for 6 consecutive days. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Successful management of a difficult cancer pain patient by appropriate adjuvant and morphine titration

    Directory of Open Access Journals (Sweden)

    Shiv PS Rana

    2011-01-01

    Full Text Available Morphine has been used for many years to relieve cancer pain. Oral morphine (in either immediate release or modified release form remains the analgesic of choice for moderate or severe cancer pain. The dose of oral morphine is titrated up to achieve adequate relief from pain with minimal side effects. Antidepressant and anticonvulsant drugs, when used in addition to conventional analgesics, give excellent relief from cancer pain. Most cancer pain responds to pharmacological measures with oral morphine but some pain like neuropathic and bony pain, pain in children and elderly age group, and advanced malignancy pain are very difficult to treat. Here, we report the management of a similar patient of severe cancer pain and the difficulty that we came across during dose titration of oral morphine and adjuvant analgesic.

  15. 21 CFR 520.812 - Enrofloxacin tablets.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Enrofloxacin tablets. 520.812 Section 520.812 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.812 Enrofloxacin tablets. (a) Specifications. Each tablet contains either 22.7, 68.0, or 136.0 milligrams of enrofloxacin. (b) Sponsor. See No...

  16. Oral pyridoxine can substitute for intravenous pyridoxine in managing patients with severe poisoning with isoniazid and rifampicin fixed dose combination tablets: a case report.

    Science.gov (United States)

    Dilrukshi, M D S A; Ratnayake, C A P; Gnanathasan, C A

    2017-08-08

    Fixed drug combination of isoniazid and rifampicin is a rare cause of poisoning even in endemic countries for tuberculosis infection. Severe poisoning can cause severe morbidity and mortality if not treated promptly. Though intravenous pyridoxine is the preferred antidote for severe standard isoniazid poisoning it is not freely available even in best of care centers. We describe a case of severe poisoning with fixed drug combination of isoniazid and rifampicin successfully managed with oral pyridoxine at national hospital of Sri Lanka. A 22 year old, Sri Lankan female presented to a local hospital 1 h after self-ingestion of 28 tablets of fixed drug combination of isoniazid and rifampicin which contained 4.2 g of standard isoniazid and 7.2 g of rifampicin. One and half hours after ingestion she developed generalized tonic-clonic seizure with loss of consciousness. She was given intravenous diazepam 5 mg immediately and transferred to national hospital of Sri Lanka, for further care. Upon arrival to tertiary care hospital in 3.5 h of poisoning she had persistent vomiting, dizziness and headache. On examination, she was drowsy but arousable, orange-red discoloration of the body was noted even with the dark skin complexion. She also had orange-red colour urine and vomitus. Pulse rate was 104 beats/min, blood pressure 130/80 mmHg, respiratory rate was 20 breaths/min. The arterial blood gas analysis revealed compensated metabolic acidosis and mildly elevated lactic acid level. Considering the clinical presentation with neurological toxicity and the large amount of isoniazid dose ingested, crushed oral tablets of pyridoxine 4.2 g (equal to standard isoniazid dose ingested) administered immediately via a nasogastric tube since intravenous preparation was not available in the hospital. Simultaneously forced diuresis using intravenous 0.9% saline was commenced in order to enhance excretion of toxic metabolites via kidneys. She had no recurrence of seizures but had

  17. Evaluation of who oral rehydration solution (ORS) and salt tablets in resuscitating adult patients with burns covering more than 15% of total body surface area (TBSA).

    Science.gov (United States)

    Moghazy, A M; Adly, O A; Elbadawy, M A; Hashem, R E

    2016-03-31

    Intra-venous (IV) burn resuscitation is effective; nevertheless it has its disadvantages. WHO Oral Rehydration Solution (ORS) has shown high effectiveness in treating dehydration. WHO-ORS, with salt supplement, seems to be suitable for burn resuscitation, where IV resuscitation is not available, feasible or possible. The objective of the study was to evaluate acute phase efficacy and safety, as well as limitations and complications of burn resuscitation using WHO-ORS and salt tablets. This randomized controlled clinical trial was conducted in the Burn Unit, Suez Canal University Hospital, Ismailia, Egypt. The study group was given WHO-ORS (15% of body weight/day) with one salt tablet (5gm) per liter according to Sørensen's formula. The control group was given IV fluids according to the Parkland formula. Patients' vital signs and urine output were monitored for 72 hours after starting resuscitation. Both groups were comparable regarding age, sex, and percentage, etiology and degree of burns. For all assessed parameters, there were no major significant differences between the study group (10 cases) and control group (20 cases). Even where there was a significant difference, apart from blood pressure in the first hour of the first day, the study group never crossed safe limits for pulse, systolic blood pressure, urine output, respiratory rate and conscious level. WHO-ORS with 5gm salt tablets, given according to Sørenson's formula, is a safe and efficient alternative for IV resuscitation. It could even be a substitute, particularly in low resource settings and fire disasters.

  18. A novel and discriminative method of in vitro disintegration time for preparation and optimization of taste-masked orally disintegrating tablets of carbinoxamine maleate.

    Science.gov (United States)

    Liu, Yali; Li, Peng; Qian, Rong; Sun, Tianyu; Fang, Fangzhi; Wang, Zonghua; Ke, Xue; Xu, Bohui

    2018-08-01

    The primary objective of this study was to mask bitter taste and decrease the disintegration time of carbinoxamine maleate (CAM) orally disintegrating tablets (ODTs). In order to screen the prescription of ODTs, a novel modified in vitro disintegration method (MIVDM) was developed to measure the in vitro disintegration time. In this method, different concentrations of ethanol served as disintegration medium in order to delay the in vitro water absorption and disintegration process of tablets. The MIVDM demonstrated good in vitro and in vivo correlation and proved more precise and discriminative than other reported methods. In this research, ion exchange resins (IERs) were used to mask bitter taste for improving mouthfeel. The drug-resin ratio and reaction temperature were investigated to obtain the optimum carbinoxamine resin complexes (CRCs). The characterization of CRCs revealed an amorphous state. ODTs were prepared by direct compression. Superdisintegrants and diluents of ODTs were screened first. Further optimization was carried out by using Box-Behnken design. The effect of (X 1 ) mannitol/microcrystalline cellulose ratio, (X 2 ) the amount of low-substituted hydroxypropylcellulose and (X 3 ) the hardness was investigated for achieving the lowest (Y) in vitro disintegration time. Technological characterization, wetting time, water absorption ratio, and roughness degree were evaluated. The CRCs and ODTs proved successful taste-masking efficiency. The end product improved patients' compliance. The developed MIVDM was practical for commercial use.

  19. Human gliomas contain morphine

    DEFF Research Database (Denmark)

    Olsen, Peter; Rasmussen, Mads; Zhu, Wei

    2005-01-01

    BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogeno...... of the solutions used in the study nor was it present as a residual material in blank HPLC runs. CONCLUSIONS: Morphine is present in human gliomas, suggesting that it may exert an action that effects tumour physiology/pathology.......BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous...

  20. Efficacy and safety of oral robenacoxib (tablet) for the treatment of pain associated with soft tissue surgery in client-owned dogs.

    Science.gov (United States)

    Friton, Gabriele; Thompson, Caryn Marie; Karadzovska, Daniela; King, Stephen; King, Jonathan N

    2017-06-26

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been proven to be effective in controlling peri-operative pain in dogs. Robenacoxib is an NSAID with high selectivity for the cyclooxygenase (COX)-2 isoform. The objective of this study was to assess the efficacy and safety of an oral tablet formulation of robenacoxib in client-owned dogs undergoing soft tissue surgery. The study was a prospective, multi-center, randomized, masked, placebo-controlled, parallel-group clinical trial. A total of 239 dogs were included and randomly allocated in a 1:1 ratio to receive either robenacoxib or placebo. Each dog received an oral tablet administration of either robenacoxib, at a target dose of 2 mg/kg, or placebo once prior to surgery and for two additional days post-operatively. All dogs also received a pre-anesthetic dose of 0.2 mg/kg butorphanol (intravenous or intramuscular). Pain assessments were performed using the short form of the Glasgow Composite Measure Pain Scale. Robenacoxib was compared to the placebo group on a success/failure basis. Treatment failure was defined as the need for rescue therapy to control post-operative pain. Significantly (P = 0.019) more dogs administered robenacoxib were considered treatment successes (89 of 116, 76.72%) compared to dogs given placebo (74 of 115, 64.35%). The percentage of treatment failure was therefore 23.28% in the robenacoxib and 35.65% in the placebo group. The least squares mean total pain scores were significantly different between groups and in favor of robenacoxib at 3 and 5 hours (P dogs receiving robenacoxib versus placebo (P dogs.

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

    Directory of Open Access Journals (Sweden)

    Isbel Nicole M

    2009-07-01

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

  2. Human gliomas contain morphine

    DEFF Research Database (Denmark)

    Olsen, Peter; Rasmussen, Mads; Zhu, Wei

    2005-01-01

    BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous...

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

    DEFF Research Database (Denmark)

    Sverrisdóttir, Eva; Foster, David John Richard; Upton, Richard Neil

    2015-01-01

    The aim of this study was to develop population pharmacokinetic-pharmacodynamic models for morphine in experimental pain induced by skin heat and muscle pressure, and to evaluate the experimental pain models with regard to assessment of morphine pharmacodynamics. In a randomized, double......-blind, placebo-controlled, crossover study, 39 healthy volunteers received an oral dose of 30 mg morphine hydrochloride or placebo. Non-linear mixed effects modelling was used to describe the plasma concentrations of morphine and metabolites, and the analgesic effect of morphine on experimental pain in skin...... and muscle. Baseline pain metrics varied between individuals and occasions, and were described with interindividual and interoccasion variability. Placebo-response did not change with time. For both pain metrics, morphine effect was proportional to baseline pain and was described with a linear model...

  4. [The enantioselective pharmacokinetic study of desvenlafaxine sustained release tablet in Chinese healthy male volunteers after oral administration].

    Science.gov (United States)

    Chen, Yin-xia; Du, Jiang-bo; Zhang, Yi-fan; Chen, Xiao-yan; Zhong, Da-fang

    2015-04-01

    A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS) enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral column (150 mm x 4.6 mm, 5 μm). The assay was linear over the concentration range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and C(max) of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.

  5. Oral matrix tablet formulations for concomitant controlled release of anti-tubercular drugs: design and in vitro evaluations.

    Science.gov (United States)

    Hiremath, Praveen S; Saha, Ranendra N

    2008-10-01

    The aim of the present investigation was to develop controlled release (C.R.) matrix tablet formulations of rifampicin and isoniazid combination, to study the design parameters and to evaluate in vitro release characteristics. In the present study, a series of formulations were developed with different release rates and duration using hydrophilic polymers hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC). The duration of rifampicin and isoniazid release could be tailored by varying the polymer type, polymer ratio and processing techniques. Further, Eudragit L100-55 was incorporated in the matrix tablets to compensate for the pH-dependent release of rifampicin. Rifampicin was found to follow linear release profile with time from HPMC formulations. In case of formulations with HPC, there was an initial higher release in simulated gastric fluid (SGF) followed by zero order release profiles in simulated intestinal fluid (SIFsp) for rifampicin. The release of isoniazid was found to be predominantly by diffusion mechanism in case of HPMC formulations, and with HPC formulations release was due to combination of diffusion and erosion. The initial release was sufficiently higher for rifampicin from HPC thus ruling out the need to incorporate a separate loading dose. The initial release was sufficiently higher for isoniazid in all formulations. Thus, with the use of suitable polymer or polymer combinations and with the proper optimization of the processing techniques it was possible to design the C.R. formulations of rifampicin and isoniazid combination that could provide the sufficient initial release and release extension up to 24h for both the drugs despite of the wide variations in their physicochemical properties.

  6. Orally disintegrating and oral standard olanzapine tablets similarly elevate the homeostasis model assessment of insulin resistance index and plasma triglyceride levels in 12 healthy men: a randomized crossover study.

    Science.gov (United States)

    Vidarsdottir, Solrun; Vlug, Pauline; Roelfsema, Ferdinand; Frölich, Marijke; Pijl, Hanno

    2010-09-01

    Treatment with olanzapine is associated with obesity, diabetes mellitus, and dyslipidemia. Reports have indicated that orally disintegrating tablets (ODT) cause less weight gain than oral standard tablets (OST). The aim of this study was to compare the effect of short-term treatment with these 2 distinct olanzapine formulations on glucose and lipid metabolism in healthy men. Twelve healthy men (mean ± SEM age: 25.1 ± 5.5 years) received olanzapine ODT (10 mg od, 8 days), olanzapine OST (10 mg od, 8 days), or no intervention in a randomized crossover design. At breakfast and dinner, glucose, insulin, free fatty acids (FFA), and triglyceride concentrations were measured at 10-minute intervals from 30 minutes prior to 2 hours after ingestion of standard meals. Leptin and adiponectin concentrations were measured at 20- and 30-minute intervals, respectively, between 0000h-1200h. Physical activity was assessed with an accelerometer. Fuel oxidation was measured in fasting condition by indirect calorimetry. The study was conducted from April 2006 through September 2006. Treatment with olanzapine ODT and OST equally elevated the homeostasis model assessment of insulin resistance (HOMA-IR) (P = .005). At breakfast, both formulations equally increased fasting and postprandial triglyceride concentrations (P = .013 and P = .005, respectively) while decreasing fasting and postprandial FFA concentrations (P = .004 and P = .009, respectively). Body weight, body composition, physical activity, or fuel oxidation did not differ between treatment modalities. Eight days of treatment with both olanzapine formulations similarly increased HOMA-IR and triglyceride concentrations and decreased FFA concentrations in response to standard meals without affecting anthropometrics or physical activity. These data suggest that olanzapine hampers insulin action via mechanistic routes other than body adiposity or physical inactivity. controlled-trials.com. Identifier: ISRCTN17632637. © Copyright

  7. Pharmaceutical development of an oral tablet formulation containing a spray dried amorphous solid dispersion of docetaxel or paclitaxel

    NARCIS (Netherlands)

    Sawicki, Emilia; Beijnen, Jos H|info:eu-repo/dai/nl/071919570; Schellens, Jan H M|info:eu-repo/dai/nl/073926272; Nuijen, Bastiaan

    2016-01-01

    Previously, it was shown in Phase I clinical trials that solubility-limited oral absorption of docetaxel and paclitaxel can be drastically improved with a freeze dried solid dispersion (fdSD). These formulations, however, are unfavorable for further clinical research because of limitations in

  8. Driving ability in cancer patients receiving long-term morphine analgesia.

    Science.gov (United States)

    Vainio, A; Ollila, J; Matikainen, E; Rosenberg, P; Kalso, E

    1995-09-09

    When given in single doses to healthy volunteers, opioid analgesics impair reaction time, muscle coordination, attention, and short-term memory sufficiently to affect driving and other skilled activities. Despite the increasing use of oral morphine daily, little is known about the effect of long-term opioid therapy on psychomotor performance. To examine the effects of continuous morphine medication, psychological and neurological tests originally designed for professional motor vehicle drivers were conducted in two groups of cancer patients who were similar apart from experience of pain. 24 were on continuous morphine (mean 209 mg oral morphine daily) for cancer pain; and 25 were pain-free without regular analgesics. Though the results were a little worse in the patients taking morphine, there were no significant differences between the groups in intelligence, vigilance, concentration, fluency of motor reactions, or division of attention. Of the neural function tests, reaction times (auditory, visual, associative), thermal discrimination, and body sway with eyes open were similar in the two groups; only balancing ability with closed eyes was worse in the morphine group. These results indicate that, in cancer patients receiving long-term morphine treatment with stable doses, morphine has only a slight and selective effect on functions related to driving.

  9. Comparative pharmacokinetics of swertiamarin in rats after oral administration of swertiamarin alone, Qing Ye Dan tablets and co-administration of swertiamarin and oleanolic acid.

    Science.gov (United States)

    Xu, Gui-li; Li, Hong-liang; He, Jian-chang; Feng, En-fu; Shi, Pan-pan; Liu, Yue-qiong; Liu, Chang-xiao

    2013-08-26

    Qing Ye Dan is a well-known herbal drug that is widely used to treat viral hepatitis in the Yi and Hani minority regions in the Yunnan province of China. An LC-MS/MS method was developed to determine the levels of swertiamarin in rat plasma. Swertiamarin and naringin (internal standard, IS) were extracted from rat plasma using solid-phase extraction (SPE) to purify the samples. The pharmacokinetics of the following different administration methods of swertiamarin in rats were studied: oral administration of swertiamarin alone, a Qing Ye Dan tablet (QYDT) and co-administration of swertiamarin and oleanolic acid, with each method delivering approximately 20mg/kg of swertiamarin. Non-compartmental pharmacokinetic profiles were constructed by using the software DAS (version 2.1.1), and the pharmacokinetic parameters were compared using an unpaired Student's t-test. The results showed that the pharmacokinetic parameters Cmax, AUC0-∞, Vz/F and CLz/F were significantly different (P<0.05) among the three types of swertiamarin administration. The data indicate that oleanolic acid and the other ingredients present in QYDT could affect the pharmacokinetic behaviour of swertiamarin in rats. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Evaluation of palatability of 10 commercial amlodipine orally disintegrating tablets by gustatory sensation testing, OD-mate as a new disintegration apparatus and the artificial taste sensor.

    Science.gov (United States)

    Uchida, Takahiro; Yoshida, Miyako; Hazekawa, Mai; Haraguchi, Tamami; Furuno, Hiroyuki; Teraoka, Makoto; Ikezaki, Hidekazu

    2013-09-01

    The purpose of this study was to evaluate and compare the palatability of 10 formulations (the original manufacturer's formulation and nine generics) of amlodipine orally disintegrating tablets (ODTs) by means of human gustatory sensation testing, disintegration/dissolution testing and the evaluation of bitterness intensity using a taste sensor. Initially, the palatability, dissolution and bitterness intensity of the ODTs were evaluated in gustatory sensation tests. Second, the disintegration times of the ODTs were measured using the OD-mate, a newly developed apparatus for measuring the disintegration of ODTs, and lastly, the bitterness intensities were evaluated using an artificial taste sensor. Using factor analysis, the factors most affecting the palatability of amlodipine ODTs were found to be disintegration and taste. There was high correlation between the disintegration times of the 10 amlodipine ODTs estimated in human gustatory testing and those found using the OD-mate. The bitterness intensities of amlodipine ODTs 10, 20 and 30 s after starting the conventional brief dissolution test and the values determined by the taste sensor were highly correlated with the bitterness intensities determined in gustatory sensation testing. The OD-mate and the taste sensor may be useful for predicting the disintegration and bitterness intensity of amlodipine ODTs in the mouth. © 2013 Royal Pharmaceutical Society.

  11. Bioequivalence of 250 mg lysine clonixinate tablets after a single oral dose in a healthy female Mexican population under fasting conditions.

    Science.gov (United States)

    Marcelín-Jiménez, G; Angeles, A C P; García, A; Morales, M; Rivera, L; Martín-Del-Campo, A

    2010-05-01

    To evaluate the bioequivalence between two 250 mg-tablets of lysine clonixinate, Dorixina Forte (Siegfried Rhein, México) as reference product, and Prestodol (Farmaceúticos Rayere, S.A., México) as test formulation. 26 healthy adult female Mexican volunteers received a single oral dose of 250-mg lysine clonixinate under fasting conditions. The drug was administered following a randomized, two-period, two-sequence, cross-over design. Twelve serial blood samples were collected up to 8 h after dosing, and clonixin (CLX) was measured by ultra-performance liquid chromatography (UPLC) coupled with tandem mass spectrometry. Decimal logarithm values of Cmax and area under the curve (AUC) were used to construct a classic confidence interval at 90% (90% CI). Bioequivalence was established if 90% CI of mean ratios (test/reference) fall within the 0.8-1.25 range. Volunteers formed a homogeneous population in terms of age (27.2 +/- 6.3 years), weight (55.9 +/- 6.5 kg), height (1.6 +/- 0.04 m), and body mass index (BMI) (22.91 +/- 2.03 kg/m(2)). Reference formulation exhibited the following pharmacokinetics: C(max) (32.39 +/- 8.32 microg/ml); t(max) (0.64 +/- 0.2 h); AUC0-8h (48.92 +/- 16.51 microg x h/ml); t1/2 (1.3 +/- 0.24 h); CLapp (5.64 +/- 1.99 l/h), and Vdapp (10.22 +/- 2.9 l). Concerning bioequivalence, 90% CI were: C(max) (82.32 - 98.79), AUC0-t (94.59-106.29), and AUC(0-inf) (94.61-106.42), with a statistical power of > 0.90 at every tested interval. This single-dose study found that both 250-mg immediate-release tablets of lysine clonixinate met the Mexican regulatory criteria for bioequivalence in these volunteers.

  12. A randomized, double-blind, crossover, placebo-controlled clinical trial to assess effects of the single ingestion of a tablet containing lactoferrin, lactoperoxidase, and glucose oxidase on oral malodor.

    Science.gov (United States)

    Nakano, Manabu; Shimizu, Eiju; Wakabayashi, Hiroyuki; Yamauchi, Koji; Abe, Fumiaki

    2016-03-22

    The main components of oral malodor have been identified as volatile sulfur compounds (VSCs) including hydrogen sulfide (H2S) and methyl mercaptan (CH3SH). VSCs also play an important role in the progression of periodontal disease. The aim of the present study was to assess the effects of the single ingestion of a tablet containing 20 mg of lactoferrin, 2.6 mg of lactoperoxidase, and 2.6 mg of glucose oxidase on VSCs in the mouth. Subjects with VSCs greater than the olfactory threshold in their mouth air ingested a test or placebo tablet in two crossover phases. The concentrations of VSCs were monitored at baseline and 10 and 30 min after ingestion of the tablets using portable gas chromatography. Thirty-nine subjects were included in the efficacy analysis based on a full analysis set (FAS). The concentrations of total VSCs and H2S at 10 min were significantly lower in the test group than in the placebo group (-0.246 log ng/10 ml [95 % CI -0.395 to -0.098], P = 0.002; -0.349 log ng/10 ml; 95 % CI -0.506 to -0.192; P oxidase has suppressive effects on oral malodor. This trial was registered with the University Hospital Medical Information Network Clinical Trial Registry (number: UMIN000015140 , date of registration: 16/09/2014).

  13. 21 CFR 520.1157 - Iodinated casein tablets.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Iodinated casein tablets. 520.1157 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1157 Iodinated casein tablets. (a) Specifications. Each 1-gram tablet contains 25 milligrams of iodinated casein. (b) Sponsor...

  14. Modulation of morphine antinociceptive tolerance and physical dependence by co-administration of simvastatin.

    Science.gov (United States)

    Mansouri, Mohammad Taghi; Khodayar, Mohammad Javad; Tabatabaee, Amirhossein; Ghorbanzadeh, Behnam; Naghizadeh, Bahareh

    2015-10-01

    Statins, 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors, are widely used in the management of different diseases beyond their primary indication for lowering cholesterol. Previous studies have demonstrated the neuroprotective effects of simvastatin in different animal models. In the present study, we examined the effects of simvastatin (30, 60, 100 and 300mg/kg, p.o.) on the development and expression of morphine-induced tolerance and dependence in mice. For the induction of morphine tolerance and dependence, mice were twice daily treated with morphine (10mg/kg, s.c.) for 5 consecutive days. Tolerance was evaluated by the hot-plate test and physical dependence by naloxone challenge, on the sixth day. The results showed that oral administration of simvastatin produced antinociceptive activity in a dose-dependent way. Co-administration of simvastatin with morphine did not affect the acute morphine-induced analgesia (10mg/kg, s.c.). However, repeated co-administration of simvastatin with morphine significantly attenuated the development of tolerance to the analgesic effect of morphine and inhibited the naloxone (5mg/kg, s.c.)-precipitated withdrawal signs (jumping and body weight loss). Also, simvastatin at doses of 100 and 300mg/kg attenuated the expression of morphine-induced tolerance and dependence. These data indicated that, while simvastatin can alleviate both development and expression of morphine-induced tolerance, it cannot enhance morphine-induced antinociception. Taken together, simvastatin may be used as an adjutant therapeutic agent in combination with morphine and or other opioids in patients with severe chronic pain. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Taste-masked and affordable donepezil hydrochloride orally disintegrating tablet as promising solution for non-compliance in Alzheimer's disease patients.

    Science.gov (United States)

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

    2015-04-01

    Manufacturing process and superdisintegrants used in orally disintegrating tablet (ODT) formulation are often time discussed. However, the effect of suitable filler for ODT formulation is not explored thoroughly. The aim of this study was to develop a novel taste masked and affordable donepezil hydrochloride ODT with fast disintegration time and stable to improve medication compliance of Alzheimer's disease patient. The ODT was manufactured using simple wet-granulation method. Crospovidone XL-10 was used as superdisintegrant and optimization was done by comparing the effect of three grades of lactose monohydrate compound as filler: Starlac®, Flowlac® and Tablettose®. Formulations containing higher amount of colloidal silicon dioxide showed increase in hardness, weight, disintegration time and wetting time after stability study. Formulation E which containing 50% of Starlac® was found with shortest in vitro disintegration time (21.7 ± 1.67 s), in vivo disintegration time (24.0 ± 1.05 s) and in vitro disintegration time in artificial salvia (22.5 ± 1.67 s). Physical stability studies at 40 °C/75% RH for 6 months, Fourier transform infrared spectroscopy analysis and X-ray diffraction results showed that the formulation was stable. The drug-released profile showed that 80% of donepezil hydrochloride was released within 1 min. A single-dose, fasting, four-period, seven-treatment, double-blinded study involving 16 healthy human volunteers was performed to evaluate the palatability of ODT. Formulation VII containing 10 mg of ammonium glycyrrhizinate was able to mask the bitter taste of the drug. The product has the potential to be commercialized and it might serve as solution for non-compliance among the Alzheimer's disease patients.

  16. Reduction in the volume of water for ingesting orally disintegrating tablets of solifenacin (Vesicare® OD), and the clinical disintegration time of Vesicare® OD after unit-dose packaging.

    Science.gov (United States)

    Uchida, Shinya; Yoshita, Tomohiro; Namiki, Noriyuki

    2013-03-25

    This study aimed to determine the amount of water required for ingesting an orally disintegrating tablet (ODT) of solifenacin (Vesicare(®), VES) and VES conventional tablets (VES-CT). We measured the disintegration time of VES-ODT in the oral cavity (clinical disintegration time) before and after unit-dose packaging. Thirty healthy volunteers participated in this randomized crossover trial. The participants were asked to drink water during the intake placebos of VES and after the disintegration of placebos of VES-ODT in their oral cavity. The amounts of water required for ingesting placebos of VES-CT and of VES-ODT were 42.8±27.0 mL and 20.0±23.7 mL, respectively, which indicated that the amount of water required for ingesting ODTs was significantly lesser than that for ingesting CTs. Furthermore, 5 (16.7%) participants did not require water for ingesting the ODTs. Clinical disintegration time of VES-ODT was 21.4s in 10 healthy volunteers. This clinical disintegration time did not change significantly after unit-dose packaging or subsequent storage for 56 days. This study showed that the amount of water required for ingesting VES-ODT is lower than that for ingesting VES-CT. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  17. [History of opium poppy and morphine].

    Science.gov (United States)

    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

  18. Hospital morphine preparation for abstinence syndrome in newborns exposed to buprenorphine or methadone.

    Science.gov (United States)

    Colombini, Nathalie; Elias, Riad; Busuttil, Muriel; Dubuc, Myriam; Einaudi, Marie-Ange; Bues-Charbit, Martine

    2008-06-01

    This study was undertaken to evaluate the adequacy of a hospital formulated oral morphine preparation for management of neonatal abstinence syndrome (NAS) and to compare clinical features in infants exposed to methadone or buprenorphine in utero. Between October 1998 and October 2004 all infants born to mothers treated with buprenorphine or methadone during pregnancy were enrolled into this prospective study. Morphine hydrochloride solution (0.2 mg/ml) was prepared without preservatives under a flow laminar air box (class 100). Morphine solution: quantitative and qualitative HPLC analysis and microbiological study at regular intervals during storage at 4 degrees C for 6 months. Maternal characteristics: age, opiate dose during pregnancy. Neonatal characteristics: gestational age at delivery, birth weight, Lipsitz scores. Morphine dose: daily morphine dose, maximum morphine dose, duration of NAS, and duration of treatment required to achieve stable Lipsitz scores below 4. Kruskal-Wallis test for comparison of median values. Microbiological and HPLC analysis showed that the morphine preparation remained stable for 6 months at 4 degrees C. Nine methadone-exposed infants and 13 buprenorphine-exposed infants were included in the study. All infants presented NAS requiring treatment with the morphine solution. Lipsitz scores at birth were significantly different in the methadone and buprenorphine groups (P methadone group required significantly higher doses of morphine preparation than the buprenorphine group during the first 38 days of treatment (P methadone-exposed infants (range 6-24 h) and within 48 h after birth in buprenorphine-exposed infants (range 24-168 h). Due to the possibility of delayed onset of NAS up to 7 days, infants born to mothers treated with buprenorphine should be kept in the hospital for an appropriate surveillance period. Treatment time was significantly longer (45 vs. 28 days) and the mean morphine doses were higher (1.7 fold) in methadone

  19. Tablet telerounding.

    Science.gov (United States)

    Kaczmarek, Bartosz F; Trinh, Quoc-Dien; Menon, Mani; Rogers, Craig G

    2012-12-01

    To evaluate the feasibility of remote rounding using commercially available standard tablets with videoconferencing system and assess patient satisfaction. Thirty-two patients with at least 2 postoperative days of hospital stay after robotic urologic procedures were included in the study. On the first postoperative day, the physician-patient encounter was performed as telerounding with videoconferencing due to the physician's duties scheduled in another affiliated hospital. On the second day, the personal bedside encounter took place. The tablet we used was an iPad2 (Apple, iOS 5.1; Apple, Cupertino, CA) with a videoconferencing application. A telerounding satisfaction survey was fulfilled by all patients on the touchscreen of the tablet. Average time of telerounding encounter was 4.5 minutes (range, 1.0-13.5 minutes), average age of the patient was 57.7 years (range, 19-80 years), and 19 were men (59%). Patients expressed a high level of satisfaction with 91% of patients stating that their care was better using telerounding and 97% of patients stating that telerounding should be a regular part of patient care in the hospital. Additionally, 94% of patients stated that they could easily communicate with their doctor over the telerounding system, 84% of patients agreed that they would feel comfortable with telerounding daily if they were hospitalized again and 81% of patients would prefer telerounding communication with their doctor than be directly seen by another doctor. Tablet telerounding using videoconferencing can be a strong supplementing tool in doctor-patient communication. It is convenient for the physician and increases the patient's hospital stay satisfaction. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. 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.

    Science.gov (United States)

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

    2013-10-01

    To compare the bioavailability of two brands of phenytoin sodium tablets available in the Indian market using Eptoin™ as the reference. 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. 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. 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.

  1. Resveratrol reverses morphine-induced neuroinflammation in morphine-tolerant rats by reversal HDAC1 expression

    Directory of Open Access Journals (Sweden)

    Ru-Yin Tsai

    2016-06-01

    Conclusion: Resveratrol restores the antinociceptive effect of morphine by reversing morphine infusion-induced spinal cord neuroinflammation and increase in TNFR1 expression. The reversal of the morphine-induced increase in TNFR1 expression by resveratrol is partially due to reversal of the morphine infusion-induced increase in HDAC1 expression. Resveratrol pretreatment can be used as an adjuvant in clinical pain management for patients who need long-term morphine treatment or with neuropathic pain.

  2. Efeitos da associação entre pequenas doses subaracnóideas de morfina e cetoprofeno venoso e oral em pacientes submetidas à cesariana Efectos de la asociación entre pequeñas dosis subaracnóideas de morfina y cetoprofeno venoso y oral en pacientes sometidas a cesariana Effects of low spinal morphine doses associated to intravenous and oral ketoprofen in patients submitted to cesarean sections

    Directory of Open Access Journals (Sweden)

    Eliana Marisa Ganem

    2003-08-01

    de efectos colaterales en pacientes sometidas a cesariana, bajo anestesia subaracnóidea con bupivacaína hiperbárica y morfina en las dosis de 0,05 mg y 0,1 mg, asociadas al cetoprofeno por las vías venosa y oral. MÉTODO: Participaron del estudio 60 gestantes de término, estado físico ASA I y II, que fueron sometidas a cesariana electiva. Las pacientes fueron divididas en dos grupos: grupo 1 - morfina 0,1 mg, grupo 2 - 0,05 mg, asociada a 15 mg de bupivacaína hiperbárica. Todas recibieron cetoprofeno (100 mg por vía venosa en el per-operatorio y por vía oral a cada 8 horas en el primer día del pos-operatorio. Las pacientes fueron evaluadas 6, 12 y 24 horas después del término de la cirugía, con relación a la intensidad del dolor y presencia de efectos colaterales (sedación, prurito, náusea y vómito. La presencia de estos últimos también fue evaluada en el per-operatorio. RESULTADOS: Ambos grupos fueron idénticos cuanto a los datos antropométricos y la duración de la cirugía y de la anestesia. También fueron homogéneos con relación a la intensidad del dolor pos-operatorio y a la presencia de prurito, sedación, náusea y vómito. CONCLUSIONES: La morfina, en las dosis de 0,05 mg y 0,1 mg administradas en el espacio subaracnóideo, asociada al cetoprofeno por las vías venosa y oral, presentó la misma calidad de analgesia pos-operatoria y determinó la misma ocurrencia de efectos colaterales.BACKGROUND AND OBJECTIVES: Low spinal morphine doses are effective in relieving postoperative pain of patients submitted to Cesarean sections, with low incidence of side-effects. This study aimed at evaluating postoperative analgesia and the incidence of side-effects in patients submitted to Cesarean sections under spinal anesthesia with hyperbaric bupivacaine and 0.05 mg and 0.1 mg morphine associated to intravenous and oral ketoprofen. METHODS: Sixty pregnant women, physical status ASA I and II, undergoing elective Cesarean sections, were divided in

  3. Continuous intravenous morphine infusion for postoperative analgesia following posterior spinal fusion for idiopathic scoliosis.

    Science.gov (United States)

    Poe-Kochert, Connie; Tripi, Paul A; Potzman, Jennifer; Son-Hing, Jochen P; Thompson, George H

    2010-04-01

    A retrospective study of postoperative pain management. Evaluate the efficacy and safety of continuous intravenous morphine infusion for postoperative pain management in patients with idiopathic scoliosis (IS) undergoing posterior spinal fusion (PSF) and segmental spinal instrumentation (SSI). Postoperative pain is a common problem following surgery for IS. There are no published reports regarding the use of a continuous intravenous morphine infusion for this patient population. We retrospectively reviewed data regarding 339 consecutive patients with IS who underwent PSF and SSI between 1992 and 2006. All patients received intrathecal morphine after the induction of general anesthesia. Following surgery, preordered morphine infusion (0.01 mg/kg/h) was started at first reported pain. The infusion rate was titrated based on vital signs, visual analog scale (VAS) pain scores (0-10), and clinical status. It was continued until patients were able to take oral analgesics. We reviewed intrathecal morphine dosage, VAS pain scores through the third postoperative day, interval to start of morphine infusion, total morphine requirements in the first 48 hours, and any adverse reactions (nausea/vomiting, pruritus, respiratory depression, and pediatric intensive care unit admission). Mean intrathecal morphine dose was 15.5 +/- 3.9 microg/kg and mean interval to start of the intravenous morphine infusion was 17.5 +/- 5 hours. Mean VAS pain scores were 3.1, 4.5, 4.5, and 4.6 at 12 hours, 1, 2, and 3 days after surgery, respectively.The total mean morphine dose in the first 48 hours postoperatively was 0.03 +/- 0.01 mg/kg/h. Total morphine received was 1.44 +/- 0.5 mg/kg. Nausea/vomiting and pruritus, related to the morphine infusion occurred in 45 patients (13.3%) and 14 patients (4.1%), respectively. No patients had respiratory depression or required Pediatric Intensive Care Unit admission. A low frequency of adverse events and a mean postoperative VAS pain score of 5 or less

  4. A comparative study of aripiprazole orally disintegrating tablets and Haloperidol treatment for tic disorders%阿立哌唑口腔崩解片与氟哌啶醇治疗抽动障碍的对比研究

    Institute of Scientific and Technical Information of China (English)

    郑庆梅; 李耀东; 邓良华; 谭助英

    2015-01-01

    Objective To evaluate the efficacy and tolerability of Aripiprazole orally disintegrating tablets and Haloperidol treatment in children with tic disorders. Method 61 Tourette patients were randomly divided into two groups,treatment with Aripiprazole orally disintegra-ting tablets and Haloperidol for 8 weeks. Before treatment and in the second,fourth and eighth weekend,YGTSSS and TESS were used to eval-uate efficacy and side effects. Results In the 2nd,4th and 8th weekend vocal tic,total damage and total scores of YGTSS both in Aripiprazole group and Haloperidol group significantly decreased. But in the second weekend motor tics score worse than haloperidol. In terms of safety,side effects and tolerance of Aripiprazole orally disintegrating tablets was better. Conclusion Aripiprazole orally disintegrating tabletsis effective for treatment of tic disorder,and high safety.%目的:比较阿立哌唑口腔崩解片和氟哌啶醇治疗抽动障碍的临床疗效和安全性。方法:将符合抽动障碍的61例儿童随机分为两组,分别接受氟哌啶醇和阿立哌唑口腔崩解片治疗,并在治疗2周、4周及8周末分别进行耶鲁综合抽动严重程度量表(Yale Global Tic Severity Scale,YGTSS)、不良反应量表(treatment emergent symptomscale,TESS)评估其疗效和安全性。结果:阿立哌唑口腔崩解片与氟哌啶醇组在治疗的2、4、8周末在YGTSS量表发声抽动、整体损害和YGTSS总分疗效评分上均无明显差异,在2周末运动抽动疗效评分上较氟哌啶醇差;在安全性方面,阿立哌唑口腔崩解片不良反应更小,耐受性更好。结论:阿立哌唑口腔崩解片在治疗抽动障碍上有显著的疗效,和更好地安全性。

  5. Antibacterial Properties of Tebipenem Pivoxil Tablet, a New Oral Carbapenem Preparation against a Variety of Pathogenic Bacteria in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Qi Yao

    2016-01-01

    Full Text Available Aims: To systemically investigate the in vitro and in vivo antibacterial properties of tebipenem pivoxil tablet. In addition, acute toxicity of this preparation was also studied. Methods: In vitro, minimum inhibitory concentration (MIC or minimal inhibitory concentration (MBC were determined by using the serial 2-fold broth or agar dilution methods. Further, cumulative MIC inhibition curves were then made to assess the antibacterial effects of the drug at various concentrations. In vivo, minimum lethal dose (MLD in combination with maximum tolerance dose (MTD was used to measure the acute toxicity of the tebipenem pivoxil tablet in mice. After that, sepsis mouse models challenged with Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, respectively, were established to evaluate the anti-infective effect of this preparation. Results: The MIC90 values of tebipenem pivoxil against Gram-positive bacteria such as methicillin-sensitive Staphylococcus aureus (MSSA, methicillin-resistant Staphylococcus aureus (MRSA, methicillin-sensitive Staphylococcus epidermidis (MSSE, methicillin-resistant Staphylococcus epidermidis (MRSE, Pyogenic streptococcus, and Enterococcus faecalis were ≤0.125, 16, 0.5, 8, ≤0.125, and 32 μg/mL, respectively. Correspondingly, the MIC90 values of tebipenem pivoxil against Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Haemophilus influenzae, Pseudomonas aeruginosa, and Acinetobacter baumannii were 1, 0.5, ≤0.125, 0.25, 64, 64 μg/mL, respectively. The MBC values of tebipenem pivoxil against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae were 0.016–2, 0.063–32, 0.031–32 μg/mL, respectively. The acute toxicity study showed that the MLD of the tebipenem pivoxil tablet was 4.00 g/kg and the MTD was 3.40 g/kg in mice. In all the sepsis mouse models, the simultaneous administration of the tebipenem pivoxil tablets significantly reduced mortality of

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

    Science.gov (United States)

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

    2014-10-01

    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. 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 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. 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.

  7. Study Of Morphological Changes Of Uterine Horn Of Surri Mouse Depended To Morphine Before Puberty And DuringPuberty

    Directory of Open Access Journals (Sweden)

    Shadkhast M

    2003-11-01

    Full Text Available : Morphine is the most important alkaloid of opium family which is found as much as ten percent in opium, and is in two types the sulfate morphine and the hydrochloride morphine."nMaterials and Methods: In this study morphological changes of uterus of surri mice due to oral consumption of sulfate morphine were studied. It was shown that, female surri mice following gradually increasing of morphine to water (0.1 and 0.01 mg/ml were depended to morphine. Female surri mice were classified in two age groups before puberty and depended to morphine during puberty. Each age group took morphine for 21 days. After finishing the period, the mice anesthetizing were weighted, then were anesthetizing and uterus was studied the length, width and apparent features."nResults&ConcIusion: In this study it was distinguished that length and width of uterine horn, between experimental and control groups, were significant (P< 0.01. Morphological changes such as anemia, the thinness and fragitidily walls of uterus and filiformity of uterine horns were observed."n"n"n"n"n"n 

  8. Tablet Use within Medicine

    Science.gov (United States)

    Hogue, Rebecca J.

    2013-01-01

    This paper discusses the scholarly literature related to tablet computer use in medicine. Forty-four research-based articles were examined for emerging categories and themes. The most studied uses for tablet computers include: patients using tablets to complete diagnostic survey instruments, medical professionals using tablet computers to view…

  9. Effects of casoxin 4 on morphine inhibition of small animal intestinal contractility and gut transit in the mouse

    Directory of Open Access Journals (Sweden)

    Glen S Patten

    2011-02-01

    Full Text Available Glen S Patten1,2, Richard J Head1, Mahinda Y Abeywardena1,21CSIRO Preventative Health National Research Flagship, Adelaide, Australia; 2CSIRO Food and Nutritional Sciences, Adelaide, AustraliaBackground and aims: Chronic opioid analgesia has the debilitating side-effect of constipation in human patients. The major aims of this study were to: 1 characterize the opioid-specific antagonism of morphine-induced inhibition of electrically driven contraction of the small intestine of mice, rats, and guinea pigs; and 2 test if the oral delivery of small milk-derived opioid antagonist peptides could block morphine-induced inhibition of intestinal transit in mice.Methods: Mouse, rat, and guinea pig intact ileal sections were electrically stimulated to contract and inhibited with morphine in vitro. Morphine inhibition was then blocked by opioid subtype antagonists in the mouse and guinea pig. Using a polymeric dye, Poly R-478, the opioid antagonists casoxin 4 and lactoferroxin A were tested orally for blocking activity of morphine inhibition of gut transit in vivo by single or double gavage techniques.Results: The guinea pig tissue was more sensitive to morphine inhibition compared with the mouse or the rat (IC50 [half maximal inhibitory concentration] values as nmol/L ± SEM were 34 ± 3, 230 ± 13, and 310 ± 14 respectively (P < 0.01. The inhibitory influence of opioid agonists (IC50 in electrically driven ileal mouse preparations were DADLE ([D-Ala2, D-Leu5]-enkephalin ≥ met-enkephalin ≥ dynorphin A ≥ DAMGO ([D-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin > morphine > morphiceptin as nmol/L 13.9, 17.3, 19.5, 23.3, 230, and 403 respectively. The mouse demonstrated predominantly Κ- and δ-opioid receptor activity with a smaller µ-opioid receptor component. Both mouse and guinea pig tissue were sensitive to casoxin 4 antagonism of morphine inhibition of contraction. In contrast to naloxone, relatively high oral doses of the µ-opioid receptor antagonists

  10. Diclofenac systemic bioavailability of a topical 1% diclofenac + 3% menthol combination gel vs. an oral diclofenac tablet in healthy volunteers: a randomized, open-label, crossover study
.

    Science.gov (United States)

    Moreira, Sebastian A; Liu, D Jeffery

    2017-04-01

    Evaluate systemic exposure with repeated topical application of a fixed-combination topical gel product containing 1% diclofenac sodium and 3% menthol in either of 2 formulation packages relative to oral administration. In this phase 1, single-center, 4-way crossover study, healthy volunteers aged 18 - 50 years underwent consecutive 3-day treatment regimens in a randomly assigned sequence with each of 4 treatment groups: 4 g of topical 1% diclofenac + 3% menthol gel administered via an aluminum tube or roll-on device applied 4 times daily; 4 g of topical 1% diclofenac sodium gel (Voltaren Gel) applied 4 times daily; and oral diclofenac sodium tablets 50 mg 3 times daily. Treatment regimens were separated by 2-day washout periods. A total of 18 subjects enrolled and completed the study. Relative to oral administration, area under the concentration time curve from 48 to 72 hours (AUC48-72) with topical administration of 1% diclofenac + 3% menthol gel from a tube or roll-on device was 16.1% (90% CI: 12.2 - 21.1%) and 14.4% (90% CI: 11.0 - 19.0%), respectively. The diclofenac/menthol combination delivered significantly higher exposures of diclofenac compared with Voltaren Gel. A higher number of adverse events (AEs) occurred with the topical diclofenac/menthol combination (61%) vs. Voltaren Gel (22%) or oral diclofenac (6%); most were local skin reactions. No difference in systemic AEs was observed among the groups. As expected, systemic exposure was significantly lower with the topical diclofenac/menthol treatment regimens compared with oral diclofenac. Local skin AEs were increased with the topical combination product, but the risk of systemic AEs was low.
.

  11. 'Tablet burden' in patients with metastatic breast cancer.

    Science.gov (United States)

    Milic, Marina; Foster, Anna; Rihawi, Karim; Anthoney, Alan; Twelves, Chris

    2016-03-01

    The implications for patients with cancer, of the 'tablet burden' resulting from increasing use of oral anticancer drugs and medication for co-morbidities have not previously been well explored. We sought to (i) quantify tablet burden in women with metastatic breast cancer (MBC), (ii) establish which groups of drug contribute most to this burden and (iii) gain insight into patients' attitudes towards oral anti-cancer treatment. One hundred patients with MBC anonymously completed a questionnaire describing their medication histories and attitudes towards their tablets. The patients (mean age 60, range 31-95) were all female and taking a median of six tablets (range 0-31) daily; 37 patients were taking >10 tablets. Oral anticancer treatment constituted the category of treatment taken by the highest proportion of patients, followed by symptomatic cancer treatments, proton pump inhibitors and cardiovascular medication. Numerically, however, symptomatic drugs accounted for 44% of all tablets and specific anti-cancer treatment for 15%; medication not directly related to the cancer accounted for the remaining 40% of tablets. A quarter of patients reported inconvenience in taking their tablets, the main reason being tablet size and one third reported forgetting their tablets at least once a week. Nearly two thirds of patients expressing a preference favoured oral anticancer treatment, the commonest reason being greater convenience. Tablet burden is considerable for many patients with MBC and can be problematic. A significant proportion of tablets represent treatment for co-morbidities, the significance of which may be questionable in women with MBC. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Geraniin attenuates Naloxone-Precipitated Morphine Withdrawal and Morphine-Induced Tolerance in Mice

    Directory of Open Access Journals (Sweden)

    Ella Anle Kasanga

    2017-06-01

    Conclusion: Geraniin does not produce any tolerant effects like morphine and also reduced the signs associated with naloxone-precipitated morphine withdrawal in mice. [J Complement Med Res 2017; 6(2.000: 199-205

  13. A pharmacokinetic-pharmacodynamic model of morphine exposure and subsequent morphine consumption in postoperative pain

    DEFF Research Database (Denmark)

    Juul, Rasmus Vestergaard; Nyberg, Joakim; Lund, Trine Meldgaard

    2016-01-01

    Purpose To characterize the pharmacokinetic-pharmacodynamic (PK-PD) relationship between exposure of morphine and subsequent morphine consumption and to develop simulation tools for model validation. Methods Dose, formulation and time of morphine administration was available from a published study...

  14. Effect of antacids in didanosine tablet on bioavailability of isoniazid.

    OpenAIRE

    Gallicano, K; Sahai, J; Zaror-Behrens, G; Pakuts, A

    1994-01-01

    The antacids in two didanosine placebo tablets had no significant effect on the plasma pharmacokinetics of a single oral dose of 300 mg of isoniazid administered to 12 healthy volunteers. These results suggest that isoniazid bioavailability will be unaffected by the antacids in didanosine tablets when the two medications are administered simultaneously to human immunodeficiency virus-seropositive patients.

  15. Effect of antacids in didanosine tablet on bioavailability of isoniazid.

    Science.gov (United States)

    Gallicano, K; Sahai, J; Zaror-Behrens, G; Pakuts, A

    1994-04-01

    The antacids in two didanosine placebo tablets had no significant effect on the plasma pharmacokinetics of a single oral dose of 300 mg of isoniazid administered to 12 healthy volunteers. These results suggest that isoniazid bioavailability will be unaffected by the antacids in didanosine tablets when the two medications are administered simultaneously to human immunodeficiency virus-seropositive patients.

  16. 21 CFR 520.2150b - Stanozolol chewable tablets.

    Science.gov (United States)

    2010-04-01

    ....2150b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... treatment in dogs. (2) Administered orally to small breeds of dogs, 1/2 to 1 tablet twice daily for several weeks; to large breeds of dogs, 1 to 2 tablets twice daily for several weeks. (3) Federal law restricts...

  17. 21 CFR 520.2362 - Thenium closylate tablets.

    Science.gov (United States)

    2010-04-01

    ....2362 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...) Conditions of use. (1) The tablets are administered orally to dogs as a single day treatment of canine... Uncinaria stenocephala (hookworms). Dogs weighing 10 pounds and over are administered 1 tablet as a single...

  18. Evaluation of the ease of taking mini-tablets compared with other tablet formulations in healthy volunteers.

    Science.gov (United States)

    Hayakawa, Yoshiyuki; Uchida, Shinya; Namiki, Noriyuki

    2016-03-10

    "Mini-tablets" (MTs) are tablets of diameter≤3mm and have been widely studied and developed. However, reports comparing MTs with other tablet formulations are few. We wished to evaluate the ease of taking a MT quantitatively in comparison with an orally disintegrating mini-tablet (ODMT), conventional tablet (CT) and conventional orally disintegrating tablet (ODT). Four types of tablets were prepared. We prepared tablets of two diameters (3mm for MTs and ODMTs vs. 8mm for CTs and ODTs) and two formulations (MTs and CTs vs. ODMTs and ODTs). Our randomized crossover trial in 18 healthy volunteers (8 men and 10 women; mean age, 22.5years) indicated that the visual analog scale (VAS) score for the ease and amount of water required for intake of MTs was significantly lower than those of CTs. An ODMT required the least amount of water and smallest VAS score for the ease of taking a tablet. Our results showed that the advantage of MTs with regard to the ease of taking and decreased amount of water required was exerted for a unit of dosing comprising tablets. These data suggested the usefulness of MTs and the importance of the number of MTs for comfortable consumption by patients. Copyright © 2015. Published by Elsevier B.V.

  19. MTN-001: randomized pharmacokinetic cross-over study comparing tenofovir vaginal gel and oral tablets in vaginal tissue and other compartments.

    Directory of Open Access Journals (Sweden)

    Craig W Hendrix

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

  20. Relative bioavailability of a newly developed 5-mg levomethadone hydrochloride IR tablet (L-Polamidon® 5 mg tablets) in comparison with the 5-mg levomethadone hydrochloride oral solution (L-Polamidon® solution for substitution) as reference product.

    Science.gov (United States)

    Blume, Henning H; Wedemeyer, Ralf-Steven; Donath, Frank; Roscher, Katrin; Elvert, Gerd; Wagner, Daniel; Bley, Oliver; Vuia, Alexander; Todorova-Sanjari, Marina; Villalobos, Ramon; Schug, Barbara

    2015-04-01

    To establish the relative bioavailability (rBA) between two p.o. 5-mg levomethadone hydrochloride formulations, i.e., L-Polamidon® 5 mg tablets (test) vs. L-Polamidon® solution for substitution (reference). To assess the safety and tolerability of both formulations. A total of 33 healthy male subjects, aged 29 ± 6 years (BMI: 23.9 ± 2.5 kg/m2) completed this single center, open-label, randomized, 2-period cross-over study with single dose administrations under fasting conditions and coadministration with naltrexone for safety reasons. Administrations of both investigational products were separated by a washout period of at least 2 weeks, i.e., 13 treatmentfree days. The total dose for each subject was 2 x 5 mg resulting in 10 mg levomethadone hydrochloride. For pharmacokinetic evaluation, blood samples were withdrawn until 72 hours postdose. A validated non-stereoselective liquid chromatography-tandem mass spectroscopy method (LC-MS/MS) was applied for the determination of levomethadone in plasma. The lower limit of quantitation was 0.100 ng/mL. Adverse events were descriptively analyzed in the study population. The geometric means of the parameters related with the extent of total exposure of levomethadone, i.e., AUC(0-tlast) and AUC(0-∞), were 244.422 ng x h/mL and 332.999 ng x h/mL for test and 246.837 ng x h/mL and 329.467 ng×h/mL for reference, respectively. The geometric means of the peak exposure for levomethadone, i.e., Cmax, were 8.923 ng/mL for test and 8.635 ng/mL for reference. The point estimates (PEs) of the Test/Reference (T/R) adjusted geometric mean ratios of AUC(0-last), AUC(0-∞), and C(max) were 99.20%, 101.42%, and 104.11%, respectively, and all of them showed 90%-confidence intervals (CIs) within the range of 80.00 - 125.00% as suggested by regulatory requirements for bioequivalence assessment In total, 21 subjects experienced 55 AEs during the study, the most frequently reported AE, i.e., headache, accounted for 13 out of the total

  1. A randomized, double-blind study of hydromorphone hydrochloride extended-release tablets versus oxycodone hydrochloride extended-release tablets for cancer pain: efficacy and safety in Japanese cancer patients (EXHEAL: a Phase III study of EXtended-release HydromorphonE for cAncer pain reLief

    Directory of Open Access Journals (Sweden)

    Inoue S

    2017-08-01

    Full Text Available Satoshi Inoue,1 Yoji Saito,2 Satoru Tsuneto,3 Etsuko Aruga,4 Azusa Ide,1 Yasuyuki Kakurai5 1Clinical Development Department, R&D Division, Daiichi Sankyo, Tokyo,2Department of Anesthesiology, Faculty of Medicine, Shimane University, Shimane, 3Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, 4Department of Palliative Medicine, School of Medicine, Teikyo University, Tokyo, 5Biostatistics and Data Management Department, R&D Division, Daiichi Sankyo, Tokyo, Japan Background: In Japan, there are limited options for switching opioid analgesics. Hydromorphone is an opioid analgesic that is routinely used instead of morphine for cancer pain; however, it is not yet available in Japan. The aim of this study was to assess the efficacy and safety of hydromorphone (DS-7113b extended-release tablets in opioid-naïve patients with cancer pain not relieved by non-opioid analgesics.Subjects and methods: This was a multicenter, randomized, double-blind, parallel-group trial. A double-dummy method was used for blinding. Each randomized subject received either hydromorphone extended-release tablets plus placebo oxycodone hydrochloride extended-release tablets 4 mg/day (n=88 or placebo hydromorphone extended-release tablets plus oxycodone hydrochloride extended-release tablets 10 mg/day (n=93 orally for 7 days (once-daily dosing for hydromorphone and twice-daily dosing for oxycodone. The doses were adjusted as necessary. Efficacy was evaluated by change in visual analog scale (VAS score from baseline to completion of treatment.Results: The between-group difference in least squares mean changes in VAS score from baseline to completion or discontinuation of treatment was −0.4 mm (95% CI −5.9 to 5 mm by analysis of covariance where the baseline VAS score was used as a covariate. The upper limit of the 95% CI was below 10 mm, which was predefined as the noninferiority limit. This verified the noninferiority of hydromorphone tablets

  2. Diclofenac transdermal patch versus the sustained release tablet: A ...

    African Journals Online (AJOL)

    polyvinyl pyrrolidone K30, with turpentine oil and sesame oil as penetration enhancers. ... therapeutic advantages over conventional oral tablets in terms of prolonged release and improvement of ..... is simple to adopt and cost-effective. In this ...

  3. The effect of post-conditioning exposure to morphine on the retention of a morphine-induced conditioned taste aversion.

    Science.gov (United States)

    Jacobs, W J; Zellner, D A; LoLordo, V M; Riley, A L

    1981-06-01

    In the following experiment, multiple injections of morphine sulfate following the acquisition of a morphine-induced taste aversion had no effect on the retention of the previously acquired aversion. Post-conditioning injections of morphine resulted in the development of physical dependence to morphine and led to a decrement in the ability of morphine to induce a subsequent aversion to a second novel taste. This failure of post-conditioning exposures to morphine to affect a previously acquired morphine-induced taste aversion even though tolerance to morphine had occurred was discussed in the context of Rescorla's event-memory model of conditioning.

  4. Study of drug release and tablet characteristics of silicone adhesive matrix tablets.

    Science.gov (United States)

    Tolia, Gaurav; Li, S Kevin

    2012-11-01

    Matrix tablets of a model drug acetaminophen (APAP) were prepared using a highly compressible low glass transition temperature (T(g)) polymer silicone pressure sensitive adhesive (PSA) at various binary mixtures of silicone PSA/APAP ratios. Matrix tablets of a rigid high T(g) matrix forming polymer ethyl cellulose (EC) were the reference for comparison. Drug release study was carried out using USP Apparatus 1 (basket), and the relationship between the release kinetic parameters of APAP and polymer/APAP ratio was determined to estimate the excipient percolation threshold. The critical points attributed to both silicone PSA and EC tablet percolation thresholds were found to be between 2.5% and 5% w/w. For silicone PSA tablets, satisfactory mechanical properties were obtained above the polymer percolation threshold; no cracking or chipping of the tablet was observed above this threshold. Rigid EC APAP tablets showed low tensile strength and high friability. These results suggest that silicone PSA could eliminate issues related to drug compressibility in the formulation of directly compressed oral controlled release tablets of poorly compressible drug powder such as APAP. No routinely used excipients such as binders, granulating agents, glidants, or lubricants were required for making an acceptable tablet matrix of APAP using silicone PSA. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Amnesia induced by morphine in spatial memory retrieval inhibited in morphine-sensitized rats.

    Science.gov (United States)

    Farahmandfar, Maryam; Naghdi, Nasser; Karimian, Seyed Morteza; Kadivar, Mehdi; Zarrindast, Mohammad-Reza

    2012-05-15

    The present study investigated the effect of morphine sensitization on the impairment of spatial memory retrieval induced by acute morphine in adult male rats. Spatial memory was assessed by 2-day Morris water maze task which included training and test day. On the training day, rats were trained by a single training session of 8 trials. On the test day, a probe trial consisting of 60s free swim period without a platform and the visible test were administered. Morphine sensitization was induced by subcutaneous (s.c.) injection of morphine, once daily for 3 days followed by 5 days without drug treatment before training. The results indicated that acute administration of morphine (7.5mg/kg, s.c.) before testing impaired spatial memory on the test day. Pre-test morphine-induced amnesia decreased in morphine-sensitized (15 and 20mg/kg, s.c.) rats. Improvement in spatial memory retrieval in morphine-sensitized rats was inhibited by once daily administration of naloxone (1 and 2mg/kg, s.c.) 30 min prior to the injection of morphine for three days. The results suggest that morphine sensitization reverses the impairment of spatial memory retrieval induced by acute morphine and it is implied that mu-opioid receptors may play an important role in this effect. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Orthostatic hypotension during postoperative continuous thoracic epidural bupivacaine-morphine in patients undergoing abdominal surgery

    DEFF Research Database (Denmark)

    Crawford, M E; Møiniche, S; Orbæk, Janne

    1996-01-01

    Fifty patients undergoing colonic surgery received combined thoracic epidural and general anesthesia followed by continuous epidural bupivacaine 0.25% and morphine 0.05 mg/mL, 4 mL/h, for 96 h postoperatively plus oral tenoxicam 20 mg daily. Heart rate (HR) and arterial blood pressure (BP) were...... hypotension. The results suggest that patients undergoing abdominal surgery and treated with continuous small-dose thoracic epidural bupivacaine-morphine are subjected to a decrease of BP at rest and during mobilization, but not to an extent that seriously impairs ambulation in most patients....

  7. 21 CFR 520.1380 - Methocarbamol tablets.

    Science.gov (United States)

    2010-04-01

    ... 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...) Conditions of use. (1) The drug is administered to dogs and cats as an adjunct to therapy for acute...

  8. 21 CFR 520.804 - Enalapril tablets.

    Science.gov (United States)

    2010-04-01

    ... 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 § 520.804 Enalapril tablets. (a...). Enalapril maleate is administered as conjunctive therapy with furosemide and digoxin in the treatment of...

  9. Pharmacology of morphine and morphine-3-glucuronide at opioid, excitatory amino acid, GABA and glycine binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Bartlett, S.E.; Smith, M.T. (Department of Pharmacy, The University of Queensland (Australia)); Dood, P.R. (Clinical Research Centre, Royal Brisbane Hospital Foundation, Brisbane (Australia))

    1994-07-01

    Morphine in high doses and its major metabolite, morphine-3-glucuronide, cause CNS excitation following intrathecal and intracerebroventricular administration by an unknown mechanism. This study investigated whether morphine and morphine-3-glucuronide interact at major excitatory (glutamate), major inhibitory (GABA or glycine), or opioid binding sites. Homogenate binding assays were performed using specific radioligands. At opioid receptors, morphine-3-glucuronide and morphine caused an equipotent sodium shift, consistent with morphine-3-glucuronide behaving as an agonist. This suggests that morphine-3-glucuronide-mediated excitation is not caused by an interaction at opioid receptors. Morphine-3-glucuronide and morphine caused a weak inhibition of the binding of [sup 3]H-MK801 (non-competitive antagonist) and [sup 125]I-ifenprodil (polyamine site antagonist), but at unphysiologically high concentrations. This suggests that CNS excitation would not result from an interaction of morphine-3-glucuronide and high-dose morphine with these sites on the NMDA receptor. Morphine-3-glucuronide and morphine inhibited the binding of [sup 3]H-muscimol (GABA receptor agonist), [sup 3]H-diazepam and [sup 3]H-flunitraxepam (benzodiazepine agonists) binding very weakly, suggesting the excitatory effects of morphine-3-glucuronide and high-dose morphine are not elicited through GABA[sub A] receptors. Morphine-3-glucuronide and high-dose morphine did not prevent re-uptake of glutamate into presynaptic nerve terminals. In addition, morphine-3-glucuronide and morphine did not inhibit the binding of [sup 3]H-strychnine (glycine receptor antagonist) to synaptic membranes prepared from bovine spinal cord. It is concluded that excitation caused by high-dose morphine and morphine-3-glucuronide is not mediated by an interaction with postsynaptic amino acid receptors. (au) (30 refs.).

  10. Urinary concentrations of morphine and codeine after consumption of poppy seeds.

    Science.gov (United States)

    Thevis, Mario; Opfermann, Georg; Schänzer, Wilhelm

    2003-01-01

    A quantitative analysis of morphine and codeine in human urine was performed after oral intake of cakes containing commercially available poppy seeds in order to estimate the possibility of positive doping results. Therefore, eight products from different manufacturers (poppy seeds or baking mixtures) and origin were obtained and analyzed by gas chromatography-mass spectrometry for the presence of the alkaloids. One selected batch of poppy seeds was used as an ingredient in a typical cake and was the object of an excretion study with nine volunteers. After application, several urine specimens contained morphine with concentrations higher than 1 microg/mL, and peak values of approximately 10.0 microg/mL were detected. Because the International Olympic Committee set a cutoff limit for morphine at 1 microg/mL, high-performance athletes could possibly test positive in doping control after consumption of products containing poppy seeds.

  11. The Combination of Mitragynine and Morphine Prevents the Development of Morphine Tolerance in Mice

    Directory of Open Access Journals (Sweden)

    Sharida Fakurazi

    2013-01-01

    Full Text Available Mitragynine (MG is the major active alkaloid found in Mitragyna speciosa Korth. In the present study, we investigated the enhancement of analgesic action of MG when combined with morphine and the effect of the combination on the development of tolerance towards morphine. Mice were administered intraperitoneally with a dose of MG (15 and 25 mg/kg b.wt combined with morphine (5 mg/kg b.wt respectively for 9 days. The antinociceptive effect was evaluated by a hot plate test. The protein expression of cyclic adenosine monophosphate (cAMP and cAMP response element binding (CREB was analyzed by immunoblot. Toxicological parameters especially liver and kidney function tests were assessed after the combination treatment with MG and morphine. The concurrent administration of MG and morphine showed significant (p < 0.05 increase in latency time when compared to morphine alone group and the outstanding analgesic effects in the combination regimens were maintained until day 9. For the protein expression, there was a significant increment of cAMP and CREB levels (p < 0.05 in group treated with 5 mg/kg morphine but there was no significant change of these protein expressions when MG was combined with morphine. There was a significant changes in toxicological parameters of various treated groups. The combination treatment of MG and morphine effectively reduce the tolerance due to the chronic administration of morphine.

  12. A Single-Dose, Single-Period Pharmacokinetic Assessment of an Extended-Release Orally Disintegrating Tablet of Methylphenidate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Childress, Ann; Newcorn, Jeffrey; Stark, Jeffrey G; McMahen, Russ; Tengler, Mark; Sikes, Carolyn

    2016-08-01

    To determine the pharmacokinetic (PK) profile of a proprietary formulation of methylphenidate (MPH) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in a phase 1 study. Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) combine two technologies in a single-tablet formulation-an extended-release profile that was designed for once-daily dosing in an ODT that does not require water or chewing for ingestion. This was a single-dose, open-label, single-period, single-treatment study, in which 32 children with ADHD who were receiving MPH in doses of 40 or 60 mg before beginning the study each received a 60-mg dose (2 × 30 mg) of MPH XR-ODT. The following plasma PK parameters of MPH were determined for participants grouped by age (6-7, 8-9, 10-12, and 13-17 years old): maximum concentration (Cmax), time to maximum concentration (Tmax), elimination half-life (T½), area under the curve from 0 hours to infinity (AUCinf), oral clearance (CL/F), and volume of distribution in the terminal phase (Vz/F). Safety and tolerability were also assessed. A total of 32 participants received the study drug. For all participants, plasma concentration-time profiles of MPH exhibited a broad peak after administration of MPH XR-ODT through ∼8 hours, indicating extended release from the formulation, followed by an apparent first-order elimination phase. As age increased, MPH exposure decreased and mean estimates of CL/F increased; however, weight-normalized CL/F values were comparable across age groups. Similarly, mean estimates of Vz/F increased with age, but weight-normalization decreased differences across age groups, with the exception of the youngest age group, which had higher values. All adverse events (AEs) were mild. This XR-ODT formulation of MPH demonstrated weight-normalized clearance rates that were consistent across all age groups, a PK profile consistent with once-daily dosing, and an AE profile consistent with

  13. Comparison of efficacy of intra-articular morphine and steroid in patients with knee osteoarthritis

    Directory of Open Access Journals (Sweden)

    Serbülent Gökhan Beyaz

    2012-01-01

    Full Text Available Introduction: Primary therapeutic aim in treatment of osteoarthritis of the knee is to relieve the pain of osteoarthritis. The aim of this study was to compare the efficacy of intra-articular triamcinolone with intra-articular morphine in pain relief due to osteoarthritis of the knee in the elderly population. Materials and Methods: Patients between 50 and 80 years of age were randomized into three groups. Group M received morphine plus bupivacaine intra-articularly, Group T received triamcinolone plus bupivacaine intra-articularly, and Group C received saline plus bupivacaine intra-articularly. Patients were evaluated before injection and in 2nd, 4th, 6th, and 12th weeks after injection. First-line supplementary analgesic was oral paracetamol 1500 mg/day. If analgesia was insufficient with paracetamol, oral dexketoprofen trometamol 50 mg/day was recommended to patients. Results: After the intra-articular injection, there was statistically significant decrease in visual analog scale (VAS scores in Groups M and T, when compared to Group C. The decrease of VAS scores seen at the first 2 weeks continued steadily up to the end of 12th week. There was a significant decrease in Groups M and T in the WOMAC scores, when compared to Group C. There was no significant difference in the WOMAC scores between morphine and steroid groups. Significantly less supplementary analgesics was used in the morphine and steroid groups. Conclusion: Intra-articular morphine was as effective as intra-articular triamcinolone for analgesia in patients with osteoarthritis knee. Intra-articular morphine is possibly a better option than intra-articular steroid as it has lesser side effects.

  14. Phenobarbital versus morphine in the management of neonatal abstinence syndrome, a randomized control trial.

    Science.gov (United States)

    Nayeri, Fatemeh; Sheikh, Mahdi; Kalani, Majid; Niknafs, Pedram; Shariat, Mamak; Dalili, Hosein; Dehpour, Ahmad-Reza

    2015-05-15

    Evaluating the efficacy of the loading and tapering dose of Phenobarbital versus oral Morphine in the management of NAS. This randomized, open-label, controlled trial was conducted on 60 neonates born to illicit drugs dependent mothers at Vali-Asr and Akbar-Abadi hospitals, Tehran, Iran, who exhibited NAS requiring medical therapy. The neonates were randomized to receive either: Oral Morphine Sulfate or a loading dose of Phenobarbital followed by a tapering dose. The duration of treatment required for NAS resolution, the total hospital stay and the requirement for additional second line treatment were compared between the treatment groups. The Mean ± Standard Deviation for the duration of treatment required for the resolution of NAS was 8.5 ± 5 days in the Morphine group and 8.5 ± 4 days in the Phenobarbital group (P = 0.9). The duration of total hospital stay was 12.6 ± 5.6 days in the Morphine group and 12.5 ± 5.3 days in the Phenobarbital group (P = 0.7). 3.3 % in the Morphine group versus 6.6 % in the Phenobarbital group required adjunctive treatment (P = 0.5). There were no significant differences in the duration of treatment, duration of hospital stay, and the requirement for adjunctive treatment, between the neonates with NAS who received Morphine Sulfate and neonates who received a loading and tapering dose of Phenobarbital. This study is registered at the Iranian Registry of Clinical Trials ( www.irct.ir ) which is a Primary Registry in the WHO Registry Network. (Registration Number =  IRCT201406239568N8 ).

  15. Effects of chronic morphine and morphine withdrawal on gene expression in rat peripheral blood mononuclear cells.

    OpenAIRE

    Desjardins , Stephane; Belkai , Emilie; Crete , Dominique; Cordonnier , Laurie; Scherrmann , Jean-Michel; Noble , Florence; Marie-Claire , Cynthia

    2008-01-01

    International audience; Chronic morphine treatment alters gene expression in brain structures. There are increasing evidences showing a correlation, in gene expression modulation, between blood cells and brain in psychological troubles. To test whether gene expression regulation in blood cells could be found in drug addiction, we investigated gene expression profiles in peripheral blood mononuclear (PBMC) cells of saline and morphine-treated rats. In rats chronically treated with morphine, th...

  16. Influence of renal function on the elimination of morphine and morphine glucuronides

    DEFF Research Database (Denmark)

    Wolff, Jesper; Bigler, Dennis Richard; Christensen, C B

    1988-01-01

    plasma. No significant correlation was found between total body clearance of unconjugated morphine and 51Cr-EDTA clearance. However, patients with renal insufficiency had impaired elimination of morphine glucuronides, and the apparent clearance was significantly correlated with the 51Cr-EDTA clearance (r...... = 0.94, p less than 0.001). A relatively long terminal elimination of half-life of morphine was found in all patients (mean +/- SD: 9.2 +/- 2.5 h), irrespective of glomerular function....

  17. Effect of environmental enrichment on physical and psychological dependence signs and voluntary morphine consumption in morphine-dependent and morphine-withdrawn rats.

    Science.gov (United States)

    Hammami-Abrand Abadi, Arezoo; Miladi-Gorji, Hossein; Bigdeli, Imanollah

    2016-04-01

    This study was designed to examine the effect of environmental enrichment during morphine dependency and withdrawal on the severity of naloxone-precipitated withdrawal signs, anxiety, and depressive-like behaviors and voluntary morphine consumption in morphine-dependent rats. The rats were injected with bi-daily doses (10 mg/kg, 12 h intervals) of morphine for 14 days following rearing in a standard environment (SE) or enriched environment (EE) during the development of morphine dependence and withdrawal. Then, rats were tested for withdrawal signs after naloxone injection, anxiety (the elevated plus maze) and depression-related behavior (sucrose preference test), and voluntary consumption of morphine using a two-bottle choice paradigm, in morphine-dependent and morphine-withdrawn rats. The results showed that EE decreased naloxone-precipitated withdrawal signs, but not anxiety or sucrose preference during dependence on morphine. The EE-withdrawn rats showed an increase in the elevated plus maze open arm time and entries and higher levels of sucrose preference than SE rats. Voluntary consumption of morphine was lower in the EE-withdrawn rats than in the SE groups in the second period of drug intake. Thus, exposure to EE reduced the severity of morphine dependence and voluntary consumption of morphine, alongside reductions in anxiety and depression-related behavior in morphine-withdrawn rats.

  18. Morphine

    Science.gov (United States)

    ... difficulty falling asleep or staying asleep; chills; back, muscle, or joint pain; nausea; vomiting; loss of appetite; ... your stomach or intestines; seizures; difficulty swallowing; prostatic hypertrophy (enlargement of a male reproductive gland); urinary problems; ...

  19. [Pain control by continuous infusion of morphine using subarachnoid catheter access to the port--a report of a home death case].

    Science.gov (United States)

    Kawagoe, Koh; Matsuura, Shinobu

    2008-12-01

    This is a case of a 50s male with cecal cancer suffering from severe pain caused by osteolytic metastasis to the lumbar vertebra, right iliac bone, and the head of the right femur. The pain was palliated by continuous infusion of morphine using a subarachnoid catheter that had access to the subcutaneous "Port". The maximum dose of morphine used a day was 384 mg, which corresponded to 57,600 mg/day of oral morphine. Sixty eight days after the start of home hospice care, the patient died at home because of diffuse peritonitis caused by intestinal rupture.

  20. The effect of morphine on biliary dynamics

    International Nuclear Information System (INIS)

    Pedersen, S.A.; Oester-Joergensen, E.; Kraglund, K.

    1987-01-01

    The effect of morphine on biliary dynamics was studied by cholescintigraphy with 99m Tc-HIDA. Among 30 normals without morphine injection 3 did not demonstrate intestinal radioactivity after 1 h, whereas all visualized the gallbladder. Eight normals with morphine injection did not demonstrate intestinal radioactivity after 2 h, but all had gallbladder visualization very early. Variables of the time-activity curves from liver areas did not point to impaired uptake or excretion. Morphine-induced increase in resistance to passage from the common duct to the intestines in normals is of a magnitude that forces the total amount of bile to accumulate in the gallbladder. Results from 11 patients after cholecystectomy indicate that the increase in pressure is less than the maximal secretory pressure of the liver. The resorptive capacity and the compliance of the gallbladder enable these events to take place without signs of secondary liver impairment

  1. Morphine Induces Splenocyte Trafficking into the CNS

    OpenAIRE

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

    2011-01-01

    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 th...

  2. Neural mechanisms underlying morphine withdrawal in addicted patients: a review

    Directory of Open Access Journals (Sweden)

    Nima Babhadiashar

    2015-06-01

    Full Text Available Morphine is one of the most potent alkaloid in opium, which has substantial medical uses and needs and it is the first active principle purified from herbal source. Morphine has commonly been used for relief of moderate to severe pain as it acts directly on the central nervous system; nonetheless, its chronic abuse increases tolerance and physical dependence, which is commonly known as opiate addiction. Morphine withdrawal syndrome is physiological and behavioral symptoms that stem from prolonged exposure to morphine. A majority of brain regions are hypofunctional over prolonged abstinence and acute morphine withdrawal. Furthermore, several neural mechanisms are likely to contribute to morphine withdrawal. The present review summarizes the literature pertaining to neural mechanisms underlying morphine withdrawal. Despite the fact that morphine withdrawal is a complex process, it is suggested that neural mechanisms play key roles in morphine withdrawal.

  3. Pavlovian conditioning analysis of morphine tolerance.

    Science.gov (United States)

    Siegel, S

    1978-01-01

    It has been demonstrated that many conditional responses to a variety of drugs are opposite in direction to the unconditional effects of the drug, and the conditioning analysis of morphine tolerance emphasizes the fact that subjects with a history of morphine administration display morphine-compensatory conditional responses when confronted with the usual administration procedure but without the drug. Thus, when the drug is presented in the context of the usual administration cues, these conditional morphine-compensatory responses would be expected to attenuate the drug-induced unconditional responses, thereby decreasing the observed response to the drug. Research has been summarized which supports this compensatory conditioning model of tolerance by demonstrating that the display of tolerance is specific to the environment in which the drug has been previously administered. Further evidence supporting this theory of tolerance has been provided by studies establishing that extinction, partial reinforcement, and latent inhibition--non-pharmacological manipulations known to be effective in generally affecting the display of conditional responses--similarly affect the display of morphine tolerance. Additional research has suggested many parallels between learning and morphine tolerance: Both processes exhibit great retention, both are disrupted by electroconvulsive shock and frontal cortical stimulation, both are retarded by inhibitors of protein synthesis, and both are facilitated by antagonists of these metabolic inhibitors.

  4. 21 CFR 520.623 - Diethylcarbamazine citrate, oxibendazole chewable tablets.

    Science.gov (United States)

    2010-04-01

    ... tablets. 520.623 Section 520.623 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... dogs—(1) Amount. Administer orally to dogs at a dosage level of 6.6 milligrams of diethylcarbamazine...

  5. Delayed postoperative gastric emptying following intrathecal morphine and intrathecal bupivacaine.

    LENUS (Irish Health Repository)

    Lydon, A M

    2012-02-03

    PURPOSE: A decrease in the rate of gastric emptying can delay resumption of enteral feeding, alter bioavailability of orally administered drugs, and result in larger residual gastric volumes, increasing the risk of nausea and vomiting. We compared the effects of 1) intrathecal bupivacaine (17.5 mg) and 2) the combination of intrathecal morphine (0.6 mg) and intrathecal bupivacaine (17.5 mg) on the rate of gastric emptying in patients undergoing elective hip arthroplasty. METHODS: Twenty four fasting ASA 1-3 patients were randomly assigned, in a double blind manner, to receive intrathecal hyperbaric bupivacaine (17.5 mg), either alone (group 1), or followed by intrathecal morphine (0.6 mg) (group 2). Gastric emptying was measured (using an acetaminophen absorption technique), twice in each patient; preoperatively, and approximately one hour postoperatively. Gastric emptying parameters are: AUC (area under the plasma acetaminophen concentration time curve), maximum plasma acetaminophen concentration (Cmax), and time to Cmax (tCmax), analyzed using paired Student\\'s t tests. RESULTS: Gastric emptying rates were reduced in both group 1 (AUC = 14.98 (3.8) and 11.05 (4.6) pre- and postoperatively, respectively) and group 2 (AUC = 13.93 (3.59) and 6.4 (3.42) pre- and postoperatively, respectively); the magnitude of the reduction was greater in group 2 [AUC (P = 0.04), Cmax (P = 0.05), tCmax (P = 0.13)]. CONCLUSION: The combination of intrathecal morphine (0.6 mg) and intrathecal bupivacaine (17.5 mg) delays gastric emptying postoperatively.

  6. Evaluation of the effect of gabapentin on postoperative analgesia with epidural morphine after abdominal hysterectomy

    Directory of Open Access Journals (Sweden)

    Diptesh Aryal

    2017-07-01

    Full Text Available Background & Objectives: Gabapentin has been used successfully as a non-opioid analgesic adjuvant for postoperative pain management. We hypothesized that the preoperative use of gabapentin prolonged the analgesic effect of epidural morphine without an increase in adverse effects of morphine. Materials & Methods: In a randomized, double blind study sixty ASA PS I and II patients undergoing abdominal hysterectomy were assigned to receive either placebo or gabapentin 1200mg 1 hour before surgery. Postoperatively, 0.125% bupivacaine with morphine 50 µg per kg body weight was used for epidural analgesia. Vital parameters, time to the first request for analgesic, visual analogue scale scoring for pain at rest and during movement, 24-hour morphine consumption, and side effects were studied.Results: The patients were comparable with respect to age, weight, ASA PS, baseline hemodynamic parameters and duration of surgery. Gabapentin significantly decreased the duration of analgesia compared to placebo (1078.26 min Vs. 303.5 min; P value <0.0001. The VAS scores at rest and during movement at 1, 2, 4, 8, 12, and 24h were significantly lower in gabapentin group. The total amount of morphine consumption in 24 h postoperatively was significantly lower in gabapentin group (1.93mg Vs. 6.30mg; P value <0.0001. The incidence of nausea and pruritus was significantly lower with gabapentin. Conclusion: Oral gabapentin 1200 mg as a premedication decreases the dose requirement of epidural morphine and postoperative pain after total abdominal hysterectomy. It also decreases the pain scores at rest and during movement significantly. 

  7. Using Tablet on Education

    Science.gov (United States)

    Algoufi, Rateeba

    2016-01-01

    Technological advancements in digital devices have made educational methodology to adopt new strategies and procedures to suit the Mobile learning era. Mobile devices such as tablets are growing to be the focus of research studies and educational use around the globe in the present day. With the influence of handy computing tablets in the hands of…

  8. Ghost tablet in feces.

    Science.gov (United States)

    Iwamuro, Masaya; Morishita, Yosuke; Urata, Haruo; Okada, Hiroyuki

    2017-12-01

    Recently, we encountered a female patient who identified the presence of a ghost tablet in her fecal matter. Interestingly, although the patient was prescribed potassium chloride capsules, elemental composition analysis by energy-dispersive X-ray spectroscopy was unable to detect the presence of either potassium or chloride in the fecal tablet remnant.

  9. Population Pharmacokinetics of Morphine and Morphine-6-Glucuronide following Rectal Administration

    DEFF Research Database (Denmark)

    Brokjær, Anne; Kreilgaard, Mads; Olesen, Anne Estrup

    2015-01-01

    INTRODUCTION: To safely and effectively administer morphine as liquid formulation via the rectal route, a thorough understanding of the pharmacokinetics is warranted. The aims were: 1) to develop a population pharmacokinetic model of liquid rectal morphine and morphine-6-glucoronide (M6G), 2...... cm from the anal verge. A 2 mg morphine hydrochloride dose was administered intravenously as reference. Blood samples were drawn at baseline and at nine time points post dosing. Serum was obtained by centrifugation and assayed for contents of morphine and M6G with a validated high performance liquid...... chromatographic method. Modelling was performed using NONMEM 7.2 and the first order conditional estimation method with interaction. RESULTS: A two compartment distribution model with one absorption transit compartment for rectal administration and systemic clearance from the central compartment best described...

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

    Science.gov (United States)

    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 (Pmorphine-dependent and withdrawn rats exhibited an increase in EPM open arm time and entries (Pmorphine was less in the swimmer morphine-withdrawn rats than the sedentary groups during four periods of the intake of drug (Pmorphine 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Morphine sparing effect of low dose ketamine during patient ...

    African Journals Online (AJOL)

    Adele

    2003-09-12

    Sep 12, 2003 ... KEY WORDS: Ketamine, morphine sparing effect, patient controlled intravenous analgesia. ... Measurements: Morphine consumption, visual analogue pain score (VAPS), pulse ..... Brain Research, 1990; 518: 218-222. 7.

  12. Repeated morphine treatment influences operant and spatial learning differentially

    Institute of Scientific and Technical Information of China (English)

    Mei-Na WANG; Zhi-Fang DONG; Jun CAO; Lin XU

    2006-01-01

    Objective To investigate whether repeated morphine exposure or prolonged withdrawal could influence operant and spatial learning differentially. Methods Animals were chronically treated with morphine or subjected to morphine withdrawal. Then, they were subjected to two kinds of learning: operant conditioning and spatial learning.Results The acquisition of both simple appetitive and cued operant learning was impaired after repeated morphine treatment. Withdrawal for 5 weeks alleviated the impairments. Single morphine exposure disrupted the retrieval of operant memory but had no effect on rats after 5-week withdrawal. Contrarily, neither chronic morphine exposure nor 5-week withdrawal influenced spatial learning task of the Morris water maze. Nevertheless, the retrieval of spatial memory was impaired by repeated morphine exposure but not by 5-week withdrawal. Conclusion These observations suggest that repeated morphine exposure can influence different types of learning at different aspects, implicating that the formation of opiate addiction may usurp memory mechanisms differentially.

  13. Amorphization within the tablet

    DEFF Research Database (Denmark)

    Doreth, Maria; Hussein, Murtadha Abdul; Priemel, Petra A.

    2017-01-01

    , the feasibility of microwave irradiation to prepare amorphous solid dispersions (glass solutions) in situ was investigated. Indomethacin (IND) and polyvinylpyrrolidone K12 (PVP) were tableted at a 1:2 (w/w) ratio. In order to study the influence of moisture content and energy input on the degree of amorphization......, tablet formulations were stored at different relative humidity (32, 43 and 54% RH) and subsequently microwaved using nine different power-time combinations up to a maximum energy input of 90 kJ. XRPD results showed that up to 80% (w/w) of IND could be amorphized within the tablet. mDSC measurements...

  14. Android tablets for dummies

    CERN Document Server

    Gookin, Dan

    2015-01-01

    Learn all you need to know about your Android tablet in one quick and easy reference! It's not a computer and it's not a smartphone-so what in the world is it? Whether you're new to Android or new to tablets altogether, you're about to experience mobile computing like never before with this fun, full-color guide! Inside, longtime and bestselling author Dan Gookin walks you through setting up your Android tablet, navigating the interface, browsing the web, setting up email, connecting to social media, finding plenty of apps, music, books, and movies to indulge your interests-and so much more.

  15. The role of GABAB receptors in morphine self-administration

    Directory of Open Access Journals (Sweden)

    Effat Ramshini

    2013-01-01

    Full Text Available Background: There is only little information about the effects of GABA receptors agonist and antagonist on morphine self-administration. Present study was designed to assess role of GABAB receptors in the regulation of morphine-reinforced self-administration. Methods: This study was performed in four groups of rats: (1 Saline group, which received saline in the self-administration session. (2 Morphine group, which received morphine in saline solution in the self-administration session. (3 Baclofen + Morphine group, which received both baclofen 20 min before self- administration test and morphine in the self-administration session. (4 Phaclofen + Morphine group, which received both phaclofen 20 min before self- administration test and morphine in the self-administration session. The number of lever pressing and self-infusion were recorded. Results: Morphine significantly increased the number of active lever pressing dose dependently in self-administration session in comparative with saline group. Administration of baclofen, 20 min before morphine self-administration produced significant decrease in the initiation of morphine self-administration during all session. Conversely, pre-treatment of phaclofen increased the number of active lever pressing and self-infusion in this test. Conclusion: Our results indicated a short-term treatment by baclofen, reduced morphine-maintenance response in a dose-dependent manner, suggesting that GABAB receptor agonists could be useful for reversing the neuroadaptations related to opiates.

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

    Science.gov (United States)

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

    2013-09-01

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

  17. Grasp interaction with tablets

    CERN Document Server

    Wolf, Katrin

    2015-01-01

    This book presents guidelines for a future device type: a tablet that allows ergonomic front- and back-of-device interaction. These guidelines help designers and developers of user interfaces to build ergonomic applications for tablet devices, in particular for devices that enable back-of-device interaction. In addition, manufacturers of tablet devices obtain arguments that back-of-device interaction is a promising extension of the interaction design space and results in increased input capabilities, enriched design possibilities, and proven usability. The guidelines are derived from empirical studies and developed to fit the users’ skills to the way the novel device type is held. Three particular research areas that are relevant to develop design guidelines for tablet interaction are investigated: ergonomic gestures, interaction areas, and pointing techniques.

  18. Development of fast disintegrating compressed tablets using amino acid as disintegration accelerator: evaluation of wetting and disintegration of tablet on the basis of surface free energy.

    Science.gov (United States)

    Fukami, Jinichi; Ozawa, Asuka; Yoshihashi, Yasuo; Yonemochi, Etsuo; Terada, Katsuhide

    2005-12-01

    A fast disintegrating compressed tablet was formulated using amino acids, such as L-lysine HCl, L-alanine, glycine and L-tyrosine as disintegration accelerator. The tablets having the hardness of about 4 kgf were prepared and the effect of amino acids on the wetting time and disintegration time in the oral cavity of tablets was examined on the basis of surface free energy of amino acids. The wetting time of the tablets increased in the order of L-lysine HCl, L-alanine, glycine and L-tyrosine, whereas the disintegration time in the oral cavity of the tablets increased in the order of L-alanine, glycine, L-lysine HCl and L-tyrosine. These behaviors were well analyzed by the introduction of surface free energy. When the polar component of amino acid was large value or the dispersion component was small value, faster wetting of tablet was observed. When the dispersion component of amino acid was large value or the dispersion component was small value, faster disintegration of tablet was observed, expect of L-tyrosine tablet. The fast disintegration of tablets was explained by the theory presented by Matsumaru.

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

    Science.gov (United States)

    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. Copyright © 2011 John Wiley & Sons, Ltd.

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

    Directory of Open Access Journals (Sweden)

    Chris Martini

    Full Text Available 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.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.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

  1. Efficacy, Safety, and Feasibility of the Morphine Microdose Method in Community-Based Clinics.

    Science.gov (United States)

    Wilkes, Denise M; Orillosa, Susan J; Hustak, Erik C; Williams, Courtney G; Doulatram, Gulshan R; Solanki, Daneshvari R; Garcia, Eduardo A; Huang, Li-Yen M

    2017-06-13

    The goal of this study was to assess the success of the morphine microdose method in a community pain clinic setting by monitoring follow-up frequency, dose escalation, and monotherapy/polytherapy ratio. The morphine microdose method involves a pretrial reduction or elimination of systemic opioids followed by a period of abstinence. Intrathecal (IT) morphine is then started at doses of less than 0.2 mg per day. Systemic opioid abstinence is then continued after pump implant and IT morphine monotherapy. Retrospective review of medical records. Private and academic pain clinic practices. Chronic noncancer pain patients. We reviewed the charts of 60 patients who had completed a microdose regimen and had an IT pump implanted between June 11, 2008, and October 11, 2014. During IT therapy, dose change over time, pain scores, side effects, max dose, and duration were recorded. The majority of patients (35/60, 58%) were successfully managed solely on morphine microdose monotherapy. These patients did not require additional oral therapy. There was a significant reduction in mean pain scores, from 7.4 ± 0.32 before microdose therapy to 4.8 ± 0.3 after microdose therapy. Microdose therapy achieved analgesia, improved safety, and avoided systemic side effects. The safety of IT therapy was increased by using a lower concentration (2 mg/mL) and lower daily doses (microdose therapy was feasible, safe, and cost-effective in the outpatient setting. 2017 American Academy of Pain Medicine. This work is written by US Government employees and is in the public domain in the US.

  2. 76 FR 51037 - Determination That Halflytely and Bisacodyl Tablets Bowel Prep Kit (Containing Two Bisacodyl...

    Science.gov (United States)

    2011-08-17

    ... determined that Halflytely and Bisacodyl Tablets Bowel Prep Kit (polyethylene glycol (PEG) 3350, sodium... kits containing PEG-3350, sodium chloride, sodium bicarbonate, and potassium chloride for oral solution... that the Agency determine whether Halflytely and Bisacodyl Tablets Bowel Prep Kit (PEG- 3350, sodium...

  3. Feasibility of mini-tablets as a flexible drug delivery tool.

    Science.gov (United States)

    Mitra, Biplob; Chang, Jessica; Wu, Sy-Juen; Wolfe, Chad N; Ternik, Robert L; Gunter, Thomas Z; Victor, Michael C

    2017-06-15

    Mini-tablets have potential applications as a flexible drug delivery tool in addition to their generally perceived use as multi-particulates. That is, mini-tablets could provide flexibility in dose finding studies and/or allow for combination therapies in the clinic. Moreover, mini-tablets with well controlled quality attributes could be a prudent choice for administering solid dosage forms as a single unit or composite of multiple mini-tablets in patient populations with swallowing difficulties (e.g., pediatric and geriatric populations). This work demonstrated drug substance particle size and concentration ranges that achieve acceptable mini-tablet quality attributes for use as a single or composite dosage unit. Immediate release and orally disintegrating mini-tablet formulations with 30μm to 350μm (particle size d 90 ) acetaminophen and Compap™ L (90% acetaminophen) at concentrations equivalent to 6.7% and 26.7% acetaminophen were evaluated. Mini-tablets achieved acceptable weight variability, tensile strength, friability, and disintegration time at a reasonable solid fraction for each formulation. The content uniformity was acceptable for mini-tablets of 6.7% formulations with ≤170μm drug substance, mini-tablets of all 26.7% formulations, and composite dosage units containing five or more mini-tablets of any formulation. Results supported the manufacturing feasibility of quality mini-tablets, and their applicability as a flexible drug delivery tool. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Optimisation of Ondansetron Orally Disintegrating Tablets Using ...

    African Journals Online (AJOL)

    HP

    Methods: Different amounts of two different commercial superdisintegrants commonly used in ODT ... analysed using gene expression programming (GEP) and neuro-fuzzy logic (NFL) models. ..... analyse historical data derived from different.

  5. A new tablet brittleness index.

    Science.gov (United States)

    Gong, Xingchu; Sun, Changquan Calvin

    2015-06-01

    Brittleness is one of the important material properties that influences the success or failure of powder compaction. We have discovered that the reciprocal of diametrical elastic strain at fracture is the most suitable tablet brittleness indices (TBIs) for quantifying brittleness of pharmaceutical tablets. The new strain based TBI is supported by both theoretical considerations and a systematic statistical analysis of friability data. It is sufficiently sensitive to changes in both tablet compositions and compaction parameters. For all tested materials, it correctly shows that tablet brittleness increases with increasing tablet porosity for the same powder. In addition, TBI increases with increasing content of a brittle excipient, lactose monohydrate, in the mixtures with a plastic excipient, microcrystalline cellulose. A probability map for achieving less than 1% tablet friability at various combinations of tablet tensile strength and TBI was constructed. Data from marketed tablets validate this probability map and a TBI value of 150 is recommended as the upper limit for pharmaceutical tablets. This TBI can be calculated from the data routinely obtained during tablet diametrical breaking test, which is commonly performed for assessing tablet mechanical strength. Therefore, it is ready for adoption for quantifying tablet brittleness to guide tablet formulation development since it does not require additional experimental work. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Seaweed tablet: a natural source of iodine

    International Nuclear Information System (INIS)

    Briones, Annabelle V.; Ambal, Wilhelmina O.; Monroyo, Evangelina C.; Bonifacio, Teresita S.; Sison, Fe M.

    1997-01-01

    Species of seaweeds namely: Halymenia durvillaei, Laurencia flexilis and Sargassum gigantifolium were processed into dried form and formulated as tablet. Prior to tablet formulation, the seaweeds were assayed for iodine and trace elements. The seaweeds that exhibited significance values of iodine and trace elements were further analyzed for the presence of heavy metals followed by acute oral toxicity test (LD 50 ). Among the seaweeds evaluated, H. durvilaei was found to contain high level of iodine (0.255% w/w) and magnesium (1.65% w/w) with sufficient amount of zinc (25.69 ppm) and phosporous (11.68 ppm). Analysis of heavy metals showed minute amount of mercury (0.0055 ppm), cadmium (0.67 ppm) and lead (1.80 ppm). The median lethal dose (LD 50 ) of H. durvillaei administered orally in Swiss male mice is 119.1489 ± 4.9873 g/kg. Tablet formulation was based on the U.S. recommended daily allowance of 0.15 mg. of iodine per adult and children. The final product was comparable to imported Kelp pills (available in the local market) in terms of physical properties and iodine content. (Author)

  7. Fast disintegrating tablets: Opportunity in drug delivery system

    Directory of Open Access Journals (Sweden)

    Ved Parkash

    2011-01-01

    Full Text Available 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.

  8. Intrathecal morphine plus general anesthesia in cardiac surgery: effects on pulmonary function, postoperative analgesia, and plasma morphine concentration

    Directory of Open Access Journals (Sweden)

    Luciana Moraes dos Santos

    2009-04-01

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

  9. 21 CFR 520.2260c - Sulfamethazine sustained-release tablets.

    Science.gov (United States)

    2010-04-01

    ... response within 2 to 3 days, reevaluate therapy. Do not crush tablets. Treated animals must not be... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520...

  10. Investigation and analysis of oncologists' knowledge of morphine usage in cancer pain treatment

    Directory of Open Access Journals (Sweden)

    Liu W

    2014-05-01

    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.Keywords: pain management, training, clinical application

  11. Effect of preemptive intra-articular morphine and ketamine on pain after arthroscopic rotator cuff repair: a prospective, double-blind, randomized controlled study.

    Science.gov (United States)

    Khashan, M; Dolkart, O; Amar, E; Chechik, O; Sharfman, Z; Mozes, G; Maman, E; Weinbroum, A A

    2016-02-01

    Rotator cuff tear is a leading etiology of shoulder pain and disability. Surgical treatment is indicated in patients with persistent pain who fail a trial of non-surgical treatment. Pain reduction following rotator cuff repair, particularly within the first 24-48 h, is a major concern to both doctors and patients. This study aimed to compare the postoperative antinociceptive additive effects of pre-incisional intra-articular (IA) ketamine when combined with morphine with two times the dose of morphine or saline. In this prospective, randomized, double blind, controlled trial patients undergoing arthroscopic rotator cuff tear repair (ARCR) under general anesthesia were enrolled. Patients were randomly assigned to one of the three intervention groups. Twenty minutes prior to incision, morphine (20 mg/10 ml), ketamine (50 mg + morphine 10 mg/10 ml), or saline (0.9 % 10 ml) (n = 15/group), were administered to all patients. First 24 h postoperative analgesia consisted of intravenous patient controlled analgesia (IV-PCA) morphine and oral rescue paracetamol 1000 mg or oxycodone 5 mg. 24-h, 2-week and 3-month patient rated pain numeric rating scale (NRS) and analgesics consumption were documented. Patients' demographic and perioperative data were similar among all groups. The 24-h and the 2-week NRSs were significantly (p pain in the first 2 weeks after arthroscopic rotator cuff repair. Further research is warranted to elucidate the optimal timing and dosing of IA ketamine and morphine for postoperative analgesic effects.

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

    Science.gov (United States)

    Skaftason, Jóhannes F; Jóhannesson, Thorkell

    2013-04-01

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

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

    Science.gov (United States)

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

    2014-09-01

    Aloe vera is a medicinal herb used as an anti-inflammatory and sedative agent. The current study aimed to evaluate the effect of Aloe vera aqueous extract on morphine withdrawal symptoms in morphine-dependent female rats. 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 E were significantly higher than those of others groups; however, these symptoms in group C were significantly lower than those of the other groups. 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 .

  14. 21 CFR 520.2150a - Stanozolol tablets.

    Science.gov (United States)

    2010-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... 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 large...

  15. 21 CFR 520.2042 - Pyrantel pamoate tablets.

    Science.gov (United States)

    2010-04-01

    ... and Uncinaria stenocephala). (3) Limitations. Administer orally directly or in a small amount of food... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Pyrantel pamoate tablets. 520.2042 Section 520.2042 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

  16. 21 CFR 520.903e - Febantel tablets.

    Science.gov (United States)

    2010-04-01

    ...) Limitations. Do not use in pregnant animals. Consider alternative therapy or use with caution in animals with... 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 § 520.903e Febantel tablets. (a...

  17. Opiate and non-opiate aspects of morphine induced seizures.

    Science.gov (United States)

    Frenk, H; Liban, A; Balamuth, R; Urca, G

    1982-12-16

    The intraperitoneal administration of morphine hydrochloride at doses of 300 mg/kg produced analgesia, catalepsy, and electrographic spiking in rats that developed into electrographic seizure patterns after approximately 2.5 h. Whereas naltrexone (12 mg/kg) reversed analgesia and catalepsy, and diminished electrographic spiking, it precipitated electrographic seizure activity similar to that observed following intraperitoneal morphine alone. These seizures were accompanied by behavioral convulsions. No tolerance to these seizures developed with repeated paired administration of morphine and naltrexone or in morphine tolerant rats, but rather potentiation was observed. The epileptogenic effects were found to be potentiated in amygdaloid kindled rats, as well. It was concluded that morphine at these doses activates two different epileptogenic mechanisms, one mediated by opiate receptors, the other not. The possibility of the simultaneous activation of a morphine sensitive anticonvulsant mechanism is discussed.

  18. The Neurodevelopmental Impact of Neonatal Morphine Administration

    Directory of Open Access Journals (Sweden)

    Stephanie Attarian

    2014-04-01

    Full Text Available 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.

  19. Teach yourself visually Fire tablets

    CERN Document Server

    Marmel, Elaine

    2014-01-01

    Expert visual guidance to getting the most out of your Fire tablet Teach Yourself VISUALLY Fire Tablets is the comprehensive guide to getting the most out of your new Fire tablet. Learn to find and read new bestsellers through the Kindle app, browse the app store to find top games, surf the web, send e-mail, shop online, and much more! With expert guidance laid out in a highly visual style, this book is perfect for those new to the Fire tablet, providing all the information you need to get the most out of your device. Abundant screenshots of the Fire tablet graphically rich, touch-based Androi

  20. The Nebusarsekim Tablet

    NARCIS (Netherlands)

    Stadhouders, H.A.I.

    2008-01-01

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

  1. Radioactive labelling of alkaloids with morphine skeleton

    International Nuclear Information System (INIS)

    Toth, Geza; Sirokman, Ferenc

    1985-01-01

    Results achieved by the sup(14)C, sup(125)I and sup(3)H labelling of alkaloids with morphine skeleton for kinetic, receptor, metabolims and pharmacological investigations are summarized and evaluated. The methods for the preparation of sup(3)H labelled dihydromorphine, dihydroethylmorphine, dihydrocodeine, naloxone and naloxazone are described. The compounds have higher specific molar activity than those referred to in literature which makes them suitable for a number of investigations. (author)

  2. Metabolism and pharmacokinetics of morphine in neonates: A review

    Directory of Open Access Journals (Sweden)

    Gian Maria Pacifici

    Full Text Available Morphine is an agonist of the µ and k receptors, whose activation results in analgesia. Morphine-like agonists act through the µ opioid receptors to cause pain relief, sedation, euphoria and respiratory depression. Morphine is glucuronidated and sulfated at positions 3 and 6; the plasma concentration ratios correlate positively with birth weight, which probably reflects increased liver weight with increasing birth weight. Moreover, morphine clearance correlates positively with gestational age and birth weight. Steady-state morphine plasma concentrations are achieved after 24-48 hours of infusion, but the glucuronide metabolite plasma concentrations do not reach steady state before 60 hours. The morphine-3-glucuronide metabolite has lower clearance, a shorter half-life and a smaller distribution volume compared with the morphine-6 metabolite, which is the most active morphine-like agonist. Ordinary doses cause constipation, urinary retention and respiratory depression. Neonatal pain relief may require a blood level of approximately 120 ng/ml, whereas lower levels (20-40 ng/ml seem adequate for children. A bibliographic search was performed using the PubMed database and the keywords “morphine metabolism neonate” and “morphine pharmacokinetics neonate”. The initial and final cutoff points were January 1990 and September 2015, respectively. The results indicate that morphine is extensively glucuronidated and sulfated at positions 3 and 6, and that the glucuronidation rate is lower in younger neonates compared with older infants. Although much is known about morphine in neonates, further research will be required to ensure that recommended therapeutic doses for analgesia in neonates are evidence based.

  3. Usefulness of MR cholangiopancreatography after intravenous morphine administration

    International Nuclear Information System (INIS)

    Lee, So Jung; Ko, Ji Ho; Cho, Young Duk; Jung, Mi Hee; Yoon, Byung Chull

    2007-01-01

    We wanted to assess the usefulness of MRCP after intravenous morphine administration in the evaluation of the hepatopancreatic pancreatico-biliary ductal system. We studied 15 patients who were suspected of having disease of hepatopancreatic ductal system and they did not have any obstructive lesion on ultrasonography and/or CT. MRCP was acquired before and after morphine administration (0.04 mg/kg, intravenously). Three radiologists scored the quality of the images of the anatomic structures in the hepatopancreatic ductal system. We directly compared the quality of the images obtained with using the two methods and the improvement of the artifacts by pulsatile vascular compression. The MRCP images obtained after intravenous morphine administration were better than those obtained before morphine administration for visualizing the hepatopancreatic ductal system. On direct comparison, the MRCP images obtained after morphine administration were better in 12 cases, equivocal in two cases, and the images before morphine administration were better in only one case. In three patients, MRCP before morphine injection showed signal loss at the duct across the pulsatile hepatic artery. In two of three patients, MRCP after morphine injection showed no signal loss in this ductal area. MRCP after intravenous morphine administration enables physicians to see the hepatopancreatic ductal system significantly better and the artifacts caused by pulsation of the hepatic artery can be avoided

  4. A review of morphine and morphine-6-glucuronide's pharmacokinetic-pharmacodynamic relationships in experimental and clinical pain

    DEFF Research Database (Denmark)

    Sverrisdóttir, Eva; Lund, Trine Meldgaard; Olesen, Anne Estrup

    2015-01-01

    Morphine is a widely used opioid for treatment of moderate to severe pain, but large interindividual variability in patient response and no clear guidance on how to optimise morphine dosage regimen complicates treatment strategy for clinicians. Population pharmacokinetic-pharmacodynamic models can...... a detailed overview of the published human population pharmacokinetic-pharmacodynamic studies for morphine analgesia in addition to basic drug disposition and pharmacological properties of morphine and its analgesic active metabolite, morphine-6-glucuronide, that may help identify future covariates....... Furthermore, based on simulations from key pharmacokinetic-pharmacodynamic models, the contribution of morphine-6-glucuronide to the analgesic response in patients with renal insufficiency was investigated. Simulations were also used to examine the impact of effect-site equilibration half-life on time course...

  5. Central neuraxial opioid analgesia after caesarean section: comparison of epidural diamorphine and intrathecal morphine.

    Science.gov (United States)

    Caranza, R; Jeyapalan, I; Buggy, D J

    1999-04-01

    In a prospective, randomized, double-blind study in 55 women undergoing elective caesarean section under spinal anaesthesia, we compared epidural diamorphine 3 mg (2 distinct boluses, group ED) with single-dose intrathecal morphine 0.2 mg (group SM), in terms of analgesic efficacy, patient satisfaction and side-effects at 2, 3, 4, 8, 12, 16, 24 and 28 h postoperatively. There were no significant differences between groups in pain (assessed by 100 mm visual analogue scale), incidence of pruritus, sedation or respiratory depression measured by continuous pulse oximetry. However, time to first request for supplementary oral analgesia was longer in SM than in ED (mean +/- SD: 22.3+/-12.0 h vs. 13.8+/-6.5 h, P=0.04). The incidence of nausea or vomiting was significantly higher in SM than ED (73% vs. 41%, P=0.01). In ED, the mean +/- SD time to requirement of the second bolus was 6.7+/-3.2 h. There was a high level of satisfaction in both groups. We conclude that two boluses of epidural diamorphine 3 mg and single-dose intrathecal morphine 0.2 mg provide satisfactory analgesia after caesarean section, but spinal morphine was associated with both delayed requirement for supplementary analgesia and a higher incidence of nausea and vomiting.

  6. Bioavailability and stability of erythromycin delayed release tablets.

    Science.gov (United States)

    Ogwal, S; Xide, T U

    2001-12-01

    Erythromycin is available as the free base, ethylsuccinate, estolate, stearate, gluceptate, and lactobionate derivatives. When given orally erythromycin and its derivatives except the estolate are inactivated to some extent by the gastric acid and poor absorption may result. To establish whether delayed release erythromycin tablets meet the bioequivalent requirement for the market. Sectrophotometric analysis was used to determine the dissolution percentage of the tablets in vitro. High performance liquid chromatography and IBM/XT microcomputer was used to determine the bioavailability and pharmacokinetic parameters in vivo. Dissolution percentage in thirty minutes reached 28.9% and in sixty minutes erythromycin was completely released. The parameters of the delayed release tablets were Tlag 2.3 hr, Tmax.4.5 hr, and Cmax 2.123 g/ml Ka 0.38048 hr(-1) T (1/2) 1.8 hr, V*C/F 49.721 AUC 12.9155. The relative bioavailability of erythromycin delayed release tablet to erythromycin capsules was 105.31% The content, appearance, and dissolution bioavailability of delayed release erythromycin tablets conforms to the United States pharmacopoeia standards. The tablets should be stored in a cool and dry place in airtight containers and the shelf life is temporarily assigned two years.

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

    Science.gov (United States)

    Mohamad Zen, Nur Izzati; Shamsudin, Rosnah

    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

  8. Comparison of Morphine, Morphine-Lidocaine, and Morphine-Lidocaine-Ketamine Infusions in Dogs Using an Incision-Induced Pain Model.

    Science.gov (United States)

    Chiavaccini, Ludovica; Claude, Andrew K; Meyer, Robert E

    We aimed to compare antinociceptive effects of IV infusions of morphine (M), morphine-lidocaine (ML), or morphine-lidocaine-ketamine (MLK) combined, in a mild-to-moderate pain model in dogs. Eighteen adult hounds were heavily sedated with IV morphine (0.2 mg/kg) and dexmedetomidine to undergo thoracic skin incisions. After reversal, dogs were randomly assigned to receive loading doses of lidocaine and ketamine (MLK), lidocaine and saline (ML), or equivalent volume of saline (M), followed by 18 hr constant infusions of morphine (0.12 mg/kg/hr), lidocaine (3 mg/kg/hr) and ketamine (0.6 mg/kg/hr); morphine (0.12 mg/kg/hr) and lidocaine (3 mg/kg/hr); or morphine (0.12 mg/kg/hr), respectively. Pain was assessed with Short Form Glasgow Composite Measure Pain Scale and mechanical nociception with von Frey filaments (VFFS). Data were analyzed with linear mixed model on ranks. Independently of treatment, Short Form Glasgow Composite Measure Pain Scale was significantly higher than baseline for 24 hr (p < .0001), while VFFS was significantly lower than baseline for 48 hr post-recovery (p < .0001), with no difference between MLK and M groups. The ML group recorded significantly lower VFFS (p = .02) than the M group for the entire study. In conclusion, there was no significant analgesic difference between MLK and M alone.

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

    Science.gov (United States)

    Karamese, Mehtap; Akdağ, Osman; Kara, İnci; Yıldıran, Gokce Unal; Tosun, Zekeriya

    2015-01-01

    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. The aim of this study was to examine the use of intrathecal morphine (ITM) in breast reduction surgery with patient-controlled analgesia (PCA). 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. 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. Intrathecal morphine may effectively control pain with lower total morphine consumption following breast reduction surgery.

  10. In vitro evaluation of extemporaneously compounded slow-release capsules containing morphine sulfate or oxycodone hydrochloride.

    Science.gov (United States)

    Glowiak, Dana L; Green, Julie L; Bowman, Bill J

    2005-01-01

    The in vitro performance of extemporaneously compounded morphine sulfate and oxycodone hydrochloride slow-release capsules was evaluated. Capsules containing varying amoutns of morphine sulfate (15, 60, 200 mg) or oxycodone hydrochloride (10, 80, 200 mg) were prepared and provided by a Phoenix, Arizona, pharmacy. The capsules also contained 40% Methocel E4M Premium to slow the release of their active ingredient and sufficient lactose to fill the capsules. Three batches of each capsule strength were prepared, and replicates from each batch were evlauated using United Stated Pharmacopeia dissolution apparatus II. Samples were taken at regular time intervals over 24 hours. After 1 hour the pH of the dissolution medium was adjusted form 1.2 to 4.0, and after 2 hours the pH was adjusted to 6.8. The amount of drug released at each time point was determined spectrophotometrically. The compounded capsules released 14% to 23%, 67% to 85% and 93% to 98% of their active ingredient after 0.5, 4 and 12 hours, respectively. The relative standard deviations between the replicates from each batch were less than 10% for most time points. The percent of drug released over the first 4 hours was linear (r squared = 0.9409-0.9999) when plotted versus time 1/2, indicating adherence to the simplified Higuchi model. Statistical analysis of the Higuchi dissolution constants indicated a significant difference (P less than 0.05) between batch No.3 and the other two batches of 200-mg oxycodone hydrochloride capsules. There was also a statistical difference between most of the Higuchi dissolution constants for the different-strength slow-release capsules and most slow-release capsules and equivalent strength controlled-release manufactured tablets (P less than 0.05). Using 40% Methocel E4M Premium slowed the release of morphine sulfate and oxycodone hydrochloride from extemporaneously compounded capsules. The in vitro performance of the slow-release capsules showed little intrabatch variation

  11. Development and optimization of fluoxetine orally disintegrating ...

    African Journals Online (AJOL)

    Behnken design and has also been manufactured efficiently using direct compression technique. Keywords: Box-Behnken experimental design, Orally disintegrating tablets, Direct compression,. Antidepressant ... production of ODTs [4,5].

  12. Adolescents' struggles with swallowing tablets: barriers, strategies and learning.

    Science.gov (United States)

    Hansen, Dana Lee; Tulinius, Ditte; Hansen, Ebba Holme

    2008-01-01

    To explore adolescents' struggles with taking oral medications. Copenhagen, Denmark. Semi-structured qualitative interviews were conducted with 89 adolescents (33 boys, 56 girls) between the ages of 11 and 20. Adolescents were recruited through four public schools. To identify struggles with taking oral medication, interview transcripts were systematically searched for statements including the terms swallow, chew, crush and eat. Thematic analysis of the identified statements was carried out to reveal dominant themes in the adolescents' accounts. Over one-third of the adolescents spontaneously provided accounts of the difficulties they experienced with taking oral medications, especially with swallowing tablets. Three themes were dominant in their narratives: barriers, strategies and learning. Barriers experienced by the adolescents involved the medications' properties, e.g. taste. Adolescents developed strategies to overcome these barriers, e.g. crushing tablets. Via a process of learning-by-doing and the acquisition of increased experience and autonomy, many adolescents mastered the skill of swallowing tablets. Many adolescents experienced barriers in their attempts to swallow tablets. They developed various strategies to overcome these barriers and gradually mastered taking medicines in a learning-by-doing process.

  13. ORODISPERSIBLE TABLET: A Patient Friendly Dosage Form (a Review

    Directory of Open Access Journals (Sweden)

    C. K. Rameesa

    2015-03-01

    Full Text Available Background: The most common and preferred route of drug administration is through the oral route. Orodispersible tablets are gaining importance among novel oral drug delivery system as they have improved patient compliance and have some additional advantages compared to other formulation. They are also solid unit dosage forms, which disintegrate in the mouth within a minute in the presence of saliva due to superdisintegrants in the formulation. Thus this type of drug delivery helps a proper per oral administration in pediatric and geriatric population where swallowing is a matter of trouble. Various scientists have prepared orodispersible tablets by following various methods. However, the most common method is the direct compression method. Other special methods are Freeze Drying,Tablet Molding, Sublimation, Spray Drying, Mass extrusion, Phase transition process, etc. Since these tablets dissolve directly in the mouth, so, their taste is also an important factor. Various approaches have been taken in order to mask the bitter taste of the drug. A number of scientists have explored several drugs in this field. Like all other solid dosage forms, they are also evaluated in the field of hardness, friability, wetting time, moisture uptake, disintegration test and dissolution test.

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

    Science.gov (United States)

    Leppert, Wojciech; Majkowicz, Mikolaj; Forycka, Maria

    2013-12-01

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

  15. Changing M3G/M6G ratios and pharmacodynamics in a cancer patient during long-term morphine treatment

    DEFF Research Database (Denmark)

    Andersen, Gertrud; Christrup, Lona Louring; Sjøgren, Per

    2002-01-01

    A cancer patient receiving long-term oral sustained-release morphine treatment and periodically presenting with unusually high plasma M3G/M6G ratios is described. We found the patient's formation of M6G more unstable and perhaps delayed compared to the formation of M3G. There is no apparent...... explanation for this phenomenon and the high M3G/M6G ratios had no implications for the patient's pain experience or side effects from the morphine treatment....

  16. Pharmaceutical equivalence of gabapentin tablets with various extragranular binders Pharmaceutical equivalence of gabapentin tablets with various extragranular binders

    Directory of Open Access Journals (Sweden)

    SWATI C. JAGDALE

    2010-06-01

    Full Text Available Gabapentin is a high-dose drug widely used as an oral anti-epilepticagent. Due to high crystalline and has poor compaction properties it is difficult to form tablets by direct compression. The aim of this study was to develop gabapentin tablets, pharmaceutically equivalent to the reference product Neurontin (marketed in USA. Gabapentin 800mg tablets were produced by wet granulation by keeping intragranular binder as well as its concentration constant and by changing with various extragranular binders with its concentration (A = PVPK 30, B = HPMC 15 cps, C = Kollidon VA 64, D =Klucel EXF.The tablet having no weight, thickness and hardness variation and having appropriate, friability as well as disintegration profile were coated with a 3% film coating solution .Seven formulations F1 (A in lower concentration F2 (A in higher concentration, F3 (B in lower concentration and F4 (B in higher concentration, F5 (C in lower concentration, F6 (C in higher concentration, F7 (D in lower concentration were formulated. Among them F6 demonstrated adequate hardness, friability, disintegration, uniformity of content, and total drug dissolution after 45minutes. The dissimilarity factor (f1 is 5.93 and the similarity factor (f2 is 67.85. So F6 was found to be equivalent to Neurontin.Gabapentin is widely used as an oral anti-epileptic agent. However, owing to its high crystallinity and poor compaction properties, it is difficult to form tablets of this drug by direct compression. The aim of this study was to develop gabapentin tablets, pharmaceutically equivalent to the brand-name pioneer product Neurontin® (marketed in USA. Gabapentin 800mg tablets were produced by wet granulation with a constant concentration of intragranular binder and a varying concentration of extragranular binders (A = polyvinylpyrrolidone K30, B = hydroxypropylmethylcellulose 15 cps, C = Kollidon VA64, D =Klucel EXF. The tablets that did not vary in weight, thickness or hardness and had

  17. Epidural morphine for postoperative pain relief in children

    DEFF Research Database (Denmark)

    Henneberg, S W; Hole, P; Haas, Inge Madsen De

    1993-01-01

    the investigation. We observed a change in the sleeping pattern with an increased number of sleep-induced myoclonia during the administration of epidural morphine. In conclusion, the use of epidural morphine in children for postoperative pain relief is very efficient. The minimal effective dose has not been...

  18. Peripheral antinociceptive effects of morphine after burn injury

    DEFF Research Database (Denmark)

    Møiniche, S; Dahl, J B; Kehlet, H

    1993-01-01

    In a double-blind study, 2 mg of morphine in saline, or saline only, was given subcutaneously into a second-degree bilateral leg-burn injury in 12 volunteers. Heat-pain thresholds and pressure-pain thresholds were significantly increased by local morphine administration. These results confirm...

  19. Blood-brain distribution of morphine-6-glucuronide in sheep

    DEFF Research Database (Denmark)

    Villesen, H H; Foster, D J R; Upton, R N

    2006-01-01

    At present there are few data regarding the rate and extent of brain-blood partitioning of the opioid active metabolite of morphine, morphine-6-glucuronide (M6G). In this study the cerebral kinetics of M6G were determined, after a short-term intravenous infusion, in chronically instrumented...

  20. Utilization of prodrugs to enhance the transdermal absorption of morphine

    DEFF Research Database (Denmark)

    Drustrup, J.; Fullerton, A.; Christrup, Lona Louring

    1991-01-01

    . The esters showed generally a higher water and lipid solubility than morphine and were also much more lipophilic than the parent drug in terms of octanol-buffer partition coefficients. Diffusion experiments in vitro using human skin samples showed that whereas morphine did not penetrate the skin to any...

  1. Effect of Potassium Channel Modulators on Morphine Withdrawal in Mice

    Directory of Open Access Journals (Sweden)

    Vikas Seth

    2010-01-01

    Full Text Available The present study was conducted to investigate the effect of potassium channel openers and blockers on morphine withdrawal syndrome. Mice were rendered dependent on morphine by subcutaneous injection of morphine; four hours later, withdrawal was induced by using an opioid antagonist, naloxone. Mice were observed for 30 minutes for the withdrawal signs ie, the characteristic jumping, hyperactivity, urination and diarrhea. ATP-dependent potassium (K + ATP channel modulators were injected intraperitoneally (i.p. 30 minutes before the naloxone. It was found that a K + ATP channel opener, minoxidil (12.5–50 mg/kg i.p., suppressed the morphine withdrawal significantly. On the other hand, the K + ATP channel blocker glibenclamide (12.5–50 mg/kg i.p. caused a significant facilitation of the withdrawal. Glibenclamide was also found to abolish the minoxidil's inhibitory effect on morphine withdrawal. The study concludes that K + ATP channels play an important role in the genesis of morphine withdrawal and K + ATP channel openers could be useful in the management of opioid withdrawal. As morphine opens K + ATP channels in neurons, the channel openers possibly act by mimicking the effects of morphine on neuronal K + currents.

  2. Evaluation of matrix type mucoadhesive tablets containing indomethacin for buccal application.

    Science.gov (United States)

    Ikeuchi-Takahashi, Yuri; Sasatsu, Masanaho; Onishi, Hiraku

    2013-09-10

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are administered for pain relief from oral mucositis. However, the systemic administration of NSAIDs is limited due to systemic side effects. To avoid these side effects and treat local lesions effectively, a matrix type mucoadhesive tablet was developed. A mixture of hard fat, ethylcellulose (EC) and polyethylene glycol (PEG) was used as a matrix base, and indomethacin (IMC) was used as the principal agent. In tablets consisting of hard fat, EC and IMC, the drug release was sustained. In tablets consisting of hard fat, EC, considerable amounts of PEG and IMC, the drug release was relatively increased and IMC existed as the molecular phase or in an amorphous state. The in vitro adhesive force of the tablets consisting of hard fat, EC, considerable amounts of PEG and IMC was significantly increased as compared with the tablets consisting of hard fat and IMC. A significantly high tissue concentration and significantly low plasma concentration were observed after buccal administration of this matrix type mucoadhesive tablet as compared with that after oral administration of IMC. Thus, the matrix type mucoadhesive tablet has good potential as a preparation for the treatment of pain due to oral aphtha. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. 75 FR 13292 - Determination That HalfLytely and Bisacodyl Tablets Bowel Prep Kit (Containing 4 Bisacodyl...

    Science.gov (United States)

    2010-03-19

    ... determined that HALFLYTELY AND BISACODYL TABLETS BOWEL PREP KIT (polyethylene glycol (PEG) 3350, sodium... kits containing PEG-3350, sodium chloride, sodium bicarbonate, and potassium chloride for oral solution... whether HALFLYTELY AND BISACODYL TABLETS BOWEL PREP KIT (PEG-3350, sodium chloride, sodium bicarbonate...

  4. Effect of molecular weight and glass transition on relaxation and release behaviour of poly(DL-lactic acid) tablets

    NARCIS (Netherlands)

    Steendam, R.; Van Steenbergen, M.J.; Hennink, W.E.; Frijlink, H.W.; Lerk, C.F.

    2001-01-01

    Different molecular weight grades of poly(DL-lactic acid) were applied as release controlling excipients in tablets for oral drug administration. The role of molecular weight and glass transition in the mechanism of water-induced volume expansion and drug release of PDLA tablets was investigated.

  5. The Influence of Tablet-Based Technology on the Development of Communication and Critical Thinking Skills: An Interdisciplinary Study

    Science.gov (United States)

    Bagdasarov, Zhanna; Luo, Yupeng; Wu, Wei

    2017-01-01

    The purpose of this interdisciplinary study was to explore the impacts of tablet technology in a college classroom on students' perceptions of their own learning. Students were asked about oral, written, and graphical communication and critical thinking skills. Mid-semester and end-of-semester surveys were administered to tablet-enabled classes…

  6. Effects of chronic morphine and morphine withdrawal on gene expression in rat peripheral blood mononuclear cells.

    Science.gov (United States)

    Desjardins, Stephane; Belkai, Emilie; Crete, Dominique; Cordonnier, Laurie; Scherrmann, Jean-Michel; Noble, Florence; Marie-Claire, Cynthia

    2008-12-01

    Chronic morphine treatment alters gene expression in brain structures. There are increasing evidences showing a correlation, in gene expression modulation, between blood cells and brain in psychological troubles. To test whether gene expression regulation in blood cells could be found in drug addiction, we investigated gene expression profiles in peripheral blood mononuclear (PBMC) cells of saline and morphine-treated rats. In rats chronically treated with morphine, the behavioral signs of spontaneous withdrawal were observed and a withdrawal score was determined. This score enabled to select the time points at which the animals displayed the mildest and strongest withdrawal signs (12 h and 36 h after the last injection). Oligonucleotide arrays were used to assess differential gene expression in the PBMCs and quantitative real-time RT-PCR to validate the modulation of several candidate genes 12 h and 36 h after the last injection. Among the 812 differentially expressed candidates, several genes (Adcy5, Htr2a) and pathways (Map kinases, G-proteins, integrins) have already been described as modulated in the brain of morphine-treated rats. Sixteen out of the twenty-four tested candidates were validated at 12 h, some of them showed a sustained modulation at 36 h while for most of them the modulation evolved as the withdrawal score increased. This study suggests similarities between the gene expression profile in PBMCs and brain of morphine-treated rats. Thus, the searching of correlations between the severity of the withdrawal and the PBMCs gene expression pattern by transcriptional analysis of blood cells could be promising for the study of the mechanisms of addiction.

  7. Epidural morphine for postoperative pain relief in children

    DEFF Research Database (Denmark)

    Henneberg, S W; Hole, P; Haas, Inge Madsen De

    1993-01-01

    Epidural morphine for postoperative pain relief is in general use, and has proved to be very efficient in adults. The epidural technique and the use of epidural morphine are much less frequent in children. For 2 years we have prospectively followed 76 children who had epidural morphine...... for postoperative pain relief after major abdominal surgery. The age distribution was from newborn to 13 years, with a median age of 12 months. It was estimated that 94% of the patients had good analgesia for the first 24 postoperative hours and no other opioids were given. The side effects were few, but one case...... the investigation. We observed a change in the sleeping pattern with an increased number of sleep-induced myoclonia during the administration of epidural morphine. In conclusion, the use of epidural morphine in children for postoperative pain relief is very efficient. The minimal effective dose has not been...

  8. Morphine and Codeine in Biological Fluids: Approaches to Source Differentiation.

    Science.gov (United States)

    ElSohly, M A; Jones, A B

    1989-06-01

    Heroin, morphine, and codeine are among the most abused opiate analgesics today. Analysis of individuals' urines for morphine and codeine is sued as an indication of prior ingestion of these dugs. Poppy seeds and products containing poppy seeds are found to have small amounts of morphine and codeine (usually less than 200 µg morphine/g seeds and much less codeine), which is enough to produce a positive urine test for opiates. This manuscript reviews current data on the analysis of various poppy seed products and urine specimens from individuals ingesting these products. A brief review of the metabolism and elimination of these drugs is presented, with general guidelines for differentiation of poppy seed use versus condone, morphine, or heroin abuse. Copyright © 1989 Central Police University.

  9. Oral calcitonin

    Directory of Open Access Journals (Sweden)

    Hamdy RC

    2012-09-01

    Full Text Available Ronald C Hamdy,1,2 Dane N Daley11Osteoporosis Center, College of Medicine, East Tennessee State University, 2Veterans Affairs Medical Center, Johnson City, TN, USAAbstract: 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 β-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

  10. Improving the hardness of dry granulated tablets containing sodium lauryl sulfate.

    Science.gov (United States)

    Moore, Francis; Okelo, Geoffrey; Colón, Ivelisse; Kushner, Joseph

    2010-11-15

    The impact of the addition of a wetting agent, the surfactant sodium lauryl sulfate (SLS), on the tablet hardness of a dry granulated, solid oral dosage form was investigated. In three batches, SLS was added concurrently with: (1) a poorly soluble, highly hydrophobic active pharmaceutical ingredient (API) and the other excipients prior to the initial blending step, (2) magnesium stearate prior to roller compaction, or (3) magnesium stearate prior to tableting. A fourth batch, which did not contain SLS, served as a control. The maximum hardness of 100 mg, 1/4″-SRC tablets for the four batches--SLS added initially, prior to roller compaction, prior to tableting, and no SLS--were 61±3, 71±3, 89±5, and 86±3N, respectively, suggesting reduced processing of SLS improves tablet hardness by ∼50%. Dissolution of the tablets in 900 ml of simulated gastric fluid with paddles at 75 rpm showed that: (1) there was no impact on the insertion point of SLS into the process on API dissolution, and (2) that the presence of SLS improved dissolution by 5% compared to the control tablets. Adding SLS just prior to tableting can improve tablet hardness and yield similar dissolution performance relative to SLS addition prior to the initial blending step. Copyright © 2010 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2015-07-05

    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. Copyright © 2015. Published by Elsevier B.V.

  12. Attenuation by dextromethorphan on the higher liability to morphine-induced reward, caused by prenatal exposure of morphine in rat offspring

    Directory of Open Access Journals (Sweden)

    Tao Pao-Luh

    2009-11-01

    Full Text Available Abstract Co-administration of dextromethorphan (DM with morphine during pregnancy and throughout lactation has been found to reduce morphine physical dependence and tolerance in rat offspring. No evidence was presented, however, for the effect of DM co-administered with morphine during pregnancy on morphine-induced reward and behavioral sensitization (possibly related to the potential to induce morphine addiction in morphine-exposed offspring. Conditioned place preference and locomotor activity tests revealed that the p60 male offspring of chronic morphine-treated female rats were more vulnerable to morphine-induced reward and behavioral sensitization. The administration of a low dose of morphine (1 mg/kg, i.p. in these male offspring also increased the dopamine and serotonin turnover rates in the nucleus accumbens, which implied that they were more sensitive to morphine. Co-administration of DM with morphine in the dams prevented this adverse effect of morphine in the offspring rats. Thus, DM may possibly have a great potential in the prevention of higher vulnerability to psychological dependence of morphine in the offspring of morphine-addicted mothers.

  13. Neonatal morphine enhances nociception and decreases analgesia in young rats.

    Science.gov (United States)

    Zhang, Guo Hua; Sweitzer, Sarah M

    2008-03-14

    The recognition of the impact of neonatal pain experience on subsequent sensory processing has led to the increased advocacy for the use of opioids for pain relief in infants. However, following long-term opioid exposure in intensive care units more than 48% of infants exhibited behaviors indicative of opioid abstinence syndrome, a developmentally equivalent set of behaviors to opioid withdrawal as seen in adults. Little is known about the long-term influence of repeated neonatal morphine exposure on nociception and analgesia. To investigate this, we examined mechanical and thermal nociception on postnatal days 11, 13, 15, 19, 24, 29, 39 and 48 following subcutaneous administration of morphine (3 mg/kg) once daily on postnatal days 1-9. The cumulative morphine dose-response was assessed on postnatal days 20 and 49, and stress-induced analgesia was assessed on postnatal days 29 and 49. Both basal mechanical and thermal nociception in neonatal, morphine-exposed rats were significantly lower than those in saline-exposed, handled-control rats and naive rats until P29. A rightward-shift of cumulative dose-response curves for morphine analgesia upon chronic neonatal morphine was observed both on P20 and P49. The swim stress-induced analgesia was significantly decreased in neonatal morphine-exposed rats on P29, but not on P49. These data indicate that morphine exposure equivalent to the third trimester of gestation produced prolonged pain hypersensitivity, decreased morphine antinociception, and decreased stress-induced analgesia. The present study illustrates the need to examine the long-term influence of prenatal morphine exposure on pain and analgesia in the human pediatric population.

  14. Impairment of the in vitro Release of Carbamazepine from Tablets

    Directory of Open Access Journals (Sweden)

    Alija Uzunović

    2010-08-01

    Full Text Available Carbamazepine belongs to the class II biopharmaceutical classification system (BCS which is characterized by a high per-oral dose, a low aqueous solubility and a high membrane permeability. The bioavailability of such a drug is limited by the dissolution rate. The present study deals with the formulations of immediate release tablets of poorly soluble carbamazepine. As model tablets for this investigation, two formulations (named “A” and “B” formulations of carbamazepine tablets labeled to contain 200 mg were evaluated. The aim of this study was to establish possible differences in dissolution profile of these two formulations purchased from the local market.The increased crystallinity together with enlarged particle size, enhanced aggregation and decreased wettability of the drug, resulted in insufficient dissolution rate for formulation “B’.’ From the dissolution point of view, this formulation was inferior to the formulation “A, due to the solubilization effect.

  15. A comparative pharmacokinetic study of three flavonoids and three anthraquinones in normal and gastrointestinal motility disorders rat plasma after the oral administration of Wei-Chang-Shu tablet using high-performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Ren, Yan; Zhao, Weiwei; Zhao, Juanjuan; Chen, Xiangming; Yu, Chen; Liu, Mengan

    2017-11-01

    A simple, fast and reliable high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification and pharmacokinetic study of three flavonoids (liquiritigenin, isoliquiritigenin and formononetin) and three anthraquinones (emodin, rhein and aloe-emodin), which are the bioactive ingredients of Wei-Chang-Shu tablet found in rat plasma. After extraction by liquid-liquid extraction with ethyl acetate, chromatographic separation was achieved on an Agilent Zorbax SB-C 18 column (4.6 × 150 mm, 5 μm) at a flow rate of 1 mL/min by gradient elution using 0.1% aqueous acetic acid and acetonitrile. The detection was performed using a triple quadrupole mass spectrometer equipped with electrospray ionization source in the negative ionization and selected reaction monitoring mode. Method validation was performed in terms of specificity, carryover, linearity (r > 0.99), intra-/inter-day precision (1.0-10.1%), accuracy (relative error, <7.6%), stability (0.6-13.2%), extract recovery (74.9-91.9%) and matrix effect (89.1-109%). The lower limits of quantification of the six analytes varied from 0.92 to 10.4 ng/mL. The validated method was successfully applied to compare the pharmacokinetic properties of Wei-Chang-Shu tablet in normal rats and in rats with gastrointestinal motility disorders. The results indicated that there were obvious differences in the pharmacokinetic behavior between normal and model rats. This study will be helpful in the clinical application of Wei-Chang-Shu tablet. Copyright © 2017 John Wiley & Sons, Ltd.

  16. No morphine sparing effect of ketamine added to morphine for patient-controlled intravenous analgesia after uterine artery embolization

    DEFF Research Database (Denmark)

    Jensen, Luana Leonora; Handberg, Gitte; Helbo-Hansen, H S

    2008-01-01

    BACKGROUND: Pain following embolization of the uterine arteries (UAEs) is variable and may be very severe requiring large doses of parenteral opioids for relief. The present study tested the hypothesis that the addition of ketamine to i.v. patient-controlled morphine reduces the amount of morphine...... required for pain-control during the first 24 h after UAE embolization. METHODS: Fifty-six patients undergoing UAE embolization for treatment of symptomatic uterine leiomyomata were randomized to receive either 2 mg/ml of morphine (Control group, n=30) or 2 mg/ml of both morphine and ketamine (Ketamine......, visual disturbances, anxiety, dreaming and hallucinations, if any, were recorded for 24 h after embolization. RESULTS: The mean +/- SD 24-h consumption of patient-controlled morphine was 38.3 +/- 21.0 mg in the Ketamine group vs. 33.3 +/- 18.3 mg in the Control group (NS). The difference between...

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

    Directory of Open Access Journals (Sweden)

    Labib GS

    2015-09-01

    effervescent tablets in an orodispersible dosage form can improve oral drug bioavailability and act as an attractive pediatric dosage form. Keywords: antihistaminic, effervescent tablets, 2-hydroxypropyl-β-cyclodextrin, mannitol, taste masking 

  18. A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol.

    Science.gov (United States)

    Currow, David; Watts, Gareth John; Johnson, Miriam; McDonald, Christine F; Miners, John O; Somogyi, Andrew A; Denehy, Linda; McCaffrey, Nicola; Eckert, Danny J; McCloud, Philip; Louw, Sandra; Lam, Lawrence; Greene, Aine; Fazekas, Belinda; Clark, Katherine C; Fong, Kwun; Agar, Meera R; Joshi, Rohit; Kilbreath, Sharon; Ferreira, Diana; Ekström, Magnus

    2017-07-17

    Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended- release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0-10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. NCT02720822; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Short-term treatment with olanzapine does not modulate gut hormone secretion: olanzapine disintegrating versus standard tablets

    DEFF Research Database (Denmark)

    Vidarsdottir, Solrun; Roelfsema, Ferdinand; Streefland, Trea

    2009-01-01

    BACKGROUND: Treatment with olanzapine (atypical antipsychotic drug) is frequently associated with various metabolic anomalies, including obesity, dyslipidemia, and diabetes mellitus. Recent data suggest that olanzapine orally disintegrating tablets (ODT), which dissolve instantaneously in the mouth...

  20. Tablets i skolen

    DEFF Research Database (Denmark)

    Lorentzen, Rasmus Fink

    2012-01-01

    Denne rapport afslutter CELMS undersøgelse af Odder Kommunes projekt med indførelse af iPads på alle kommunens skoler. Undersøgelsen har til formål at belyse om der er pædagogiske og læringsmæssige fordele forbundet med brugen af tablets i undervisningen i grundskolen og i givet fald hvilke...... designer og tablet’ens egenskaber i et generelt perspektiv. Rapporten afsluttes med en række anbefalinger til henholdsvis lærere og skoleledere med henblik på videre udvikling af indsatsen....

  1. Tabletted guar gum microspheres of piroxicam for targeted adjuvant therapy for colonic adenocarcinomas.

    Science.gov (United States)

    Vats, Anima; Pathak, Kamla

    2012-11-01

    In recent years, nonsteroidal anti-inflammatory drugs have been found to be cogent as an adjuvant therapeutic agent in mitigating colorectal cancer. Thus, this present investigation was aimed to formulate an oral, targeted tablet of piroxicam microspheres for sustained and targeted adjuvant therapy for colonic adenocarcinomas. Crosslinked guar gum microspheres of piroxicam were directly compressed into matrix tablet and coated with Eudragit S100. The optimized tablet that displayed 0% release in simulated gastric fluid, 15% in simulated intestinal fluid and 97.1% in simulated colonic fluid underwent roentgenographic study in rabbits to check its safe transit to the colon. x-ray images revealed intactness of the tablet until it reached the colon where the tablet matrix eroded. The designed, conceptual formulation emerged as potential carrier for targeted adjuvant therapy of piroxicam.

  2. Endogenous cholinergic neurotransmission contributes to behavioral sensitization to morphine.

    Directory of Open Access Journals (Sweden)

    Dusica Bajic

    Full Text Available 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.

  3. Mechanisms of morphine enhancement of spontaneous seizure activity.

    Science.gov (United States)

    Saboory, Ehsan; Derchansky, Miron; Ismaili, Mohammed; Jahromi, Shokrollah S; Brull, Richard; Carlen, Peter L; El Beheiry, Hossam

    2007-12-01

    High-dose opioid therapy can precipitate seizures; however, the mechanism of such a dangerous adverse effect remains poorly understood. The aim of our study was to determine whether the neuroexcitatory activity of high-dose morphine is mediated by selective stimulation of opioid receptors. Mice hippocampi were resected intact and bathed in low magnesium artificial cerebrospinal fluid to induce spontaneous seizure-like events recorded from CA1 neurons. Application of morphine had a biphasic effect on the recorded spontaneous seizure-like events. In a low concentration (10 microM), morphine depressed electrographic seizure activity. Higher morphine concentrations (30 and 100 microM) enhanced seizure activity in an apparent dose-dependent manner. Naloxone, a nonselective opiate antagonist blocked the proconvulsant action of morphine. Selective mu and kappa opiate receptor agonists and antagonists enhanced and suppressed the spontaneous seizure activity, respectively. On the contrary, delta opioid receptor ligands did not have an effect. The proseizure effect of morphine is mediated through selective stimulation of mu and kappa opiate receptors but not the activation of the delta receptor system. The observed dose-dependent mechanism of morphine neuroexcitation underscores careful adjustment and individualized opioid dosing in the clinical setting.

  4. Effect of Morphine Withdrawal Syndrome on Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Mohammad Allahtavakoli

    2011-01-01

    Full Text Available Objective(sOpioid abuse is still remained a major mental health problem, a criminal legal issue and may cause ischemic brain changes including stroke and brain edema. In the present study, we investigated whether spontaneously withdrawal syndrome might affect stroke outcomes.Materials and MethodsAddiction was induced by progressive incremental doses of morphine over 7 days. Behavioral signs of withdrawal were observed 24, 48 and 72 hr after morphine deprivation and total withdrawal score was determined. Cerebral ischemia was induced 18-22 hr after the last morphine injection by placing a natural clot into the middle cerebral artery (MCA. Neurological deficits were evaluated at 2, 24 and 48 hr after ischemia induction, and infarct size and brain edema were determined at 48 hr after stroke.ResultsMorphine withdrawal animals showed a significant increase in total withdrawal score and decrease of weight gain during the 72 hr after the last morphine injection. Compared to the addicted and control animals, infarct volume and brain edema were significantly increased in the morphine deprived animals (P< 0.05 at 48 hr after cerebral ischemia. Also, neurological deficits were higher in the morphine-withdrawn rats at 48 hr after stroke (P< 0.05. ConclusionOur data indicates that spontaneous withdrawal syndrome may worsen stroke outcomes. Further investigations are necessary to elucidate mechanisms of opiate withdrawal syndrome on stroke.

  5. Morphine tolerance offers protection from radiogenic performance deficits

    International Nuclear Information System (INIS)

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

    1983-01-01

    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 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

  6. Development of tablets containing semipurified extract of guaraná (Paullinia cupana

    Directory of Open Access Journals (Sweden)

    Traudi Klein

    2012-12-01

    Full Text Available This study evaluated the technological feasibility of producing a semipurified extract of guaraná (Paullinia cupana Kunth, Sapindaceae in tablet form, using a direct-compression process. Maltodextrin and gum arabic were used to produce the extract microparticles, in order to protect the microparticles against such factors as temperature, oxidation, and humidity. Using pharmacopoeial methodologies, technological and physicochemistry tests (determination of residual moisture, of bulk and tapped density, Hausner ratio, compressibility and compactibility index, appearance, mean weight, hardness, friability, disintegration time, determination of EPA amount in tablets and in vitro release profile were conducted. The formulation containing 200 mg of microparticles, 170 mg microcrystalline cellulose, and 10 mg lactose gave the best results in terms of hardness (116 N, friabilility (0.28%, mean weight (0.3821 g, and disintegration time (25 min for a tablet designed for oral administration. The results met pharmacopoeial specifications, and the tablets are suitable for oral administration.

  7. Effects of environmental enrichment during abstinence in morphine dependent parents on anxiety, depressive-like behaviors and voluntary morphine consumption in rat offspring.

    Science.gov (United States)

    Pooriamehr, Alireza; Sabahi, Parviz; Miladi-Gorji, Hossein

    2017-08-24

    Chronic morphine exposure during puberty increased morphine-induced rewarding effects and sensitization in the next generation. Given the well-known beneficial effects of environmental enrichment on the severity of physical and psychological dependence on morphine, we examined effects of enriched environment during morphine abstinence in morphine dependent parental rats before mating on the anxiety and depressive-like behaviors, and voluntary morphine consumption in their offspring. Paternal and/or maternal rats were injected with bi-daily doses (10mg/kg, 12h intervals) of morphine for 14days followed by rearing in a standard environment (SE) or enriched environment (EE) during 30days of morphine abstinence before mating. The pubertal male and female rat offspring were tested for anxiety (the elevated plus maze- EPM) and depression (sucrose preference test-SPT), and voluntary morphine consumption using a two-bottle choice (TBC) paradigm. The results showed that EE experience in morphine-dependent both parents result in an increase in the percentage of time spent into open arms/time spent on both arms using EPM in male offspring, higher levels of sucrose preference in female offspring and lower levels of voluntary morphine consumption in male and female offspring. Thus, EE experience in morphine-dependent both parents reduced anxiety, depressive-like behavior and also the voluntary morphine consumption in their offspring during puberty which may prevent the vulnerability of the next generation to drug abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Effects of morphine and naloxone on feline colonic transit

    International Nuclear Information System (INIS)

    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

  9. Improvement of buccal delivery of morphine using the prodrug approach

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Jørgensen, A.; Christensen, C.B.

    1997-01-01

    relationship to the lipophilicity of the compounds. In the in vitro studies the optimal permeation was achieved for the prodrug morphine-3-propionate having a log P value of approximately 0.7. In contrast to that optimal in vivo absorption was obtained for the prodrug morphine-3-acetate having a log P value...... Improved by using ester prodrugs with higher lipophilicity than morphine itself. However, the enzymatic stability of the prodrugs in saliva also play an important role for the overall improvement in absorption properties....

  10. Effects of morphine and naloxone on feline colonic transit

    Energy Technology Data Exchange (ETDEWEB)

    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.

  11. STUDIES ON NATURAL AND SYNTHETIC POLYMERS FOR CONTROLLED RELEASE MATRIX TABLET OF ACECLOFENAC

    OpenAIRE

    Abhishek S. Joshi *, Deepak A. Joshi , Avinash V. Dhobale , Sandhya S. Bundel , Vijay R. Chakote, Gunesh N. Dhembre

    2018-01-01

    The present study was aimed to design new oral controlled release matrix tablets of new NSAID Aceclofenac for once a day by using 10, 15, 20 and 25% of GG:HPMC and XG:HPMC mixture in the ratio 1:1 by wet granulation method. The prepared tablets subjected to in vitro drug release studies in pH 7.4 buffer solution. All the formulation meets the pre-compression and compression characteristics. All the tablets prepared with 10, 15, 20 and 25% of HPMC: XG mixture in the ratio 1:1 fails to meet the...

  12. A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol.

    Science.gov (United States)

    Slater, Rebeccah; Hartley, Caroline; Moultrie, Fiona; Adams, Eleri; Juszczak, Ed; Rogers, Richard; Norman, Jane E; Patel, Chetan; Stanbury, Kayleigh; Hoskin, Amy; Green, Gabrielle

    2016-11-15

    Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants. A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP) screening and heel lancing provides effective analgesia. 
156 infants between 34 and 42 weeks' gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg) or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration. The primary outcome will be the Premature Infant Pain Profile-revised (PIPP-R) score 30 seconds after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as an Accepted Protocol Summary by The Lancet .

  13. Intra-articular morphine in horses

    DEFF Research Database (Denmark)

    Lindegaard, Casper

    separated by a three week washout period. Before each treatment, radiocarpal synovitis was induced by IA injection of lipopolysaccharide (LPS). For each of the two 168-hours study periods, local and systemic measures of pain and inflammation as well as blood and synovial fluid (SF) samples...... for pharmacological analysis were obtained repeatedly. Pain was evaluated by degree of lameness as well as using a visual analogue scale of pain intensity (VAS) and a composite measure pain scale (CMPS), developed for this purpose. Intra-articular injection of LPS elicited a marked synovitis resulting in lameness...... and pain. Intra-articularly administered morphine showed a significant analgesic effect as measured by reduced lameness scores, less administered rescue analgesia and lower pain scores. A significant anti-inflammatory effect was demonstrated by reduced joint swelling, reduced SF serum amyloid A (SAA...

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

    Science.gov (United States)

    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-β-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

  15. Long-term Morphine-treated Rats are more Sensitive to Antinociceptive Effect of Diclofenac than the Morphine-naive rats

    OpenAIRE

    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-de...

  16. Morphine-assisted cholescintigraphy in the diagnosis of acalculous cholecystitis

    International Nuclear Information System (INIS)

    Sajewicz, Z.; Paradowski, L.; Kowal, A.

    2001-01-01

    Detecting acalculous cholecystitis still causes difficulties. The aim of the study was to assess the usefulness of morphine-assisted cholescintigraphy in the diagnosis of acute and chronic acalculous cholecystitis. Sixteen patients with suspicion of acute or chronic acalculous cholecystitis were examined. in the above mentioned patients choscintigraphy was performed by the intravenous administration of 5 mCi 99mTc-HIDA. None of the patients displayed the gallbladder within 60 min. The intravenous administration of 0.04 mg/kg b.w. morphine did not result in filling a tracer into the gallbladder in 10 patients, which allowed to confirm that acute acalculous cholecystitis. In the remaining 6 patients the morphine induction caused influx of radiotracer into the gallbladder, which allowed to diagnose the chronic acalculous cholecystitis. Morphine-assisted cholescintigraphy turned out to be useful in detecting acute and chronic cholecystitis. (author)

  17. Attenuation of morphine tolerance and dependence by thymoquinone in mice

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    Hossein Hosseinzadeh

    2016-01-01

    Full Text Available Objectives: Dependence and tolerance are major restricting factors in the clinical use of opioid analgesics. In the present study, the effects of thymoquinone, the major constituent of Nigella sativa seeds, on morphine dependence and tolerance were investigated in mice. Materials and Methods: Male adult NMRI mice were made tolerant and dependent by repeated injections of morphine (50, 50, and 75 mg/kg, i.p. on 9 a.m., 1 p.m., and 5 p.m., respectively during a 3-day administration schedule. The hot-plate test was used to assess tolerance to the analgesic effects of morphine. Naloxone (2 mg/kg, i.p. was injected to precipitate withdrawal syndrome in order to assess the morphine dependence. To evaluate the effects of thymoquinone on tolerance and dependence to morphine, different single or repeated doses of thymoquinone were administered in mice. Rotarod was used to assess the motor coordination. Results: Administration of single or repeated doses of thymoquinone (20 and 40 mg/kg, i.p. significantly decreased the number of jumps in morphine dependent animals. Repeated administration of thymoquinone (20 and 40 mg/kg, for 3 days and also single injection of thymoquinone (40 mg/kg, on the fourth day attenuated tolerance to the analgesic effect of morphine. None of the thymoquinone doses (10, 20, and 40 mg/kg produced any antinociceptive effects on their own. Motor coordination of animals was impaired by the high dose of thymoquinone (40 mg/kg. Conclusion: Based on these results, it can be concluded that thymoquinone prevents the development of tolerance and dependence to morphine.

  18. Sustained Morphine Administration Induces TRPM8-Dependent Cold Hyperalgesia.

    Science.gov (United States)

    Gong, Kerui; Jasmin, Luc

    2017-02-01

    It is not uncommon for patients chronically treated with opioids to exhibit opioid-induced hyperalgesia, and this has been widely reported clinically and experimentally. The molecular substrate for this hyperalgesia is multifaceted, and associated with a complex neural reorganization even in the periphery. For instance, we have recently shown that chronic morphine-induced heat hyperalgesia is associated with an increased expression of GluN2B containing N-methyl-D-aspartate receptors, as well as of the neuronal excitatory amino acid transporter 3/excitatory amino acid carrier 1, in small-diameter primary sensory neurons only. Cold allodynia is also a common complaint of patients chronically treated with opioids, yet its molecular mechanisms remain to be understood. Here we present evidence that the cold sensor TRPM8 channel is involved in opioid-induced hyperalgesia. After 7 days of morphine administration, we observed an upregulation of TRPM8 channels using patch clamp recording on sensory neurons and Western blot analysis on dorsal root ganglia. The selective TRPM8 antagonist RQ-00203078 blocked cold hyperalgesia in morphine-treated rats. Also, TRPM8 knockout mice failed to develop cold hyperalgesia after chronic administration of morphine. Our results show that chronic morphine upregulates TRPM8 channels, which is in contrast with the previous finding that acute morphine triggers TRPM8 internalization. Patients receiving chronic opioid are sensitive to cold. We show in mice and rats that sustained morphine administration induces cold hyperalgesia and an upregulation of TRPM8. Knockout or selectively blocking TRPM8 reduces morphine-induced cold hyperalgesia suggesting TRPM8 is regulated by opioids. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  19. Impacts of morphine addiction on spermatogenesis in rats

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    Nasrin Takzare

    2016-05-01

    Full Text Available Background: There are numerous investigations on wide range of issues that disrupt regulatory spermatogenesis, individuals who are exposed to drug abuse faced infertility and immature spermatogenesis. Objective: The aim of this study was to evaluate the addiction effects of morphine and its derivatives on rats spermatogenesis. Materials and Methods: 40 male Wistar rats were randomly divided into 5 equal groups, which were exposed either with intravenous morphine, naloxone, naloxone and morphine, sham (with normal saline injection and a control group without infusion. Spermatogenesis was assessed after three months via histological sections with hematoxylin and eosin staining, using a light microscope based on measurement of spermatogonia, spermatocyte, spermatid, and spermatozoa. Results: Those rats that received opioids had changes in spermatogenesis function. The population of spermatogenesis cycle cells at spermatogonia, spermatocyte, spermatid, and spermatozoa stages was significantly decreased in those rats that received opioid in comparison to the control group (p<0.05. Histological studies revealed that changes in different groups of opioid application might affect sperm formation. Sperm count in morphine group was (0±0 and in naloxone group, naloxone+morphine, sham and control were 235±3.77, 220±3.81, 247.12±6.10 and 250±6.54, respectively (p<0.001. Conclusion: Morphine could affect all spermatogenesis stages

  20. Picrotoxin-induced seizures modified by morphine and opiate antagonists.

    Science.gov (United States)

    Thomas, J; Nores, W L; Kenigs, V; Olson, G A; Olson, R D

    1993-07-01

    The effects of naloxone, Tyr-MIF-1, and MIF-1 on morphine-mediated changes in susceptibility to picrotoxin-induced seizures were studied. Rats were pretreated with naloxone, MIF-1, Tyr-MIF-1, or saline. At 15-min intervals, they received a second pretreatment of morphine or saline and then were tested for seizures following a convulsant dose of picrotoxin. Several parameters of specific categories of seizures were scored. Morphine increased the number of focal seizure episodes, duration of postseizure akinesis, and incidence of generalized clonic seizures. Naloxone tended to block the morphine-mediated changes in susceptibility. Tyr-MIF-1 had effects similar to naloxone on duration of postseizure immobility but tended to potentiate the effects of morphine on focal seizure episodes. The effects of morphine and the opiate antagonists on focal seizure episodes and postseizure duration suggest the general involvement of several types of opiate receptors in these picrotoxin-induced behaviors. However, the observation of antagonistic effects for Tyr-MIF-1 on immobility but agonistic effects for focal seizures suggests that the type of effect exerted by opiate agents may depend upon other neuronal variables.

  1. Mitragynine attenuates withdrawal syndrome in morphine-withdrawn zebrafish.

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    Beng-Siang Khor

    Full Text Available 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.

  2. Effect of irradiation on analgesia induced by morphine and endorphin

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Kyu; Lee, Byoung Hun; Hyun, Soung Hee; Chung, Ki Myung [KAERI, Daejeon (Korea, Republic of)

    2003-07-01

    Morphine and endorphin administered intracerebroventricularly (i.c.v.) produce analgesia by activating different descending pain inhibitory systems. Gamma irradiation attenuates the acute analgesic action of i.c.v. injected morphine in mice. This study was done to investigate the effect of-irradiation on the analgesia produced by i.c.v. injected morphine and endorphin in male ICR mice. In one group, mice were exposed to whole-body irradiation at a dose of 5 Gy from a {sup 60}Co source and the analgesic effects were tested 5, 30, 60, 90 and 180 min after irradiation using the acetic acid-induced writhing test. The analgesic effect was produced time-dependently and reached its maximum at 90 min after irradiation. Thus, time was fixed in the following studies. In another group, mice were irradiated with 5 Gy and tested 90 minutes later for analgesia produced by i.c.v. administration of morphine or endorphin. Irradiation significantly potentiated the analgesia produced by endorphin. However, the antinociception produced by morphine was not affected by irradiation. These results support the hypothesis that morphine and endorphin administered supraspinally produce antinocieception by different neuronal mechanisms.

  3. Effect of irradiation on analgesia induced by morphine and endorphin

    International Nuclear Information System (INIS)

    Kim, Jin Kyu; Lee, Byoung Hun; Hyun, Soung Hee; Chung, Ki Myung

    2003-01-01

    Morphine and endorphin administered intracerebroventricularly (i.c.v.) produce analgesia by activating different descending pain inhibitory systems. Gamma irradiation attenuates the acute analgesic action of i.c.v. injected morphine in mice. This study was done to investigate the effect of-irradiation on the analgesia produced by i.c.v. injected morphine and endorphin in male ICR mice. In one group, mice were exposed to whole-body irradiation at a dose of 5 Gy from a 60 Co source and the analgesic effects were tested 5, 30, 60, 90 and 180 min after irradiation using the acetic acid-induced writhing test. The analgesic effect was produced time-dependently and reached its maximum at 90 min after irradiation. Thus, time was fixed in the following studies. In another group, mice were irradiated with 5 Gy and tested 90 minutes later for analgesia produced by i.c.v. administration of morphine or endorphin. Irradiation significantly potentiated the analgesia produced by endorphin. However, the antinociception produced by morphine was not affected by irradiation. These results support the hypothesis that morphine and endorphin administered supraspinally produce antinocieception by different neuronal mechanisms

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

    Directory of Open Access Journals (Sweden)

    Michal eBajo

    2014-06-01

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

  5. A randomised trial of glucose tablets to aid smoking cessation.

    Science.gov (United States)

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

    2010-01-01

    Oral glucose has been found to decrease tobacco craving among abstaining smokers. One study has demonstrated an effect of glucose on short-term abstinence. There is a need to examine any long-term benefit of glucose on abstinence. To assess whether glucose tablets improve 6-month continuous abstinence rates compared with low-calorie placebo tablets. Smokers attempting to stop (n = 928) were randomised to receive glucose or sorbitol (placebo) in a double-blind placebo-controlled trial. All participants received group-based psychological support, and approximately half (n = 474) received nicotine replacement therapy (NRT), buproprion, or both. Smokers were seen weekly for 5 weeks and used tablets ad libitum, with a recommended minimum of 12 per day. Participants were recruited through general practitioner referral, word of mouth, and advertising. The participants were 38% male, smoked an average of 23.5 cigarettes per day, and had a mean age of 44 years. There were no significant pretreatment differences between groups. The primary outcome measure was continuous, CO-verified abstinence from the target quit date for 6 months. No significant effect of glucose tablets on abstinence was found (14.6% vs 13.4% abstinence in the glucose and placebo groups, respectively). However, there was a significant interaction with a glucose effect observed in smokers also receiving other medication (18.2% vs 12.6%, p < 0.05) but not otherwise (10.7% vs 14.3% ; p < 0.05 for the interaction). No significant effect of glucose tablets over and above sweet tasting tablets could be detected overall, but the possibility of an effect as an adjunct to NRT or bupropion merits further investigation.

  6. [Application of β-cyclodextrin in the formulation of ODT tablets containing ibuprofen].

    Science.gov (United States)

    Zimmer, Łukasz; Kasperek, Regina; Poleszak, Ewa

    2014-01-01

    Oral disintegrating tablet (ODT) dissolves or disintegrates in saliva and then it is swallowed. Diluent in direct compression formulation has a dual role: it increases bulk of the dosage form and it promotes binding of the constituent particles of the formulation. Hence, selection of diluent is important in tablets produced by direct compression method. The aim of this work was to exame feasibility of preparing and optimizing oral disintegrating tablet formulation using β-cyclodextrin as a diluent. 400 mg round tablets were prepared by direct compression method on single punch tablet press using flat plain-face. 60% β-CD and MCC (microcrystalline cellulose - MCC-Vivapur 102) were used at different proportions for all the formulations. 5% of Kollidon CL was added as superdisintegrant. The eight formulations prepared were assessed for weight variation, thickness, disintegration time, hardness and dissolution rate according to FP IX. A dissolution test was performed at 37ºC using the paddle method at 50 rpm with 900 mL phosphate buffer (pH 6.8) as a dissolution medium. The content of ibuprofen sodium was found inside the ± 5% of the theoretical value. Hardness values of presented tablets were in the range 0.11-0.15 kG/mm2. Friability of the tablets lower than 1% indicates that the developed formulations can be processed and handled without excessive care. Disintegration time was in the range of 86 to 161 s. The results confirm the good mechanical properties of tablets containing β-CD. A composition with 20% β-CD and 40% MCC fulfilled a maximum requisite of an optimum formulation. These properties were similar to Ludiflash, the formulation used for comparison purposes. In the present study, higher concentration of β cyclodextrin was found to improve the hardness of tablets without increasing the disintegration time.

  7. Fast Track Liver Resection: The Effect of a Comprehensive Care Package and Analgesia with Single Dose Intrathecal Morphine with Gabapentin or Continuous Epidural Analgesia

    Directory of Open Access Journals (Sweden)

    Jonathan B. Koea

    2009-01-01

    Full Text Available Background. A comprehensive care package for patients undergoing hepatectomy was developed with the aim of minimal physiological disturbance in the peri-operative period. Peri-operative analgesia with few gastrointestinal effects and reduced requirement for intravenous (IV fluid therapy was central to this plan. Methods. Data on 100 consecutive patients managed with continuous epidural infusion (n = 50; bupivicaine 0.125% and fentanyl 2 g/mL at 0.1 mL/kg/hr or intrathecal morphine (n = 50; 300 g in combination with oral gabapentin 1200 mg preoperatively and 400 mg bd postoperatively was compared. Results. The epidural and intrathecal morphine groups were equivalent in terms of patient demographics, procedures and complications. Patients receiving intrathecal morphine received less intra-operative IV fluids (median 1500 mL versus 2200 mL, =.06, less postoperative IV fluids (median 1200 mL versus 4300 mL, =.03 than patients receiving epidural infusion. Patients managed with intrathecal morphine established a normal dietary intake sooner (16 hours versus 20 hours, =.05 and had shorter hospital stays than those managed with epidural infusions (4.7 ± 0.9 days versus 6.8 ± 1.2 days, =.02. Conclusions. Single dose intrathecal morphine is a safe and effective means of providing peri-operative analgesia. Patients managed with intrathecal morphine have reduced peri-operative physiological disturbance and return home within a few days of hepatic resection.

  8. Combination therapy with solifenacin and tamsulosin oral controlled absorption system in a single tablet for lower urinary tract symptoms in men: efficacy and safety results from the randomised controlled NEPTUNE trial

    NARCIS (Netherlands)

    van Kerrebroeck, Philip; Chapple, Christopher; Drogendijk, Ted; Klaver, Monique; Sokol, Roman; Speakman, Mark; Traudtner, Klaudia; Drake, Marcus J.; Kiss, G.; Marberger, M.; Strotski, A. V.; Varaksa, A. N.; Vashchula, V.; Dewilde, T.; Braeckman, J.; Roumeguere, T.; Wyndaele, J. J.; Ameye, F.; Everaert, K.; van Cleynenbruegel, B.; de Leval, J.; Vanderkerken, J.; Ackaert, K.; Hiblbauer, J.; Zhanel, P.; Klecka, J.; Lukes, M.; Novak, J.; Lisec, M.; Vrtal, R.; Ondra, D.; Liehne, J.; Tuma, J.; Azzouzi, A.-R.; Wellerand, H.; Jung, J.-L.; Mourey, E.; Colombel, M.; Claude, R.; Ibrahim, H.; Desgrandchamps, F.; Haab, F.; Zerbib, M.; Ruffion, A.; Vincendeau, S.; Haillot, O.; Hentschel, M.; Gerhardt, U.; Hechelmann, W.; de la Rosette, J.

    2013-01-01

    Storage symptoms are particularly bothersome in men with lower urinary tract symptoms (LUTS) but may not be adequately treated by α-blocker monotherapy. To assess the efficacy and safety of a fixed-dose combination (FDC) of solifenacin and an oral controlled absorption system (OCAS) formulation of

  9. Inability of naloxone to change brain morphine levels in tolerant mice

    International Nuclear Information System (INIS)

    Dum, J.; Meyer, G.; Hoellt, V.; Herz, A.; Catlin, D.H.

    1977-01-01

    The effect of naloxone on brain morphine concentrations was measured in naive and morphine-dependent mice using radioimmunoassay and gas-liquid chromatography. No displacement of morphine from the brain by naloxone could be observed in naive mice acutely injected with morphine or in pellet-implanted mice at increasing intervals after removal of the morphine pellets. The suggestion of a change in affinity of opiate receptors during the development of tolerance/dependence, which had been made on the basis of the displacement of morphine by naloxone found by other workers, is thus not supported by the present results

  10. Perioperative analgesia after intrathecal fentanyl and morphine or morphine alone for cesarean section: A randomized controlled study.

    Science.gov (United States)

    Weigl, Wojciech; Bieryło, Andrzej; Wielgus, Monika; Krzemień-Wiczyńska, Świetlana; Kołacz, Marcin; Dąbrowski, Michał J

    2017-12-01

    Intrathecal morphine is used in the postoperative management of pain after caesarean section (CS), but might not be optimal for intraoperative analgesia. We hypothesized that intrathecal fentanyl could supplement intraoperative analgesia when added to a local anesthetic and morphine without affecting management of postoperative pain. This prospective, randomized, double-blind, parallel-group study included 60 parturients scheduled for elective CS. Spinal anesthesia consisted of bupivacaine with either morphine 100 μg (M group), or fentanyl 25 μg and morphine 100 μg (FM group). The frequency of intraoperative pain and pethidine consumption in the 24 hours postoperatively was recorded. Fewer patients in the FM group required additional intraoperative analgesia (P fentanyl and morphine may provide better perioperative analgesia than morphine alone in CS and could be useful when the time from anesthesia to skin incision is short. However, an increase in PONV and possible acute spinal opioid tolerance after addition of intrathecal fentanyl warrants further investigation using lower doses of fentanyl.

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

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    Wiederhold NP

    2015-12-01

    Full Text Available Nathan P Wiederhold Departments of Pathology and Medicine/Infectious Diseases, University of Texas Health Science Center at San Antonio, South Texas Reference Laboratories, San Antonio, TX, USA Abstract: 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

  12. Treadmill exercise attenuates the severity of physical dependence, anxiety, depressive-like behavior and voluntary morphine consumption in morphine withdrawn rats receiving methadone maintenance treatment.

    Science.gov (United States)

    Alizadeh, Maryam; Zahedi-Khorasani, Mahdi; Miladi-Gorji, Hossein

    2018-05-30

    This study was designed to examine whether treadmill exercise would attenuate the severity of physical dependence, methadone-induced anxiety, depression and voluntary morphine consumption in morphine withdrawn rats receiving methadone maintenance treatment (MMT). The rats were chronically treated with bi-daily doses (10 mg/kg, at 12 h intervals) of morphine for 14 days. The exercising rats receiving MMT were forced to run on a motorized treadmill for 30 days during morphine 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 (TBC) paradigm. The results showed that naloxone- precipitated opioid withdrawal signs were decreased in exercising morphine-dependent rats receiving MMT than sedentary rats. Also, the exercising morphine-dependent rats receiving MMT exhibited an increased time on open arms, preference for sucrose and a lower morphine preference ratio than sedentary rats. We conclude that treadmill exercise decreased the severity of physical dependence, anxiety/depressive-like behaviors and also the voluntary morphine consumption in morphine withdrawn rats receiving MMT. Thus, exercise may benefit in the treatment of addicts during MMT. Copyright © 2018. Published by Elsevier B.V.

  13. Physical compatibility of binary and ternary mixtures of morphine and methadone with other drugs for parenteral administration in palliative care.

    Science.gov (United States)

    Destro, Massimo; Ottolini, Luca; Vicentini, Lorenza; Boschetti, Silvia

    2012-10-01

    The parenteral administration of combinations of drugs is often necessary in palliative medicine, particularly in the terminal stage of life, when patients are no longer able to take medication orally. The use of infusers to administer continuous subcutaneous infusions is a well-established practice in the palliative care setting and enables several drugs to be given simultaneously, avoiding the need for repeated administrations and the effects of peaks and troughs in the doses of medication. The method is also appreciated by patients and caregivers in the home care setting because the devices and infusion sites are easy to manage. Despite their frequent use, however, the mixtures of drugs adopted in clinical practice are sometimes not supported by reliable data concerning their chemical and physical compatibility. The present study investigates the chemical compatibility of binary mixtures (morphine with ketorolac) and the physical compatibility of binary (morphine or methadone with ketorolac) or ternary mixtures (morphine with ketorolac and/or haloperidol, and/or dexamethasone, and/or metoclopramide, and/or hyoscine butylbromide) with a view to reducing the aleatory nature of the empirical use of such combinations, thereby increasing their safety and clinical appropriateness.

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

    Directory of Open Access Journals (Sweden)

    Abolfazl Aslani

    2013-08-01

    Full Text Available 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.

  15. FDA-Approved Natural Polymers for Fast Dissolving Tablets

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    Md Tausif Alam

    2014-01-01

    Full Text Available 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.

  16. Development and evaluation of novel antihypertensive orodispersible tablets.

    Science.gov (United States)

    Khan, Hafeez Ullah; Hanif, Muhammad; Sarfraz, Rai M; Maheen, Safirah; Afzal, Samina; Sher, Muhammad; Afzal, Khurram; Mahmood, Asif; Shamim, Ayesha

    2017-09-01

    Objective of present study was to enhance patient compliance in pediatrics and geriatrics patients of Hypertension. To achieve this target, innovative orodispersible tablets of atenolol and atorvastatin was developed to produce instant action by rapidly disintegrating into oral cavity. Three different techniques like direct compression, effervescent and sublimation methods were used to prepare these tablets (Five batches of tablets by each method) by using two superdisintegrants like Sodium starch glycolate and pregelatinized starch alone and in combination. Pre-formulation studies including rheological analysis (Bulk density, tapped density, Angle of repose, Carr's compressibility index, Hausner's ratio), compatibility studies such as Fourier transform infrared spectrophotometry (FTIR) and Differential scanning colorimetry (DSC), Post-compression and stability studies were also performed. Finally, results were statistically evaluated by the applying one way ANOVA test and mean. It was concluded that the formulation F8 containing Sodium starch glycolate 2% and pregelatinized starch 6% found best regarding disintegration time, wetting volume, wetting time, release studies etc. The order in which drug release was quicker is Pregelatinized starch plus Sodium starch glycolate > Pregelatinized starch > Sodium starch glycolate (primojel). It was concluded that sublimation method was the best among three methods used for orodispersible tablets formulations.

  17. The biology of deception: emotion and morphine.

    Science.gov (United States)

    Stefano, G B; Fricchione, G L

    1995-01-01

    The biology of deception suggests that denial-like processes are at the core of the cognitive coping. In this regard, with cognitive ability, one associates or assumes that this process occurs by way of a 'rational' mind. Such a detailed cognitive process as being rational would also lead, counter intuitively, to inactivity and or major delays in conclusion reaching. Thus, our perceived rationality may also be a deceptive behavioral response. Of equal noteworthyness, man is also 'emotional'. We surmise that emotion represents the pre-cognitive short-cut to overcome this potential for excessive rationality. In this light, we may explain certain psychiatric disorders such as obsessive-compulsive behavior as emotional extremes dealing with cognitive habits used to bind anxiety operating most probably at the pre-cognitive level. Given recent discoveries in neuroimmunology and an understanding of naturally occurring morphine as both an immune and neurological down-regulatory substance we hypothesize that abnormalities associated with emotional extremes may be due, in part, to morphinergic imbalances.

  18. Tablet splitting and weight uniformity of half-tablets of 4 medications in pharmacy practice.

    Science.gov (United States)

    Tahaineh, Linda M; Gharaibeh, Shadi F

    2012-08-01

    Tablet splitting is a common practice for multiple reasons including cost savings; however, it does not necessarily result in weight-uniform half-tablets. To determine weight uniformity of half-tablets resulting from splitting 4 products available in the Jordanian market and investigate the effect of tablet characteristics on weight uniformity of half-tablets. Ten random tablets each of warfarin 5 mg, digoxin 0.25 mg, phenobarbital 30 mg, and prednisolone 5 mg were weighed and split by 6 PharmD students using a knife. The resulting half-tablets were weighed and evaluated for weight uniformity. Other relevant physical characteristics of the 4 products were measured. The average tablet hardness of the sampled tablets ranged from 40.3 N to 68.9 N. Digoxin, phenobarbital, and prednisolone half-tablets failed the weight uniformity test; however, warfarin half-tablets passed. Digoxin, warfarin, and phenobarbital tablets had a score line and warfarin tablets had the deepest score line of 0.81 mm. Splitting warfarin tablets produces weight-uniform half-tablets that may possibly be attributed to the hardness and the presence of a deep score line. Digoxin, phenobarbital, and prednisolone tablet splitting produces highly weight variable half-tablets. This can be of clinical significance in the case of the narrow therapeutic index medication digoxin.

  19. Formulation Optimization and In-vitro Evaluation of Oral Floating ...

    African Journals Online (AJOL)

    matrix tablets and to systematically optimize its drug release using varying levels of xanthan gum and hydroxypropyl ... stomach and improve oral bioavailability of drugs that have ... which can affect its sustained release formulation. [19].

  20. Safety of pain control with morphine: new (and old) aspects of ...

    African Journals Online (AJOL)

    Safety of pain control with morphine: new (and old) aspects of morphine ... In addition, nursing staff failed to recognise that snoring can indicate a dangerously ... monitor of respiratory depression; (iv) training in airway management should be ...

  1. Narp regulates long-term aversive effects of morphine withdrawal

    Science.gov (United States)

    Reti, Irving M.; Crombag, Hans S.; Takamiya, Kogo; Sutton, Jeffrey M.; Guo, Ning; Dinenna, Megan L.; Huganir, Richard L.; Holland, Peter C.; Baraban, Jay M.

    2008-01-01

    Although long-lasting effects of drug withdrawal are thought to play a key role in motivating continued drug use, the mechanisms mediating this type of drug-induced plasticity are unclear. As Narp is an immediate early gene product that is secreted at synaptic sites and binds to AMPA receptors, it has been implicated in mediating enduring forms of synaptic plasticity. In previous studies, we found that Narp is selectively induced by morphine withdrawal in the extended amygdala, a group of limbic nuclei that mediate aversive behavioral responses. Accordingly, in this study, we evaluated whether long-term aversive effects of morphine withdrawal are altered in Narp KO mice. We found that acute physical signs of morphine withdrawal are unaffected by Narp deletion. However, Narp KO mice acquire and sustain more aversive responses to the environment conditioned with morphine withdrawal than WT controls. Paradoxically, Narp KO mice undergo accelerated extinction of this heightened aversive response. Taken together, these studies suggest that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal and, therefore, may regulate plasticity processes underlying drug addiction. PMID:18729628

  2. The significance of the adenosinergic system in morphine dependence

    Directory of Open Access Journals (Sweden)

    Lupina Malgorzata

    2015-09-01

    Full Text Available Addiction is a chronic and recurrent disease. In its pathology, neuroadaptive changes within the dopaminergic pathways inside the mesolimbic system play a predominant role. Of note, the manner in which various neurotransmitters act on their receptors, may modulate the addictive process. Adenosine, an important neuromodulator in the central nervous system, is able to modify the opioid dependence, doing so mainly by its activity on the adenosine A1 and A2A receptors. In the present manuscript, the actual state of knowledge on the relationships between adenosinergic receptors and opioid dependence has been described. Various literature data on the involvement of adenosine ligands, mainly in the signs of morphine withdrawal, as well as morphine-induced sensitization, were also collected. Additionally, in this paper, some important interactions between adenosine and other neurotransmitters (e.g. dopamine, glutamate are described. It is put forward that these connections are the major mechanism of involvement of the adenosinergic system in morphine addiction. The repeatedly confirmed effectiveness of adenosine ligands in morphine dependence, as seen in various experimental protocols, suggests that adenosine ligands may be useful tools for developing new strategies for attenuating morphine dependence.

  3. Electromechanical coupling in rat basilar artery in response to morphine.

    Science.gov (United States)

    Waters, A; Harder, D R

    1983-12-01

    Force development, intracellular membrane potential (Em), and voltage vs. current curves were measured in rat basilar artery to help elucidate the mechanism of action of morphine sulfate and a synthetic narcotic, meperidine hydrochloride, on this preparation. Morphine sulfate caused a dose-dependent contraction of these vessels, which was reversible with naloxone. Electrical studies show that morphine may act upon this vascular smooth muscle preparation by decreasing potassium conductance (gk). This hypothesis is supported by the findings that morphine sulfate depolarized these cells and increased the input resistance (rin) determined by the application of rectangular hyperpolarizing and depolarizing current pulses through the microelectrode during impalement and recording of the associated voltage changes (delta V). Meperidine hydrochloride had significantly less effect on this preparation than morphine sulfate. Further studies show that the vehicular medium used for the commercially available preparation of naloxone (viz. the methyl and propyl esters of p-hydroxybenzoic acid in a ratio of 9:1) is, in vitro, a vasodilator of cerebral vascular smooth muscle.

  4. How do tablet properties influence swallowing behaviours?

    Science.gov (United States)

    Yamamoto, Shinya; Taniguchi, Hiroshige; Hayashi, Hirokazu; Hori, Kazuhiro; Tsujimura, Takanori; Nakamura, Yuki; Sato, Hideaki; Inoue, Makoto

    2014-01-01

    Behavioural performance of tablet swallowing was evaluated with different tablet conditions in terms of size, number and surface coating. Four different types of tablets were prepared: small or large, and with or without a surface coating. Fourteen normal male adults were instructed to swallow the prepared tablets with 15 ml of water. The number of tablets in one trial was changed from one to three. To evaluate swallowing and tablet transport, electromyographic activity was recorded in the left suprahyoid muscles, and videofluorographic images were examined. All tablet conditions (size, number and surface coating) affected the swallowing performance in terms of total number of swallows, electromyographic burst patterns and location of remaining tablets. Increases in the size and number of tablets increased the number of swallows and electromyographic burst area and duration. In addition, all of these parameters increased while swallowing tablets without a coating compared with tablets with a coating. Location of the remaining tablets was mainly within the mouth. This study only clarified the normal pattern of tablet swallowing under several conditions in healthy subjects, but the results may facilitate comprehensive evaluation and treatment planning in terms of administering medication to dysphagic patients. © 2013 Royal Pharmaceutical Society.

  5. Evaluation of crushed ticagrelor tablet doses: recovery following crushing and naso-gastric tube passage ex vivo.

    Science.gov (United States)

    Crean, Barry; Finnie, Cindy; Crosby, Anna

    2013-06-01

    Orally available ticagrelor in combination with low-dose aspirin (75-100 mg/day) is indicated for adult patients with acute coronary syndromes. However, patients with swallowing difficulties may be unable to consume the currently available 90-mg tablet. It is hypothesized that ticagrelor could be given to this patient cohort as a crushed dose administered either orally or via a naso-gastric (NG) tube. To investigate the potential use of crushed ticagrelor tablets (90- and 180-mg doses) for oral dose or NG tube administration. Ticagrelor tablets (90 or 180 mg [two 90-mg tablets]) were prepared to emulate oral and NG tube administration by similar methods. For the oral dose, ticagrelor tablets were crushed using a mortar and pestle and transferred to a dosing cup. 100 mL of water was added to the mortar, stirred, and the contents were transferred to the dosing cup and stirred to form a suspension. At this stage, where the suspension would normally be administered to a patient, it was collected for high performance liquid chromatography (HPLC) analysis. The mortar was then flushed with 100 mL of water, and the contents were again transferred to the dosing cup, stirred, and collected for HPLC analysis. For the NG dose, polyvinylchloride, polyurethane, and silicone size CH10 NG tubes were used. The tablets were crushed using a mortar and pestle, diluted with 50 mL of water, and stirred. At this stage, where the suspension would normally be administered to a patient through an NG tube using a syringe, it was collected for HPLC analysis. The mortar was then flushed with two additional 50 mL aliquots of water and the contents were passed through the NG tube. HPLC analysis examined the recoverability of ticagrelor in each of the dose suspensions and flushes and the stability of the suspension when held in a syringe for up to 2 h. One or two crushed 90-mg ticagrelor tablets, prepared for either oral or NG tube administration, delivers a mean dose of ≥97% of the original

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

    International Nuclear Information System (INIS)

    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 30 min ischemia and 2 h 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 (ΔΨm) 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 ΔΨm 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. - Highlights: • Morphine induced mito-Src phosphorylation and reduced infarct size in rat hearts. • Morphine failed to reduce I/R-induced LDH release in Src-silencing HL-1 cells. • Morphine prevented mitochondria damage caused by I/R through Src. • Morphine reduced

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

    Energy Technology Data Exchange (ETDEWEB)

    He, Haiyan [Department of Physiology & Pathophysiology, Tianjin Medical University, Tianjin 300070 (China); Department of Pharmacology, Tianjin Medical University, Tianjin 300070 (China); Huh, Jin [Department of Anesthesia and Pain Medicine, Medical College, Kangwon National University, Chuncheon City (Korea, Republic of); Wang, Huihua [Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang Province (China); Kang, Yi; Lou, Jianshi [Department of Pharmacology, Tianjin Medical University, Tianjin 300070 (China); Xu, Zhelong, E-mail: zxu@tmu.edu.cn [Department of Physiology & Pathophysiology, Tianjin Medical University, Tianjin 300070 (China)

    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 30 min ischemia and 2 h 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 (ΔΨm) 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 ΔΨm 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. - Highlights: • Morphine induced mito-Src phosphorylation and reduced infarct size in rat hearts. • Morphine failed to reduce I/R-induced LDH release in Src-silencing HL-1 cells. • Morphine prevented mitochondria damage caused by I/R through Src. • Morphine

  8. Galileo's Telescopy and Jupiter's Tablet

    Science.gov (United States)

    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.

  9. Maternal swimming exercise during pregnancy attenuates anxiety/depressive-like behaviors and voluntary morphine consumption in the pubertal male and female rat offspring born from morphine dependent mothers.

    Science.gov (United States)

    Torabi, Masoumeh; Pooriamehr, Alireza; Bigdeli, Imanollah; Miladi-Gorji, Hossein

    2017-10-17

    This study was designed to examine whether maternal swimming exercise during pregnancy would attenuate prenatally morphine-induced anxiety, depression and voluntary consumption of morphine in the pubertal male and female rat offspring. Pregnant rats during the development of morphine dependence were allowed to swim (30-45min/d, 3days per a week) on gestational days 11-18. Then, the pubertal male and female rat offspring were tested for the elevated plus-maze (EPM), sucrose preference test (SPT) and voluntary morphine consumption using a two-bottle choice (TBC) paradigm. The results showed that male and female rat offspring born of the swimmer morphine-dependent mothers exhibited an increase in EPM open arm time and entries, higher levels of sucrose preference than their sedentary control mothers. Voluntary consumption of morphine was less in the male and female rat offspring born of the swimmer morphine-dependent mothers as compared with their sedentary control mothers during three periods of the intake of drug. Thus, swimming exercise in pregnant morphine dependent mothers decreased anxiety, depressive-like behavior and also the voluntary morphine consumption in the pubertal male and female offspring, which may prevent prenatally morphine-induced behavioral sensitization in offspring. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. In vitro disintegration and dissolution studies of once-weekly copies of alendronate sodium tablets (70 mg) and in vivo implications.

    Science.gov (United States)

    Dansereau, Richard J; Crail, Debbie J; Perkins, Alan C

    2008-04-01

    The aim of this study was to evaluate the in vitro disintegration and dissolution of 26 alendronic acid tablets (70 mg) on the market in Canada, Germany, the Netherlands, and the United Kingdom compared to the branded product (Fosamax). The disintegration and dissolution times were determined using the methods described in the United States Pharmacopeia 30 (USP 30). The disintegration of four orally disintegrating tablets (non-bisphosphonates) and branded film-coated risedronate sodium tablets were included for comparison. The mean disintegration times of the alendronic acid tablets ranged from 14 s for Pharmachemie (Netherlands) to 342 s (5.7 min) for Betapharm (Germany). The mean disintegration time of the branded product tablets ranged from 43 to 78 s. Six of the 26 companies market alendronic acid tablets with very rapid disintegration times which are similar to those of orally disintegrating tablets (non-bisphosphonates). The alendronic acid tablets with very rapid mean disintegration times are as follows: Pharmachemie (Netherlands), 14 s; Novopharm (Canada), 13-24 s; GRY-Pharma (Germany), 21 s; Juta Pharma (Germany), 30 s; APS/Teva (United Kingdom), 26 and 37 s; and Teva (UK), 14-29 s. Since there is no established disintegration time for alendronic acid tablets there can be no assurance that the copy tablets are equivalent to the branded product in terms of esophageal drug exposure. However, the in vitro disintegration times have not been correlated with in vivo disintegration and performance. The dissolution of all the bisphosphonate tablets was rapid with greater than 80% dissolved in 15 min and all products conformed to the USP 30 specification. The dissolution of all alendronic acid tablets was rapid and complete and conformed to the established USP 30 specifications which should ensure adequate drug absorption from the copy products. However, copies of alendronic acid tablets are approved based on the results of single-dose bioavailability studies in

  11. Development and Evaluation of Mucoadhesive Chlorhexidine Tablet ...

    African Journals Online (AJOL)

    Purpose: To formulate mucoadhesive chlorhexidine tablets and evaluate their drug release characteristics and mechanism. Methods: Chlorhexidine buccal adhesive tablets were prepared by direct compression using a blend of hydroxypropyl methylcellulose (HPMC) and chitosan as the bioadhesive polymers.

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

    Directory of Open Access Journals (Sweden)

    Nur Izzati Mohamad Zen

    2015-01-01

    Full Text Available 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.

  13. [Effects of morphine on pupillary light reflex in monkeys].

    Science.gov (United States)

    Meng, Zhi-Qiang; Zhang, Yu-Hua; Chen, Nan-Hui; Miao, Ying-Da; Hu, Xin-Tian; Ma, Yuan-Ye

    2010-06-01

    The pupil size of both human and other animals can be affected by light. Many kinds of psychiatrical and psychological disorders, such as drug abuse, associate with abnormal properties of pupillary light reflex. Thus, the properties of pupillary light reflex could serve as an indicator for drug abuse detection. However, the effect of drug abuse on pupillary light reflex is till unclear. To assess the effects of addictive drugs on pupillary light reflex quantificationally, in the present study, we examined the effects of morphine on pupil diameter and pupillary light reflex in rhesus monkeys. By measuring the pupil diameter at different timing points before and after the administration of morphine, we found that morphine administration reduced the diameter of pupil and decreased the constriction rate. Our present results provide an experimental support for applying the properties of pupillary light reflex as a reference in addicts' detection.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation.

    Science.gov (United States)

    Ohashi-Doi, Katsuyo; Kito, Hirokazu; Du, Weibin; Nakazawa, Hiroshi; Ipsen, Henrik; Gudmann, Pernille; Lund, Kaare

    2017-01-01

    In sublingual immunotherapy (SLIT), the immune system is addressed by solubilized allergen that interacts with immunocompetent cells of the oral mucosa, the efficiency of which is governed by 2 main factors of SLIT allergen bioavailability: the allergen concentration and the mucosal contact time. Recently, 3 house dust mite (HDM) SLIT tablets were developed that differ with regard to allergen content, nominal strength (maintenance doses: 6 SQ-HDM/10,000 Japanese Allergen Units [JAU], 12 SQ-HDM/ 20,000 JAU, and 300 IR/57,000 JAU), and formulation (freeze-dried/compressed). Here, the importance of the SLIT tablet formulation for HDM major allergen bioavailability is examined. The HDM major allergen content, tablet disintegration times, and allergen release kinetics were determined. Dissolution kinetics (allergen concentration vs. time) of Der f 1, Der p 1, and Der 2 were measured. Area under the curve (AUC) was used as a surrogate parameter for allergen bioavailability. The release of HDM major allergens from the freeze-dried tablets was complete after 30 s, while only partial release was achieved with the compressed tablets, even after prolonged dissolution. At 1 min, i.e., the recommended sublingual holding time for the freeze-dried tablets, the allergen bioavailability (AUC) of the compressed 300 IR/57,000 JAU tablet was 4.7-fold (Der f 1), 10.8-fold (Der p 1), and 23.6-fold (Der 2) lower than that of the freeze-dried 12 SQ-HDM/20,000 JAU tablet and similar to (Der f 1) and 5.3-fold (Der p 1) and 12.5-fold (Der 2) lower than that of the freeze-dried 6 SQ-HDM/10,000 JAU tablet. SLIT tablet allergen bioavailability depends highly on the tablet formulation. Only the fast-dissolving freeze-dried tablets provide maximal delivery of soluble allergens and achieve allergen concentrations that reflect the nominal tablet strengths within the recommended sublingual holding time. © 2017 S. Karger AG, Basel.

  16. The effectiveness of Patient Controlled Analgesia (PCA morphine-ketamine compared to Patient Controlled Analgesia (PCA morphine to reduce total dose of morphine and Visual Analog Scale (VAS in postoperative laparotomy surgery

    Directory of Open Access Journals (Sweden)

    I Gusti Ngurah Mahaalit Aribawa

    2017-05-01

    Full Text Available Background: Laparotomy may cause moderate to severe after surgery pain, thus adequate pain management is needed. The addition of ketamine in patient controlled analgesia (PCA morphine after surgery can be the option. This study aims to evaluate the effectiveness of PCA morphine-ketamine compared to PCA morphine in patient postoperative laparotomy surgery to reduce total dose of morphine requirement and pain intensity evaluated with visual analog scale (VAS. Methods: This study was a double-blind RCT in 58 patients of ASA I and II, age 18-64 years, underwent an elective laparotomy at Sanglah General Hospital. Patients were divided into 2 groups. Group A, got addition of ketamine (1mg/ml in PCA morphine (1mg/ml and patients in group B received morphine (1mg/ml by PCA. Prior to surgical incision both group were given a bolus ketamine 0,15mg/ kg and ketorolac 0,5mg/kg. The total dose of morphine and VAS were measured at 6, 12, and 24 hours postoperatively. Result: Total dose of morphine in the first 24 hours postoperatively at morphine-ketamine group (5,1±0,8mg is lower than morphine only group (6,5±0,9mg p<0,001. VAS (resting 6 and 12 hour postoperative in morphine-ketamine group (13,4±4,8 mm and (10,7±2,6 mm are lower than morphine (17,9±4,1mm p≤0,05 and (12,8±5,3mm p≤0,05. VAS (moving 6, 12, and 24 hour postoperative morphineketamine group (24,8±5,1mm, (18±5,6mm and (9±5,6mm are lower than morphine (28,7±5,2mm p≤0,05, (23,1±6,0mm p≤0,05, and (12,8±5,3mm p≤0,05. Conclusions: Addition of ketamine in PCA morphine for postoperative laparotomy surgery reduces total morphine requirements in 24 hours compared to PCA morphine alone.

  17. Preparation of fluconazole buccal tablet and influence of formulation expedients on its properties.

    Science.gov (United States)

    Mohamed, Saifulla P; Muzzammil, Shariff; Pramod, Kumar T M

    2011-04-01

    The aim of present study was to prepare buccal tablets of fluconazole for oral candidiasis. The dosage forms were designed to release the drug above the minimum inhibitory concentration for prolonged period of time so as to reduce the frequency of administration and to overcome the side effects of systemic treatment. The buccal tablets were prepared by using Carbopol 71G and Noveon AA-1 by direct compression method. Microcrystalline cellulose was used as the filler and its effect was also studied. The prepared dosage forms were evaluated for physicochemical properties, in vitro release studies and mucoadhesive properties using sheep buccal mucosa as a model tissue. Tablets containing 50% of polymers (Carbopol & Noveon) were found to be the best with moderate swelling along with favorable bioadhesion force, residence time and in vitro drug release. The in vitro drug release studies revealed that drug released for 8 h, which in turn may reduce dosing frequency and improved patient compliance in oral candidiasis patients.

  18. Pharmaceutical equivalence of metformin tablets with various binders

    Directory of Open Access Journals (Sweden)

    L. C. Block

    2009-01-01

    Full Text Available

    Metformin hydrochloride is a high-dose drug widely used as an oral anti-hyperglycemic agent. As it is highly crystalline and has poor compaction properties, it is difficult to form tablets by direct compression. The aim of this study was to develop adequate metformin tablets, pharmaceutically equivalent to the reference product, Glucophage® (marketed as Glifage® in Brazil. Metformin 500mg tablets were produced by wet granulation with various binders (A = starch, B = starch 1500®, C = PVP K30®, D = PVP K90®. The tablets were analyzed for their hardness, friability, disintegration, dissolution, content uniformity and dissolution profile (basket apparatus at 50 rpm, pH 6.8 phosphate buffer. The 4 formulations, F1 (5% A and 5% C, F2 (5% B and 5% C, F3 (10% C and F4 (5% D, demonstrated adequate uniformity of content, hardness, friability, disintegration and total drug dissolution after 30 minutes (F1, F2 and F4, and after 60 minutes (F3. The drug release time profiles fitted a Higuchi model (F1, F2 and F3, similarly to the pharmaceutical reference, or a zero order model (F4. The dissolution efficiency for all the formulations was 75%, except for F3 (45%. F1 and F2 were thus equivalent to Glifage®. Keywords: dissolution; metformin; tablet; binder; pharmaceutical equivalence

  19. Sex differences in locomotor effects of morphine in the rat

    OpenAIRE

    Craft, Rebecca M.; Clark, James L.; Hart, Stephen P.; Pinckney, Megan K.

    2006-01-01

    Sex differences in reinforcing, analgesic and other effects of opioids have been demonstrated; however, the extent to which sex differences in motoric effects of opioids contribute to apparent sex differences in their primary effects is not known. The goal of this study was to compare the effects of the prototypic mu opioid agonist morphine on locomotor activity in male vs. female rats. Saline or morphine (1-10 mg/kg) was administered s.c. to adult Sprague-Dawley rats, which were placed into ...

  20. Methyl Parathion Masks Withdrawal from Physical Dependence on Morphine

    OpenAIRE

    Zhu, Hong; Ho, Ing K.; Kramer, Robert E.; Baker, Rodney C.; Rockhold, Robin W.

    2002-01-01

    Abstract: The cholinergic system has been proposed to participate in the development of dependence on opioids. The present study examined effects of dermal pretreatment with methyl parathion (MP), an acetylcholinesterase inhibitor, on the development of physical dependence on morphine. Opioid dependence was induced by continuous intracerebroventricular (i.c.v.) infusion of morphine (26 nmol/μl/h) for 3 days in adult male Sprague-Dawley rats. Each rat received two doses of MP, 12.5 mg/kg, d...

  1. Principles of Tablet Computing for Educators

    Science.gov (United States)

    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…

  2. Touch Screen Tablets and Emergent Literacy

    Science.gov (United States)

    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…

  3. TabletGaze: Unconstrained Appearance-based Gaze Estimation in Mobile Tablets

    OpenAIRE

    Huang, Qiong; Veeraraghavan, Ashok; Sabharwal, Ashutosh

    2015-01-01

    We study gaze estimation on tablets, our key design goal is uncalibrated gaze estimation using the front-facing camera during natural use of tablets, where the posture and method of holding the tablet is not constrained. We collected the first large unconstrained gaze dataset of tablet users, labeled Rice TabletGaze dataset. The dataset consists of 51 subjects, each with 4 different postures and 35 gaze locations. Subjects vary in race, gender and in their need for prescription glasses, all o...

  4. Exploration of central dopamine transporter and D2 receptor in morphine abstinent rats

    International Nuclear Information System (INIS)

    Lin Yansong; Wang Bocheng; Wang Shizhen; Ding Shiyu; Chen Zhengping; Zhang Manda

    2006-01-01

    The experiment was designed to investigate the variation of DAT and D2 receptor in morphine administered and 1,2,3 day abstinent rats. Morphine exposure was induced by repeated morphine (i.p.) treatment for 8 days. Conditioned place preference test was conducted to evaluate the drug seeking behaviour and morphine dependence of rats with morphine exposure. Biodistribution of the imaging agents 125 I-β-CIT and 125 I-IBZM was used to evaluate the central DAT and D2 receptor during morphine exposure and 1,2,3 day's abstinence. Results reveal the following facts. (1) The morphine abstinent rats showed diarrhea and body-shake 1 day after morphine withdrawal. (2) For morphine group, 125 I-β-CIT %ID/g in ST and NAC was higher than that of the 1,2,3 day's abstinent rats and control (P 0.05). (3) 125 I-IBZM %ID/g in ST, NAC and HIP in morphine rats were lower than those of the abstinent and control rats (P 125 I-IBZM %ID/g in ST and NAC gradually increased with the abstinent days. While in ST the %ID/g among the abstinent rats was all lower than that of the control rats, in NAC the %ID/g was still lower in 1 day's abstinent rats (P 0.05), indicating the reduction of hyper-activated DAT and the increase of down-regulatory D2 receptor induced by morphine during morphine withdrawal. Our results confirmed that the dopamine system, especially DAT and D2 receptor in mesolimbic and meso-striatum pathway, has been implicated in morphine treatment. The rewarding properties of morphine and the somatic expression of morphine abstinence were related to changes in mesolimbic and meso-striatum dopaminergic activity. (authors)

  5. Characterization of a Single Chain Fv Antibody that Reacts with Free Morphine

    OpenAIRE

    Matsukizono, Miho; Kamegawa, Mariko; Tanaka, Koichi; Kohra, Shinya; Arizono, Koji; Hamazoe, Yuta; Sugimura, Kazuhisa

    2013-01-01

    An immune phage library derived from mice, hyperimmunized with morphine-conjugated BSA, was used to isolate a single-chain Fv (scFv) clone, M86, with binding activity to morphine-conjugated thyroglobulin (morphine-C-Tg) but not to codeine-, cocaine-, or ketamine-conjugated Tg. Surface plasmon resonance analysis using a morphine-C-Tg-coupled CM5 sensor chip showed that the Kd value was 1.26 × 10−8 M. To analyze its binding activity to free morphine and related compounds, we performed a competi...

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

    Science.gov (United States)

    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

    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. 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. 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. 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

  7. Pharmacological consequences of long-term morphine treatment in patients with cancer and chronic non-malignant pain

    DEFF Research Database (Denmark)

    Andersen, Gertrud; Sjøgren, Per; Hansen, Steen Honoré

    2004-01-01

    In patients with pain of malignant origin morphine may be administered in high and often increasing doses during extended periods of time. In patients with chronic pain of non-malignant origin morphine may be an important remedy, and in these cases the goal is to keep the morphine dose stable. Th....... The pharmacokinetic as well as the pharmacodynamic consequences of long-term morphine treatment with special reference to the two most important metabolites of morphine morphine-6-glucuronide (M-6-G) and morphine-3-glucuronide (M-3-G) remain to be settled....

  8. Learning, Tablet, Culture-Coherence?

    Science.gov (United States)

    Norqvist, Lars

    2016-01-01

    This paper presents understandings of learning in schools where Internet-enabled Information and Communication Technologies (ICTs) are taken for granted. The context is a full-scale 1:1 tablet project in Danish municipality schools where this study bring forward expressions of learning from one class (12-13 year old children) in order to offer…

  9. Acetaminophen and non-steroidal anti-inflammatory drugs interact with morphine and tramadol analgesia for the treatment of neuropathic pain in rats.

    Science.gov (United States)

    Shinozaki, Tomonari; Yamada, Toshihiko; Nonaka, Takahiro; Yamamoto, Tatsuo

    2015-06-01

    Although non-steroidal anti-inflammatory drugs and acetaminophen have no proven efficacy against neuropathic pain, they are frequently prescribed for neuropathic pain patients. We examined whether the combination of opioids (tramadol and morphine) with indomethacin or acetaminophen produce favorable effects on neuropathic pain and compared the efficacy for neuropathic pain with that for inflammatory pain. The carrageenan model was used as the inflammatory pain model while the tibial neuroma transposition (TNT) model was used as the neuropathic pain model. The tibial nerve is transected in the TNT model, with the tibial nerve stump then transpositioned to the lateral aspect of the hindlimb. Neuropathic pain (mechanical allodynia and neuroma pain) is observed after TNT injury. Drugs were administered orally. In the carrageenan model, all drugs produced anti-allodynic effects and all drug combinations, but not tramadol + indomethacin combination, produced synergistic anti-allodynic effects. In the TNT model, tramadol and morphine, but not acetaminophen and indomethacin, produced anti-neuropathic pain effects. In the combination, with the exception of morphine + acetaminophen combination, both acetaminophen and indomethacin reduced the 50% effective dose (ED50) of tramadol and morphine as compared with the ED50s for the single drug study in the TNT model. The ED50s of tramadol and morphine in the carrageenan combination test were not statistically significantly different from the ED50s in the TNT model combination study. The combination of opioids with indomethacin or acetaminophen produced a synergistic analgesic effect both in inflammatory and neuropathic pain with some exceptions. The efficacy of these combinations for neuropathic pain was not different from that for inflammatory pain.

  10. [Effects of odor cue on morphine-induced dependence and craving in mice].

    Science.gov (United States)

    Liu, Xiao-Fen; Yang, Guang; Yang, Rui; Jia, Qiang; Guan, Su-Dong

    2012-04-01

    The olfactory system may play a pivotal role in drug addiction. To clarify the issues, we investigated the morphine dependence and psychological craving in morphine addicted mice using the conditioned place preference (CPP) paradigm by taking an only odor cue as the conditioned stimulus (CS). The results showed that by pairing morphine with odor, the CPP could be induced in mice. When the morphine addicted mice were exposed to a novel environment during morphine withdrawal, they spent significantly longer time in the chamber with morphine-paired odor than in the control chamber. The effects of odor cue on the morphine CPP were blocked by the administration of dopamine D1 or D2 antagonists. The studies indicated that olfactory system plays an important role in drug addiction.

  11. Steady-state kinetics and dynamics of morphine in cancer patients

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Sjøgren, P; Jensen, N H

    1999-01-01

    Eighteen patients suffering from chronic pain due to cancer completed a balanced, double-blind, double-dummy, two period cross-over trial comparing the pharmacokinetics (PK) and pharmacodynamics (PD) of morphine and its metabolites, morphine-3-glucuronide and morphine-6-glucuronide, after...... samples for analysis of morphine, morphine-3-glucuronide, and morphine-6-glucuronide were obtained. Pain intensity, sedation, and continuous reaction time (CRT) were assessed. No significant differences could be demonstrated in AUC/dose, Cmin, Cmax or fluctuation index values between the two treatments...... and the variability in the data, the statistical power of the test was only 0.074. The risk of a type II error is 0.926. These data demonstrate the PK and PD similarities and differences between CR and IR morphine. They suggest that there may be a relationship between Tmax (determined by absorption rate) and sedation...

  12. Stage control of tablets manufacturing

    Directory of Open Access Journals (Sweden)

    L. I. Kucherenko

    2014-08-01

    Full Text Available Today in Ukraine tuberculosis is the wide-spread infectious disease causing the death in most cases; about 700 thousand persons are suffering from it. In Ukraine epidemic of tuberculosis is progressing and spreading. In spite of all protective measures three inhabitants of our country contract tuberculosis per hour, every hour one patient dies and in common about 1.5% of the population is ill with tuberculosis. Isoniazid is antituberculous drug of the first line and it is the most effective one. Chemotherapy of tuberculosis requests long-lasting administration of antituberculous drugs that causes high risk of side effects. To prevent or lessen side effects of antituberculous medicines antioxidants use in complex therapy is perspective. Fulfilled investigations showed efficacy of combining two medical substances – isoniazid andthiotriazolin – in one dosage form. Objective.The aim of our investigation is working out the methods of standardization, in particularquantitative determination of isoniazid andthiotriazolin content in tablet mass by high-performance liquid chromatography (HPLC. Materials and Methods.During in-process investigations combined tableted remedy containing isoniazid andthiotriazolin and proper amount of adjuvants has been developed (it contains active substances isoniazid – 0.2 g,thiotriazolin – 0.05 g and adjuvants up to the 0.4 g of the tablet. During stage control of tablets manufacturingspecial attention is paid to the control of tablet mass quality. Especially it concerns quantitative determination of active substances in it. More and more attention is paid to modern physical-chemical methods of standardization in up-to-date analysis of drug products, such as ultraviolet spectrometry, high-performance liquid chromatography (HPLC etc. In previous scientific investigations we proved the possibility of standardization of active substances artificial compound by HPLC method and optimal conditions of analysis performing

  13. Quantitative Appearance Inspection for Film Coated Tablets.

    Science.gov (United States)

    Yoshino, Hiroyuki; Yamashita, Kazunari; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

    2016-01-01

    The decision criteria for the physical appearance of pharmaceutical products are subjective and qualitative means of evaluation that are based entirely on human interpretation. In this study, we have developed a comprehensive method for the quantitative analysis of the physical appearance of film coated tablets. Three different kinds of film coated tablets with considerable differences in their physical appearances were manufactured as models, and their surface roughness, contact angle, color measurements and physicochemical properties were investigated as potential characteristics for the quantitative analysis of their physical appearance. All of these characteristics were useful for the quantitative evaluation of the physical appearances of the tablets, and could potentially be used to establish decision criteria to assess the quality of tablets. In particular, the analysis of the surface roughness and film coating properties of the tablets by terahertz spectroscopy allowed for an effective evaluation of the tablets' properties. These results indicated the possibility of inspecting the appearance of tablets during the film coating process.

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

    OpenAIRE

    Karamese, Mehtap; 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 (I...

  15. Modulation of dopaminergic neurotransmission by morphine in the rat

    NARCIS (Netherlands)

    P. Moleman (Peter)

    1977-01-01

    textabstractThe pleasant effects of opium were already known 6000 years ago and opium has been used for medical purposes for at least 3500 years. Opium, and its r.1ain constituent morphine, evoke a feeling of well-being and always relieve pain of any origin, in other words, a perfect analgesic and

  16. Stress-opioid interactions: a comparison of morphine and methadone.

    Science.gov (United States)

    Taracha, Ewa; Mierzejewski, Paweł; Lehner, Małgorzata; Chrapusta, Stanisław J; Kała, Maria; Lechowicz, Wojciech; Hamed, Adam; Skórzewska, Anna; Kostowski, Wojciech; Płaźnik, Adam

    2009-01-01

    The utility of methadone and morphine for analgesia and of methadone for substitution therapy for heroin addiction is a consequence of these drugs acting as opioid receptor agonists.We compared the cataleptogenic and antinociceptive effects of single subcutaneous doses of methadone hydrochloride (1-4 mg/kg) and morphine sulfate (2.5-10 mg/kg) using catalepsy and hot-plate tests, and examined the effects of the highest doses of the drugs on Fos protein expression in selected brain regions in male Sprague-Dawley rats. Methadone had greater cataleptogenic and analgesic potency than morphine. Fos immunohistochemistry revealed substantial effects on the Fos response of both the stress induced by the experimental procedures and of the drug exposure itself. There were three response patterns identified: 1) drug exposure, but not stress, significantly elevated Fos-positive cell counts in the caudate-putamen; 2) stress alone and stress combined with drug exposure similarly elevated Fos-positive cell counts in the nucleus accumbens and cingulate cortex; and 3) methadone and morphine (to a lesser extent) counteracted the stimulatory effect of nonpharmacological stressors on Fos protein expression in the somatosensory cortex barrel field, and Fos-positive cell counts in this region correlated negatively with both the duration of catalepsy and the latency time in the hot-plate test. The overlap between brain regions reacting to nonpharmacological stressors and those responding to exogenous opioids suggests that stress contributes to opioid-induced neuronal activation.

  17. Morphine sparing effect of low dose ketamine during patient ...

    African Journals Online (AJOL)

    Measurements: Morphine consumption, visual analogue pain score (VAPS), pulse oximetry oxygen saturation (SpO2), respiratory rate (RR), verbal descriptive sedation score (VDSS), nausea, pruritis, dreaming, and hallucinations were recorded at 1, 4, 24 and 48 hours. Equivalence of the two groups was assessed by ...

  18. Mighty Morphin Power Ranger Play: Research and Reality.

    Science.gov (United States)

    Crosser, Sandra

    1995-01-01

    Explores the question of whether or not Mighty Morphin Power Rangers-type aggressive play is developmentally appropriate for the early childhood classroom. Compares results from research in child development to the reality of television programming, highlighting the relationship between television violence and children's aggressive behavior. (AA)

  19. Morphine more fine? Its effects in critically ill newborns

    NARCIS (Netherlands)

    S.H.P. Simons (Sinno)

    2004-01-01

    textabstractThe pharmacist Sertürner first isolated morphine from opium in 1803 and named it after Morpheus, the god of dreams in Greco-Roman mythology. Ever since, it has been one of the most frequently used drugs to relieve pain, for a variety of age groups. In our days, however, there is still

  20. Comparison of Patient-Controlled Analgesia Using Morphine With and Without Paracetamol in Postoperative Pain Control

    Directory of Open Access Journals (Sweden)

    Mehryar Taghavi Gilani

    2016-04-01

    Full Text Available Introduction: Postoperative pain control plays a pivotal role in reducing postoperative complications, hospitality time, and increasing satisfaction. This study aimed to evaluate the effect of paracetamol on the pain and complications caused by gastrectomy. Materials and Methods: This randomized prospective study was conducted on 60 patients (two same group who were candidate for gastrectomy in Imam Reza Hospital of Mashhad, Iran during August-September 2015. The first group received Patient-Controlled Analgesia (PCA with morphine only, and in the second group, paracetamol (1 gram infused with morphine every six hours. Level of pain, morphine intake, and side effects were evaluated in both groups. Results:No significant difference was observed in the four-scale score of pain in the patients (morphine group: 0.64±0.1, morphine-paracetamol group: 0.6±0.1 (P=0.72. During the first 24 hours after the surgery, the morphine group had lower consciousness level (2.3±0.2 compared to the morphine-paracetamol group (1.7±0.3 (P=0.001. Moreover, infusion of paracetamol with morphine to control the pain after gastrectomy reduced the need for morphine analgesia. Morphine intake was 21.4±7.7 in morphine group, while it was 14.3±5.8 in the morphine-paracetamol group within the first 24 hours after the surgery (P=0.001. However, this level had no significant effect on postoperative complications such as itching, nausea, and arterial oxygen saturation. Conclusion: According to the results of this study, intravenous paracetamol (one gram administered every six hours with PCA using morphine could decrease morphine intake leading to better consciousness level during the first 24 hours after gastrectomy without further complications.

  1. Expression changes of hippocampal energy metabolism enzymes contribute to behavioural abnormalities during chronic morphine treatment

    Institute of Scientific and Technical Information of China (English)

    Xiao-Lan Chen; Jing-Gen Liu; Gang Lu; Ying-Xia Gong; Liang-Cai Zhao; Jie Chen; Zhi-Qiang Chi; Yi-Ming Yang; Zhong Chen; Qing-lin Li

    2007-01-01

    Dependence and impairment of learning and memory are two well-established features caused by abused drugs such as opioids. The hippocampus is an important region associated with both drug dependence and learning and memory. However, the molecular events in hippocampus following exposure to abused drugs such as opioids are not well understood. Here we examined the effect of chronic morphine treatment on hippocampal protein expression by proteomic analyses. We found that chronic exposure of mice to morphine for 10 days produced robust morphine withdrawal jumping and memory impairment, and also resulted in a significant downregulation of hippocampal protein levels of three metabolic enzymes, including Fe-S protein 1 of NADH dehydrogenase, dihydrolipoamide acetyltransferase or E2 component of the pyruvate dehydrogenase complex and lactate dehydrogenase 2. Further real-time quantitative PCR analyses confirmed that the levels of the corresponding mRNAs were also remarkably reduced. Consistent with these findings, lower ATP levels and an impaired ability to convert glucose into ATP were also observed in the hippocampus of chronically treated mice. Opioid antagonist naltrexone administrated concomitantly with morphine significantly suppressed morphine withdrawal jumping and reversed the downregulation of these proteins. Acute exposure to morphine also produced robust morphine withdrawal jumping and significant memory impairment, but failed to decrease the expression of these three proteins. Intrahippocampal injection of D-glucose before morphine administration significantly enhanced ATP levels and suppressed morphine withdrawal jumping and memory impairment in acute morphine-treated but not in chronic morphine-treated mice. Intraperitoneal injection of high dose of D-glucose shows a similar effect on morphine-induced withdrawal jumping as the central treatment. Taken together, our results suggest that reduced expression of the three metabolic enzymes in the hippocampus as

  2. Development and Characterization of Novel Floating-Mucoadhesive Tablets Bearing Venlafaxine Hydrochloride

    Directory of Open Access Journals (Sweden)

    Raghvendra Misra

    2016-01-01

    Full Text Available The present investigation is concerned about the development of floating bioadhesive drug delivery system of venlafaxine hydrochloride which after oral administration exhibits a unique combination of floating and bioadhesion to prolong gastric residence time and increase drug bioavailability within the stomach. The floating bioadhesive tablets were prepared by the wet granulation method using different ratios of hydroxypropyl methyl cellulose (HPMC K4MCR and Carbopol 934PNF as polymers. Sodium bicarbonate (NaHCO3 and citric acid were used as gas (CO2 generating agents. Tablets were characterized for floating properties, in vitro drug release, detachment force, and swelling index. The concentration of hydroxypropyl methyl cellulose and Carbopol 934PNF significantly affects the in vitro drug release, floating properties, detachment force, and swelling properties of the tablets. The optimized formulation showed the floating lag time 72±2.49 seconds and duration of floating 24.50±0.74 hr. The in vitro release studies and floating behavior were studied in simulated gastric fluid (SGF at pH 1.2. Different drug release kinetics models were also applied. The in vitro drug release from tablets was sufficiently sustained (more than 18 hr and the Fickian transports of the drug from the tablets were confirmed. The radiological evidence suggests that the tablets remained buoyant and altered position in the stomach of albino rabbit and mean gastric residence time was prolonged (more than > 6 hr.

  3. Experimental study of tensile strength of pharmaceutical tablets: effect of the diluent nature and compression pressure

    Directory of Open Access Journals (Sweden)

    Juban Audrey

    2017-01-01

    Full Text Available In the pharmaceutical field, tablets are the most common dosage form for oral administration in the world. Among different manufacturing processes, direct compression is widely used because of its economics interest and it is a process which avoids the steps of wet granulation and drying processes. Tablets are composed of at least two ingredients: an active pharmaceutical ingredient (API which is mixed with a diluent. The nature of the powders and the processing conditions are crucial for the properties of the blend and, consequently, strongly influence the mechanical characteristics of tablets. Moreover, tablets have to present a suitable mechanical strength to avoid crumbling or breaking when handling, while ensuring an appropriate disintegration after administration. Accordingly, this mechanical property is an essential parameter to consider. Experimental results showed that proportion of the diluent, fragmentary (DCPA or plastic (MCC, had a large influence on the tensile strength evolution with API content as well as the compression load applied during tableting process. From these results a model was developed in order to predict the tensile strength of binary tablets by knowing the compression pressure. The validity of this model was demonstrated for the two studied systems and a comparison was made with two existing models.

  4. Experimental study of tensile strength of pharmaceutical tablets: effect of the diluent nature and compression pressure

    Science.gov (United States)

    Juban, Audrey; Briançon, Stéphanie; Puel, François; Hoc, Thierry; Nouguier-Lehon, Cécile

    2017-06-01

    In the pharmaceutical field, tablets are the most common dosage form for oral administration in the world. Among different manufacturing processes, direct compression is widely used because of its economics interest and it is a process which avoids the steps of wet granulation and drying processes. Tablets are composed of at least two ingredients: an active pharmaceutical ingredient (API) which is mixed with a diluent. The nature of the powders and the processing conditions are crucial for the properties of the blend and, consequently, strongly influence the mechanical characteristics of tablets. Moreover, tablets have to present a suitable mechanical strength to avoid crumbling or breaking when handling, while ensuring an appropriate disintegration after administration. Accordingly, this mechanical property is an essential parameter to consider. Experimental results showed that proportion of the diluent, fragmentary (DCPA) or plastic (MCC), had a large influence on the tensile strength evolution with API content as well as the compression load applied during tableting process. From these results a model was developed in order to predict the tensile strength of binary tablets by knowing the compression pressure. The validity of this model was demonstrated for the two studied systems and a comparison was made with two existing models.

  5. Morphine as first medication for treatment of cancer pain

    Directory of Open Access Journals (Sweden)

    Beatriz C. Nunes

    2014-07-01

    Full Text Available BACKGROUND AND OBJECTIVES: the medications used according to the recommendation of the World Health Organization do not promote pain relief in a number of patients with cancer pain. The aim of this study was to evaluate the use of morphine as first medication for the treatment of moderate cancer pain in patients with advanced and/or metastatic disease, as an option to the recommendations of the World Health Organization analgesic ladder. METHOD: sixty patients without opioid therapy, with >18 years of age, were randomized into two groups. G1 patients received medication according to the analgesic ladder and started treatment with non-opioids in the first, weak opioids in the second, and strong opioids in the third step; G2 patients received morphine as first analgesic medication. The efficacy and tolerability of initial use of morphine were evaluated every two weeks for three months. RESULTS: the groups were similar with respect to demographic data. There was no significant difference between the groups regarding pain intensity, quality of life, physical capacity, satisfaction with treatment, need for complementation and dose of morphine. In G1 there was a higher incidence of nausea (p = 0.0088, drowsiness (p = 0.0005, constipation (p = 0.0071 and dizziness (p = 0.0376 in the second visit and drowsiness (p = 0.05 in the third. CONCLUSIONS: the use of morphine as first medication for pain treatment did not promote better analgesic effect than the ladder recommended by World Health Organization, with higher incidence of adverse effects.

  6. Influence of fentanyl and morphine on intestinal circulation

    International Nuclear Information System (INIS)

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

    1985-01-01

    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 86 Rb and 9-micron spheres labeled with 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 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

  7. Influence of fentanyl and morphine on intestinal circulation

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. A randomized study of the effects of single-dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy

    DEFF Research Database (Denmark)

    Dirks, Jesper; Fredensborg, Birgitte B; Christensen, Dennis

    2002-01-01

    BACKGROUND: The anticonvulsant gabapentin has proven effective for neuropathic pain in three large placebo-controlled clinical trials. Experimental and clinical studies have demonstrated antihyperalgesic effects in models involving central neuronal sensitization. It has been suggested that central...... neuronal sensitization may play an important role in postoperative pain. The aim of the study was to investigate the effect of gabapentin on morphine consumption and postoperative pain in patients undergoing radical mastectomy. METHODS: In a randomized, double-blind, placebo-controlled study, 70 patients...... received a single dose of oral gabapentin (1,200 mg) or placebo 1 h before surgery. Patients received patient-controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10 min for 4 h postoperatively. Pain was assessed on a visual analog scale at rest and during movement, and side...

  9. Long-term safety and efficacy of single-tablet combinations of solifenacin and tamsulosin oral controlled absorption system in men with storage and voiding lower urinary tract symptoms: results from the NEPTUNE Study and NEPTUNE II open-label extension.

    Science.gov (United States)

    Drake, Marcus J; Chapple, Christopher; Sokol, Roman; Oelke, Matthias; Traudtner, Klaudia; Klaver, Monique; Drogendijk, Ted; Van Kerrebroeck, Philip

    2015-02-01

    Short-term trials have demonstrated the efficacy and safety of combination therapy using antimuscarinics and α-blockers in men with lower urinary tract symptoms (LUTS). The Study of Solifenacin Succinate and Tamsulosin Hydrochloride OCAS (oral controlled absorption system) in Males with Lower Urinary Tract Symptoms (NEPTUNE) II is the first long-term study using solifenacin (Soli) and the oral controlled absorption system formulation of tamsulosin (TOCAS). To evaluate long-term (up to 52 wk) safety and efficacy of flexible dosing of two fixed-dose combinations (FDC) of Soli plus TOCAS in men with moderate to severe storage symptoms and voiding symptoms. Patients with both storage and voiding LUTS, maximum urinary flow rate of 4.0-12.0 ml/s, prostate size storage and voiding subscores, micturition diary variables, and quality of life parameters. In all, 1066 men completed NEPTUNE and received one dose or more of study medication in NEPTUNE II. Treatment-emergent adverse events were reported in 499 (46.8%) patients who participated in NEPTUNE II; most were mild or moderate. Urinary retention occurred in 13 of 1208 (1.1%) patients receiving one or more FDCs in NEPTUNE and/or NEPTUNE II; 8 (0.7%) required catheterisation (acute urinary retention [AUR]). Reductions in total IPSS and TUFS during NEPTUNE were maintained for up to 52 wk of FDC treatment, with mean reductions of 9.0 (standard deviation [SD]: 5.7) and 10.1 (SD: 9.2), respectively, from baseline to end of treatment. Clinically relevant improvements were also observed for secondary efficacy end points. Long-term treatment with FDC Soli plus TOCAS was well tolerated and efficacious in men with storage and voiding LUTS, with a low incidence of AUR. Treatment with solifenacin plus tamsulosin in a fixed-dose combination tablet was well tolerated by men with lower urinary tract symptoms. Improvements in symptoms were achieved after 4 wk of treatment, with further improvements at week 16 maintained for up to 52 wk

  10. Evaluation of the Effectiveness of Two Morphine Protocols to Treat Neonatal Abstinence Syndrome in a Level II Nursery in a Community Hospital.

    Science.gov (United States)

    DeAtley, Heather N; Burton, Amanda; Fraley, Michelle DeLuca; Haltom, Joan

    2017-07-01

    The authors sought to evaluate the impact on length of hospital stay and treatment duration of morphine after implementation of a change in the institutional protocol for managing neonatal abstinence syndrome (NAS) in an effort to improve patient outcomes. A single-center, retrospective chart review was conducted at a Level II nursery in a community hospital in Kentucky. Fifty-nine neonates born between January 1, 2014, and December 31, 2015, who were diagnosed with NAS and received morphine for treatment were included. The protocol 1 group consisted of 33 neonates who received an initial dose of morphine 0.04 mg/kg/dose administered orally every 4 hours (January 1-December 31, 2014), and the protocol 2 group consisted of 26 neonates who received an initial dose of morphine 0.06 mg/kg/dose administered orally every 3 hours (January 1-November 30, 2015), after a change in the protocol for managing NAS was implemented on January 1, 2015. Data were reviewed and compared between the two protocol groups to determine the impact that the dosage change had on length of hospital stay and morphine treatment duration. The average length of stay decreased by 7 days in the protocol 2 group compared with the protocol 1 group (21 vs 28.65 days). The average duration of treatment decreased by 7 days in the protocol 2 group compared with the protocol 1 group (18.3 vs 25.4 days). These differences between groups were not statistically significant, however, because the population size was not large enough to achieve adequate power. These results indicate that protocol 2 displayed the potential to decrease length of stay and duration of treatment compared with protocol 1 at this facility; however, balancing higher starting doses with the risk of oversedation will continue to challenge the health care team. Concern for oversedation when using the higher starting dose in protocol 2 has prompted further research (e.g., protocol 3, initial morphine 0.05 mg/kg/dose every 3 hrs). Continued

  11. Long-term morphine delivery via slow release morphine pellets or osmotic pumps: Plasma concentration, analgesia, and naloxone-precipitated withdrawal.

    Science.gov (United States)

    McLane, Virginia D; Bergquist, Ivy; Cormier, James; Barlow, Deborah J; Houseknecht, Karen L; Bilsky, Edward J; Cao, Ling

    2017-09-15

    Slow-release morphine sulfate pellets and osmotic pumps are common routes of chronic morphine delivery in mouse models, but direct comparisons of these drug delivery systems are lacking. In this study, we assessed the efficacy of slow-release pellets versus osmotic pumps in delivering morphine to adult mice. Male C57BL/6NCr mice (8weeksold) were implanted subcutaneously with slow-release pellets (25mg morphine sulfate) or osmotic pumps (64mg/mL, 1.0μL/h). Plasma morphine concentrations were quantified via LC-MS/MS, analgesic efficacy was determined by tail flick assay, and dependence was assessed with naloxone-precipitated withdrawal behaviors (jumping) and physiological effects (excretion, weight loss). Morphine pellets delivered significantly higher plasma drug concentrations compared to osmotic pumps, which were limited by the solubility of the morphine sulfate and pump volume/flow rate. Within 96h post-implantation, plasma morphine concentrations were indistinguishable in pellet vs. pump-treated samples. While osmotic pump did not have an antinociceptive effect in the tail flick assay, pumps and pellets induced comparable dependence symptoms (naloxone-precipitated jumping behavior) from 24-72h post-implantation. In this study, we compared slow-release morphine pellets to osmotic minipumps for morphine delivery in mice. We found that osmotic pumps and subcutaneous morphine sulfate pellets yielded significantly different pharmacokinetics over a 7-day period, and as a result significantly different antinociceptive efficacy. Nonetheless, both delivery methods induced dependence as measured by naloxone-precipitated withdrawal. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Esophageal transit and in vivo disintegration of branded risedronate sodium tablets and two generic formulations of alendronic acid tablets: a single-center, single-blind, six-period crossover study in healthy female subjects.

    Science.gov (United States)

    Perkins, Alan C; Blackshaw, P Elaine; Hay, Peter D; Lawes, Simon C; Atherton, Clare T; Dansereau, Richard J; Wagner, Leigh K; Schnell, Dan J; Spiller, Robin C

    2008-05-01

    Delayed esophageal transit or disintegration of oral bisphosphonate tablets before they enter the stomach may be of concern with respect to iatrogenic complications among patients receiving longterm treatment. Different formulations of generic bisphosphonate tablets meeting regulatory requirements may have substantial differences in pharmaceutical attributes from the branded product that may result in different characteristics during esophageal transit. The primary objective of this study was to evaluate and compare esophageal transit times and in vivo disintegration of 3 bisphosphonate formulations, one branded and the others generic, that are commercially available in Canada and the United Kingdom. This was a single-center, randomized, singleblind, 6-period crossover study in healthy postmenopausal women aged >50 years. Each subject received a single oral dose of a branded risedronate sodium 35-mg tablet and 2 generic formulations of alendronic acid 70-mg tablets (Novopharm Limited, Toronto, Canada, and Teva UK Limited, Morley, United Kingdom) in both the erect and semisupine (45 degrees ) positions. Although the products are labeled to be taken in the erect position, the semisupine position was included to simulate dosing in bedridden patients. Subjects took tablets with 30 mL of water in the morning after an overnight fast. The tablets were radiolabeled with technetium-99m ion-exchange resins to enable visualization and measurement of esophageal transit time and disintegration using a gamma camera. Dynamic scintigraphic images were obtained for a total of 10 minutes: 2 images per second for the first 30 seconds and 1 image every 15 seconds for 9.5 minutes. This was a mechanistic study and tolerability was not assessed. The study was conducted in 20 healthy white female subjects with a mean age of 62 years (range, 51-77 years). The effect of body position was statistically significant (P = 0.043), with the estimated hazard ratio (HR) of 0.74 indicating longer

  13. Implementation of Quality by Design for Formulation of Rebamipide Gastro-retentive Tablet.

    Science.gov (United States)

    Ha, Jung-Myung; Seo, Jeong-Woong; Kim, Su-Hyeon; Kim, Ju-Young; Park, Chun-Woong; Rhee, Yun-Seok; Park, Eun-Seok

    2017-11-01

    The purpose of the present study was to develop a rebamipide (RBM) gastro-retentive (GR) tablet by implementing quality by design (QbD). RBM GR tablets were prepared using a sublimation method. Quality target product profile (QTPP) and critical quality attributes (CQAs) of the RBM GR tablets were defined according to the preliminary studies. Factors affecting the CQAs were prioritized using failure mode and effects analysis (FMEA). Design space and optimum formulation were established through a mixture design. The validity of the design space was confirmed using runs within the area. The QTPP of the RBM GR tablets was the orally administered GR tablet containing 300 mg of RBM taken once daily. Based on the QTPP, dissolution rate, tablet friability, and floating property were chosen as CQAs. According to the risk assessment, the amount of sustained-release agent, sublimating material, and diluent showed high-risk priority number (RPN) values above 40. Based on the RPN, these factors were further investigated using mixture design methodology. Design space of formulations was depicted as an overlaid contour plot and the optimum formulation to satisfy the desired responses was obtained by determining the expected value of each response. The similarity factor (f2) of the release profile between predicted response and experimental response was 89.463, suggesting that two release profiles are similar. The validity of the design space was also confirmed. Consequently, we were able to develop the RBM GR tablets by implementing the QbD concept. These results provide useful information for development of tablet formulations using the QbD.

  14. 3D extrusion printing of high drug loading immediate release paracetamol tablets.

    Science.gov (United States)

    Khaled, Shaban A; Alexander, Morgan R; Wildman, Ricky D; Wallace, Martin J; Sharpe, Sonja; Yoo, Jae; Roberts, Clive J

    2018-03-01

    The manufacture of immediate release high drug loading paracetamol oral tablets was achieved using an extrusion based 3D printer from a premixed water based paste formulation. The 3D printed tablets demonstrate that a very high drug (paracetamol) loading formulation (80% w/w) can be printed as an acceptable tablet using a method suitable for personalisation and distributed manufacture. Paracetamol is an example of a drug whose physical form can present challenges to traditional powder compression tableting. Printing avoids these issues and facilitates the relatively high drug loading. The 3D printed tablets were evaluated for physical and mechanical properties including weight variation, friability, breaking force, disintegration time, and dimensions and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). X-ray Powder Diffraction (XRPD) was used to identify the physical form of the active. Additionally, XRPD, Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC) were used to assess possible drug-excipient interactions. The 3D printed tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed a profile characteristic of the immediate release profile as intended based upon the active/excipient ratio used with disintegration in less than 60 s and release of most of the drug within 5 min. The results demonstrate the capability of 3D extrusion based printing to produce acceptable high-drug loading tablets from approved materials that comply with current USP standards. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Near-Infrared Spatially Resolved Spectroscopy for Tablet Quality Determination.

    Science.gov (United States)

    Igne, Benoît; Talwar, Sameer; Feng, Hanzhou; Drennen, James K; Anderson, Carl A

    2015-12-01

    Near-infrared (NIR) spectroscopy has become a well-established tool for the characterization of solid oral dosage forms manufacturing processes and finished products. In this work, the utility of a traditional single-point NIR measurement was compared with that of a spatially resolved spectroscopic (SRS) measurement for the determination of tablet assay. Experimental designs were used to create samples that allowed for calibration models to be developed and tested on both instruments. Samples possessing a poor distribution of ingredients (highly heterogeneous) were prepared by under-blending constituents prior to compaction to compare the analytical capabilities of the two NIR methods. The results indicate that SRS can provide spatial information that is usually obtainable only through imaging experiments for the determination of local heterogeneity and detection of abnormal tablets that would not be detected with single-point spectroscopy, thus complementing traditional NIR measurement systems for in-line, and in real-time tablet analysis. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Rebeccah Slater

    2016-11-01

    Full Text Available Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants.   A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP screening and heel lancing provides effective analgesia. 
156 infants between 34 and 42 weeks’ gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration.   The primary outcome will be the Premature Infant Pain Profile–revised (PIPP-R score 30 seconds after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as an Accepted Protocol Summary by The Lancet.

  17. Effect of Nimodipine on Morphine-related Withdrawal Syndrome in Rat Model: An Observational Study

    Science.gov (United States)

    Mishra, Pravash Ranjan; Barik, Mayadhar; Ray, Subrata Basu

    2017-01-01

    Objective: To observe the effect of L-type calcium channel blocker like nimodipine on morphine's withdrawal when it was administered continuously along with morphine versus a single bolus dose of nimodipine, which was administered at the end of the experiment before the precipitation of withdrawal reaction in morphine-dependent rats. Materials and Methods: Four groups of adult male Wistar rats were rendered morphine dependent by subcutaneous injections of morphine at a dose of 10 mg/kg for 10 days. Nimodipine 10 mg/kg intraperitoneally (ip) administered to one group once daily before morphine administration in the entire experimental period, and another group received nimodipine only once at the end of the experiment as a single bolus dose 2 mg/kg before the administration of naloxone. Naloxone 3 mg/kg was administered ip to all the groups to precipitate withdrawal reactions. The withdrawal reactions were evaluated and scored as per the Gellert and Holtzman global withdrawal rating scale. Results: Nimodipine when administered as a single bolus dose before naloxone administration in morphine-dependant rats reduced the features of withdrawal reactions more effectively than continuous administration of nimodipine along with morphine throughout the experimental period. Conclusion: We discovered that nimodipine helps in attenuating the severity of morphine withdrawal having potential role encountered during pharmacotherapy with morphine management of opioid dependence, well memory, impairement, cell signaling and phosphorylation of neuron. PMID:28553371

  18. PolyMorphine: an innovative biodegradable polymer drug for extended pain relief.

    Science.gov (United States)

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

    2012-09-28

    Morphine, a potent narcotic analgesic used for the treatment of acute and chronic pain, was chemically incorporated into a poly(anhydride-ester) backbone. The polymer termed "PolyMorphine", was designed to degrade hydrolytically releasing morphine in a controlled manner to ultimately provide analgesia for an extended time period. PolyMorphine was synthesized via melt-condensation polymerization and its structure was characterized using proton and carbon nuclear magnetic resonance spectroscopies, and infrared spectroscopy. The weight-average molecular weight and the thermal properties were determined. The hydrolytic degradation pathway of the polymer was determined by in vitro studies, showing that free morphine is released. In vitro cytocompatibility studies demonstrated that PolyMorphine is non-cytotoxic towards fibroblasts. In vivo studies using mice showed that PolyMorphine provides analgesia for 3 days, 20 times the analgesic window of free morphine. The animals retained full responsiveness to morphine after being subjected to an acute morphine challenge. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    1987-01-01

    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-[ 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 14 CO 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 α 2 -adrenergic agonist

  20. Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit

    Directory of Open Access Journals (Sweden)

    MIKI TSUJITA

    2007-01-01

    Full Text Available Morphine is often used in cancer pain and postoperative analgesic management but induces respiratory depression. Therefore, there is an ongoing search for drug candidates that can antagonize morphine-induced respiratory depression but have no effect on morphine-induced analgesia. Acetylcholine is an excitatory neurotransmitter in central respiratory control and physostigmine antagonizes morphine-induced respiratory depression. However, physostigmine has not been applied in clinical practice because it has a short action time, among other characteristics. We therefore asked whether donepezil (a long-acting acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease can antagonize morphine-induced respiratory depression. Using the anesthetized rabbit as our model, we measured phrenic nerve discharge as an index of respiratory rate and amplitude. We compared control indices with discharges after the injection of morphine and after the injection of donepezil. Morphine-induced depression of respiratory rate and respiratory amplitude was partly antagonized by donepezil without any effect on blood pressure and end-tidal C0(2. In the other experiment, apneic threshold PaC0(2 was also compared. Morphine increased the phrenic nerve apnea threshold but this was antagonized by donepezil. These findings indicate that systemically administered donepezil partially restores morphine-induced respiratory depression and morphine-deteriorated phrenic nerve apnea threshold in the anesthetized rabbit

  1. Enhancement of Cisplatin Nephrotoxicity by Morphine and Its Attenuation by the Opioid Antagonist Naltrexone

    Directory of Open Access Journals (Sweden)

    Atefeh Aminian

    2016-07-01

    Full Text Available Nephrotoxicity is a major side effect of cisplatin, a widely used chemotherapy agent. Morphine and other opioids are also used extensively in different types of cancer for the clinical management of pain associated with local or metastatic neoplastic lesions. In addition to its analgesic effects, morphine has also been reported to possess potential immunomodulatory and antioxidant properties. Herein, we investigated the effects of morphine in a rat model of cisplatin-induced nephrotoxicity. Following administration of a single dose of cisplatin (5 mg/kg, animals received intraperitoneal injections of morphine (5 mg/kg/day and/or naltrexone (20 mg/kg/day, an opioid antagonist, for 5 days. Cisplatin-induced nephrotoxicity was detected by a significant increase in plasma urea and creatinine levels in addition to alterations in kidney tissue morphology. Levels of TNF-α and IL-1β were significantly increased in the renal tissue in cisplatin group. Moreover, glutathione (GSH concentration and superoxide dismutase activity were significantly reduced in renal tissue in cisplatin group compared with control animals. Treatment with morphine aggravated the deleterious effects of cisplatin at clinical, biochemical and histopathological levels; whereas naltrexone diminished the detrimental effects of morphine in animals receiving morphine and cisplatin. Morphine or naltrexone alone had no effect on the mentioned parameters. Our findings indicate that concomitant treatment with morphine might intensify cisplatin-induced renal damage in rats. These findings suggest that morphine and other opioids should be administered cautiously in patients receiving cisplatin chemotherapy.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Characterization of a Single Chain Fv Antibody that Reacts with Free Morphine

    Directory of Open Access Journals (Sweden)

    Kazuhisa Sugimura

    2013-02-01

    Full Text Available An immune phage library derived from mice, hyperimmunized with morphine-conjugated BSA, was used to isolate a single-chain Fv (scFv clone, M86, with binding activity to morphine-conjugated thyroglobulin (morphine-C-Tg but not to codeine-, cocaine-, or ketamine-conjugated Tg. Surface plasmon resonance analysis using a morphine-C-Tg-coupled CM5 sensor chip showed that the Kd value was 1.26 × 10−8 M. To analyze its binding activity to free morphine and related compounds, we performed a competitive ELISA with M86 and morphine-C-Tg in the absence or presence of varying doses of free morphine and related compounds. IC50 values for opium, morphine, codeine, and heroin were 257 ng/mL, 36.4, 7.3, and 7.4 nM, respectively. Ketamine and cocaine exhibited no competitive binding activity to M86. Thus, we established a phage library-derived scFv, M86, which recognized not only free morphine and codeine as opium components but also heroin. This characteristic of M86 may be useful for developing therapeutic reagents for opiate addiction and as a free morphine-specific antibody probe.

  4. Dose Uniformity of Scored and Unscored Tablets: Application of the FDA Tablet Scoring Guidance for Industry.

    Science.gov (United States)

    Ciavarella, Anthony B; Khan, Mansoor A; Gupta, Abhay; Faustino, Patrick J

    This U.S. Food and Drug Administration (FDA) laboratory study examines the impact of tablet splitting, the effect of tablet splitters, and the presence of a tablet score on the dose uniformity of two model drugs. Whole tablets were purchased from five manufacturers for amlodipine and six for gabapentin. Two splitters were used for each drug product, and the gabapentin tablets were also split by hand. Whole and split amlodipine tablets were tested for content uniformity following the general chapter of the United States Pharmacopeia (USP) Uniformity of Dosage Units , which is a requirement of the new FDA Guidance for Industry on tablet scoring. The USP weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. All whole tablets met the USP acceptance criteria for the Uniformity of Dosage Units. Variation in whole tablet content ranged from 0.5 to 2.1 standard deviation (SD) of the percent label claim. Splitting the unscored amlodipine tablets resulted in a significant increase in dose variability of 6.5-25.4 SD when compared to whole tablets. Split tablets from all amlodipine drug products did not meet the USP acceptance criteria for content uniformity. Variation in the weight for gabapentin split tablets was greater than the whole tablets, ranging from 1.3 to 9.3 SD. All fully scored gabapentin products met the USP acceptance criteria for weight variation. Size, shape, and the presence or absence of a tablet score can affect the content uniformity and weight variation of amlodipine and gabapentin tablets. Tablet splitting produced higher variability. Differences in dose variability and fragmentation were observed between tablet splitters and hand splitting. These results are consistent with the FDA's concerns that tablet splitting can have an effect on the amount of drug present in a split tablet and available for absorption. Tablet splitting has become a very common practice in the United States and throughout the

  5. Comparison of desmopressin (DDAVP tablet and intranasal spray in the treatment of central diabetes insipidus

    Directory of Open Access Journals (Sweden)

    "Bagher Larijani

    2005-07-01

    Full Text Available Desmoperssin is the drug of choice for treatment of central diabetes insipidus and most commonly it is used as intranasal spray. In this study, efficacy and side effects of oral desmopressin was compared with the intranasal spray. This study was before -after clinical trial on 14 outpatients (9 F, 5 M, age 14 -50 Y with central diabetes insipidus who had been treated with intranasal spray of desmopressin previously. Weight, pulse rate and blood pressure (sitting -standing, biochemical profile, serum electrolytes, 24h urine volume, specific gravity of urine and LFT was measured before and after 1 month study. Starting dose for each patient was one oral tablet of DDAVP (0.1 mg per 8 hours. Paired Samples T-Test was used for data analysis. No clinically significant changes were found as regard to weight, pulse rate, blood pressure, blood chemistry, electrolyte and urinalysis. Single reported adverse effect was headache (43% in tablet group and dyspnea (7% in spray group. Both dosage forms were able to control diurnal polyuria and nocturnal polyuria. The antidiuretic dose - equivalence ratio for intranasal to oral desmopressin was 1: 18. Spray was superior in terms of rapid onset of action and duration of antidiuretic action in 100% and 78% of cases (not significant, respectively. Tablets were more available and much more easily consumed as reported by patients, in 86% (P=0.0006. Treatment with tablets offers a good alternative to the intranasal route, especially in patients with chronic rhinitis or common cold and similar conditions.

  6. Antagonism of the morphine-induced locomotor activation of mice by fructose: comparison with other opiates and sugars, and sugar effects on brain morphine.

    Science.gov (United States)

    Brase, D A; Ward, C R; Bey, P S; Dewey, W L

    1991-01-01

    The mouse locomotor activation test of opiate action in a 2+2 dose parallel line assay was used in a repeated testing paradigm to determine the test, opiate and hexose specificities of a previously reported antagonism of morphine-induced antinocociception by hyperglycemia. In opiate specificity studies, fructose (5 g/kg, i.p.) significantly reduced the potency ratio for morphine and methadone, but not for levorphanol, meperidine or phenazocine when intragroup comparisons were made. In intergroup comparisons, fructose significantly reduced the potencies of levorphanol and phenazocine, but not methadone or meperidine. In hexose/polyol specificity studies, tagatose and fructose significantly reduced the potency ratio for morphine, whereas glucose, galactose, mannose and the polyols, sorbitol and xylitol, caused no significant decrease in potency. Fructose, tagatose, glucose and mannose (5 g/kg, i.p.) were tested for effects on brain morphine levels 30 min after morphine (60 min after sugar), and all four sugars significantly increased brain morphine relative to saline-pretreated controls. It is concluded that the antagonism of morphine by acute sugar administration shows specificity for certain sugars and occurs despite sugar-induced increases in the distribution of morphine to the brain. Furthermore, the effects of fructose show an opiate specificity similar to that of glucose on antinociception observed previously in our laboratory, except that methadone was also significantly inhibited in the present study, when a repeated-testing experimental design was used.

  7. Colour Reproduction on Tablet Devices

    Directory of Open Access Journals (Sweden)

    Vladimir Zorić

    2014-07-01

    Full Text Available With the advent of Internet and mobile devices client services and other print production are migrating more and more to online platforms. In a recent technology changeover it is obvious that there is growing number of printers as well need from the customers for the print service providers to expand their business to online and mobile platforms. With this technological transition there are some open questions regarding the possibilities of using the tablet devices for colour soft proofing and other colour related operations. As a display devices on a hardware level there are large similarities with the desktop display devices but the operating systems which are driving them are not yet colour smart. There have been some initial attempts to characterize the colour reproduction on this type of devices and find a possibility of using them not just for information content but also for colour managed content. In this study we have tested several tablets (Apple iPad2,Asus Transformer TF101, Samsung Galaxy Tab 1 with different display and OS technology and tested a software which is intended for colour managed viewing of the reproduction. We have measured the colour reproduction of the tablets with the digital version of the GretagMacbeth ColorChecker card and have calculated the colour differences between the colour chart data and the displayed data. We have calibrated the Ipad2 with the only existing colour management tool the Spyder Gallery and we have also tested the chart display with and without the colour correction of the software. We have found that there are differences in the colour reproduction of the display technologies and that the possibilities of a real colour managed workflow has yet to be resolved on the OS level of tablet and mobile devices

  8. Effects of BDNF receptor antagonist on the severity of physical and psychological dependence, morphine-induced locomotor sensitization and the ventral tegmental area-nucleus accumbens BDNF levels in morphine- dependent and withdrawn rats.

    Science.gov (United States)

    Khalil-Khalili, Masoumeh; Rashidy-Pour, Ali; Bandegi, Ahmad Reza; Yousefi, Behpoor; Jorjani, Hassan; Miladi-Gorji, Hossein

    2018-03-06

    This study examined the effects of systemic administration of the TrkB receptor antagonist (ANA-12) on the severity of physical and psychological dependence and morphine-induced locomotor sensitization, the ventral tegmental area (VTA)-nucleus accumbens (NAc) BDNF levels in morphine-dependent and withdrawn rats. Rats were injected with bi-daily doses (10 mg/kg, at 12 h intervals) of morphine for 10 days. Then, rats were tested for naloxone-precipitated morphine withdrawal signs, the anxiety (the elevated plus maze-EPM) after the last morphine injection and injection of ANA12 (ip). Also, morphine-induced locomotor sensitization was evaluated after morphine challenge followed by an injection of ANA-12 in morphine-withdrawn rats. The VTA-NAc BDNF levels were assessed in morphine-dependent and withdrawn rats. The overall Gellert-Holtzman score was significantly higher in morphine-dependent rats receiving ANA-12 than in those receiving saline. Also, the percentage of time spent in the open arms in control and morphine-dependent rats receiving ANA-12 were higher compared to the Cont/Sal and D/Sal rats, respectively. There was no significant difference in the locomotor activity and the VTA-NAc BDNF levels between D/Sal/morphine and D/ANA-12/morphine groups after morphine withdrawal. We conclude that the systemic administration of ANA-12 exacerbates the severity of physical dependence on morphine and partially attenuates the anxiety-like behavior in morphine-dependent rats. However, ANA-12 did not affect morphine-induced locomotor sensitization and the VTA-NAc BDNF levels in morphine-dependent and withdrawn rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Can Tablet Computers Enhance Faculty Teaching?

    Science.gov (United States)

    Narayan, Aditee P; Whicker, Shari A; Benjamin, Robert W; Hawley, Jeffrey; McGann, Kathleen A

    2015-06-01

    Learner benefits of tablet computer use have been demonstrated, yet there is little evidence regarding faculty tablet use for teaching. Our study sought to determine if supplying faculty with tablet computers and peer mentoring provided benefits to learners and faculty beyond that of non-tablet-based teaching modalities. We provided faculty with tablet computers and three 2-hour peer-mentoring workshops on tablet-based teaching. Faculty used tablets to teach, in addition to their current, non-tablet-based methods. Presurveys, postsurveys, and monthly faculty surveys assessed feasibility, utilization, and comparisons to current modalities. Learner surveys assessed perceived effectiveness and comparisons to current modalities. All feedback received from open-ended questions was reviewed by the authors and organized into categories. Of 15 eligible faculty, 14 participated. Each participant attended at least 2 of the 3 workshops, with 10 to 12 participants at each workshop. All participants found the workshops useful, and reported that the new tablet-based teaching modality added value beyond that of current teaching methods. Respondents developed the following tablet-based outputs: presentations, photo galleries, evaluation tools, and online modules. Of the outputs, 60% were used in the ambulatory clinics, 33% in intensive care unit bedside teaching rounds, and 7% in inpatient medical unit bedside teaching rounds. Learners reported that common benefits of tablet computers were: improved access/convenience (41%), improved interactive learning (38%), and improved bedside teaching and patient care (13%). A common barrier faculty identified was inconsistent wireless access (14%), while no barriers were identified by the majority of learners. Providing faculty with tablet computers and having peer-mentoring workshops to discuss their use was feasible and added value.

  10. Specifications development for "Karbatril" codenamed tablets

    Directory of Open Access Journals (Sweden)

    L. I. Kucherenko

    2017-08-01

    Full Text Available Introduction. According to current legislation of Ukraine the specifications of tablets include the following indicators: description, identification, average weight, disintegration and assay. The aim of the study. The development of specifications and project of quality control methods for "Karbatril" codenamed tablets. Materials and methods. During the study we analyzed 6 series of tablets "Karbatril." For the description, identification, determination of the average mass, disintegration, active ingredients quantify of "Karbatril" codenamed tablets we used appropriate methods and instruments. Results and discussion. Tablets "Karbatril" were analyzed for the following parameters: - Overview - Tablets white or nearly white; - Average weight - during the study the average weight of 6 series of obtained tablets ranged from 339,0 mg to 369,9 mg according to SPU from 337,0 mg to 373,0 mg; - Disintegration – according to SPU the disintegration for tablet without shell shall not exceed 15 min. Analyzed tablets disintegrated in the period from 5 to 10 minutes; - Identification and quantification of the active ingredients of tablets were conducted using modified HPLC methods. During the identification obtained chromatograms show compliance with SPU. In quantitative determination of the active ingredients content in "Karbatril" codenamed tablets we found carbamazepine from 148.18 mg to 150.19 mg, thiotriazoline - from 98.93 mg to 99.71 mg. This data is consistent to SPU which regulates content of carbamazepine - 150 mg ± 7,5%, thiotriazoline - 100 mg ± 10%. Conclusions. This study has developed specification for "Karbatril" codenamed tablets and also methods of HPLC qualitative and quantitative determination of active ingredients. In the specification the following parameters are included: description, identification, average weight, disintegration and assay. The study drafted quality control methods which are planned to be later offered to the

  11. Pharmaceutical and analytical evaluation of triphalaguggulkalpa tablets

    OpenAIRE

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

    2011-01-01

    Aim of the Study: Development of standardized, synergistic, safe and effective traditional herbal formulations with robust scientific evidence can offer faster and more economical alternatives for the treatment of disease. The main objective was to develop a method of preparation of guggulkalpa tablets so that the tablets meet the criteria of efficacy, stability, and safety. Materials and Methods: Triphalaguggulkalpa tablet, described in sharangdharsanhita and containing guggul and triphala p...

  12. A randomized controlled trial of the effect of sublingual orally disintegrating olanzapine versus oral olanzapine on body mass index: the PLATYPUS Study

    NARCIS (Netherlands)

    Karagianis, J.; Grossman, L.; Landry, J.; Reed, V. A.; de Haan, L.; Maguire, G. A.; Hoffmann, V. P.; Milev, R.

    2009-01-01

    BACKGROUND: Patients with schizophrenia and bipolar disorder have frequently reported weight gain during olanzapine treatment. Previous studies have observed a decrease in weight gain, or weight loss, in patients switching from standard olanzapine tablets (SOT) to orally disintegrating olanzapine

  13. Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat

    Science.gov (United States)

    Lilius, T O; Jokinen, V; Neuvonen, M S; Niemi, M; Kalso, E A; Rauhala, P V

    2015-01-01

    Background and Purpose The effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance and morphine withdrawal. Experimental Approach Morphine minipumps (6 mg·day–1) induced tolerance during 5 days in Sprague–Dawley rats, after which s.c. ketamine (10 mg·kg–1) was administered. Tail flick, hot plate and rotarod tests were used for behavioural testing. Serum levels and whole tissue brain and liver concentrations of morphine, morphine-3-glucuronide, ketamine and norketamine were measured using HPLC-tandem mass spectrometry. Key Results In morphine-naïve rats, ketamine caused no antinociception whereas in morphine-tolerant rats there was significant antinociception (57% maximum possible effect in the tail flick test 90 min after administration) lasting up to 150 min. In the brain of morphine-tolerant ketamine-treated rats, the morphine, ketamine and norketamine concentrations were 2.1-, 1.4- and 3.4-fold, respectively, compared with the rats treated with morphine or ketamine only. In the liver of morphine-tolerant ketamine-treated rats, ketamine concentration was sixfold compared with morphine-naïve rats. After a 2 day morphine withdrawal period, smaller but parallel concentration changes were observed. In acute coadministration, ketamine increased the brain morphine concentration by 20%, but no increase in ketamine concentrations or increased antinociception was observed. Conclusions and Implications The ability of ketamine to induce antinociception in rats made tolerant to morphine may also be due to increased brain concentrations of morphine, ketamine and norketamine. The relevance of these findings needs to be assessed in humans. PMID:25297798

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

    Energy Technology Data Exchange (ETDEWEB)

    Wild, K.D.; Reid, L.D. (Rensselaer Polytechnic Institute, Troy, NY (USA))

    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.

  15. Effects of carprofen and morphine on the minimum alveolar concentration of isoflurane in dogs.

    Science.gov (United States)

    Ko, Jeff C H; Weil, Ann B; Inoue, Tomohito

    2009-01-01

    The minimum alveolar concentration (MAC) of isoflurane in dogs was determined following carprofen (2.2 mg/kg per os) alone, morphine (1 mg/kg intravenously) alone, carprofen and morphine, and no drug control in eight healthy adult dogs. Isoflurane MAC following administration of morphine alone (0.81%+/-0.18%) or carprofen and morphine (0.68%+/-0.31%) was significantly less than the control MAC (1.24%+/-0.15%). Isoflurane MAC after carprofen alone (1.13%+/-0.13%) was not significantly different from the control value. Results indicated that administration of morphine alone or in combination with carprofen significantly reduced the MAC of isoflurane in dogs. The isoflurane MAC reduction was additive between the effects of carprofen and morphine.

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

    Science.gov (United States)

    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.

  17. Tablet surface characterisation by various imaging techniques

    DEFF Research Database (Denmark)

    Seitavuopio, Paulus; Rantanen, Jukka; Yliruusi, Jouko

    2003-01-01

    The aim of this study was to characterise tablet surfaces using different imaging and roughness analytical techniques including optical microscopy, scanning electron microscopy (SEM), laser profilometry and atomic force microscopy (AFM). The test materials compressed were potassium chloride (KCl......) and sodium chloride (NaCl). It was found that all methods used suggested that the KCl tablets were smoother than the NaCl tablets and higher compression pressure made the tablets smoother. Imaging methods like optical microscopy and SEM can give useful information about the roughness of the sample surface...

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

    Science.gov (United States)

    Berner-Strzelczyk, Aneta; Kołodziejska, Justyna; Zgoda, Marian Mikołaj

    2006-01-01

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

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

    Science.gov (United States)

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

    2008-08-01

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

  20. Hippocampal GluA1-containing AMPA receptors mediate context-dependent sensitization to morphine

    OpenAIRE

    Xia, Yan; Portugal, George S.; Fakira, Amanda K.; Melyan, Zara; Neve, Rachael; Lee, H. Thomas; Russo, Scott J.; Liu, Jie; Morón, Jose A.

    2011-01-01

    Glutamatergic systems, including α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are involved in opiate-induced neuronal and behavioral plasticity, although the mechanisms underlying these effects are not fully understood. In the present study, we investigated the effects of repeated morphine administration on AMPAR expression, synaptic plasticity, and context-dependent behavioral sensitization to morphine. We found that morphine treatment produced changes of synaptic...

  1. PolyMorphine: an innovative biodegradable polymer drug for extended pain relief

    OpenAIRE

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

    2012-01-01

    Morphine, a potent narcotic analgesic used for the treatment of acute and chronic pain, was chemically incorporated into a poly(anhydride-ester) backbone. The polymer termed “PolyMorphine”, was designed to degrade hydrolytically releasing morphine in a controlled manner to ultimately provide analgesia for an extended time period. PolyMorphine was synthesized via melt-condensation polymerization and its structure was characterized using proton and carbon nuclear magnetic resonance spectroscopi...

  2. PolyMorphine provides extended analgesic-like effects in mice with spared nerve injury

    OpenAIRE

    Lax, Neil C; Chen, Renxun; Leep, Sarah R; Uhrich, Kathryn E; Yu, Lei; Kolber, Benedict J

    2017-01-01

    Morphine is a well-characterized and effective analgesic commonly used to provide pain relief to patients suffering from both acute and chronic pain conditions. Despite its widespread use and effectiveness, one of the major drawbacks of morphine is its relatively short half-life of approximately 4 h. This short half-life often necessitates multiple administrations of the drug each day, which may contribute to both dependence and tolerance to morphine. Here, we tested the analgesic properties ...

  3. Gastric Injury From Oral Iron Supplementation

    Science.gov (United States)

    2018-02-22

    SAUSHEC, San Antonio, TX 2. Department of Gastroenterology, SAUSHEC, San Antonio, TX ABSTRACT BODY: Learning Objective 1: Recognize that iron...pill gastritis is a known complication of oral supplementation but is not well recognized Learning Objective 2: Recognize that the toxic effect of iron...prevalence worldwide (WHO). The typical treatment for iron deficiency anemia is through oral iron tablet supplementation. Iron pill gastritis is a known

  4. Magnetic images of the disintegration process of tablets in the human stomach by ac biosusceptometry

    International Nuclear Information System (INIS)

    Cora, L A; Andreis, U; Romeiro, F G; Americo, M F; Oliveira, R B; Baffa, O; Miranda, J R A

    2005-01-01

    Oral administration of solid dosage forms is usually preferred in drug therapy. Conventional imaging methods are essential tools to investigate the in vivo performance of these formulations. The non-invasive technique of ac biosusceptometry has been introduced as an alternative in studies focusing on gastrointestinal motility and, more recently, to evaluate the behaviour of magnetic tablets in vivo. The aim of this work was to employ a multisensor ac biosusceptometer system to obtain magnetic images of disintegration of tablets in vitro and in the human stomach. The results showed that the transition between the magnetic marker and the magnetic tracer characterized the onset of disintegration (t 50 ) and occurred in a short time interval (1.1 ± 0.4 min). The multisensor ac biosusceptometer was reliable to monitor and analyse the in vivo performance of magnetic tablets showing accuracy to quantify disintegration through the magnetic images and to characterize the profile of this process

  5. Magnetic images of the disintegration process of tablets in the human stomach by ac biosusceptometry

    Energy Technology Data Exchange (ETDEWEB)

    Cora, L A [Departamento de Fisica e BioFisica, IBB, UNESP, Botucatu, SP (Brazil); Andreis, U [Departamento de Fisica e BioFisica, IBB, UNESP, Botucatu, SP (Brazil); Romeiro, F G [Departamento de ClInica Medica, FMB, UNESP, Botucatu, SP (Brazil); Americo, M F [Departamento de ClInica Medica, FMRP, USP, Ribeirao Preto, SP (Brazil); Oliveira, R B [Departamento de ClInica Medica, FMRP, USP, Ribeirao Preto, SP (Brazil); Baffa, O [Departamento de Fisica e Matematica, FFCLRP, USP, Ribeirao Preto, SP (Brazil); Miranda, J R A [Departamento de Fisica e BioFisica, IBB, UNESP, Botucatu, SP (Brazil)

    2005-12-07

    Oral administration of solid dosage forms is usually preferred in drug therapy. Conventional imaging methods are essential tools to investigate the in vivo performance of these formulations. The non-invasive technique of ac biosusceptometry has been introduced as an alternative in studies focusing on gastrointestinal motility and, more recently, to evaluate the behaviour of magnetic tablets in vivo. The aim of this work was to employ a multisensor ac biosusceptometer system to obtain magnetic images of disintegration of tablets in vitro and in the human stomach. The results showed that the transition between the magnetic marker and the magnetic tracer characterized the onset of disintegration (t{sub 50}) and occurred in a short time interval (1.1 {+-} 0.4 min). The multisensor ac biosusceptometer was reliable to monitor and analyse the in vivo performance of magnetic tablets showing accuracy to quantify disintegration through the magnetic images and to characterize the profile of this process.

  6. Magnetic images of the disintegration process of tablets in the human stomach by ac biosusceptometry

    Science.gov (United States)

    Corá, L. A.; Andreis, U.; Romeiro, F. G.; Américo, M. F.; Oliveira, R. B.; Baffa, O.; Miranda, J. R. A.

    2005-12-01

    Oral administration of solid dosage forms is usually preferred in drug therapy. Conventional imaging methods are essential tools to investigate the in vivo performance of these formulations. The non-invasive technique of ac biosusceptometry has been introduced as an alternative in studies focusing on gastrointestinal motility and, more recently, to evaluate the behaviour of magnetic tablets in vivo. The aim of this work was to employ a multisensor ac biosusceptometer system to obtain magnetic images of disintegration of tablets in vitro and in the human stomach. The results showed that the transition between the magnetic marker and the magnetic tracer characterized the onset of disintegration (t50) and occurred in a short time interval (1.1 ± 0.4 min). The multisensor ac biosusceptometer was reliable to monitor and analyse the in vivo performance of magnetic tablets showing accuracy to quantify disintegration through the magnetic images and to characterize the profile of this process.

  7. Intrathecal hypobaric versus hyperbaric bupivacaine with morphine for cesarean section.

    Science.gov (United States)

    Richardson, M G; Collins, H V; Wissler, R N

    1998-08-01

    Both hyper- and hypobaric solutions of bupivacaine are often combined with morphine to provide subarachnoid anesthesia for cesarean section. Differences in the baricity of subarachnoid solutions influence the intrathecal distribution of anesthetic drugs and would be expected to influence measurable clinical variables. We compared the effects of hyper- and hypobaric subarachnoid bupivacaine with morphine to determine whether one has significant advantages with regard to intraoperative anesthesia and postoperative analgesia in term parturients undergoing elective cesarean section. Thirty parturients were randomized to receive either hyper- or hypobaric bupivacaine (15 mg) with morphine sulfate (0.2 mg). Intraoperative outcomes compared included extent of sensory block, quality of anesthesia, and side effects. Postoperative outcomes, including pain visual analog scale scores, systemic analgesic requirements, and side effects, were monitored for 48 h. Sedation effects were quantified and compared using Trieger and digit-symbol substitution tests. We detected no differences in sensory or motor block, quality of anesthesia, quality of postoperative analgesia, incidence of side effects, or psychometric scores. Both preparations provide highly satisfactory anesthesia for cesarean section and effective postoperative analgesia. Dextrose alters the density of intrathecal bupivacaine solutions and is thought to influence subarachnoid distribution of the drug. We randomized parturients undergoing cesarean section to one of two often used spinal bupivacaine preparations, hypobaric and hyperbaric. We detected no differences in clinical outcomes between groups.

  8. [Morphine self-administration by rats using a pneumatic syringe].

    Science.gov (United States)

    Akiyama, Y; Takayama, S

    1988-06-01

    An apparatus for drug self-administration by rats using a pneumatic syringe was developed by Weeks. A microliter syringe operated by a pneumatic cylinder supplies an accurate volume of drug solution within one second. When coefficient of variation of infusion volume was compared among pneumatic syringe, infusion pump, and peristaltic pump, pneumatic syringe showed higher accuracy in infusion volume than the other two pumps. Since the infusion speed by a pneumatic syringe is very rapid (less than one second per infusion), the effect of infusion speed on reinforcing property of morphine was investigated. When rats self-administered 0.1, 0.3, 1.0, and 3.0 mg/kg/infusion of morphine by pneumatic syringes, the patterns of self-infusion were more stable, the number of self-infusions and the amount self-administered were larger, and a dose-response relationship was clearer in comparison with those self-infused the same doses of morphine for 5.6 seconds by infusion pumps or peristaltic pumps.

  9. Degradation of morphine in opium poppy processing waste composting.

    Science.gov (United States)

    Wang, Yin Quan; Zhang, Jin Lin; Schuchardt, Frank; Wang, Yan

    2014-09-01

    To investigate morphine degradation and optimize turning frequency in opium poppy processing waste composting, a pilot scale windrow composting trial was run for 55 days. Four treatments were designed as without turning (A1), every 5 days turning (A2), every 10 days turning (A3) and every 15 days turning (A4). During composting, a range of physicochemical parameters including the residual morphine degradation, temperature, pH, and the contents of total C, total N, total P and total K were investigated. For all treatments, the residual morphine content decreased below the detection limit and reached the safety standards after day 30 of composting, the longest duration of high temperature (⩾50 °C) was observed in A3, pH increased 16.9-17.54%, total carbon content decreased 15.5-22.5%, C/N ratio reduced from 46 to 26, and the content of total phosphorus and total potassium increased slightly. The final compost obtained by a mixture of all four piles was up to 55.3% of organic matter, 3.3% of total nutrient (N, P2O5 and K2O) and 7.6 of pH. A turning frequency of every ten days for a windrow composting of opium poppy processing waste is recommended to produce homogenous compost. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Morphine analgesia and cerebral opiate receptors: a developmental study

    International Nuclear Information System (INIS)

    Auguy-Valette, A.; Pontonnier, G.; Cros, J.; Gouarderes, C.; Gout, R.

    1978-01-01

    Development of the analgesic response to morphine and ontogenesis of central opiate receptors were analyzed in rats 5 to 120 days old. The analgesic effect of morphine increased until day 15, after which it decreased to reach a plateau at about day 30. With phenoperidine, on the other hand, the analgesic effect increased until day 15, remained constant between day 15 and day 30 after which it decreased slowly. The ratio of the amounts of morphine in blood over those in brain increased about 3 fold between day 15 and day 30. Opiate receptors were detected in the brain of newborn rats; stereospecific binding of [ 3 H]-naloxone at 10 and 50 nM indicated the presence of low and high affinity binding sites. The number of [ 3 H]-naloxone binding sites increased rapidly during the second and third week after birth. Their affinity for several opiates remained constant throughout development. These results indicate that the analgesic activity of opiates varies with age: until day 15, the analgesic effect of opiates increases in parallel with the number of opiate brain receptors. Then, the formation of the blood brain barrier introduces an additional step in the regulation of opiate activity. (author)

  11. Recommended use of morphine in neonates, infants and children based on a literature review

    DEFF Research Database (Denmark)

    Kart, T; Christrup, Lona Louring; Rasmussen, M

    1997-01-01

    The English language literature has been reviewed in order to evaluate the present knowledge on morphine's metabolism and pharmacokinetics in children. The majority of preterm neonates are capable of glucuronidating morphine, but birth weight; gestational and postnatal age influence the glucuroni......The English language literature has been reviewed in order to evaluate the present knowledge on morphine's metabolism and pharmacokinetics in children. The majority of preterm neonates are capable of glucuronidating morphine, but birth weight; gestational and postnatal age influence...... in term neonates aged 0-57 days, and 23.6 +/- 8.5 ml.min-1.kg-1 in infants and children more than 11 days old....

  12. Morphine potentiates seizures induced by GABA antagonists and attenuates seizures induced by electroshock in the rat.

    Science.gov (United States)

    Foote, F; Gale, K

    1983-11-25

    In a naloxone-reversible, dose-dependent manner, morphine (10-50 mg/kg i.p.) protected against seizures induced by maximal electroshock and increased the incidence and severity of seizures induced by bicuculline, in rats. Morphine also potentiated seizures induced by isoniazid and by picrotoxin. Thus, opiate activity influences the expression of seizures in contrasting ways depending upon the mode of seizure induction. Since morphine consistently potentiated seizures induced by interference with GABA transmission, it appears that GABAergic systems may be of particular significance for the elucidation of the varied effects of morphine on seizure susceptibility.

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

    Science.gov (United States)

    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. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Combined intra-articular glucocorticoid, bupivacaine and morphine reduces pain and convalescence after diagnostic knee arthroscopy

    DEFF Research Database (Denmark)

    Rasmussen, Sten; Lorentzen, Jan S; Larsen, Allan S

    2002-01-01

    We studied the effect of intra-articullar saline vs. bupivacaine + morphine or bupivacaine morphine + methylprednisolone after diagnostic knee arthroscopy. In a double-blind randomized study, 60 patients undergoing diagnostic knee arthroscopy without a therapeutic procedure were allocated to groups...... receiving intra-articular saline, intra-articular bupivacaine 150 mg + morphine 4 mg or the same dose of bupivacaine + morphine + intra-articular methylprednisolone 40 mg at the end of arthroscopy during general anesthesia. All patients were instructed to resume normal activities immediately after...

  15. Role of music in morphine rewarding effects in mice using conditioned place preference method.

    Science.gov (United States)

    Tavakoli, Farnaz; Hoseini, Seyed Ebrahim; Mokhtari, Mokhtar; Vahdati, Akbar; Razmi, Nematollah; Vessal, Mahmood

    2012-01-01

    This research aims at studying the neuroendocrine effects of music on creating morphine dependence in mice using conditioned place preference (CPP). The mice treated with 10 mg/kg morphine subcutaneously, fast music and slow music. Morphine was used to create dependence. In order to recognize the morphine rewarding effects, CPP technique was used. In the conditioning stage that lasted for 8 days, different groups of mice, after receiving the treatment were randomly placed in compartment for 30 minutes. The post-conditioning stage included the fourth day, the ninth day, the 12th day and the 16th day. Comparing place preference between morphine group and the control group, a significant increase (pmusic group compared with morphine group alone. In addition morphine + alone in the rain music group demonstrated a significantly increased conditioned place preference (pmusic acts as a positive pleasant emotion increasing the dopaminergic activity in the Nucleus Accumbens (NAc) and Ventral Tegmental Area (VTA) and through associated learning mechanisms of reward-related behavior increases morphine addiction. However, taxi girl music may act as unpleasant experiences producing negative emotions and reducing morphine addiction.

  16. Neonatal Morphine Exposure in Very Preterm Infants – Cerebral Development and Outcomes

    Science.gov (United States)

    Steinhorn, Rachel; McPherson, Chris; Anderson, Peter J; Neil, Jeffrey; Doyle, Lex W; Inder, Terrie

    2015-01-01

    Objective To investigate the association of morphine exposure in very preterm infants with cerebral volumes and neurodevelopmental outcome from birth through middle childhood. Study design Observational study of very preterm infants in the Victorian Infant Brain Study cohort. 230 infants born neonatal intensive care unit (NICU) of the Royal Women’s Hospital. 57 (25%) infants received morphine analgesia during their NICU stay at the attending physician’s discretion. Primary outcomes were regional brain volumes at term and 7 years; neurobehavioral performance at term; and cognitive, motor, emotional, behavioral, communication, and executive function scores at age 2 and 7 years. Linear regressions were used to compare outcomes between participants who did and did not receive morphine. Results At term, preterm infants who received morphine had similar rates of grey matter injury to no-morphine infants, but a trend towards smaller cortical volumes in the orbitofrontal (pleft=0.002, pright=0.01) and subgenual (pleft=0.01) regions. At seven years, cortical volumes did not differ between groups. At 2 years, morphine-exposed children were more likely to show behavioral dysregulation (p=0.007) than no-morphine children, but at seven years no detrimental impacts of morphine on neurobehavioral outcome were observed. Conclusions Low-dose morphine analgesia received during neonatal intensive care was associated with early alterations in cerebral structure and short-term neurobehavioral problems that did not persist into childhood. PMID:25919729

  17. Research Article. Kinetics and Mechanism of Drug Release from Loratadine Orodispersible Tablets Developed without Lactose

    Directory of Open Access Journals (Sweden)

    Ciurba Adriana

    2017-03-01

    Full Text Available Objective: The aim of this study is to develop lactose-free orodispersible tablets with loratadine for patients with lactose intolerance. Materials and methods: Seven compositions (F1-F7 of 10 mg loratadine were prepared in form of orally disintegrating tablets, by direct compression, using croscarmellose sodium and pre-gelatinized starch in various concentrations as superdisintegrants, diluted with microcrystalline cellulose and combined with mannitol and maltodextrin as binder agents. The tablets had been studied in terms of their pharmacotechnical characteristics, by determining: the weight uniformity of the tablets, their friability, breaking strength and disintegration time, drug content and the dissolution profile of loratadine. The statistical analyses were performed with GraphPad Prism Software Inc. As dependent variables, both the hardness of the tablets and their disintegration ability differ between batches due to their compositional differences (as independent variables. DDSolver were used for modeling the kinetic of the dissolution processes by fitting the dissolution profiles with time-dependent equations (Zero-order, First-order, Higuchi, Korsmeyer-Peppas, Peppas-Sahlin. Results: All proposed formulas shows rapid disintegration, in less than 15 seconds, and the dissolution loratadine spans a period of about 10 minutes. Akaike index as well as R2 adjusted parameter have demonstrated that the studied dissolution profiles are the best fitted by Zero-order kinetic. Conclusion: In conclusion, association of croscarmellose sodium (7.5% with pre-gelatinized starch (6% as superdisintegrants and mannitol as the binder agent (35%, positively influences the dissolution properties of loratadine from orally fast dispersible tablets.

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

    Science.gov (United States)

    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-β-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-β-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 (Ptablet. 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

  19. Analysis of Biologic Samples for Morphine and Morphine-Related Compounds by Gas Chromatographic-Mass Spectrometric Methods

    Science.gov (United States)

    1976-04-01

    formation is not necessary if the purpose is to detect diacetylinorphine or methadone but most screening procedures have as their purpose the detection of a...in the following way. Morphine hydrochloride (10.7 mg, 0.1 mM) was dissolved in 600 V1 of dimethylsulfoxide (distilled over calcium hydride). To .i...and the residue was dissolved in ethanol. Normor- phine hydrochloride was precipitated upon addition of n-pentane. Storage of the mixture (freezer

  20. Consumption of three strong opioids (morphine, oxycodone and fentanyl) in seven European countries during seven years (2003-2009).

    Science.gov (United States)

    Hudec, R; Tisonova, J; Foltan, V; Kristova, V

    2013-01-01

    The aim was to analyse the consumption of selected strong opioid analgesics during a seven-year period of 2003-2009 in order to compare Slovak consumption with that in six other European countries and to determine our position. Drug consumption data from the State Institute for Drug Control in Slovak Republic were used. As to the data from other countries, annual health statistics published on websites were used in comparison. Obviously the consumption of one of studied opioid drugs with transdermal aplication route, particularly fentanyl, tended to increase in all countries during the observed period. Oxycodone tends to yield a rapid increase in consumption as well. As opposed to the latter drugs, the consumption of morphine was decreasing throughout the observed period. The consumption of these drugs in Slovakia remains low (except for that of fentanyl). Our analysis confirmed a clear shift from oral to transdermal therapy as well as usage of newer drugs. Drug consumption data are a relatively new source of information for health research. Our analysis showed increasing trends in fentanyl (patch opioid) consumption in all compared countries as well as an increasing consumption of oxycodone and decreasing consumption of morphine (Fig. 3, Ref. 17).

  1. Product development of pumpkin tablet

    Directory of Open Access Journals (Sweden)

    Kamgoed, T.

    2007-05-01

    Full Text Available The development of pumpkin tablet was studied and the drying conditions of pumpkin using a double drum dryer were optimized. The study factors were drying agents (maltodextrin D.E.13-16 andtapioca flour at different levels (3 and 5%, drying temperatures (130 and 140oC and drum dryer speeds (4 and 5 rpm. The results showed that the optimal conditions were using 3% maltodextrin D.E.13-16, dryingtemperature of 130oC and drum dryer speed of 4 rpm. The moisture, fat, bulk density, reducing sugars and granulometric retention of the obtained pumpkin powder were 3.39%, 1.42%, 1.004 g/ml, 12.63% and 0.67%, respectively and L*, a* and b* values were 73.85, -0.60 and 35.23, respectively. A study of suitable amount of icing sugar using different contents for tablet production (0, 10, 20, 30 and 40% was performedand showed that using 20% icing sugar was the most acceptable. The obtained pumpkin tablet was subjected to chemical, physical and microbiological analysis. The ash, moisture, protein, fat, fiber and carbohydratecontents were 1.87, 3.60, 3.34, 1.00, 2.26 and 87.99%, respectively. The reducing sugars and β-carotene contents were 5.44±0.61% and 3.79±0.57 mg/100g, respectively. The Aw, hardness and solubility were 0.56,3.25 kgf and 25.00 %, respectively. The L*, a* and b* values were 79.85, 0.28 and 23.64, respectively. The total microbial count and the yeast and mould count were <10 CFU/g. The shelf life of the pumpkin tabletwas at least 4 months at room temperature (35±2oC.

  2. Tablet-teknologi i fysioterapi

    DEFF Research Database (Denmark)

    Duus, Lene; Støve, Morten Pallisgaard; Harbo, Michael

    2015-01-01

    Projektbaggrund og formål: Med projektet har vi ønsket at udvikle, afdække, implementere og afprøve funktionalitet og design af en app-baseret elektronisk genoptræningsportal. I projektet er der afprøvet en app. rettet mod fysioterapeuten og en app. rettet mod patienten. Formålet var at afdække u...... undervisning i teknologien samt løbende support højt, hvorfor tidsaspektet for deltagerne bliver vigtig. Reference: www.ucviden.dk, Duus, L & Støve Morten P, 2014. Tablet-teknologi i Fysioterapi....

  3. Microinjection of Orexin-A into the Locus Coeruleus Area Induces Morphine Withdrawal Behaviors in Morphine Independent Rats

    Directory of Open Access Journals (Sweden)

    Hosin Azizi

    2012-02-01

    Full Text Available Introduction: Orexin neuropeptide has a role in opioid withdrawal behaviors. Orexin-expressing neurons that are present in the hypothalamic nuclei send dense projections to the Locus Coeruleus (LC. Withdrawal syndrome is temporally associated with hyperactivity of LC neurons. LC neurons do not show withdrawal-induced hyperactivity in brain slices from morphine-dependent rats. Thus, it has been suggested that the increase in LC neuronal activity seen in vivo is mediated by extrinsic factors. Therefore, this study was carried out to find whether LC microinjection of orexin-A can induce withdrawal behaviors. Method: Adult male Wistar rats were used in this study. Intra-LC microinjection of orexin-A or orexin-A vehicle was performed one week after LC cannulation. Thereafter, somatic signs of withdrawal were evaluated during a period of 25 min.Findings: Orexin-A induced several signs of morphine withdrawal. Conclusion: It may be concluded that orexin at LC acts as an extrinsic factor in the expression of morphine withdrawal syndrome.

  4. Music therapy inhibits morphine-seeking behavior via GABA receptor and attenuates anxiety-like behavior induced by extinction from chronic morphine use.

    Science.gov (United States)

    Kim, Ki Jin; Lee, Sang Nam; Lee, Bong Hyo

    2018-05-01

    Morphine is a representative pain killer. However, repeated use tends to induce addiction. Music therapy has been gaining interest as a useful type of therapy for neuropsychiatric diseases. The present study examined whether Korean traditional music (KT) could suppress morphine-seeking behavior and anxiety-like behavior induced by extinction from chronic morphine use and additionally investigated a possible neuronal mechanism. Male Sprague-Dawley rats were trained to intravenously self-administer morphine hydrochloride (1.0 mg/kg) using a fixed ratio 1 schedule in daily 2 h session during 3 weeks. After training, rats who established baseline (variation less than 20% of the mean of infusion for 3 consecutive days) underwent extinction. Music was played twice a day during extinction. In the second experiment, the selective antagonists of GABA A and GABA B receptors were treated before the last playing to investigate the neuronal mechanism focusing on the GABA receptor pathway. Another experiment of elevated plus maze was performed to investigate whether music therapy has an anxiolytic effect at the extinction phase. KT but not other music (Indian road or rock music) reduced morphine-seeking behavior induced by a priming challenge with morphine. And, this effect was blocked by the GABA receptor antagonists. In addition, KT showed anxiolytic effects against withdrawal from morphine. Results of this study suggest that KT suppresses morphine-seeking behavior via GABA receptor pathway. In addition, KT showed to have anxiolytic effects, suggesting it has bi-directional effects on morphine. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Transforming the Classroom With Tablet Technology.

    Science.gov (United States)

    Sargent, Lana; Miles, Elizabeth

    Identifying the most effective models for integrating new technology into the classroom and understanding its effects on educational outcomes are essential for nurse educators. This article describes an educational intervention with tablet technology (iPads) using an innovative case-based learning model in a nursing program. Students reported positive learning outcomes when using the tablet technology for learning course content.

  6. 21 CFR 520.1510 - Nitenpyram tablets.

    Science.gov (United States)

    2010-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... order of a licensed veterinarian. (d) Conditions of use—(1) Dogs—(i) Amount—(A) One 11.4-mg tablet for dogs weighing less than 25 pounds (lb) or one 57-mg tablet for dogs weighing more than 25 lb, as needed...

  7. How Tablets Are Utilized in the Classroom

    Science.gov (United States)

    Ditzler, Christine; Hong, Eunsook; Strudler, Neal

    2016-01-01

    New technologies are a large part of the educational landscape in the 21st century. Emergent technologies are implemented in the classroom at an exponential rate. The newest technology to be added to the daily classroom is the tablet computer. Understanding students' and teachers' perceptions about the role of tablet computers is important as this…

  8. Quantitative Determination of Metformin Hydrochloride in Tablet ...

    African Journals Online (AJOL)

    Purpose: To develop and validate a suitable method for the assay of metformin hydrochloride (HCl) in tablets containing croscarmellose sodium as an additive. Methods: Methanol and ethanol (99%) were assessed as solvents for sample preparation for the assay of metformin HCl in tablets containing croscarmellose ...

  9. Breaking of scored tablets : a review

    NARCIS (Netherlands)

    van Santen, E; Barends, D M; Frijlink, H W

    The literature was reviewed regarding advantages, problems and performance indicators of score lines. Scored tablets provide dose flexibility, ease of swallowing and may reduce the costs of medication. However, many patients are confronted with scored tablets that are broken unequally and with

  10. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Comi, Giancarlo; Cook, Stuart

    2010-01-01

    Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis....

  11. Stabilization Mechanism of Roxithromycin Tablets under Gastric pH Conditions.

    Science.gov (United States)

    Inukai, Koki; Noguchi, Shuji; Kimura, Shin-Ichiro; Itai, Shigeru; Iwao, Yasunori

    2018-05-31

    Macrolide antibiotics are widely used at clinical sites. Clarithromycin (CAM), a 14-membered macrolide antibiotic, was reported to gelate under acidic conditions. Gelation allows oral administration of acid-sensitive CAM without enteric coating by hindering the penetration of gastric fluid into CAM tablets. However, it is unknown whether this phenomenon occurs in other macrolide antibiotics. In this study, we examined the gelation ability of three widely used macrolide antibiotics, roxithromycin (RXM), erythromycin A (EM), and azithromycin (AZM). The results indicated that not only CAM but also RXM gelated under acidic conditions. EM and AZM did not gelate under the same conditions. Gelation of RXM delayed the disintegration of the tablet and release of RXM from the tablet. Disintegration and release were also delayed in commercial RXM tablets containing disintegrants. This study showed that two of the four macrolides gelated, which affects tablet disintegration and dissolution and suggests that this phenomenon might also occur in other macrolides. Copyright © 2018. Published by Elsevier Inc.

  12. OPTIMIZATION OF FUROSEMIDE LIQUISOLID TABLETS PREPARATION PROCESS LEADING TO THEIR MASS AND SIZE REDUCTION.

    Science.gov (United States)

    Kurek, Mateusz; Woyna-Orlewicz, Krzysztof; Khalid, Mohammad Hassan; Jachowicz, Renata

    2016-09-01

    The great number of drug substances currently used in solid oral dosage forms is characterized by poor water solubility. Therefore, various methods of dissolution rate enhancement are an important topic of research interest in modem drug technology. The purpose of this study was to enhance the furosemide dissolution rate from liquisolid tablets while maintaining an acceptable size and mass. Two types of dibasic calcium phosphate (Fujicalin®/Emcompress®) and microcrystalline cellulose (Vivapur® 102/Vivapur® 12) were used as carriers and magnesium aluminometasilicate (Neusilin® US2) was used as a coating material. The flowable liquid retention potential for those excipients was tested by measuring the angle of slide. To evaluate the impact of used excipients on tablet properties fourteen tablet formulations were prepared. It was found that LS2 tablets containing spherically granulated dibasic calcium phosphate and magnesium aluminometasilicate exhibit the best dissolution profile and mechanical properties while tablets composed only with Neusilin® US2 was characterized by the smallest size and mass with preserved good mechanical properties and furosemide dissolution.

  13. Effect of binders on 500mg metformin hydrochloride tablets produced by wet granulation

    Directory of Open Access Journals (Sweden)

    LUCIANA CATIA BLOCK

    2009-12-01

    Full Text Available Metformin hydrochloride (MH is an oral hypoglycemic agent and a high-dose drug that has poor flow and compression properties. In this study, the feasibility of developing adequate, low cost 500mg tablets of metformin hydrochloride by wet granulation was tested with several binders (Starch / PVP K30®; Starch 1500® /PVP K30®, PVP K30® and PVP K90® in a simple tablet press of the type used in small pharmaceutical laboratories. The drug powder was tested for ability to flow, by determining Carr’s Index (CI and the Hausner ratio (HR. Differential scanning calorimetry and thermogravimetric analysis were carried out on isolated MH and 1:1 (w/w binary mixtures with the excipients. The size distribution, friability, flow properties and drug content of the granules were analyzed, as were the hardness, friability, disintegration, dissolution and uniformity of the dosage form. The drug powder showed CI > 22% and HR > 1.25, characteristic of a poor flow powder, and no significant incompatibilities with the excipients. All the granules showed adequate flow properties and were suitable for pressing into tablets, all of which complied with pharmacopeial specifications. The starch /PVP K30® and starch 1500® /PVP K30® mixtures were best for producing 500 mg MH tablets. Keywords: Metformin hydrochloride. Tablets. Wet granulation. Binders.

  14. Tablet Keiti: Does it Contain Astronomical Instructions?

    DEFF Research Database (Denmark)

    Wieczorek, Rafal

    2010-01-01

    Ethnographic data collected on Easter Island in the late XIX and first half of the XX century suggest that the extant rongorongo tablets contain songs, legends or other chanted traditions. However, we have yet to succeed in relating any one of the rongorongo texts to one of the many legends...... collected by ethnographers. An interesting observation is that, while none of the Rapanuis with whom early visitors to the island were acquainted mentioned anything about astronomy in the context of rongorongo tablets, the only piece of rongorongo texts whose meaning we are certain of is the “calendar...... tablet Mamari”. In the four lines of this tablet, also known as rongorongo text C, we encounter 30 moon glyphs arranged in a pattern that mirrors the Rapa Nui lunar calendar as recorded by early Western visitors. This presentation argues that yet another rongorongo item – tablet Keiti, also known as text...

  15. Gastric emptying of enteric-coated tablets

    International Nuclear Information System (INIS)

    Park, H.M.; Chernish, S.M.; Rosenek, B.D.; Brunelle, R.L.; Hargrove, B.; Wellman, H.N.

    1984-01-01

    To evaluate the gastric emptying time of pharmaceutical dosage forms in a clinical setting, a relatively simple dual-radionuclide technique was developed. Placebo tablets of six different combinations of shape and size were labeled with indium-111 DTPA and enteric coated. Six volunteers participated in a single-blind and crossover study. Tablets were given in the morning of a fasting stomach with 6 oz of water containing /sup 99m/Tc pertechnetate and continuously observed with a gamma camera. A scintigraph was obtained each minute. The results suggested that the size, shape, or volume of the tablet used in this study had no significant effect in the rate of gastric emptying. The tablets emptied erratically and unpredictably, depending upon their time of arrival in the stomach in relation to the occurrence of interdigestive myoelectric contractions. The method described is a relatively simple and accurate technique to allow one to follow the gastric emptying of tablets

  16. Bioequivalence of a new liquid formulation of benazepril compared with the reference tablet product.

    Science.gov (United States)

    Kelers, K; Devi, J L; Anderson, G A; Zahra, P; Vine, J H; Whittem, T

    2013-08-01

    To compare the bioequivalence and 'switchability' of two formulations of benazepril (tablet and liquid) after oral administration. Randomised cross-over design, followed by parallel comparison. Twelve mixed-breed dogs were administered either a tablet (Group A) or liquid formulation (Group B) of benazepril orally at 0.45 mg/kg daily for 4 days. With no washout period, the dogs then received the alternative treatment at the same dose for a further 4 days. Blood samples taken prior to treatment and serially after treatment were analysed for plasma concentrations of benazepril and benazeprilat and the activity and concentration of angiotensin-converting enzyme (ACE). The calculated percentage inhibition of ACE was defined as the primary outcome variable. No statistically significant differences were found between groups A and B for any variable evaluated. The mean (± SD) percentage of ACE inhibition was 85.5 ± 7.04% for the liquid formulation and 85.9 ± 6.66% for the tablet formulation. The mean of the ratios was 1.00 (80% confidence interval 0.96-1.04). No evaluated effect term (sequence, formulation or period) had any statistical effect on any outcome variable. This study supports a conclusion that, based on pharmacodynamic response, the liquid formulation of benazepril is bioequivalent to the reference tablet formulation. Further, the lack of a sequence effect supports the switchability of these two formulations. © 2013 Australian Veterinary Association.

  17. Chronic intracerebroventricular morphine and lactation in rats: dependence and tolerance in relation to oxytocin neurones.

    Science.gov (United States)

    Rayner, V C; Robinson, I C; Russell, J A

    1988-02-01

    1. Acutely, opioids inhibit oxytocin secretion. To study the responses of oxytocin neurones during chronic opioid exposure, forty-five lactating rats were infused continuously from a subcutaneous osmotically driven mini-pump via a lateral cerebral ventricle with morphine sulphate solution from day 2 post-partum for 5-7 days; the infusion rate was increased 2- or 2.5-fold each 40 h from 10 micrograms/h initially up to 50 micrograms/h; controls were infused with vehicle (1 microliter/h, twenty-eight rats) or were untreated (eight rats). 2. Maternal behaviour was disrupted in 27% of the morphine-treated rats; in rats that remained maternal morphine did not affect body weight or water intake but increased rectal temperature by 0.82 +/- 0.14 degrees C (mean +/- S.E.M.) across the first 4 days. 3. Weight gain of the litters of maternal morphine-treated rats was reduced by 32% during 7 days, predominantly in the first day of treatment when milk transfer was also reduced. Observation of pup behaviour during suckling showed decreased frequency of milk ejections on only the second day of morphine treatment. Plasma concentration of prolactin after 6 days was similar in maternal morphine-treated and control rats, but reduced by 90% in non-maternal morphine-treated rats, indicating normal control of prolactin secretion by suckling in morphine-treated rats. 4. Oxytocin and vasopressin contents, measured by radioimmunoassay, in the supraoptic and paraventricular nuclei and in the neurohypophysis were similar between fourteen maternal morphine-treated, twelve vehicle-treated and eight untreated lactating rats; thus exposure to morphine did not involve increased production and storage of oxytocin. 5. Distribution of [3H]morphine infused intracerebroventricularly into six virgin female rats for 6 days was measured by scintillation counting of tissue extracts. Morphine concentration in the hypothalamus and neurohypophysis was 2.7 and 12.8 micrograms/g, respectively, and in blood

  18. Biowaiver study of oral tabletted ethylcellulose microcapsules of a ...

    African Journals Online (AJOL)

    , UV and FTIR spectroscopy, X-ray diffractometry and thermal analysis. ... However, T2 was found closer to the reference formulation that shows a reliable prediction of the plasma concentrations obtained following a single dose of salbutamol ...

  19. Development and Evaluation of Orally Disintegrating Tablets of ...

    African Journals Online (AJOL)

    ... crospovidone and magnesium stearate as key excipients, and with cherry flavor and aspartame as flavor and sweetener, respectively. These formulations were then evaluated using pharmacopoeial and non-pharmacopoeial physical and chemical tests. Dissolution and assay tests were performed using USP apparatus II ...

  20. Design and Evaluation of an Oral Floating Matrix Tablet of ...

    African Journals Online (AJOL)

    gastric contents and remain in the stomach without affecting gastric ... increased gastric retentive time and reduced fluctuation in plasma ..... future in vivo studies. DISCUSSION. In formulation A series, sodium bicarbonate induced CO2 generation in the presence of gastric fluid. The gas generated is trapped within the gel ...

  1. Effect of intravenous paracetamol on postoperative morphine requirements in neonates and infants undergoing major noncardiac surgery: a randomized controlled trial

    NARCIS (Netherlands)

    Ceelie, Ilse; de Wildt, Saskia N.; van Dijk, Monique; van den Berg, Margreeth M. J.; van den Bosch, Gerbrich E.; Duivenvoorden, Hugo J.; de Leeuw, Tom G.; Mathôt, Ron; Knibbe, Catherijne A. J.; Tibboel, Dick

    2013-01-01

    Continuous morphine infusion as standard postoperative analgesic therapy in young infants is associated with unwanted adverse effects such as respiratory depression. To determine whether intravenous paracetamol (acetaminophen) would significantly (>30%) reduce morphine requirements in neonates and

  2. Mathematical tablets from Tell Harmal

    CERN Document Server

    Gonçalves, Carlos

    2015-01-01

    This work offers a re-edition of twelve mathematical tablets from the site of Tell Harmal, in the borders of present-day Baghdad. In ancient times, Tell Harmal was Šaduppûm, a city representative of the region of the Diyala river and of the kingdom of Ešnunna, to which it belonged for a time. These twelve tablets were originally published in separate articles in the beginning of the 1950s and mostly contain solved problem texts. Some of the problems deal with abstract matters such as triangles and rectangles with no reference to daily life, while others are stated in explicitly empirical contexts, such as the transportation of a load of bricks, the size of a vessel, the number of men needed to build a wall and the acquisition of oil and lard. This new edition of the texts is the first to group them, and takes into account all the recent developments of the research in the history of Mesopotamian mathematics. Its introductory chapters are directed to readers interested in an overview of the mathematical con...

  3. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Comi, Giancarlo; Cook, Stuart

    2010-01-01

    Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis.......Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis....

  4. Examination of formulation and process factors on the characteristics of fast dissolving and fast disintegrating tablets manufactured by a direct compression process.

    OpenAIRE

    Pabari, Ritesh M

    2010-01-01

    Oral dosage forms are the safest and most convenient dosage forms and of these tablets are the most popular with patients because of their portability, ease and convenience of dose intake and with manufacturers because of their simple and low cost manufacturing process. Fast disintegrating dissolving tablets (FDDTs), a more recent innovation, have gained a great deal of attention particularly for use in various patient groups such as the paediatric, geriatric, travelling patients and patients...

  5. A survey of patient preferences for a placebo orodispersible tablet

    Directory of Open Access Journals (Sweden)

    Wade AG

    2012-03-01

    Full Text Available Alan G Wade1, Gordon M Crawford1, David Young21CPS Research, Glasgow, UK; 2Department of Mathematics and Statistics, University of Strathclyde, Glasgow, Scotland, UKAim: To assess the attitudes and preferences of patients currently being treated for depression or anxiety disorders with traditional oral antidepressants relative to a placebo orodispersible (ODT formulation of escitalopram.Methods: This was an open study collecting patient-reported outcome data from patients with anxiety or depression that were treated with oral antidepressant medication on Day 0 before and after receiving a single placebo ODT, and on Day 3 or 4 after receiving two further daily doses of placebo ODT. Patients aged 18–80 years who were currently receiving treatment with oral antidepressants were recruited from general practice and by advertising. Patients with significant symptoms of anxiety or depression (scoring ≥9 on either the depression or anxiety subscales of the Hospital Anxiety and Depression Scale were included in the study.Results: A total of 150 patients were enrolled in and completed the study. About 37% of the patients had had trouble with swallowing tablets, and patients with higher depression scores reported more general swallowing problems than those with lower scores (P = 0.002. Most patients (75.3% believed that an ODT might work faster but that it would make no difference to the effectiveness of the medication (63.1% or the number of side effects (81.3%. About 96% of the patients reported experiencing a pleasant taste following the placebo ODT, although seven patients did not like its taste or aftertaste. This study found that 80.7% of patients reported that the tablets were easy or very easy to get out of the packaging.Conclusion: Based on the results of the placebo version of escitalopram ODT, the escitalopram ODT is likely to be well accepted by patients suffering from anxiety or depressive symptoms.Keywords: ODT, swallowing difficulties

  6. Ajoene restored behavioral patterns and liver glutathione level in morphine treated C57BL6 mice.

    Science.gov (United States)

    Yun, Jaesuk; Oliynyk, Sergiy; Lee, Yeonju; Kim, Jieun; Yun, Kyunghwa; Jeon, Raok; Ryu, Jae-Ha; Oh, Seikwan

    2017-01-01

    Oxidative stress exacerbates drug dependence induced by administration of opiate analgesics such as morphine-induced tolerance and physical dependence associated with the reduction in hepatic glutathione (GSH) level. Ajoene obtained from garlic (Allium sativum L.) has been reported for anti-tumorigenic, anti-oxidative and neuroprotective properties, however, little is known about its effect on morphine-induced dependence. Therefore, this study aimed at the effect of ajoene on physical and/or psychological dependence and liver GSH content in morphine-treated mice. Conditioned place preference (CPP) test and measurement of morphine withdrawal syndrome were performed in C57BL6 mice for behavioral experiments. Thereafter, mice were sacrificed for measurement of serum and liver GSH levels. Ajoene restored CPP and naloxone-precipitated jumping behavior in mice exposed to morphine. Moreover, the reduced level of liver GSH content in morphine treated mice was back to normal after ajoene administration. Taken together, ajoene improved behavioral patterns in mice exposed to morphine suggesting its potential therapeutic benefit against morphine-induced dependence.

  7. Acupuncture suppresses reinstatement of morphine-seeking behavior induced by a complex cue in rats.

    Science.gov (United States)

    Lee, Bong Hyo; Lim, Sung Chul; Jeon, Hyeon Jeong; Kim, Jae Su; Lee, Yun Kyu; Lee, Hyun Jong; In, Sunghyun; Kim, Hee Young; Yoon, Seong Shoon; Yang, Chae Ha

    2013-08-26

    Morphine causes physical and psychological dependence for individuals after repeated-use. Above all, our previous study showed that acupuncture attenuated reinstatement of morphine-seeking behavior induced by pharmacological cue. In this study, we investigated whether acupuncture could suppress the reinstatement of morphine-seeking behavior induced by the combination of environmental and pharmacological cues and the possible neuronal involvement. Male Sprague-Dawley rats were trained to self-administer morphine (1.0 mg/kg) for 3 weeks. Following the withdrawal phase (7 days), the effects of acupuncture on reinstatement of morphine-seeking behavior were investigated. For the investigation of neuronal involvement, the GABAA receptor antagonist bicuculline and the GABAB receptor antagonist SCH 50911 were pre-treated. Morphine-seeking behavior induced by combination of re-exposure to the operant chamber and morphine injection was suppressed perfectly by acupuncture at SI5, but not at the control acupoint LI5 and this effect was blocked by pre-treatment with the GABA receptor antagonists. This study suggests that acupuncture at SI5 can be considered as a predominant therapy for the reinstatement of morphine-seeking behavior in humans. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Withdrawal of repeated morphine enhances histamine-induced scratching responses in mice.

    Science.gov (United States)

    Abe, Kenji; Kobayashi, Kanayo; Yoshino, Saori; Taguchi, Kyoji; Nojima, Hiroshi

    2015-04-01

    An itch is experientially well known that the scratching response of conditions such as atopic dermatitis is enhanced under psychological stress. Morphine is typical narcotic drug that induces a scratching response upon local application as an adverse drug reaction. Although long-term treatment with morphine will cause tolerance and dependence, morphine withdrawal can cause psychologically and physiologically stressful changes in humans. In this study, we evaluated the effects of morphine withdrawal on histamine-induced scratching behavior in mice. Administration of morphine with progressively increasing doses (10-50 mg/kg, i.p.) was performed for 5 consecutive days. At 3, 24, 48, and 72 hr after spontaneous withdrawal from the final morphine dose, histamine was intradermally injected into the rostral part of the back and then the number of bouts of scratching in 60 min was recorded and summed. We found that at 24 hr after morphine withdrawal there was a significant increase in histamine-induced scratching behavior. The spinal c-Fos positive cells were also significantly increased. The relative adrenal weight increased and the relative thymus weight decreased, both significantly. Moreover, the plasma corticosterone levels changed in parallel with the number of scratching bouts. These results suggest that morphine withdrawal induces a stressed state and enhances in histamine-induced scratching behavior. Increased reaction against histamine in the cervical vertebrae will participate in this stress-induced itch enhancement.

  9. Pain-relieving properties of topically applied morphine on arterial leg ulcers: a pilot study.

    NARCIS (Netherlands)

    Jansen, M.M.; Horst, J.C. van der; Valk, P.G.M. van der; Kuks, P.F.M.; Zylicz, Z.; Sorge, A.A. van

    2009-01-01

    OBJECTIVE: To assess whether topical morphine is pharmacologically effective in relieving pain from ulcers caused by arterial insufficiency and identify whether this effect is centrally or peripherally mediated. METHOD: The analgesic effect of a topically applied hydrogel containing 0.5% of morphine

  10. Relationships among morphine metabolism, pain and side effects during long-term treatment

    DEFF Research Database (Denmark)

    Andersen, Gertrud; Christrup, Lona Louring; Sjøgren, Per

    2003-01-01

    The two metabolites of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), have been studied intensively in animals and humans during the past 30 years in order to elucidate their precise action and possible contribution to the desired effects and side effects seen after...... morphine administration. M3G and M6G are formed by morphine glucuronidation, mainly in the liver, and are excreted by the kidneys. The metabolites are found in the cerebrospinal fluid after single as well as multiple doses of morphine. M6G binds to opioid receptors, and animal studies have demonstrated...... of the studies have used lower doses of M6G than of morphine. M3G displays very low affinity for opioid receptors and has no analgesic activity. Animal studies have shown that M3G may antagonize the analgesic effect of morphine and M6G, but no human studies have demonstrated this. M3G has also been connected...

  11. Effect of extradural morphine on somatosensory evoked potentials to dermatomal stimulation

    DEFF Research Database (Denmark)

    Lund, C; Selmar, P; Hansen, O B

    1987-01-01

    The effect of the extradural (L2-3) administration of morphine 6 mg on early (less than 0.5 s) somatosensory evoked cortical potentials (SEP) to electrical stimulation of the L1- and S1-dermatomes was examined in eight patients. Extradural morphine did not influence SEP amplitude. SEP latency did...

  12. Morphine Protects Spinal Cord Astrocytes from Glutamate-Induced Apoptosis via Reducing Endoplasmic Reticulum Stress

    Directory of Open Access Journals (Sweden)

    Chao Zhang

    2016-10-01

    Full Text Available Glutamate is not only a neurotransmitter but also an important neurotoxin in central nervous system (CNS. Chronic elevation of glutamate induces both neuronal and glial cell apoptosis. However, its effect on astrocytes is complex and still remains unclear. In this study, we investigated whether morphine, a common opioid ligand, could affect glutamate-induced apoptosis in astrocytes. Primary cultured astrocytes were incubated with glutamate in the presence/absence of morphine. It was found that morphine could reduce glutamate-induced apoptosis of astrocytes. Furthermore, glutamate activated Ca2+ release, thereby inducing endoplasmic reticulum (ER stress in astrocytes, while morphine attenuated this deleterious effect. Using siRNA to reduce the expression of κ-opioid receptor, morphine could not effectively inhibit glutamate-stimulated Ca2+ release in astrocytes, the protective effect of morphine on glutamate-injured astrocytes was also suppressed. These results suggested that morphine could protect astrocytes from glutamate-induced apoptosis via reducing Ca2+ overload and ER stress pathways. In conclusion, this study indicated that excitotoxicity participated in the glutamate mediated apoptosis in astrocytes, while morphine attenuated this deleterious effect via regulating Ca2+ release and ER stress.

  13. Comparison of transversus abdominis plane block vs spinal morphine for pain relief after Caesarean section.

    LENUS (Irish Health Repository)

    McMorrow, R C N

    2011-05-01

    Transversus abdominis plane (TAP) block is an alternative to spinal morphine for analgesia after Caesarean section but there are few data on its comparative efficacy. We compared the analgesic efficacy of the TAP block with and without spinal morphine after Caesarean section in a prospective, randomized, double-blinded placebo-controlled trial.

  14. Morphine disinhibits glutamatergic input to VTA dopamine neurons and promotes dopamine neuron excitation.

    Science.gov (United States)

    Chen, Ming; Zhao, Yanfang; Yang, Hualan; Luan, Wenjie; Song, Jiaojiao; Cui, Dongyang; Dong, Yi; Lai, Bin; Ma, Lan; Zheng, Ping

    2015-07-24

    One reported mechanism for morphine activation of dopamine (DA) neurons of the ventral tegmental area (VTA) is the disinhibition model of VTA-DA neurons. Morphine inhibits GABA inhibitory neurons, which shifts the balance between inhibitory and excitatory input to VTA-DA neurons in favor of excitation and then leads to VTA-DA neuron excitation. However, it is not known whether morphine has an additional strengthening effect on excitatory input. Our results suggest that glutamatergic input to VTA-DA neurons is inhibited by GABAergic interneurons via GABAB receptors and that morphine promotes presynaptic glutamate release by removing this inhibition. We also studied the contribution of the morphine-induced disinhibitory effect on the presynaptic glutamate release to the overall excitatory effect of morphine on VTA-DA neurons and related behavior. Our results suggest that the disinhibitory action of morphine on presynaptic glutamate release might be the main mechanism for morphine-induced increase in VTA-DA neuron firing and related behaviors.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. Preservation of Retina Ganglion Cell Function by Morphine in a Chronic Ocular-Hypertensive Rat Model

    OpenAIRE

    Husain, Shahid; Abdul, Yasir; Crosson, Craig E.

    2012-01-01

    Morphine, a broad range opioid-receptors agonist, provides retina neuroprotection against glaucomatous injury in chronic experimental rat model. Morphine-induced retina neuroprotection in glaucoma model is mediated partly via inhibition of TNF-alpha production and caspase-3 and caspase-8 activation.

  17. Effects of morphine on replication of herpes simplex virus type 1 and 2

    African Journals Online (AJOL)

    Several drugs are being used in treatment of HSV (Herpesviridae) infection in human but still introducing an effective safe drug is desirable. We investigated the inhibitory effect of morphine on replication of HSV in vitro. The results indicated that a concentration of up to 200 ìg/ml morphine had a limited effect on Vero cell ...

  18. Amperometric morphine sensing using a molecularly imprinted polymer-modified electrode

    International Nuclear Information System (INIS)

    Yeh, W.-M.; Ho, K.-C.

    2005-01-01

    This study incorporates morphine into a molecularly imprinted polymer (MIP) for the amperometric detection of morphine. The polymer, poly(3,4-ethylenedioxythiophene), PEDOT, is an electroactive film that catalyzes morphine oxidation and lowers the oxidization potential on an indium tin oxide (ITO) electrode. The MIP-PEDOT modified electrode is prepared by electropolymerizing PEDOT onto an ITO electrode in a 0.1 M LiClO 4 solution with template addition (morphine). After template molecule extraction, the oxidizing current of the MIP-PEDOT modified electrode is measured in a 0.1 M KCl solution (pH = 5.3) at 0.75 V (versus Ag/AgCl/sat'd KCl) with the morphine concentration varying in the 0.1-5 mM range. A linear range, displaying the relationship between steady-state currents and morphine concentrations, from 0.1 to 1 mM, is obtained. The proposed amperometric sensor could be used for morphine detection with a sensitivity of 91.86 μA/cm 2 per mM. A detection limit of 0.2 mM at a signal-to-noise ratio of 3 is achieved. Moreover, the proposed method can discriminate between morphine and its analogs, such as codeine

  19. Analgesic effect of the electromagnetic resonant frequencies derived from the NMR spectrum of morphine.

    Science.gov (United States)

    Verginadis, Ioannis I; Simos, Yannis V; Velalopoulou, Anastasia P; Vadalouca, Athina N; Kalfakakou, Vicky P; Karkabounas, Spyridon Ch; Evangelou, Angelos M

    2012-12-01

    Exposure to various types of electromagnetic fields (EMFs) affects pain specificity (nociception) and pain inhibition (analgesia). Previous study of ours has shown that exposure to the resonant spectra derived from biologically active substances' NMR may induce to live targets the same effects as the substances themselves. The purpose of this study is to investigate the potential analgesic effect of the resonant EMFs derived from the NMR spectrum of morphine. Twenty five Wistar rats were divided into five groups: control group; intraperitoneal administration of morphine 10 mg/kg body wt; exposure of rats to resonant EMFs of morphine; exposure of rats to randomly selected non resonant EMFs; and intraperitoneal administration of naloxone and simultaneous exposure of rats to the resonant EMFs of morphine. Tail Flick and Hot Plate tests were performed for estimation of the latency time. Results showed that rats exposed to NMR spectrum of morphine induced a significant increase in latency time at time points (p spectrum of morphine. Our results indicate that exposure of rats to the resonant EMFs derived from the NMR spectrum of morphine may exert on animals similar analgesic effects to morphine itself.

  20. Effects of midazolam and morphine on cerebral oxygenation and hemodynamics in ventilated premature infants.

    NARCIS (Netherlands)

    Velden, A.A.E.M. van der; Hopman, J.C.W.; Klaessens, J.H.G.M.; Feuth, A.B.; Sengers, R.C.A.; Liem, K.D.

    2006-01-01

    BACKGROUND: Midazolam sedation and morphine analgesia are commonly used in ventilated premature infants. OBJECTIVES: To evaluate the effects of midazolam versus morphine infusion on cerebral oxygenation and hemodynamics in ventilated premature infants. METHODS: 11 patients (GA 26.6-33.0 weeks, BW

  1. Quasi-morphine abstinence behaviour GABA-ergic mechanisms and their localization

    NARCIS (Netherlands)

    J.W. van der Laan

    1981-01-01

    textabstractDi-n-propylacetate (DPA), generally known to be an anti-epileptic drug, induces a behavioural syndrome in rats resembling morphine abstinence behaviour, which is called, therefore, quasi-morphine abstinence beh~viour. An increase in GABA-ergic activity is probably responsible for this

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

    Science.gov (United States)

    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…

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

    International Nuclear Information System (INIS)

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

    1986-01-01

    β-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 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. β-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

  4. High concentrations of morphine sensitize and activate mouse dorsal root ganglia via TRPV1 and TRPA1 receptors

    Directory of Open Access Journals (Sweden)

    Messlinger Karl

    2009-04-01

    Full Text Available Abstract Background Morphine and its derivatives are key drugs in pain control. Despite its well-known analgesic properties morphine at high concentrations may be proalgesic. Particularly, short-lasting painful sensations have been reported upon dermal application of morphine. To study a possible involvement of TRP receptors in the pro-nociceptive effects of morphine (0.3 – 10 mM, two models of nociception were employed using C57BL/6 mice and genetically related TRPV1 and TRPA1 knockout animals, which were crossed and generated double knockouts. Hindpaw skin flaps were used to investigate the release of calcitonin gene-related peptide indicative of nociceptive activation. Results Morphine induced release of calcitonin gene-related peptide and sensitized the release evoked by heat or the TRPA1 agonist acrolein. Morphine activated HEK293t cells transfected with TRPV1 or TRPA1. Activation of C57BL/6 mouse dorsal root ganglion neurons in culture was investigated with calcium imaging. Morphine induced a dose-dependent rise in intracellular calcium in neurons from wild-type animals. In neurons from TRPV1 and TRPA1 knockout animals activation by morphine was markedly reduced, in the TRPV1/A1 double knockout animals this morphine effect was abrogated. Naloxone induced an increase in calcium levels similar to morphine. The responses to both morphine and naloxone were sensitized by bradykinin. Conclusion Nociceptor activation and sensitization by morphine is conveyed by TRPV1 and TRPA1.

  5. Differential analgesic effects of low-dose epidural morphine and morphine-bupivacaine at rest and during mobilization after major abdominal surgery

    DEFF Research Database (Denmark)

    Dahl, J B; Rosenberg, J; Hansen, B L

    1992-01-01

    In a double-blind, randomized study, epidural infusions of low-dose morphine (0.2 mg/h) combined with low-dose bupivacaine (10 mg/h) were compared with epidural infusions of low-dose morphine (0.2 mg/h) alone for postoperative analgesia at rest and during mobilization and cough in 24 patients after...... elective major abdominal surgery. All patients in addition received systemic piroxicam (20 mg daily). No significant differences were observed between the groups at any assessment of pain at rest (P greater than 0.05), whereas pain in the morphine/bupivacaine group was significantly reduced during...... mobilization from the supine into the sitting position 12 and 30 h after surgical incision and during cough 8, 12, and 30 h after surgical incision (P less than 0.05). We conclude, that low-dose epidural bupivacaine potentiates postoperative low-dose epidural morphine analgesia during mobilization and cough...

  6. A critical review on tablet disintegration.

    Science.gov (United States)

    Quodbach, Julian; Kleinebudde, Peter

    2016-09-01

    Tablet disintegration is an important factor for drug release and can be modified with excipients called tablet disintegrants. Tablet disintegrants act via different mechanisms and the efficacy of these excipients is influenced by various factors. In this review, the existing literature on tablet disintegration is critically reviewed. Potential disintegration mechanisms, as well as impact factors on the disintegration process will be discussed based on experimental evidence. Search terms for Scopus and Web of Science included "tablet disintegration", "mechanism tablet disintegration", "superdisintegrants", "disintegrants", "swelling force", "disintegration force", "disintegration mechanisms", as well as brand names of commonly applied superdisintegrants. References of identified papers were screened as well. Experimental data supports swelling and shape recovery as main mechanisms of action of disintegrants. Other tablet excipients and different manufacturing techniques greatly influence the disintegration process. The use of different excipients, experimental setups and manufacturing techniques, as well as the demand for original research led to a distinct patchwork of knowledge. Broader, more systematic approaches are necessary not only to structure the past but also future findings.

  7. Terahertz Technology: A Boon to Tablet Analysis

    Science.gov (United States)

    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

  8. Methyl Parathion Masks Withdrawal from Physical Dependence on Morphine

    Directory of Open Access Journals (Sweden)

    Robin W. Rockhold

    2002-10-01

    Full Text Available Abstract: The cholinergic system has been proposed to participate in the development of dependence on opioids. The present study examined effects of dermal pretreatment with methyl parathion (MP, an acetylcholinesterase inhibitor, on the development of physical dependence on morphine. Opioid dependence was induced by continuous intracerebroventricular (i.c.v. infusion of morphine (26 nmol/μl/h for 3 days in adult male Sprague-Dawley rats. Each rat received two doses of MP, 12.5 mg/kg, dermally, initially, 3 days prior to initiation of i.c.v. morphine infusion and again on the first day of infusion. Withdrawal was precipitated after 3 days of infusion by administering an opioid antagonist, naloxone (48 nmol/5 μl, i.c.v.. Twelve of 23 MP-treated rats exhibited signs of acetylcholinesterase inhibitor intoxication (mild tremors and showed reduced spontaneous locomotor activity (tested by an open field test, prior to naloxone. The brain cholinesterase activity in these 12 rats was 13% of levels in control rats. Eleven rats that did not show toxic signs, exhibited cholinesterase activities that were 20% of control (not significant versus toxic group. The group that showed signs of MP intoxication exhibited a significantly lower incidence of opioid withdrawal jumping, rearing and wet dog shakes compared with the non-toxic group. No differences between quantal withdrawal signs (ptosis, penis-licking, and vocalization were noted between the two groups. The results suggest that toxic inhibition of acetylcholinesterase non-specifically reduces locomotor activity and may obscure certain behavioral signs of withdrawal from opioid dependence. This indicates that caution should be used in interpreting a direct involvement of acetylcholinesterase inhibition in preventing opioid dependence.

  9. [Sertürner and morphine--a historical vignette].

    Science.gov (United States)

    Jurna, I

    2003-08-01

    Friedrich Wilhelm Sertürner was born near Paderborn in 1783. At the age of twenty he passed examinations as a pharmacist's assistant in Paderborn. In a letter to the editor of Trommsdorffs Journal der Pharmacie Vol 13 (1805) he reported on the isolation of a substance from opium which showed alkaline character and was later called by him "morphine". In 1806, Sertürner moved to Einbeck where he first worked as assistant to the tenant of the magistrate's pharmacy. In 1809, he became pharmacist and, since the tenant was already 75 years old, he intended to take charge of the pharmacy. However,he was not successful. During the invasion of Napoleon Bonaparte's troops into Europe, French legislation became valid in those parts which fell under French government. According to French law, Sertürner was allowed to open a second pharmacy. In Einbeck, Sertürner continued research work on morphine and published the results in two papers. In one of these (1817), he introduced observations made with the drug in humans and for the first time called it "morphine". The French chemist Gay-Lussac showed interest in that publication and ordered a translation into French which earned Sertürner the scientific break-through. His was the first achievement in alkaloid research, and for that he received a doctor degree from the university of Jena in 1817.When Napoleon was finally defeated, Sertürner had to close his pharmacy in Einbeck and found another one in Hameln. When asiatic cholera spread in Germany in 1831, he postulated that cholera is caused by a poisonous,animated reproducing organism and made suggestions to avoid infection which are still valid today.Sertürner was honoured by many institutions but still felt not properly esteemed. His behavior become odd and he debilitated. He died in 1841 and was buried in Einbeck.

  10. Dwarf mutant of Papaver somniferum with high morphine content

    International Nuclear Information System (INIS)

    Chauhan, S.P.; Patra, N.K.; Srivastava, H.K.

    1987-01-01

    Opium poppy, Papaver somniferum L. is an important medicinal plant known for its morphine, codeine, and thebaine alkaloids. This Institute had earlier released two latex opium yielding poppy varieties, Shyama and Shweta, which are now cultivated by the farmers under the supervision of the Narcotic Department of the Government of India. However, both these varieties became susceptible to downy mildew (Peronospora arborescens). Lodging due to heavy capsule weight is another problem affecting latex yield. With these problems in mind, we undertook mutation breeding on the above mentioned two varieties employing gamma rays (5 kR, 15 kR, 20 kR) and EMS (0.2%, 0.4%, 0.6%) and combined mutagens (5 kR + 0.2% EMS, 5 kR + 0.4% EMS and 5 kR + 0.6% EMS). M 1 from the treated seeds (405 plants) was raised in winter 1984-85. M 2 generation of 13,500 plants (i.e. 270 M 1 progenies x 50 plants) was raised in winter 1985/86. A dwarf mutant with high morphine content was identified in M 2 from the variety Shweta treated with 5 kR + 0.4% EMS. The mutant differs by its dwarf stature, compact leaf arrangements, multilocular capsules, increased capsule number, and small capsule size. The mutant is under testing for its superior morphine production. It may be used as dwarf gene source in hybridization for improving lodging resistance. This mutant is a novel type, which was not available in our germplasm collection

  11. Very long Detection Times after High and repeated intake of Heroin and Methadone, measured in Oral Fluid

    Directory of Open Access Journals (Sweden)

    Vindenes V.

    2014-12-01

    Full Text Available When detection times for psychoactive drugs in oral fluid are reported, they are most often based on therapeutic doses administered in clinical studies. Repeated ingestions of high doses, as seen after drug abuse, are however likely to cause positive samples for extended time periods. Findings of drugs of abuse in oral fluid might lead to negative sanctions, and the knowledge of detection times of these drugs are important to ensure correct interpretation. The aim of this study was to investigate the detection times of opioids in oral fluid. 25 patients with a history of heavy drug abuse admitted to a detoxification ward were included. Oral fluid and urine were collected daily and, if the patient gave consent, a blood sample was drawn during the first five days after admission. Morphine, codeine and/or 6-monoacetyl morphine (6-MAM were found in oral fluid and/or urine from 20 patients. The maximum detection times in oral fluid for codeine, morphine and 6-MAM were 1, 3 and 8 days, respectively. Positive oral fluid samples were interspersed with negative samples, mainly for concentrations around cut off. Elimination curves for methadone in oral fluid were found for two subjects, and the detection times were 5 and 8 days. Oral fluid is likely to become a good method for detection of drug abuse in the future

  12. Fatal versus non-fatal heroin "overdose": blood morphine concentrations with fatal outcome in comparison to those of intoxicated drivers.

    Science.gov (United States)

    Meissner, Christoph; Recker, Sabine; Reiter, Arthur; Friedrich, Hans Juergen; Oehmichen, Manfred

    2002-11-05

    The study was performed to distinguish fatal from non-fatal blood concentrations of morphine. For this purpose, blood levels of free morphine and total morphine (free morphine plus morphine conjugates) in 207 cases of heroin-related deaths were compared to those in 27 drivers surviving opiate intoxication. The majority of both survivors and non-survivors were found to show a concomitant use of depressants including alcohol or stimulants. Blood morphine levels in both groups varied widely, with a large area of overlap between survivors (free morphine: 0-128 ng/ml, total morphine: 10-2,110 ng/ml) and non-survivors (free morphine: 0-2,800 ng/ml, total morphine: 33-5,000 ng/ml). Five (18.5%) survivors and 87 (42.0%) non-survivors exhibit intoxication only by morphine. In these cases, too, both groups overlapped (survivors-free morphine: 28-93 ng/ml, total morphine: 230-1,451 ng/ml; non-survivors-free morphine: 0-2,800 ng/ml, total morphine: 119-4,660 ng/ml). Although the blood levels of free or total morphine do not allow a reliable prediction of survival versus non-survival, the ratio of free/total morphine may be a criterion to distinguish lethal versus survived intoxication. The mean of the ratio of free to total morphine for all lethal cases (N=207) was 0.293, for those that survived (N=27) 0.135, in cases of intoxication only by morphine 0.250 (N=87) and 0.080 (N=5), respectively. Applying a cut-off of 0.12 for free/total morphine and performing ROC analyses, fatal outcome can be predicted in 80% of the cases correctly, whereas 16% of the survivors were classified as dead. Nevertheless, in this study, all cases with a blood concentration of 200 ng/ml and more of free morphine displayed a fatal outcome.

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

    Science.gov (United States)

    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.

  14. Comparative bioavailability of a morphine suppository given rectally and in a colostomy

    DEFF Research Database (Denmark)

    Højsted, J; Rubeck-Petersen, K; Rask, H

    1990-01-01

    In eight patients with a colostomy, plasma morphine levels were followed for 8 h after administration of 20 mg morphine chloride as a suppository, first rectally and after at least 48 h via the colostomy. The bioavailability after administration in the colostomy showed very great variation......; the mean value compared to rectal bioavailability was only 43% (range 0.1-127%). In four patients the plasma concentrations of morphine after colostomy administration were lower at all times than after rectal administration, and in three only small amounts of morphine were detectable. One patient showed...... higher plasma concentrations after colostomy application than after rectal administration. It is concluded that administration of morphine suppositories in a colostomy cannot be recommended....

  15. Dissolution test for glibenclamide tablets

    Directory of Open Access Journals (Sweden)

    Elisabeth Aparecida dos Santos Gianotto

    2007-10-01

    Full Text Available The aim of this work is to develop and validate a dissolution test for glibenclamide tablets. Optimal conditions to carry out the dissolution test are 500 mL of phosphate buffer at pH 8.0, paddles at 75 rpm stirring speed, time test set to 60 min and using equipment with six vessels. The derivative UV spectrophotometric method for determination of glibenclamide released was developed, validated and compared with the HPLC method. The UVDS method presents linearity (r² = 0.9999 in the concentration range of 5-14 µg/mL. Precision and recoveries were 0.42% and 100.25%, respectively. The method was applied to three products commercially available on the Brazilian market.

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

    Energy Technology Data Exchange (ETDEWEB)

    Thomassin, J.; Tephly, T.R. (Univ. of Iowa, Iowa City (USA))

    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).

  17. Hippocampal GluA1-containing AMPA receptors mediate context-dependent sensitization to morphine.

    Science.gov (United States)

    Xia, Yan; Portugal, George S; Fakira, Amanda K; Melyan, Zara; Neve, Rachael; Lee, H Thomas; Russo, Scott J; Liu, Jie; Morón, Jose A

    2011-11-09

    Glutamatergic systems, including AMPA receptors (AMPARs), are involved in opiate-induced neuronal and behavioral plasticity, although the mechanisms underlying these effects are not fully understood. In the present study, we investigated the effects of repeated morphine administration on AMPAR expression, synaptic plasticity, and context-dependent behavioral sensitization to morphine. We found that morphine treatment produced changes of synaptic AMPAR expression in the hippocampus, a brain area that is critically involved in learning and memory. These changes could be observed 1 week after the treatment, but only when mice developed context-dependent behavioral sensitization to morphine in which morphine treatment was associated with drug administration environment. Context-dependent behavioral sensitization to morphine was also associated with increased basal synaptic transmission and disrupted hippocampal long-term potentiation (LTP), whereas these effects were less robust when morphine administration was not paired with the drug administration environment. Interestingly, some effects may be related to the prior history of morphine exposure in the drug-associated environment, since alterations of AMPAR expression, basal synaptic transmission, and LTP were observed in mice that received a saline challenge 1 week after discontinuation of morphine treatment. Furthermore, we demonstrated that phosphorylation of GluA1 AMPAR subunit plays a critical role in the acquisition and expression of context-dependent behavioral sensitization, as this behavior is blocked by a viral vector that disrupts GluA1 phosphorylation. These data provide evidence that glutamatergic signaling in the hippocampus plays an important role in context-dependent sensitization to morphine and supports further investigation of glutamate-based strategies for treating opiate addiction.

  18. Ethanol Reversal of Tolerance to the Respiratory Depressant Effects of Morphine

    Science.gov (United States)

    Hill, Rob; Lyndon, Abi; Withey, Sarah; Roberts, Joanne; Kershaw, Yvonne; MacLachlan, John; Lingford-Hughes, Anne; Kelly, Eamonn; Bailey, Chris; Hickman, Matthew; Henderson, Graeme

    2016-01-01

    Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO2 in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths. PMID:26171718

  19. Neuromodulatory effects of the dorsal hippocampal endocannabinoid system in dextromethorphan/morphine-induced amnesia.

    Science.gov (United States)

    Ghasemzadeh, Zahra; Rezayof, Ameneh

    2017-01-05

    Dextromethorphan which is an active ingredient in many cough medicines has been previously shown to potentiate amnesic effect of morphine in rats. However, the effect of dextromethorphan, that is also a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, in combination with morphine on hippocampus-based long term memory has not been well characterized. The aim of the present study was to assess the possible role of endocannabinoid system of the dorsal hippocampus in dextromethorphan /morphine-induced amnesia. Our results showed that intraperitoneal (i.p.) injection of morphine (5mg/kg) or dextromethorphan (5-15mg/kg) before testing the passive avoidance learning induced amnesia. Combination of ineffective doses of dextromethorphan (7.5mg/kg, i.p.) and morphine (2mg/kg, i.p.) also produced amnesia, suggesting the enhancing effects of the drugs. To assess the effect of the activation or inhibition of the dorsal hippocampal cannabinoid CB 1 receptors on this amnesia, ACPA or AM251 as selective receptor agonists or antagonists were respectively injected into the CA1 regions before systemic injection of dextromethorphan and morphine. Interestingly, intra-CA1 microinjection of ACPA (0.5-1ng/rat) improved the amnesic effect of dextromethorphan /morphine combination. The microinjection of AM251 into the CA1 region enhanced the response of the combination of dextromethorphan /morphine in inducing amnesia. Moreover, Intra-CA1 microinjection of AM251 inhibited the improving effect of ACPA on dextromethorphan /morphine-induced amnesia. It is important to note that intra-CA1 microinjection of the same doses of the agonist or antagonist by itself had no effects on memory formation. Thus, it can be concluded that the dorsal hippocampal endocannabinoid system, via CB 1 receptor-dependent mechanism, may be involved in morphine/dextromethorphan -induced amnesia. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Comparative investigations of tablet crushing force testers

    DEFF Research Database (Denmark)

    Sonnergaard, Jørn; Jensen, C.G.; Poulsen, L.

    2005-01-01

    The performance of 16 tablet breaking force testers was evaluated in terms of accuracy, reproducibility and repeatability. Three tablet formulations with different plastic or brittle deformation mechanisms and with target breaking forces of 50, 100 and 150 N were tested. Statistically significant...... by the concept of components of variance was 5-7 % depending on the model tablet excipient. The standard deviation within testers (repeatability) was affected by the type of model formulation showing increasing variability with increasing brittleness of the compressed material. No specific effect of altering...

  1. Teach yourself visually Windows 8 tablets

    CERN Document Server

    McFedries, Paul

    2012-01-01

    A visual guide to all the features of the new Windows 8 Tablet This must-have resource features visually rich, step-by-step instructions that show you how to get the most enjoyment from your Windows 8 tablet. Learn about the exciting new Metro UI, optimized specifically for touch devices. The most popular and commonly used apps and functions are covered too, along with the basics of syncing with a network, setting up e-mail, watching videos, listening to music, and common productivity tasks. This book provides all the guidance needed to enjoy all the best the new Windows 8 tablets have to offe

  2. Controlled-release tablet formulation of isoniazid.

    Science.gov (United States)

    Jain, N K; Kulkarni, K; Talwar, N

    1992-04-01

    Guar (GG) and Karaya gums (KG) alone and in combination with hydroxy-propylmethylcellulose (HPMC) were evaluated as release retarding materials to formulate a controlled-release tablet dosage form of isoniazid (1). In vitro release of 1 from tablets followed non-Fickian release profile with rapid initial release. Urinary excretion studies in normal subjects showed steady-state levels of 1 for 13 h. In vitro and in vivo data correlated (r = 0.9794). The studies suggested the potentiality of GG and KG as release retarding materials in formulating controlled-release tablet dosage forms of 1.

  3. Android Tablet Application Development For Dummies

    CERN Document Server

    Felker, Donn

    2011-01-01

    Get up to speed on the hottest opportunity in the application development arena App development for tablets is a booming business. Android tablets, including the popular Motorola Xoom, are gaining market share at breakneck speed, and this book can have even novice programmers creating great Android apps specifically for tablets quickly and easily. A little Java knowledge is helpful but not essential to get started creating apps. Android expert Donn Felker helps you get the Android environment up and running, use XML to create application menus, create an icon for your app, and submit your app

  4. OPRM1 c.118A>G Polymorphism and Duration of Morphine Treatment Associated with Morphine Doses and Quality-of-Life in Palliative Cancer Pain Settings

    Directory of Open Access Journals (Sweden)

    Aline Hajj

    2017-03-01

    Full Text Available Despite increased attention on assessment and management, pain remains the most persistent symptom in patients with cancer, in particular in end-of-life settings, with detrimental impact on their quality-of-life (QOL. We conducted this study to evaluate the added value of determining some genetic and non-genetic factors to optimize cancer pain treatment. Eighty-nine patients were included in the study for the evaluation of palliative cancer pain management. The regression analysis showed that age, OPRM1 single nucleotide polymorphism (SNP, as well as the duration of morphine treatment were significantly associated with morphine doses at 24 h (given by infusion pump; p = 0.043, 0.029, and <0.001, respectively. The mean doses of morphine decreased with age but increased with the duration of morphine treatment. In addition, patients with AG genotype c.118A>G OPRM1 needed a higher dose of morphine than AA patients. Moreover, metastases, OPRM1 SNP, age, and gender were significantly associated with the QOL in our population. In particular, AA patients for OPRM1 SNP had significantly lower cognitive function than AG patients, a result not previously reported in the literature. These findings could help increase the effectiveness of morphine treatment and enhance the QOL of patients in regards to personalized medicine.

  5. Enhanced bioavailability of buspirone hydrochloride via cup and core buccal tablets: formulation and in vitro/in vivo evaluation.

    Science.gov (United States)

    Kassem, Mohamed A A; Elmeshad, Aliaa N; Fares, Ahmed R

    2014-03-10

    This work aims to prepare sustained release buccal mucoadhesive tablets of buspirone hydrochloride (BH) to improve its systemic bioavailability. The tablets were prepared according to 5×3 factorial design where polymer type was set at five levels (carbopol, hydroxypropyl methylcellulose, sodium alginate, sodium carboxymethyl cellulose and guar gum), and polymer to drug ratio at three levels (1:1, 2:1 and 3:1). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h) and time for release of 50% BH (T(₅₀%)) were chosen as dependent variables. Additional BH cup and core buccal tablets were prepared to optimize BH release profile and make it uni-directional along with the tablets mucoadhesion. Tablets were evaluated in terms of content uniformity, weight variation, thickness, diameter, hardness, friability, swelling index, surface pH, mucoadhesion strength and time and in vitro release. Cup and core formula (CA10) was able to adhere to the buccal mucosa for 8h, showed the highest Q8h (97.91%) and exhibited a zero order drug release profile. Pharmacokinetic study of formula CA10 in human volunteers revealed a 5.6 fold increase in BH bioavailability compared to the oral commercial Buspar® tablets. Conducting level A in vitro/in vivo correlation showed good correlation (r²=0.9805) between fractions dissolved in vitro and fractions absorbed in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Performance of tablet disintegrants: impact of storage conditions and relative tablet density.

    Science.gov (United States)

    Quodbach, Julian; Kleinebudde, Peter

    2015-01-01

    Tablet disintegration can be influenced by several parameters, such as storage conditions, type and amount of disintegrant, and relative tablet density. Even though these parameters have been mentioned in the literature, the understanding of the disintegration process is limited. In this study, water uptake and force development of disintegrating tablets are analyzed, as they reveal underlying processes and interactions. Measurements were performed on dibasic calcium phosphate tablets containing seven different disintegrants stored at different relative humidities (5-97%), and on tablets containing disintegrants with different mechanisms of action (swelling and shape recovery), compressed to different relative densities. Disintegration times of tablets containing sodium starch glycolate are affected most by storage conditions, which is displayed in decreased water uptake and force development kinetics. Disintegration times of tablets with a swelling disintegrant are only marginally affected by relative tablet density, whereas the shape recovery disintegrant requires high relative densities for quick disintegration. The influence of relative tablet density on the kinetics of water uptake and force development greatly depends on the mechanism of action. Acquired data allows a detailed analysis of the influence of storage conditions and mechanisms of action on disintegration behavior.

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

    Energy Technology Data Exchange (ETDEWEB)

    Tadinada, Aditya; Mahdian, Mina; Sheth, Sonam; Chandhoke, Taranpreet K.; Gopalakrishna, Aadarsh; Potluri, Anitha; Yadav, Sumit [University of Connecticut School of Dental Medicine, Farmington (United States)

    2015-09-15

    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). 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. 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. Tablet computers can reliably show anatomical landmarks in panoramic and lateral cephalometric radiographs.

  8. Design and evaluation of nicorandil extended-release tablet

    Directory of Open Access Journals (Sweden)

    Ju-Young Kim

    2015-04-01

    Full Text Available The aim of this study was to design and evaluate extended-release formulations of a model drug, nicorandil, in order to achieve the desired steady-state plasma concentration of drug in vivo. Simulation was employed to estimate optimum dissolution and absorption rate of nicorandil. The dissolution test was employed using pH 1.2, 4.0, 6.8 buffer solution, or water, to measure the in vitro release behaviors of nicorandil formulations. A single dose (15 mg of each formulation was orally administered to four beagle dogs under fasted conditions, and the pharmacokinetic parameters were calculated. The in vitro/in vivo relationship of the extended-release formulation was confirmed using in vitro dissolution profiles and plasma concentrations of drug in beagle dogs. Nicorandil was released completely within 30 min from the immediate-release tablets and released for 24 h from the extended-release tablets. The nicorandil plasma concentration could be modified by adjusting the drug release rate from the extended-release formulation. The release rate of nicorandil was the rate-limiting step in the overall absorption of drug from the extended-release formulations. These results highlight the potential of a nicorandil extended-release formulation in the treatment of angina pectoris.

  9. Pharmacokinetics of hydrocodone extended-release tablets formulated with different levels of coating to achieve abuse deterrence compared with a hydrocodone immediate-release/acetaminophen tablet in healthy subjects.

    Science.gov (United States)

    Darwish, Mona; Bond, Mary; Tracewell, William; Robertson, Philmore; Yang, Ronghua

    2015-01-01

    A hydrocodone extended-release (ER) formulation employing the CIMA(®) Abuse-Deterrence Technology platform was developed to provide resistance against rapid release of hydrocodone when tablets are comminuted or taken with alcohol. This study evaluated the pharmacokinetics of three hydrocodone ER tablet prototypes with varying levels of polymer coating to identify the prototype expected to have the greatest abuse deterrence potential based on pharmacokinetic characteristics that maintain systemic exposure to hydrocodone comparable to that of a commercially available hydrocodone immediate-release (IR) product. In this four-period crossover study, healthy subjects aged 18-45 years were randomized to receive a single intact, oral 45-mg tablet of one of three hydrocodone ER prototypes (low-, intermediate-, or high-level coating) or an intact, oral tablet of hydrocodone IR/acetaminophen (APAP) 10/325 mg every 6 h until four tablets were administered, with each of the four treatments administered once over the four study periods. Dosing periods were separated by a minimum 5-day washout. Naltrexone 50 mg was administered to block opioid receptors. Blood samples for pharmacokinetic assessments were collected predose and through 72 h postdose. Parameters assessed included maximum observed plasma hydrocodone concentration (C(max)), time to C(max) (t(max)), and area under the concentration-time curve from time 0 to infinity (AUC(0-∞)). Mean C(max) values were 49.2, 32.6, and 28.4 ng/mL for the low-, intermediate-, and high-level coating hydrocodone ER tablet prototypes, respectively, and 37.3 ng/mL for the hydrocodone IR/APAP tablet; respective median t(max) values were 5.9, 8.0, 8.0, and 1.0 h. Total systemic exposure to hydrocodone (AUC(0-∞)) was comparable between hydrocodone ER tablet prototypes (640, 600, and 578 ng·h/mL, respectively) and hydrocodone IR/APAP (581 ng·h/mL). No serious adverse events or deaths were reported. The most common adverse events included

  10. Microstructure of Tablet-Pharmaceutical Significance, Assessment, and Engineering.

    Science.gov (United States)

    Sun, Changquan Calvin

    2017-05-01

    To summarize the microstructure - property relationship of pharmaceutical tablets and approaches to improve tablet properties through tablet microstructure engineering. The main topics reviewed here include: 1) influence of material properties and manufacturing process parameters on the evolution of tablet microstructure; 2) impact of tablet structure on tablet properties; 3) assessment of tablet microstructure; 4) development and engineering of tablet microstructure. Microstructure plays a decisive role on important pharmaceutical properties of a tablet, such as disintegration, drug release, and mechanical strength. Useful information on mechanical properties of a powder can be obtained from analyzing tablet porosity-pressure data. When helium pycnometry fails to accurately measure true density of a water-containing powder, non-linear regression of tablet density-pressure data is a useful alternative method. A component that is more uniformly distributed in a tablet generally exerts more influence on the overall tablet properties. During formulation development, it is highly recommended to examine the relationship between any property of interest and tablet porosity when possible. Tablet microstructure can be engineered by judicious selection of formulation composition, including the use of the optimum solid form of the drug and appropriate type and amount of excipients, and controlling manufacturing process.

  11. Development of Bilayer Tablets with Modified Release of Selected Incompatible Drugs.

    Science.gov (United States)

    Dhiman, Neha; Awasthi, Rajendra; Jindal, Shammy; Khatri, Smriti; Dua, Kamal

    2016-01-01

    The oral route is considered to be the most convenient and commonly-employed route for drug delivery. When two incompatible drugs need to be administered at the same time and in a single formulation, bilayer tablets are the most appropriate dosage form to administer such incompatible drugs in a single dose. The aim of the present investigation was to develop bilayered tablets of two incompatible drugs; telmisartan and simvastatin. The bilayer tablets were prepared containing telmisartan in a conventional release layer using croscarmellose sodium as a super disintegrant and simvastatin in a slow-release layer using HPMC K15M, Carbopol 934P and PVP K 30 as matrix forming polymers. The tablets were evaluated for various physical properties, drug-excipient interactions using FTIR spectroscopy and in vitro drug release using 0.1M HCl (pH 1.2) for the first hour and phosphate buffer (pH 6.8) for the remaining period of time. The release kinetics of simvastatin from the slow release layer were evaluated using the zero order, first order, Higuchi equation and Peppas equation. All the physical parameters (such as hardness, thickness, disintegration, friability and layer separation tests) were found to be satisfactory. The FTIR studies indicated the absence of interactions between the components within the individual layers, suggesting drug-excipient compatibility in all the formulations. No drug release from the slow-release layer was observed during the first hour of the disso