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1

Effect of filtration on morphine and particle content of injections prepared from slow-release oral morphine tablets  

PubMed Central

Background Injections of mixtures prepared from crushed tablets contain insoluble particles which can cause embolisms and other complications. Although many particles can be removed by filtration, many injecting drug users do not filter due to availability, cost or performance of filters, and also due to concerns that some of the dose will be lost. Methods Injection solutions were prepared from slow-release morphine tablets (MS Contin®) replicating methods used by injecting drug users. Contaminating particles were counted by microscopy and morphine content analysed by liquid chromatography before and after filtration. Results Unfiltered tablet extracts contained tens of millions of particles with a range in sizes from < 5 ?m to > 400 ?m. Cigarette filters removed most of the larger particles (> 50 ?m) but the smaller particles remained. Commercial syringe filters (0.45 and 0.22 ?m) produced a dramatic reduction in particles but tended to block unless used after a cigarette filter. Morphine was retained by all filters but could be recovered by following the filtration with one or two 1 ml washes. The combined use of a cigarette filter then 0.22 ?m filter, with rinses, enabled recovery of 90% of the extracted morphine in a solution which was essentially free of tablet-derived particles. Conclusions Apart from overdose and addiction itself, the harmful consequences of injecting morphine tablets come from the insoluble particles from the tablets and microbial contamination. These harmful components can be substantially reduced by passing the injection through a sterilizing (0.22 ?m) filter. To prevent the filter from blocking, a preliminary coarse filter (such as a cigarette filter) should be used first. The filters retain some of the dose, but this can be recovered by following filtration with one or two rinses with 1 ml water. Although filtration can reduce the non-pharmacological harmful consequences of injecting tablets, this remains an unsafe practice due to skin and environmental contamination by particles and microorganisms, and the risks of blood-borne infections from sharing injecting equipment.

2009-01-01

2

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

PubMed

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

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

2005-11-01

3

Orally Disintegrating Tablets: A Review  

Microsoft Academic Search

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 alternative to conventional tablets and capsules due to better patient compliance. ODTs are solid dosage forms containing medicinal substances which

Jaysukh J Hirani; Dhaval A Rathod; Kantilal R Vadalia

4

Guidance for Industry Orally Disintegrating Tablets.  

National Technical Information Service (NTIS)

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

2008-01-01

5

Prolonged Oral Morphine Therapy for Severe Angina Pectoris  

Microsoft Academic Search

Patients with intractable angina pectoris despite optimal drug therapy, who are not candidates for revascularization procedures, pose a very difficult problem. We evaluated the role of chronic opioid therapy in four such patients. The patients (mean age 79.5 years) were treated by low doses (mean 40 mg\\/day) of controlled-release oral morphine (CRM) for 1 to 5 years. The treatment was

Meir Mouallem; Eli Schwartz; Zvi Farfel

2000-01-01

6

Formulation Development of Morphine Sulfate Sustained-Release Tablets and Its Bioequivalence Study in Healthy Thai Volunteers  

Microsoft Academic Search

The objectives of this study were to develop morphine sulfate sustained-release tablet formulations and to evaluate the bioequivalence\\u000a compared with a commercial brand. The physicochemical properties of the formulated and commercial tablets were determined\\u000a and compared. The bioequivalence investigation was carried out in 15 healthy male volunteers who received a single dose in\\u000a a randomized two-way crossover design. After dosing,

Detpon Preechagoon; Viroj Sumyai; Suvatna Chulavatnatol; Poj Kulvanich; Thanee Tessiri; Khanittha Tontisirin; Thaned Pongjanyakul; Verawan Uchaipichat; Sirikul Aumpon; Chaiyasit Wongvipaporn

2010-01-01

7

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

Microsoft Academic Search

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

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

1986-01-01

8

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

Microsoft Academic Search

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

D. J. Walker; James P. Zacny

1998-01-01

9

Fast disintegrating tablets of nisoldipine for intra-oral administration.  

PubMed

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

El Maghraby, Gamal M; Elsergany, Ramy N

2014-09-01

10

Fatal morphine poisoning in a child due to accidental oral ingestion  

Microsoft Academic Search

A case of fatal intoxication of an 8 year old child due to accidental oral ingestion of morphine is presented. Following a tonsillectomy and release from the hospital the decedent was prescribed meperidine syrup 50 mg per teaspoon (tsp) to be taken 2 tsps every 4 h. A pharmacist when filling her prescription mistakenly dispensed Roxanol ® which contained 20

Alphonse Poklis; Leslie E. Edinboro; A. Shannon Wohler; Faruk Presswalla; David Barron

1995-01-01

11

Design and study of lamivudine oral controlled release tablets.  

PubMed

The objective of this study was to design oral controlled release matrix tablets of lamivudine using hydroxypropyl methylcellulose (HPMC) as the retardant polymer and to study the effect of various formulation factors such as polymer proportion, polymer viscosity, and compression force on the in vitro release of drug. In vitro release studies were performed using US Pharmacopeia type 1 apparatus (basket method) in 900 mL of pH 6.8 phosphate buffer at 100 rpm. The release kinetics were analyzed using the zero-order model equation, Higuchi's square-root equation, and the Ritger-Peppas empirical equation. Compatibility of the drug with various excipients was studied. In vitro release studies revealed that the release rate decreased with increase in polymer proportion and viscosity grade. Increase in compression force was found to decrease the rate of drug release. Matrix tablets containing 60% HPMC 4000 cps were found to show good initial release (26% in first hour) and extended the release up to 16 hours. Matrix tablets containing 80% HPMC 4000 cps and 60% HPMC 15,000 cps showed a first-hour release of 22% but extended the release up to 20 hours. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets was dependent on drug diffusion and polymer relaxation and therefore followed non-Fickian or anomalous release. No incompatibility was observed between the drug and excipients used in the formulation of matrix tablets. The developed controlled release matrix tablets of lamivudine, with good initial release (20%-25% in first hour) and extension of release up to 16 to 20 hours, can overcome the disadvantages of conventional tablets of lamivudine. PMID:18181522

Ravi, Punna Rao; Ganga, Sindhura; Saha, Ranendra Narayan

2007-01-01

12

Formulation and optimization of orally disintegrating tablets of sumatriptan succinate.  

PubMed

The aims of the present research were to mask the intensely bitter taste of sumatriptan succinate and to formulate orally disintegrating tablets (ODTs) of the taste masked drug. Taste masking was performed by coating sumatriptan succinate with Eudragit EPO using spray drying technique. The resultant microspheres were evaluated for thermal analysis, yield, particle size, entrapment efficiency and in vitro taste masking. The tablets were formulated by mixing the taste masked microspheres with different types and concentrations of superdisintegrants and compressed using direct compression method followed by sublimation technique. The prepared tablets were evaluated for weight variation, thickness, hardness, friability, drug content, water content, in vitro disintegration time and in vitro drug release. All the tablet formulations disintegrated in vitro within 37-410 s. The optimized formulation containing 5% Kollidon CL-SF released more than 90% of the drug within 15 min and the release was comparable to that of commercial product (Suminat®). In human volunteers, the optimized formulation was found to have a pleasant taste and mouth feel and disintegrated in the oral cavity within 41 s. The optimized formulation was found to be stable and bioequivalent with Suminat®. PMID:21804234

Sheshala, Ravi; Khan, Nurzalina; Darwis, Yusrida

2011-01-01

13

Preparation of Orally Disintegrating Tablets with Masking of Unpleasant Taste: Comparison with Corrective-adding Methods  

Microsoft Academic Search

Many orally disintegrating tablets have recently been developed to improve oral ingestion and usability and are widely administered clinically, resulting in improved quality of life for patients. Since orally disintegrating tablets rapid- ly disintegrate in the mouth, the masking of unpleasant taste is important. We investigated the masking of the taste of furosemide (FU) as a model drug with correctives

Yayoi KAWANO; Akihiko ITO; Masanaho SASATSU; Yoshiharu MACHIDA

2010-01-01

14

Development of oral acetaminophen chewable tablets with inhibited bitter taste.  

PubMed

Various formulations with some matrix bases and corrigents were examined for development of oral chewable tablets which suppressed the bitter taste of acetaminophen, often used as an antipyretic for infants. Corn starch/lactose, cacao butter and hard fat (Witepsol H-15) were used for matrix bases, and sucrose, cocoa powder and commercial bitter-masking powder mixture made from lecithin (Benecoat BMI-40) were used for corrigents against bitter taste. The bitter taste intensity was evaluated using volunteers by comparison of test samples with standard solutions containing quinine at various concentrations. For the tablets made of matrix base and drug, Witepsol H-15 best inhibited the bitter taste of the drug, and the bitter strength tended to be suppressed with increase in the Witepsol H-15 amount. When the inhibitory effect on the bitter taste of acetaminophen solution was compared among the corrigents, each tended to suppress the bitter taste; especially, Benecoat BMI-40 exhibited a more inhibitory effect. Further, chewable tablets were made of one matrix base and one corrigent, and of one matrix base and two kinds of corrigents, their bitter taste intensities after chewing were compared. As a result, the tablets made of Witepsol H-15/Benecoat BMI-40/sucrose, of Witepsol H-15/cocoa powder/sucrose and of Witepsol H-15/sucrose best masked the bitter taste so that they were tolerable enough to chew and swallow. The dosage forms best masking bitter taste showed good release of the drug, indicating little change in bioavailability by masking. PMID:12527182

Suzuki, Hiroyuki; Onishi, Hiraku; Takahashi, Yuri; Iwata, Masanori; Machida, Yoshiharu

2003-01-30

15

Effect of Repeated Oral Treatment with Etoposide on the Expression of Intestinal P-glycoprotein and Oral Morphine Analgesia.  

PubMed

  Currently, the World Health Organization recommends oral administration of opioid analgesics for patients with cancer to treat cancer-related pain from the initial stage of treatment. Furthermore, many anticancer drugs have been newly-developed and approved as oral form. Because of this trend, the chances of drug-drug interactions between anticancer drugs and opioid analgesics during absorption process from the intestine are likely to increase. To investigate these possible drug-drug interactions, we have focused on intestinal P-glycoprotein (P-gp) which regulates the absorption of various substrate drugs administered orally. Previously, we have found that repeated oral treatment with etoposide (ETP), an anticancer drug, attenuates analgesia of oral morphine, a substrate drug for P-gp, by increasing the expression and activity of intestinal P-gp. However, the mechanism by which ETP treatment increases the intestinal P-gp expression and decreases oral morphine analgesia remains unclear. RhoA, a small G-protein, and ROCK, an effector of RhoA, pathway has been attracted attention with regard to their involvement in the regulatory mechanism of the expression and activity of P-gp. Interestingly, this pathway is activated in response to various signaling induced by some anticancer drugs. Furthermore, it has been reported that ezrin/radixin/moesin (ERM) play a key role in the plasma membrane localization of P-gp, and that RhoA/ROCK pathway regulates the activation process of ERM. This review article introduces the result of our previous research as well as recent findings on the involvement of ERM via activation of RhoA/ROCK in the increased expression of intestinal P-gp and decreased oral morphine analgesia induced by repeated oral treatment with ETP. PMID:24882643

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

2014-01-01

16

Formulation Development, Evaluation and Comparative Study of Effects of Super Disintegrants in Cefixime Oral Disintegrating Tablets  

PubMed Central

The present work was aimed at formulation development, evaluation and comparative study of the effects of superdisintegrants in Cefixime 50 mg oral disintegrating tablets. The superdisintegrants used for the present study were sodium starch glycolate and crosscarmellose sodium. The formulated tablets were evaluated for various tableting properties, like hardness, thickness, friability, weight variation, disintegration time and dissolution rate. Comparative evaluation of the above-mentioned parameters established the superiority of the tablets formulated with crosscarmellose sodium to those formulated with sodium starch glycolate.

Remya, KS; Beena, P; Bijesh, PV; Sheeba, A

2010-01-01

17

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

PubMed

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

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

2008-01-01

18

Oral suspensions of morphine hydrochloride for controlled release: rheological properties and drug release.  

PubMed

Recent developments in pharmaceutical technology have facilitated the design and production of modified release formulas for drugs whose physical, chemical or biological properties impede release and thus might compromise their efficacy or safety. One such drug is morphine, whose short half-life requires repeated doses at short intervals. The use of biocompatible polymers such as ethylcellulose has made it possible to develop microencapsulated formulations which facilitate liquid, sustained-release pharmaceutical formulas for oral administration. We developed a stable final formulation of morphine with an acceptable release profile by comparing the rheological properties and stability of formulations with different thickeners (xanthan gum, Carbopol, and carboxymethylcellulose with microcrystalline cellulose) at different concentrations from 0.25% to 1.0%. Release assays in a Franz-type cell were done to determine the most suitable release profile for the formulation. PMID:21271730

Morales, M E; López, G; Gallardo, V; Ruiz, M A

2011-04-01

19

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

PubMed

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

Stoltenberg, I; Breitkreutz, J

2011-08-01

20

Oral malodor reduction by a palatal mucoadhesive tablet containing herbal formulation  

Microsoft Academic Search

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

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

2008-01-01

21

The reproducibility of bioavailability of oral morphine from solution under fed and fasted conditions.  

PubMed

The reproducibility in bioavailability of orally administered morphine (as a solution) under fed and fasted conditions was studied in 5 patients with chronic pain on three occasions over 1 yr (0, 6, and 12 mo). During each study period (i.e.. 0, 6, and 12 mo), patients received the 50 mg oral dose both in the fasted state (10 hr since food) and immediately after a high fat content breakfast, in randomly determined sequence. Frequent blood samples were collected for 10 hr after the dose. There was no significant difference in the maximum blood morphine concentration (Cmax) or the time to Cmax among the three study periods or between the fed and fasted states. Bioavailability, as assessed by log(AUC), was significantly greater in the fed compared to the fasted state (P less than .01) but did not differ over the three study periods (Two-factor analysis of variance). Intrapatient variability contributed 32% and 54% to total variation in log(AUC) under fed and fasted conditions, respectively. PMID:1940488

Gourlay, G K; Plummer, J L; Cherry, D A; Purser, T

1991-10-01

22

Oral malodor reduction by a palatal mucoadhesive tablet containing herbal formulation  

Microsoft Academic Search

ObjectiveThe aim of the present study was to test the effect of a palatal mucoadhesive tablet containing an herbal formulation on oral malodor production and volatile sulfide compound (VSC) levels, and to evaluate its antimicrobial activity.

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

2008-01-01

23

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

PubMed Central

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

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

2011-01-01

24

The influence of formulation and manufacturing process parameters on the characteristics of lyophilized orally disintegrating tablets.  

PubMed

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

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

2011-01-01

25

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

Microsoft Academic Search

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

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

2001-01-01

26

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

PubMed Central

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

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

2009-01-01

27

Acetaminophen-containing chewable tablets with suppressed bitterness and improved oral feeling.  

PubMed

The aim of this study was to develop acetaminophen chewable tablets with suppressed bitterness and improved oral feeling by examination of hard fats as the matrix base and of sweetening agents as corrigents. Witepsol H-15, W-35, S-55, E-75 and E-85, and Witocan H and 42/44 were used as hard fats. Witocan H and 42/44 were selected in view of improved oral feeling. Witocan H/Witocan 42/44 mixture tablets showed different melting characteristics and drug release rates dependent on their ratios, and those with the Witocan H/Witocan 42/44 ratio of 92.5% (w/w) and more showed good drug release. Sucrose, xylitol, saccharin, saccharin sodium, aspartame and sucralose were used as sweetening agents, and applied alone or with Benecoat BMI-40 or cocoa powder. The Witocan H tablet with 1% (w/w) saccharin plus 5% (w/w) Benecoat BMI-40 (Sc1-B5), and the Witocan H/Witocan 42/44 (92.5:7.5, w/w) mixture tablet with 1% (w/w) aspartame plus 5% (w/w) Benecoat BMI-40 suppressed bitterness and sweetness excellently, but the former tablet showed better drug release. Thus, the Witocan H tablet with Sc1-B5 is suggested as the best acetaminophen chewable tablet, exhibiting suppressed bitterness, low sweetness, improved oral feeling and good drug release. PMID:15158948

Suzuki, Hiroyuki; Onishi, Hiraku; Hisamatsu, Seiji; Masuda, Kosuke; Takahashi, Yuri; Iwata, Masanori; Machida, Yoshiharu

2004-06-18

28

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

Microsoft Academic Search

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

Katie Smith

29

Oral mucosal bioadhesive tablets of pectin and HPMC: in vitro and in vivo evaluation.  

PubMed

The potential of tablets containing 1:4, 1:1 and 4:1 weight ratios of pectin and hydroxypropyl methylcellulose (HPMC) for the sustained release of diltiazem by sublingual administration has been investigated. Measurements of maximum adhesive force to rat peritoneal membrane indicated a satisfactory bioadhesive strength. An in vitro sustained release of diltiazem over 5 h was achieved with bilayer tablets composed of a drug-free ethylcellulose layer in addition to the pectin/HPMC layer containing drug. Plasma concentration-time curves obtained following sublingual administration to rabbits of single and bilayer tablets with 1:1 weight ratios of pectin and HPMC showed evidence of sustained release of diltiazem. Bioavailability of diltiazem was 2.5 times that achieved by oral administration for single layer tablets and 1.8 times for the bilayered tablets. PMID:11011995

Miyazaki, S; Kawasaki, N; Nakamura, T; Iwatsu, M; Hou, W M; Attwood, D

2000-08-25

30

Serum morphine concentrations after buccal and intramuscular morphine administration.  

PubMed Central

1. This study compared serum concentrations of morphine after administration of a buccal tablet (25mg) with those after intramuscular injection (10mg). 2. Buccal morphine was administered to eleven healthy volunteers and intramuscular morphine was given to five preoperative surgical patients. Serum morphine concentrations were assayed by high performance liquid chromatography (h.p.l.c.) in samples taken up to 8 h after drug administration. 3. Mean maximum morphine concentrations were eight times lower after buccal administration than after intramuscular injection and occurred at a mean of 4 h later. Individual morphine concentration-time profiles showed marked interindividual variability after administration of the buccal tablet, consistent with considerable variation in tablet persistence time on the buccal mucosa.

Fisher, A P; Fung, C; Hanna, M

1987-01-01

31

Chitosan-based mucoadhesive tablets for oral delivery of ibuprofen.  

PubMed

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

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

2012-10-15

32

In vivo pharmacokinetics in human volunteers: oral administered guar gum-based colon-targeted 5-fluorouracil tablets  

Microsoft Academic Search

The objective of the present study is to compare the guar gum-based colon-targeted tablets of 5-fluorouracil against an immediate release tablet by in vitro dissolution and in vivo pharmacokinetic studies in human volunteers. Twelve healthy volunteers participated in the study. 5-Fluorouracil was administered at a dose of 50 mg both in immediate release tablet and colon-targeted tablet. On oral administration

Y. S. R Krishnaiah; V Satyanarayana; B Dinesh Kumar; R. S Karthikeyan; P Bhaskar

2003-01-01

33

Pharmacokinetics of desmopressin administered as tablet and oral lyophilisate formulation in children with monosymptomatic nocturnal enuresis.  

PubMed

Desmopressin 120 ?g oral lyophilisate and 200 ?g tablet are considered bioequivalent, based on extrapolation of studies in a limited number of adults and on one dose-finding study of desmopressin oral lyophilisate in children. However, no comparative pharmacokinetic study in children was executed confirming this statement. No data are available on the influence of food intake on the bioavailability of desmopressin tablet in a pediatric setting, although studies in adults have documented that food intake results in a significantly lower desmopressin plasma concentration. In this study, we analyzed plasma concentrations of desmopressin oral lyophilisate and tablet with concomitant food intake. Twenty-three children with monosymptomatic nocturnal enuresis (mean age, 12.7 years) were recruited. Two tests were performed on two separate days in identical conditions with a standardized food and fluid intake. Desmopressin was administered as desmopressin tablet or desmopressin oral lyophilisate immediately after a meal. Desmopressin plasma concentration was measured at 1 h, 2 h, and 6 h postdosing. No significant difference in plasma concentration of 120 ?g desmopressin oral lyophilisate and 200 ?g tablet was demonstrated, even with concomitant food intake. A significant difference in variability was found, identifying a smaller variance for desmopressin oral lyophilisate plasma concentrations at all time points. This study demonstrates comparable plasma levels for desmopressin oral lyophilisate, despite the lower dose. The dosage for desmopressin oral lyophilisate is more predictable due to the significantly smaller variance. Therefore, desmopressin oral lyophilisate seems more suitable, especially in the younger age group for which time interval between dinner and drug administration is limited. PMID:23989967

De Bruyne, Pauline; De Guchtenaere, Ann; Van Herzeele, Charlotte; Raes, Ann; Dehoorne, Jo; Hoebeke, Piet; Van Laecke, Erik; Vande Walle, Johan

2014-02-01

34

Formulation and in vivo evaluation of ondansetron orally disintegrating tablets using different superdisintegrants.  

PubMed

The aim of this study was to formulate cost effective taste-masked orally disintegrating tablets of ondansetron, a bitter drug using different superdisintegrants by a wet granulation technique. Microcrystalline cellulose (Avicel) as a diluent and disintegrant in addition to aspartame as a sweetener were used in all formulations. The prepared tablets were evaluated for weight variation, thickness, hardness, friability, drug content, water content, in vitro disintegration time and in vitro drug release. The tablets' hardness was maintained in the range of 2-3 kg and friability was <1% for all batches. All tablet formulations disintegrated rapidly in vitro within 5.83 to 33.0 sec. The optimized formulation containing 15% Polyplasdone XL-10 released more than 90% of drug within 5 min and the release was comparable to that of a commercial product. In human volunteers, optimized formulation was found to have a pleasant taste and mouth feel and they disintegrated in the oral cavity within 12 sec. The stability results were also satisfactory. A pharmacokinetic study with the optimized formulation was performed in comparison with a reference (Zofer MD 8®) and they were found to be bioequivalent. In conclusion, a cost effective ondansetron orally disintegrating tablet was successfully prepared with acceptable hardness, desirable taste and rapid disintegration in the oral cavity. PMID:22139694

Sheshala, Ravi; Khan, Nurzalina; Chitneni, Mallikarjun; Darwis, Yusrida

2011-11-01

35

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

PubMed

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

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

2013-06-01

36

Preparation and evaluation of orally rapidly disintegrating tablets containing taste-masked particles using one-step dry-coated tablets technology.  

PubMed

In this study, in order to address the problems with manufacturing orally rapidly disintegrating tablets (ODT) containing functional (taste masking or controlled release) coated particles, such as the low compactability of coated particles and the rupture of coated membrane during compression, a novel ODT containing taste-masked coated particles (TMP) in the center of the tablets were prepared using one-step dry-coated tablets (OSDrC) technology. As a reference, physical-mixture tablets (PM) were prepared by a conventional tableting method, and the properties of the tablets and the effect of compression on the characteristics of TMP were evaluated. OSDrC was found to have higher tensile strength and far lower friability than PM, but the oral disintegration time of OSDrC is slightly longer than that of PM following high compression pressure. Consequently, OSDrC approaches the target tablet properties of ODT, whereas PM does not. The deformation of TMP in OSDrC due to compression is slight, and the release rate of acetaminophen (AAP) from OSDrC is the same as from TMP. However, TMP on the surface of PM are considerably deformed, and the release rate of AAP from PM is faster than from TMP. These findings suggest that OSDrC technology is a useful approach for preparing ODT containing functional coated particles. Furthermore, we demonstrate that the elastic recovery of tablets can affect differences in the properties of OSDrC, PM and placebo tablets (PC). PMID:21963629

Kondo, Keita; Niwa, Toshiyuki; Ozeki, Yuichi; Ando, Masaki; Danjo, Kazumi

2011-01-01

37

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

PubMed

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

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

2014-01-01

38

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

PubMed

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

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

2003-12-01

39

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

PubMed

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

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

2008-06-01

40

The analgesic effect of oral delta-9-tetrahydrocannabinol (THC), morphine, and a THC-morphine combination in healthy subjects under experimental pain conditions  

Microsoft Academic Search

From folk medicine and anecdotal reports it is known that Cannabis may reduce pain. In animal studies it has been shown that delta-9-tetrahydrocannabinol (THC) has antinociceptive effects or potentiates the antinociceptive effect of morphine. The aim of this study was to measure the analgesic effect of THC, morphine, and a THC-morphine combination (THC-morphine) in humans using experimental pain models. THC

Myrtha Naef; Michele Curatolo; Steen Petersen-Felix; Lars Arendt-Nielsen; Alex Zbinden; Rudolf Brenneisen

2003-01-01

41

Taste Masking of Lornoxicam by polymer carrier system and formulation of oral disintegrating tablets  

Microsoft Academic Search

Lornoxicam is a non steroidal anti-inflammatory drug with analgesic properties and belongs to the class oxicams. It is extremely bitter in taste. The purpose of this research was to develop a bitterless oral disintegrating tablet of Lornoxicam. Taste masking was done by complexing Lornoxicam with aminoalkyl methacrylate copolymer (Eudragit EPO) in different ratios. In vitro release profile obtained at pH

Rajesh S. Jadon; Swadesh Nayak; Sabita Amlan; Vikas Deep Vaidya; Prashant Khemariya; Sandip Sumbhate

2009-01-01

42

Olanzapine orally disintegrating tablets in the treatment of acutely ill non-compliant patients with schizophrenia.  

PubMed

The objective of this study was to determine if the orally disintegrating tablet formulation of olanzapine, Zyprexa Zydis, would facilitate antipsychotic medication compliance in acutely ill, non-compliant patients. Eighty-five acutely ill patients with schizophrenia or schizoaffective disorder who met medication non-compliance criteria received open-label olanzapine orally disintegrating tablets (1020 mgd) for up to 6 wk. Improvement in medication compliance was assessed using various rating scales to measure changes in psychopathology, medication-taking and compliance attitudes, and nursing care burden. Safety variables were also measured. Significant improvement from baseline was demonstrated in the Positive and Negative Syndrome Scale total score at Week 1 and subsequently (p0.001). Significant improvement from baseline was also seen in various scales measuring medication compliance, attitude, and nursing care burden (p0.05). Olanzapine orally disintegrating tablets were well-tolerated. Olanzapine orally disintegrating tablets may benefit acutely ill, non-compliant schizophrenic patients by facilitating acceptance of active antipsychotic drug therapy. PMID:12890301

Kinon, Bruce J; Hill, Angela L; Liu, Hong; Kollack-Walker, Sara

2003-06-01

43

Pharmacokinetics of orally disintegrating tablets of perphenazine/hydroxypropyl-beta-cyclodextrin inclusion complex in rabbits.  

PubMed

We investigated the pharmacokinetic behavior of orally disintegrating tablets (ODTs) containing perphenazine/hydroxypropyl-beta-cyclodextrin inclusion complex (PPZ/HP-beta-CD) in rabbits and evaluated their bioequivalence with conventional tablets. In this study, a simple, sensitive and accurate high performance liquid chromatography method was developed for the determination of perphenazine concentration in rabbit plasma. The pharmacokinetic parameters were calculated by non-compartmental methods and the bioequivalence between PPZ/HP-beta-CD ODTs with conventional tablets was determined by calculating 90% confidence interval (CI) for the ratio of logarithmic transformed C(max), AUC(0-t), AUC(0-infinity) values. The pharmacokinetic parameters of test ODTs and reference tablets were as follows: C(max), 82.86 and 62.71 ng/mL; AUC(0-24), 480 and 397.56 ng/mL/h; AUC(0-infinity), 505 and 400.12 ng/mL/h; T(max), 1.04 and 3.83h. The relative bioavailabilities of two formulations for AUC(0-t) and AUC(0-infinity) were 120.77% and 126.37%, respectively. The 90% CI statistical analysis demonstrated the two formulations were not bioequivalence. In conclusion, the ODTs showed faster absorption and higher peak concentration when compared with conventional tablets, which suggests ODTs could be promising oral formulations for PPZ. PMID:24273883

Wang, Ling; Xiao, Yan-Yu; Chen, Ming-Lei; Zeng, Fan; Zong, Li

2013-10-01

44

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

Microsoft Academic Search

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

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

1999-01-01

45

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

PubMed Central

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

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

2012-01-01

46

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

PubMed

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

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

2014-07-01

47

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

PubMed

Fast disintegrating tablets (FDTs) have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. The popularity and usefulness of the formulation resulted in development of several FDT technologies. This review describes various formulations and technologies developed to achieve fast dissolution/dispersion of tablets in the oral cavity. In particular, this review describes in detail FDT technologies based on lyophilization, molding, sublimation, and compaction, as well as approaches to enhancing the FDT properties, such as spray-drying, moisture treatment, sintering, and use of sugar-based disintegrants. In addition, taste-masking technologies, experimental measurements of disintegration times, and clinical studies are also discussed. PMID:15658933

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

2004-01-01

48

Design and in vitro evaluation of zidovudine oral controlled release tablets prepared using hydroxypropyl methylcellulose.  

PubMed

Oral controlled release matrix tablets of zidovudine were prepared using different proportions and different viscosity grades of hydroxypropyl methylcellulose. The effect of various formulation factors like polymer proportion, polymer viscosity and compression force on the in vitro release of drug were studied. In vitro release studies were carried out using United States Pharmacopeia (USP) type 1 apparatus (basket method) in 900 ml of pH 6.8 phosphate buffer at 100 rpm. The release kinetics were analyzed using Zero-order model equation, Higuchi's square-root equation and Ritger-Peppas' empirical equation. Compatibility of drug with various formulations excipients used was studied. In vitro release studies revealed that the release rate decreased with increase in polymer proportion and viscosity grade. Increase in compression force was found to decrease the rate of drug release. Matrix tablets containing 10% hydroxypropyl methylcellulose (HPMC) 4000 cps were found to show a good initial drug release of 21% in the first hour and extended the release upto 16 h. Matrix tablets containing 20% HPMC 4000 cps and 10% HPMC 15000 cps showed a first hour release of 18% and extended the release upto 20 h. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets followed non-Fickian or anomalous release. No incompatibility was observed between the drug and excipients used in the formulation of matrix tablets. The developed controlled release matrix tablets of zidovudine, with good initial release (17-25% in first hour) and which extend the release upto 16-20 h, can overcome the disadvantages of conventional tablets of zidovudine. PMID:18379101

Ravi, Punna Rao; Ganga, Sindhura; Saha, Ranendra Narayan

2008-04-01

49

A Bioequivalence Study of Two Oral Desmopressin Tablet Formulations  

Microsoft Academic Search

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

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

2006-01-01

50

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

PubMed

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

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

2013-02-01

51

Association of UGT2B7 and ABCB1 genotypes with morphine-induced adverse drug reactions in Japanese patients with cancer  

Microsoft Academic Search

Purpose  To investigate the effects of genetic polymorphisms on morphine-induced adverse events in cancer patients.\\u000a \\u000a \\u000a \\u000a Methods  We examined the relation of morphine-related adverse events to polymorphisms in UDP-glucuronosyltransferase (UGT) 2B7, ATP-binding cassette, sub-family B, number 1 (ABCB1), and ?-opioid receptor 1 genes in 32 Japanese cancer patients receiving oral controlled-release morphine sulfate tablets.\\u000a \\u000a \\u000a \\u000a Results  The T\\/T genotype at 1236 or TT\\/TT diplotype at

Ken-ichi Fujita; Yuichi Ando; Wataru Yamamoto; Toshimichi Miya; Hisashi Endo; Yu Sunakawa; Kazuhiro Araki; Keiji Kodama; Fumio Nagashima; Wataru Ichikawa; Masaru Narabayashi; Yuko Akiyama; Kaori Kawara; Mari Shiomi; Hiroyasu Ogata; Hiroyasu Iwasa; Yasushi Okazaki; Takashi Hirose; Yasutsuna Sasaki

2010-01-01

52

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

PubMed

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

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

2014-07-01

53

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

PubMed

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

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

2013-11-01

54

Formulation design for orally disintegrating tablets containing enteric-coated particles.  

PubMed

The purpose of this study was to investigate the applicability of our newly developed technology (RACTAB® technology) for preparing orally disintegrating tablets (ODTs) containing enteric-coated particles. Tamsulosin hydrochloride (TAM) was used as a model drug contained in the enteric-coated particles. Enteric-coated particles containing TAM (ECP-T) were prepared by spray coating a mixture of TAM with controlled-release materials. ECP-T was then mixed with rapidly disintegrating granules (RDGs), which were prepared using the suspension spray-coating method, and was tableted to form ODTs (ODTRAC). ODTRAC was evaluated for its hardness, thickness, internal structure (X-ray-CT scanning), functional properties (controlled-release profile), and in vivo disintegration time. Since RDGs with micronized ethylcellulose (MEC) increased tablet hardness by increasing the contact frequency between granules, ODTRAC containing ECP-T exhibited high hardness (>50?N) and low friability (<0.5%) with a relatively low compression force. After tableting, the structure of ECP-T in ODTRAC remained intact and no damage was observed on the surface. ECP-T recovered from ODTRAC showed the same dissolution profile of TAM in Japanese Pharmacopoeia (JP) 1st and JP 2nd media as that of intact ECP-T, which indicated that the tableting process did not affect the acid-resistibility of the particle. In addition, ODTRAC rapidly disintegrated in vivo (< 30?s), even at a high compression force (at 9 kN). These findings clearly suggest that RACTAB® technology is a useful approach to prepare ODTs containing enteric-coated particles. PMID:24789923

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

2014-01-01

55

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

PubMed Central

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

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

2011-01-01

56

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

Microsoft Academic Search

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

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

2002-01-01

57

Formulation and in vivo evaluation of orally disintegrating tablets of clozapine/hydroxypropyl-?-cyclodextrin inclusion complexes.  

PubMed

The aim of this study was to improve the solubility and oral bioavailability of clozapine (CLZ), a poorly water-soluble drug subjected to substantial first-pass metabolism, employing cyclodextrin complexation technique. The inclusion complexes were prepared by an evaporation method. Phase solubility studies, differential scanning calorimetry, X-ray powder diffraction, and Fourier transform infrared spectroscopy were used to evaluate the complexation of CLZ with hydroxypropyl-?-cyclodextrin (HP-?-CD) and the formation of true inclusion complexes. Characterization and dissolution studies were carried out to evaluate the orally disintegrating tablets (ODTs) containing CLZ/HP-?-CD complexes prepared by direct compression. Finally, the bioavailability studies of the prepared ODTs were performed by oral administration to rabbits. The ODTs showed a higher in vitro dissolution rate and bioavailability compared with the commercial tablets. It is evident from the results herein that the developed ODTs provide a promising drug delivery system in drug development, owing to their excellent performance of a rapid onset of action, improved bioavailability, and good patient compliance. PMID:23649995

Zeng, Fan; Wang, Ling; Zhang, Wenjing; Shi, Kejing; Zong, Li

2013-06-01

58

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

PubMed

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

Venkatesh, Gopi M; Stevens, Phillip J; Lai, Jin-Wang

2012-12-01

59

Preparation and evaluation of unpleasant taste-masked pioglitazone orally disintegrating tablets.  

PubMed

This study aimed to evaluate the taste and mouth feel of newly designed orally disintegrating tablets (ODTs) of pioglitazone, which is a typical type 2 diabetes medicine with an unpleasant taste, using a visual analog scale (VAS) analysis. The ODTs were subjected to either of these 2 taste-masking procedures: a physical masking procedure that included coating the inactive core granules with mixture of pioglitazone and Eudragit(®) E PO, followed by mixing the granules with aspartame and other excipients to form the tablet (physical masking ODT); or a gustatory masking procedure that involved blending pioglitazone with both sodium chloride and aspartame, followed by mixing the blend with other excipients to form the tablet (gustatory masking ODT). From the results of the VAS analysis, physical masking could suppress the bitterness but not the astringent; therefore, the overall palatability of the ODT was considered not improved. In contrast, gustatory masking significantly suppressed both the bitterness and astringent, and offered a slight sweetness; therefore, the overall palatability of the ODT was considered improved. In conclusion, VAS is a useful tool to evaluate the taste of ODTs and that gustatory masking can effectively mask the unpleasant taste of pioglitazone ODT. PMID:23419665

Nakano, Yoshinori; Maeda, Arisa; Uchida, Shinya; Namiki, Noriyuki

2013-03-25

60

Pharmacokinetics of oral treprostinil sustained release tablets during chronic administration to patients with pulmonary arterial hypertension.  

PubMed

Pulmonary arterial hypertension (PAH) is a progressive vascular disease that ultimately leads to right ventricular failure and death. Treprostinil diolamine is an oral prostacyclin analogue; sustained release tablets of oral treprostinil are currently being evaluated for efficacy and safety as a potential therapy in patients with PAH. Previous attempts at developing an oral prostanoid have been limited by rapid absorption and short plasma half-life; thus, the aim of this study was to characterize the pharmacokinetic profile of treprostinil diolamine in PAH patients after chronic dosing. The study enrolled 74 PAH patients who had been taking treprostinil diolamine for a minimum of 4 weeks (range: 0.5-16 mg). We collected plasma samples over 12 hours and estimated pharmacokinetic parameters using noncompartmental methods. Seventy patients had complete data. After chronic twice-daily oral dosing of treprostinil diolamine, mean area under the curve (AUC0-12) of treprostinil increased from 5244 to 20,4086 pg·hr-·mL- and mean maximum observed plasma concentration (Cmax) increased from 1383 to 33588 pg/mL. The apparent clearance (CL/F) was similar across all doses, indicating a linear dose-exposure relationship after twice-daily dosing. We conclude that twice-daily oral treprostinil provides sustained and proportional treprostinil concentrations over a wide range of doses during chronic administration to PAH patients. PMID:23328389

White, R James; Torres, Fernando; Allen, Roblee; Jerjes, Carlos; Pulido, Tomas; Yehle, David; Howell, Meredith; Laliberte, Kevin; Marier, Jean-Francois; Tapson, Victor F

2013-06-01

61

A multicenter maintenance study of oral pilocarpine tablets for radiation-induced xerostomia.  

PubMed

Two hundred sixty-five patients with head and neck cancer who had previously participated in either a fixed-dose, dose-titration, or dose-ranging trial of oral pilocarpine hydrochloride tablets were enrolled in a 36-month multicenter maintenance study to evaluate the long-term safety and efficacy of oral pilocarpine for the treatment of radiation-induced xerostomia. In this open-label study, the initial drug dose was 5.0 mg tid, with possible adjustments from 2.5 to 10.0 mg tid or bid. Efficacy was evaluated by subjective measures of oral function. Safety evaluations were based on self-report of symptoms (or of adverse effects), various examinations, and laboratory tests. There was significant improvement in all criteria of oral function. Sweating was the most frequent adverse experience (55%). Less frequent side effects, mild to moderate in nature, included increased urinary frequency, lacrimation, and rhinitis. Side effects usually diminished within hours after the cessation of therapy. We conclude that oral pilocarpine at these doses effectively and safely reduces the symptoms of radiation-induced xerostomia. PMID:8723429

Jacobs, C D; van der Pas, M

1996-03-01

62

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

PubMed

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

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

1995-02-01

63

Comparative efficacy of patient-controlled administration of morphine, hydromorphone, or sufentanil for the treatment of oral mucositis pain following bone marrow transplantation  

Microsoft Academic Search

A total of 119 bone marrow transplant patients suffering from oral mucositis pain were enrolled in a randomized, double-blind, parallel-group trial comparing the efficacy of patient-controlled analgesia with morphine, hydromorphone and sufentanil. Patient ratings of pain and side-effects on visual analog scales were gathered daily from the start of patient-controlled analgesia (PCA) therapy until the discontinuation of opioid treatment either

Barbara A Coda; Barbara O'Sullivan; Gary Donaldson; Sharol Bohl; C. Richard Chapman; Danny D Shen

1997-01-01

64

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

PubMed

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

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

2005-01-01

65

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

PubMed Central

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

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

2014-01-01

66

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

PubMed

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. PMID:22881600

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

2013-01-01

67

Optimizing levodopa pharmacokinetics: intestinal infusion versus oral sustained-release tablets.  

PubMed

Continuous duodenal infusion of carbidopa/levodopa has been shown to control motor fluctuations in advanced Parkinson's disease (PD). The authors compared the pharmacokinetics of levodopa and 3-O-methyldopa in patients with advanced PD after administration of an oral sustained-release levodopa preparation and after continuous intestinal levodopa infusion with a new formulation as a gel suspension. A randomized crossover trial was carried out in 12 patients. Carbidopa/levodopa was administered as an oral sustained-release tablet and by nasoduodenal continuous infusion for 3-week periods for each treatment. Plasma levodopa concentrations and motor performance were evaluated every 30 minutes during 3 test days of each treatment period. The average intraindividual coefficient of variation for the plasma levodopa concentrations after oral therapy was 34% and was significantly lower (14%, p < 0.01) during continuous infusion. Hourly video evaluations showed a significant increase in ON time during infusion and a significant decrease in OFF time and dyskinesia. Continuous intraduodenal delivery of a new carbidopa/levodopa formulation offers a means for markedly improved control of motor fluctuations in late stages of PD. PMID:12782919

Nyholm, Dag; Askmark, Håkan; Gomes-Trolin, Cecilia; Knutson, Tina; Lennernäs, Hans; Nyström, Christer; Aquilonius, Sten-Magnus

2003-01-01

68

Efficacy and adverse effects of transdermal fentanyl and sustained-release oral morphine in treating moderate-severe cancer pain in Chinese population: a systematic review and meta-analysis  

PubMed Central

Background Previous meta-analysis suggested that transdermal fentanyl was not inferior to sustained-release oral morphine in treating moderate-severe cancer pain with less adverse effects. Now, we updated the data and performed a systematic review. Methods Updated cohort studies on transdermal fentanyl and oral morphine in the treatment of cancer pain were searched in electronic databases including CBMdisc, CNKI, VIP, Medline, EMBASE and Cochrane Library. Primary end points assessed by meta-analysis were remission rate of pain and incidence of adverse effects. Quality of life was assessed by systematic review, which was the second end point. Results 32 cohort studies, which included 2651 patients, were included in present study. The remission rate in transdermal fentanyl group and sustained-release oral morphine group were 86.60% and 88.31% respectively, there was no significant difference [RR = 1.13, 95% CI (0.92, 1.38), P = 0.23]. Compared with oral morphine group, there were less adverse effects in terms of constipation [RR = 0.35, 95% CI (0.27, 0.45), P < 0.00001], nausea/vomiting [RR = 0.57, 95% CI (0.49, 0.67), P < 0.00001], and vertigo/somnolence [RR = 0.59, 95% CI (0.51, 0.68), P < 0.00001] in transdermal fentanyl group. Six of selected trials supported either transdermal fentanyl or sustained-release oral morphine improved QOL of cancer patients and one of them showed more patients got better QOL after sustained-release oral morphine transferred to transdermal fentanyl. Conclusions Our study showed again that both transdermal fentanyl and oral morphine had the same efficacy in the treatment of moderate-severe cancer pain in Chinese population, but the former might have less adverse effects and better quality of life.

2010-01-01

69

Lessons learned from the development of oral calcitonin: the first tablet formulation of a protein in phase III clinical trials.  

PubMed

Oral delivery of proteins has been hampered by an array of difficulties. However, promising novel oral delivery systems have been developed. 5-CNAC, formulated with the peptide salmon calcitonin, is in phase III clinical trials for the treatment of osteoporosis or osteoarthritis and could become the first marketed oral peptide. This article reviews key findings and implications from studies undertaken to date with this oral formulation. Findings include these: (1) the optimal calcitonin tablet dose is 0.8 mg; (2) 0.8 mg of oral calcitonin is rapidly absorbed, reaching maximum concentration in 15 to 30 minutes, and is eliminated from plasma with a short half-life-9 to 15 minutes; (3) the 0.8-mg tablet is more highly absorbed than the marketed nasal formulation, with biomarker levels indicating significantly greater efficacy in suppression of bone resorption; (4) drug absorption is increased with dosing at least 10 minutes before a meal rather than postprandially and also with 50 mL of water; (5) the optimal timing of dosing for osteoporosis therapy is in the evening to mitigate the circadian peak in bone resorption; and (6) the oral formulations of synthetic and recombinant calcitonin have similar pharmacokinetic and pharmacodynamic properties. These key findings may aid researchers in the development of other oral formulations. PMID:20660294

Karsdal, M A; Henriksen, K; Bay-Jensen, A C; Molloy, B; Arnold, M; John, M R; Byrjalsen, I; Azria, M; Riis, B J; Qvist, P; Christiansen, C

2011-04-01

70

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

PubMed

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

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

2008-04-01

71

Oral sustained delivery of atenolol from floating matrix tablets-formulation and in vitro evaluation.  

PubMed

Floating matrix tablets of atenolol were developed to prolong gastric residence time and increase drug bioavailability. Atenolol was chosen as a model drug because it is poorly absorbed from the lower gastrointestinal tract. The tablets were prepared by direct compression technique, using polymers such as hydroxypropyl methylcellulose (HPMC K15M, K4M), guargum (GG), and sodium carboxymethylcellulose (SCMC), alone or in combination, and other standard excipients. Tablets were evaluated for physical characteristics viz. hardness, swelling index, floating capacity, thickness, and weight variation. Further, tablets were evaluated for in vitro release characteristics for 8 hr. The effect of effervescent on buoyancy and drug release pattern was also studied. In vitro release mechanism was evaluated by linear regression analysis. GG- and SCMC-based matrix tablets showed significantly greater swelling indices compared with other batches. The tablets exhibited controlled and prolonged drug release profiles while floating over the dissolution medium. PMID:16093202

Srivastava, A K; Wadhwa, Saurabh; Ridhurkar, D; Mishra, B

2005-05-01

72

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

PubMed Central

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

Nabais, Teresa; Leclair, Gregoire

2014-01-01

73

Formulation and bioequivalence of two Valsartan/Amlodipine Immediate release tablets after a single oral administration.  

PubMed

The aim of this study was to formulate a film-coated Valsartan/Amlodipine (VS/AM) immediate release tablets and to evaluate their in vivo release profile. VS/AM core tablets were manufactured using dry granulation method. Opadry aqueous coating dispersion was used as film coating material. Dissolution of the film coated tablets was tested in 900 ml of 0.5% SLS media, bioequivalence of tablets was tested by comparisons against the reference brand product. The ICH guidelines were used to evaluate the stability of the obtained tablets. The coated tablets were subjected to gastric pH, and drug release was analyzed using HPLC system to evaluate the efficiency of the film coat. The coated tablets had no defects. VS/AM release met the FDA guidelines for bioequivalence studies. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between test and reference. These findings suggest that aqueous film coating with Opadry system is an easy and economical approach for preparing stable film coated VS/AM tablets without compromising their in vivo drugs release. PMID:25015436

Zaid, Abdel Naser; Natur, Salam; Qaddomi, Aiman; Abualhasan, Murad; Al-Ramahi, Rowa; Shraim, Naser; Khammash, Saed; Jaradat, Nidal

2014-07-01

74

Safety of stabilized, orally absorbable, reduced nicotinamide adenine dinucleotide (NADH): a 26-week oral tablet administration of ENADA/NADH for chronic toxicity study in rats.  

PubMed

The safety of the stabilized, orally absorbable form of reduced nicotinamide adenine dinucleotide (NADH), known under the brand name ENADA, was investigated over a period of 26 weeks. Eighty healthy rats (40 males and 40 females) were divided into two groups. One tablet ENADA/NADH 5 mg per day was administered orally to one group while identical-looking white tablets not containing NADH (placebo) were given to the other group. The following parameters were statistically analyzed: body weight, body weight gain, food consumption, hematology, clinical chemistry, organ weight and organ histology. Clinical signs and mortality were recorded. There were no deaths associated with the study drug and no treatment-releated clinical signs. No differences in body weight between the placebo and the ENADA-treated males were observed. In the second half of the treatment period (weeks 13-26) females treated with NADH gained significantly (p < 0.05) more body weight than the controls. Food consumption in the treated males was similar to that in controls. From approximately week 15, the treated females consumed up to 10% more food than the controls. No differences were observed between the control and the treated groups in terms of hematology or clinical chemistry parameters. There was no apparent treatment-related effect on urine analysis parameters or on either the absolute or the relative organ weight. Furthermore, no macroscopic evidence of specific target organ toxicity associated with the test drug was observed. Histological findings in the treated rats were generally similar to those in control rats. A daily dose of 5 mg in a rat corresponds to a dose of 175 mg per day in a 70-kg human. This is 175 times the recommended daily dosage of 1 ENADA tablet per day. Hence ENADA/NADH 5 mg tablets can be generally regarded as safe. PMID:12635493

Birkmayer, J G D; Nadlinger, K

2002-01-01

75

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

PubMed Central

Posaconazole oral suspension, a marketed extended-spectrum triazole with proven efficacy as antifungal treatment and prophylaxis, should be taken with food to maximize absorption. New tablet and capsule formulations have been developed in an attempt to optimize absorption and bioavailability. The aims of this exploratory open-label, partially randomized, 2-part, 4-way, single-dose crossover study in 16 healthy adults were to characterize pharmacokinetics for posaconazole tablet and capsule formulations relative to those for posaconazole oral suspension under fasted and fed conditions and to assess safety and tolerability. Under fasted conditions, posaconazole exposures (area under the curve [AUC]) for the tablet and capsule formulations were similar (mean AUC from time zero to infinity [AUC0–?], tablet A, 11,700 ng · h/ml [coefficient of variation {CV}, 26%]; tablet B, 11,300 ng · h/ml [CV, 22%]; capsule, 11,000 ng · h/ml [CV, 25%]) and were substantially higher than the exposure for the oral suspension (mean AUC0–?, 3,420 ng · h/ml [CV, 44%]). Tablets and capsule showed less variability in exposure than the oral suspension. In fed subjects, tablets and capsule resulted in similar AUC values (mean AUC0–?, tablet A, 11,900 ng · h/ml [23%]; tablet B, 12,400 ng · h/ml [CV, 25%]; capsule, 12,300 ng · h/ml [CV, 28%]) and slightly higher exposure than the oral suspension (mean AUC0–?, 8,750 [CV, 24%]). Median times to the maximum concentration of drug in plasma were 4 to 5 h (fasted conditions) and 6 to 8 h (fed conditions). Mean half-lives values were similar for all formulations under fed and fasted conditions (23.1 to 29.2 h). Consistent with previous data, exposure for the oral suspension increased 2.5- to 3-fold when it was given with a high-fat meal. Conversely, exposures for tablets and capsule were not markedly affected by food. All formulations of posaconazole at 100 mg were safe and well tolerated.

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

2012-01-01

76

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

PubMed

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

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

2012-08-01

77

BIOEQUIVALENCE OF TWO BRANDS OF CITALOPRAM 40 mg TABLETS AFTER SINGLE ORAL ADMINISTRATION TO HEALTHY VOLUNTEERS  

Microsoft Academic Search

A randomized, two-way, crossover, bioequivalence study was conducted in 26 fasting, healthy, male volunteers to compare two brands of citalopram 40 mg tablets, Citol (Abdi Ibrahim ?laç San. ve Tic A.?., Istanbul, Turkey) as a test and Cipramil® (H. Lundbeck A\\/S, Copenhagen, Denmark) as a reference product. One tablet of either formulation was administered with low-carbonate water after 10 h

Luis Mendoza; Marián Hajdúchb; Hana Kekulováa; Xenia Svobodová; Vladimír Mihálb; Michal Svoboda; M. Hajdúch; V. Mihál

78

Formulation and Bioequivalence of Two Valsartan Tablets After a Single Oral Administration  

PubMed Central

The aim of this study is to assess the quality of Valzan® tablet (160 mg, valsartan immediate release test formulation) by comparing its pharmacokinetic parameters with Diovan® tablet (160 mg, valsartan reference formulation). Valzan® tablets were prepared according to a dry granulation method (roll compaction). To assess the bioequivalence of Valzan® tablets a randomized, two-way, crossover, bioequivalence study was performed in 24 healthy male volunteers. The selected volunteers were divided into two groups of 12 subjects. One group was treated with the reference formulation (Diovan®) and the other one with the generic Valzan®, with a cross-over after the drug washout period of 14 days. Blood samples were collected at fixed time intervals and valsartan concentrations were determined by a validated HPLC assay method. The pharmacokinetic parameters AUC0–48, AUC0–?, Cmax, Tmax, Ke and T1/2 were determined for both the tablets and were compared statistically to evaluate the bioequivalence between the two brands of valsartan, using the statistical model recommended by the FDA. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals (CI) fell within the acceptable range for bioequivalence. Based on this statistical evaluation it was concluded that the test tablets (Valzan®) is well formulated, since it exhibits pharmacokinetic profile comparable to the reference brand Diovan®.

Zaid, Abdel Naser; Cortesi, Rita; Qaddomi, Aiman; Khammash, Saed

2011-01-01

79

A new solid oral tablet formulation of posaconazole: a randomized clinical trial to investigate rising single- and multiple-dose pharmacokinetics and safety in healthy volunteers  

PubMed Central

Objectives Posaconazole is an extended-spectrum triazole with proven efficacy as antifungal treatment and prophylaxis. The marketed oral suspension should be taken with food to maximize systemic absorption. A new solid oral tablet has been developed with improved bioavailability that can be administered without regard to food. The aim of this study was to evaluate rising single- and multiple-dose pharmacokinetics, safety and tolerability of the new tablet. Methods This was a single-centre, randomized, placebo-controlled, Phase I, rising single- and multiple-dose study of healthy subjects aged 18–65 years who received a posaconazole tablet as 200 mg once daily, 200 mg twice daily or 400 mg once daily. The 24 subjects were studied in two cohorts of 12 subjects each (9 active and 3 placebo). Results After single or multiple oral dose administration of posaconazole tablets (200 and 400 mg), exposure increased in a dose-related manner. Peak posaconazole concentrations were attained at a median Tmax of 4–5 h. Mean half-life was similar for 200 and 400 mg posaconazole doses (25 and 26 h). The accumulation ratio upon multiple doses over 8 days was ?3 for 200 and 400 mg once daily and ?5 for 200 mg twice daily. Cavg values exceeded 1300 ng/mL. The posaconazole oral tablet was safe and well tolerated, although mild, transient elevations in liver function were reported in some patients. Conclusions Posaconazole exposure increased in a dose-related manner. The pharmacokinetics of this new solid oral tablet of posaconazole supports the clinical evaluation of once-daily dosing regimens for fungal infections.

Krishna, G.; Ma, L.; Martinho, M.; Preston, R. A.; O'Mara, E.

2012-01-01

80

Optimization of acyclovir oral tablets based on gastroretention technology: factorial design analysis and physicochemical characterization studies.  

PubMed

The purpose of this research was to prepare a floating drug delivery system of acyclovir. Floating matrix tablets of acyclovir were developed to prolong gastric residence time and increase its bioavailability. The tablets were prepared by direct compression technique, using polymers such as hydroxypropylmethylcellulose 4000, Compritol 888. Sodium bicarbonate was used as a gas-generating agent. A 3² factorial design using the Design Expert Software (version 7.1.6) was applied to optimize the drug release profile systematically. The amounts of hydroxypropylmethylcellulose 4000 (X?) and Compritol 888 (X?) were selected as independent variables and the percentage drug released in 1 (Q?), 6 (Q?), and 12 (Q??) h as dependent variables. The results of factorial design indicated that a high level of both hydroxypropylmethylcellulose 4000 (X?) and Compritol 888 (X?) favors the preparation of floating controlled-release of acyclovir tablets. Also, a good correlation was observed between predicted and actual values of the dependent variables chosen for the study. By fitting the data into zero-order, first-order, and Higuchi models, we concluded that the release followed Higuchi diffusion kinetics. Storage of the prepared formulations at 40°C/75% relative humidity for 3 months showed no significant change in drug release profiles and buoyancy of the floating tablets. We can conclude that a combination of hydroxypropylmethylcellulose 4000, Compritol 888, and sodium bicarbonate can be used to increase the gastric residence time of the dosage form up to 12?h. These floating tablets seem to be a promising gastroretentive drug delivery system. PMID:21401342

El Gamal, Safaa S; Naggar, Viviane F; Allam, Ahmed N

2011-07-01

81

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

PubMed

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

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

2007-01-01

82

In vitro effect of fluoride oral hygiene tablets on artificial caries lesion formation and remineralization in human enamel  

PubMed Central

Background Aim of this in-vitro-study was to assess the remineralization potential of a tooth cleaning tablet with different fluoride content. Methods Twenty three caries free impacted third molars were examined, enamel surfaces were wax coated leaving two 3 × 4 mm windows for exposure to demineralization/remineralization cycles. The teeth were randomly assigned to 4 groups of 5 control and 6 experimental teeth. Demineralization by standardised HEC-gel, pH 4.7 at 37°C for 72 h, was alternated by rinsing in remineralization solution, pH 7.0 at 37°C for 72 h, total challenge time 432 h. The negative control group N was treated during remineralization cycles with saline; positive control group P was treated with remineralization solution; experimental group D1 was exposed to remineralization solution containing Denttabs®-tablets with 1450 ppm F; experimental group D2 was exposed to remineralization solution and Denttabs®-tablets with 4350 ppm F. Each tooth was cut into serial sections and analyzed by polarized light microscopy for assessment of the different zones of white-spot lesions in 3 representative sections. Statistical analysis was based on the Mann-Whitney-Test. Results Both control groups N(-) and P(+) exhibited characteristic white-spot lesions. The remineralization and the demineralization inhibition of the lesions increased considerably from N

oral hygiene product and the remineralization is correlated to the fluoride content.

Gangler, Peter; Kremniczky, Thomas; Arnold, Wolfgang H

2009-01-01

83

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  

PubMed Central

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.

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

2009-01-01

84

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

PubMed

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

Mu?ko, Monika; Sznitowska, Ma?gorzata

2013-01-01

85

Bioequivalence assessment of ambroxol tablet after a single oral dose administration to healthy male volunteers  

Microsoft Academic Search

A bioequivalence study of the ambroxol hydrochloride tablets was conducted. Twenty-four healthy male Korean volunteers received each medicine at the ambroxol hydrochloride dose of 30mg in a 2×2 cross-over study. There was a 1-week washout period between the doses. Plasma concentrations of ambroxol were monitored by a high-performance liquid chromatography (HPLC) for over a period of 24h after the administration.

Hee Joo Lee; Sun Koung Joung; Yoon Gyoon Kim; Jeong-Yeon Yoo; Sang Beom Han

2004-01-01

86

A bioequivalence study of Levothyroxine tablets versus an oral Levothyroxine solution in healthy volunteers  

Microsoft Academic Search

Summary  Probably for genetic reasons a substantial part of the Greek population requires Levothyroxine treatment. Since commercially\\u000a available Levothyroxine was first marketed, the manufacture and storage of the drug in tablet form has been complicated and\\u000a difficult; and as cases of therapeutic failure have frequently been reported following treatment with this medicinal agent,\\u000a quality control is an essential factor. Due to

N. Yannovits; E. Zintzaras; A. Pouli; G. Koukoulis; S. Lyberi; E. Savari; S. Potamianos; F. Triposkiadis; I. Stefanidis; E. Zartaloudis; A. Benakis

2006-01-01

87

Medroxyprogesterone acetate pharmacokinetics following oral high-dose administration in humans: a bioavailability evaluation of a new MPA tablet formulation.  

PubMed

The pharmacokinetics of medroxyprogesterone acetate (MPA) in healthy female volunteers have been investigated following oral administration of single doses of six different high-dose MPA tablet formulations. Blood samples were obtained over 96 hrs following administration. The plasma was separated and analyzed in duplicate for MPA by radioimmunoassay (RIA) after extraction with petroleum ether. A two compartment open model with first order absorption was computer-fitted to the plasma concentration of MPA. Following oral administration MPA is rapidly transferred from the gastrointestinal tract to the blood circulation with a half-life of the absorption process of 15-30 min. The peak plasma concentration is reached 1-3 hrs after administration, and the biological half-life of MPA is 40-60 hrs. Following administration of 1000 mg MPA the areas under the plasma concentration-time curves (AUC 0-infinity) were calculated to (mean and S.E.): 3357 (438) nmol/l and 2403 (245) nmol/l for Leo formulation A and Farlutal, respectively (P less than 0.02). Following administration of 500 mg the areas were: 2325 (389) nmol/l, 1793 (312) nmol/l, 1778 (239) nmol/l, 1178 (209) nmol/l, and 556 (89) nmol/l for Gestapuran, Leo formulation A (P = n.s.), Leo formulation B (P = n.s.), Provera (P less than 0.001), and Lutopolar (P less than 0.001), respectively. The in vitro dissolution rates of MPA from the tablet formulations were determined and compared with the results of the bioavailability studies, indicating that a rapid dissolution rate as well as the particle size of MPA are two important factors to ensure optimal absorption of MPA from the gastrointestinal tract. PMID:2943134

Johansson, E D; Johansen, P B; Rasmussen, S N

1986-05-01

88

Comparison of the pharmacokinetics of miconazole after administration via a bioadhesive slow release tablet and an oral gel to healthy male and female subjects  

PubMed Central

Aims The aim of this study was to compare salivary miconazole pharmacokinetics following once daily application of bioadhesive tablets (50 or 100 mg), vs the current treatment with a gel (3 times a day, 375 mg day?1). Methods A three way cross over study was carried out in 18 healthy subjects (nine males, nine females) with a 1 week washout period between each treatment. Plasma and salivary pharmacokinetics of miconazole were assessed over a 24-h period. Results In all subjects the tablets gave higher and more prolonged salivary miconazole concentrations than the gel. Thus salivary miconazole AUC(0,24 h) was 37.2 times greater for the 100 mg tablet (90% confidence interval [CI] 22.9, 60.5) and 18.9 times greater for the 50 mg tablet (CI 11.7, 30.6) compared with the gel. Similarly, Cmax was 17.2 times greater (CI 11.8, 25.2) and 7.8 times greater (CI 5.3, 11.4) for the 100 mg tablet and 50 mg tablet, respectively. Comparison of the 100 mg and 50 mg tablets gave ratios of 2.2 and 2.0 for Cmax and AUC(0,24 h), respectively (CI 1.5, 3.2 and 1.2, 3.2). The mean time that salivary miconazole concentrations were above 0.4 µg ml?1 (the concentration reached 3 h after application of the oral gel according to published data) or above 1.0 µg ml?1 (the MIC of some Candida species) was greater for both bioadhesive tablets than for the oral gel (10–14 h vs 1.5 h and 7 h vs 0.6 h). Only 19 plasma samples from eight subjects had concentrations of miconazole above 0.4 µg ml?1. Ten of these were taken from five subjects after administration of the gel and nine from three subjects after administration of the tablets. Conclusions These data strongly support the further development of miconazole bioadhesive tablets as a sustained release formulation leading to improved antifungal exposure in the buccal cavity. A single daily application should improve compliance, whereas the low systemic absorption of miconazole will alleviate concerns regarding drug interactions and adverse effects.

Cardot, J-M; Chaumont, C; Dubray, C; Costantini, D; Aiache, J-M

2004-01-01

89

Development and evaluation of chitosan based oral controlled matrix tablets of losartan potassium  

PubMed Central

Aim and Background: The novelty of the present study was to control the release profile of matrix tablets of losartan potassium prepared by using different concentrations of chitosan and trisodium citrate as cross-linking agent with combination of various release retardant polymers. Materials and Methods: Twelve formulations were prepared using HPMC K100M, carbopol 934P, and xanthan gum as polymers. Matrix tablets were prepared by wet granulation technique. The granules were subjected to precompression parameters such as angle of repose, loose bulk density, tapped bulk density, compressibility index. Tablets were evaluated for weight variation, hardness, drug content, in-vitro dissolution, stability studies, respectively. Drug -polymer compatibility studies were determined by FTIR spectroscopy. Further stability studies were carried out for 3months in accelerated conditions at 40°C and 75%RH. The granules of all formulations exhibited good flow and compressibility. In-vitro dissolution studies were carried out for 24 h using 0.1 N HCl for the first 2 h and pH 6.8 phosphate buffers for the remaining 22h. Results: It was found that among the 12 formulations F11 and F12 showed good dissolution profile to control the drug release. The release data was fitted to various mathematical models such as, Higuchi, Korsmeyer, first-order, and zero-order to evaluate the kinetics and the drug release. The drug release follows zero-order kinetics and the mechanism was found to be diffusion controlled and Case II transport. FT-IR spectroscopic studies revealed no interaction between drug and polymer. The stability studies indicated that F11 and F12 formulations were stable for 3months. Conclusion: The above results concluded that by combining different classes of polymers an acceptable release profile can be obtained in the fluctuating in vivo environment.

Rao, Tallapaneni Vishnuvardhan; Kumar, GB Kiran; Ahmed, Mohammed Gulzar; Joshi, Vedamurthy

2012-01-01

90

The bioavailability of nasogastric versus tablet-form oral trovafloxacin in healthy subjects  

Microsoft Academic Search

Background: Patients in the hospital, as well as those in home care settings, often require nutritional supplementation with enteral feeding solutions. In addition, patients with serious infections who are clinically unstable often cannot maintain adequate intake by mouth and may require an alternative to oral antibiotic administration. However, delivery of crushed oral formulations of drugs via nasogastric tubes is often

John Vincent; Renli Teng; Shawn M. Pelletier; Susan A. Willavize; Hylar L. Friedman

1998-01-01

91

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

PubMed

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

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

2010-11-15

92

Pharmacokinetics and bioequivalence study of irbesartan tablets after a single oral dose of 300 mg in healthy Thai volunteers.  

PubMed

Objective: Pharmacokinetics and bioequivalence of 300 mg irbesartan tablets were studied in 26 healthy Thai male volunteers. Methods: A single oral dose of one 300 mg tablet of the test product and the reference product was given to each volunteer according to a randomized two-way crossover design with 1-week wash out period. Blood samples were collected at predetermined time intervals until 72 hours post dose and irbesartan concentration was quantified with a validated HPLC method. Individual plasma irbesartan concentration-time profile was analyzed for pharmacokinetic parameters. Results: Maximum plasma concentrations (Cmax) of 3,617.19 and 3,295.77 ng/mL for test and reference, respectively, were achieved. Areas under the plasma concentration-time curve; AUC0-t and AUC0-? were 15,304.65 and 15,638.90 ng×h/mL for test and 15,389.21 and 15,730.34 ng×h/mL for reference. The median tmax was 1.50 hours and 1.25 hours for test and reference, respectively. Plasma elimination half-lives (t1/2) were 7.35 hours and 8.09 hours for test and reference, respectively. Primary pharmacokinetic parameters Cmax, AUC0-t, and AUC0-? were tested parametrically by analysis of variance (ANOVA), and it revealed no statistically significant difference (defined as p < 0.05) between the corresponding Cmax, AUC0-t, and AUC0-? with respect to sequence, volunteers, period and formulation. The 90% confidence intervals for the ratio of test and reference product of the parameters Cmax, AUC0-t, and AUC0-? were within 80 - 125% (100.13 - 121.40% for Cmax, 90.83 - 106.86% for AUC0-t and 91.11 - 106.55% for AUC0-?). Conclusion: The two products were bioequivalent in terms of both rate and extent of drug absorption into systemic circulation. PMID:24725445

Wittayalertpanya, Supeecha; Chariyavilaskul, Pajaree; Prompila, Nantaporn; Sayankuldilok, Nonlanee; Eiamart, Wanna

2014-05-01

93

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

PubMed Central

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

2014-01-01

94

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

PubMed Central

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

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

2010-01-01

95

Olanzapine orally disintegrating tablets (Zyprexa Zydis) rapidly improve excitement components in the acute phase of first-episode schizophrenic patients: an open-label prospective study.  

PubMed

An open-label study was performed to investigate the clinical efficacy and tolerability of olanzapine orally disintegrating tablets (Zyprexa Zydis) in ameliorating excitement symptoms in the acute phase of schizophrenia. Fifty-three patients meeting DSM-IV criteria for first-episode schizophrenia and treated with olanzapine monotherapy were evaluated with regard to their clinical improvement, behavioural response to medication, and extrapyramidal side effects using the Positive and Negative Syndrome Scale Excited Component (PANSS-EC), Nursing Assessment of Medication Acceptance (NAMA), and Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS), respectively. Scores of PANSS-EC were significantly reduced after 3 days of olanzapine administration. A reduction in NAMA scores was also observed 7 days after administration of olanzapine. The DIEPSS score was unaffected by olanzapine administration. These results suggest that olanzapine orally disintegrating tablets are effective and well-tolerated for treatment excitement in the acute phase of schizophrenic patients. In addition, it is possible that adherence to medications is improved by using olanzapine orally disintegrating tablets. PMID:19707954

Hori, Hikaru; Ueda, Nobuhisa; Yoshimura, Reiji; Yamamoto, Hiroshi; Wani, Kenta; Etoh, Yoshinori; Haraga, Kensuke; Kitahara, Junichi; Nakamura, Jun

2009-01-01

96

Bioequivalence study of two oral tablet formulations containing tenofovir disoproxil fumarate in healthy volunteers.  

PubMed

Tenofovir disoproxil fumarate (TDF, CAS 147127-20-6) is a nucleotide reverse transcriptase inhibitor which is indicated in combination with other antiretroviral agents for the management of HIV-1 infection. The objective of this study was to compare the rate and extent of absorption and to assess the bioequivalence between a new pharmaceutical equivalent tablet formulation containing 300 mg of TDF and the innovator product. A randomized, single-center, open-label, single-dose, two-way crossover bioequivalence study in 40 healthy adult subjects was conducted. Dosing was separated by a wash-out period of 14 days. Blood samples were collected over 48 h and plasma levels of tenofovir (TFV) were determined by a validated HPLC assay. Rate and extent of absorption were similar between products. The 90% confidence interval (CI) of the ratio of the geometric means for log-transformed C(max), AUC(last) and AUC(inf) values were used to assess bioequivalence between the two formulations using the equivalence interval of 80 and 125%. In healthy subjects, the point estimate and 90% CI of the ratios of C(max), AUC(last) and AUC(inf) values were 0.99 (0.92-1.02), 0.99 (0.95-1.03) and 0.93 (0.85-1.02), respectively. Both treatments exhibited similar tolerability and safety. It was concluded that the new pharmaceutical product was bioequivalent to the innovator. PMID:21355446

Yerino, Gustavo A; Halabe, Emilia K; Zini, Elvira; Feleder, Ethel C

2011-01-01

97

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

PubMed Central

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.

Rivera-Leyva, J. C.; Garcia-Flores, M.; Valladares-Mendez, A.; Orozco-Castellanos, L. M.; Martinez-Alfaro, M.

2012-01-01

98

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

PubMed

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

Stange, Ulrike; Führling, Christian; Gieseler, Henning

2014-04-01

99

Maternal oral consumption of morphine increases Bax/Bcl-2 ratio and caspase 3 activity during early neural system development in rat embryos.  

PubMed

Maternal morphine consumption has been shown to result in physical and neurobehavioral defects in fetus and offspring, but the underlying molecular mechanisms of these defects remain unclear. Regarding the critical role of apoptosis in normal development of central nervous system, the present study was designed to investigate the effect of intrauterine morphine exposure on programmed cell death of neuroblasts during the early development of neural system. Pregnant Wistar rats received morphine sulfate through drinking water at the concentration of 0.01 mg/ml (20 ml water per day for each rat) from the first day of gestation to the time of sampling. Control groups received tap water. Control and morphine-treated pregnant rats, each in five separated groups, were killed on gestational days 9.5 to 13.5, and the embryos were taken out, fixed, and embedded in paraffin. Immunohistochemical assay was used to reveal the protein expression of Bax, Bcl2, and the activation of caspase 3. The results showed a significant increase in Bax immunoreactivity in all of the mentioned embryonic days (E9.5 to E13.5) and a significant decrease in Bcl-2 immunoreactivity at days E10.5 and E12.5 in morphine-treated groups compared with control. Data analysis revealed that Bax/Bcl2 ratio was increased in all of the morphine-exposed groups. Consistent with these results, immunostaining of cleaved caspase 3 showed a significant increase at days E11.5 to E13.5. These findings suggest that morphine exposure during the first embryonic days may enhance the susceptibility of neuroblasts to apoptosis by upregulating the ratio of Bax to Bcl-2 protein expression and increasing downstream caspase-3 activity. The increased probability of neuroblast apoptosis may be the cause of morphine-induced defects in the central nervous system development and its structural and neurobehavioral consequences. PMID:19936637

Nasiraei-Moghadam, Shiva; Kazeminezhad, Behrang; Dargahi, Leila; Ahmadiani, Abolhassan

2010-05-01

100

Bioequivalence assessment of ambroxol tablet after a single oral dose administration to healthy male volunteers.  

PubMed

A bioequivalence study of the ambroxol hydrochloride tablets was conducted. Twenty-four healthy male Korean volunteers received each medicine at the ambroxol hydrochloride dose of 30 mg in a 2 x 2 cross-over study. There was a 1-week washout period between the doses. Plasma concentrations of ambroxol were monitored by a high-performance liquid chromatography (HPLC) for over a period of 24h after the administration. AUC(t) (the area under the plasma concentration-time curve from time 0 to last sampling time, 24h) was calculated by the linear-log trapezoidal rule method. C(max) (maximum plasma drug concentration) and T(max) (time to reach C(max)) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC(t) and C(max), and untransformed T(max). The geometric mean of AUC(t) was 495.8 ng ml(-1)h(-1) (test medication) and 468.3 ng ml(-1)h(-1) (reference medication). C(max) of 61.5 and 57.3 ng ml(-1) were achieved for the test and the reference medication, respectively. The point estimates and 90% confidence intervals for AUC(t) (parametric) and C(max) (parametric) were, in point estimate (90% confidence interval), 1.058 (0.989-1.134) and 1.073 (1.007-1.142), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration Guidelines. The corresponding value of T(max) was 0.229 (0.015-0.444). These results indicate that the two medications of ambroxol hydrochloride are bioequivalent and, thus, may be prescribed interchangeably. PMID:14597158

Lee, Hee Joo; Joung, Sun Koung; Kim, Yoon Gyoon; Yoo, Jeong-Yeon; Han, Sang Beom

2004-01-01

101

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

PubMed

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

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

2014-05-01

102

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

PubMed

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

Gasperini, Claudio; Ruggieri, Serena; Pozzilli, Carlo

2010-01-01

103

Novel taste-masked orally disintegrating tablets for a highly soluble drug with an extremely bitter taste: design rationale and evaluation.  

PubMed

The purpose of this study was to evaluate the taste masking potential of novel solid dispersions (SDs) using Eudragit® EPO as the excipient when incorporated into the orally disintegrating tablets (ODTs) for delivering a highly soluble drug with an extremely bitter taste. The pyridostigmine bromides (PB) SDs (PBSDs) were prepared by solvent evaporation-deposition method. The physicochemical properties of PBSDs were investigated by means of differential scanning calorimetry and Fourier transformed infrared spectroscopy. The dissolution test showed that only about 8% of PB was released from PBSDs in the simulated salivary fluid in 30 s. Therefore, PBSDs were considered taste-masked and selected for formulation of PBODTs. A central composite design was employed for process optimization. Multiple linear regression analysis for process optimization revealed that the optimal PBODTs were obtained, when the microcrystalline cellulose and crospovidone were 17.16 and 5.55 (%, w/w), respectively, and the average in vivo disintegration time was 25 s. The bitterness threshold of PB was examined by a sensory test, and the threshold value was set as 3?mg in each tablet. Taste evaluation of PBODTs in 18 volunteers revealed considerable taste masking with bitterness below the threshold value. PBODTs also revealed rapid drug release (around 99%, 2?min) in the simulated gastric fluid. The mean PB plasma concentration-time profiles of PBODTs and that of the commercial tablets were comparable, with closely similar pattern. Bioequivalence assessment results demonstrated that PBODTs and the commercial tablets were bioequivalent. In conclusion, PBODTs are prepared successfully, with taste masking and rapid disintegration in the oral cavity. PMID:22994163

Tan, Qunyou; Zhang, Li; Liu, Guodong; He, Dan; Yin, Huafeng; Wang, Hong; Wu, Jianyong; Liao, Hong; Zhang, Jingqing

2013-09-01

104

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

PubMed

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

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

2008-06-01

105

A Double-Blind, Randomized, Crossover Comparison Between Single-Dose and Double-Dose Immediate-Release Oral Morphine at Bedtime in Cancer Patients  

Microsoft Academic Search

The European Association for Palliative Care guidelines for treatment of cancer pain recommend a double dose (DD) of immediate-release morphine at bedtime instead of single doses (SD) repeated every four hours throughout the night. A previous open controlled study reported more side effects after DD than after SD. The present study was a randomized, double-blind, crossover study comparison of DD

Ola Dale; Maria Piribauer; Stein Kaasa; Kristin Moksnes; Heidi Knobel; Pål Klepstad

2009-01-01

106

Single blind comparison of ketoconazole 200 mg oral tablets and clotrimazole 100 mg vaginal tablets and 1% cream in treating acute vaginal candidosis.  

PubMed Central

A single blind study of 103 women with vaginal candidosis was undertaken to compare treatment with conventional topical clotrimazole and oral ketoconazole. Both treatment regimens were equally effective in terms of clinical symptoms, negative results on culture for Candida albicans, and relapse rates. As treatment for vaginal candidosis takes several days, patient compliance is important and the success of a treatment regimen may depend on its acceptability to patients. Those in this study who had previously been treated for vaginal candidosis were asked to compare their current and previous treatments. Significantly more (p less than 0.001) of those treated with ketoconazole than those treated with clotrimazole found it more acceptable than previous treatment. This indicated a strong preference for oral treatment, and oral antifungal agents may be the treatment of choice for vaginal candidosis in the future.

Bingham, J S

1984-01-01

107

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

PubMed

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

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

2011-05-01

108

Pharmacokinetic and bioequivalence comparison between orally disintegrating and conventional tablet formulations of flurbiprofen: A single-dose, randomized-sequence, open-label, two-period crossover study in healthy chinese male volunteers  

Microsoft Academic Search

Background: Flurbiprofen, an NSAID, is used for the treatment of inflammation and pain caused by rheumatoid arthritis and osteoarthritis as well as soft-tissue injuries. A new orally disintegrating tablet (ODT) of flurbiprofen has recently been developed; this study was conducted to provide support for this drug to obtain marketing authorization in China.Objective: The aim of the study was to compare

Yan-Mei Liu; Gang-Yi Liu; Yun Liu; Shui-Jun Li; Jing-Ying Jia; Meng-Qi Zhang; Chuan Lu; Yong-Mei Zhang; Xue-Ning Li; Chen Yu

2009-01-01

109

Oral Antidiabetic Drugs: Effect of Food on Absorption of Pioglitazone and Metformin From a Fixed-Dose Combination Tablet  

Microsoft Academic Search

An open-label, randomized, crossover study involving 28 healthy subjects was conducted to compare the peak (C max) and total (AUC lqc, AUC?) exposures to pioglitazone and metformin after single-dose administration of a fixed-dose combination tablet containing 15 mg of pioglitazone plus 850 mg metformin when given under fasted versus fed states, with a washout period of 7 days between treatments.

Aziz Karim; Margaret Slater; Dawn Bradford; Lisa Schwartz; Aziz Laurent

2007-01-01

110

Tableting of coated pellets  

Microsoft Academic Search

Oral sustained\\/controlled release multiple unit dosage forms are becoming more popular when compared to single unit dosage forms. With regard to the final dosage form, the multiparticulates are usually formulated into single unit dosage forms such as filling them into hard gelatin capsules or compacting them into tablets. Although there is abundant literature available on the preparation of pellets and

Roland Bodmeier

1997-01-01

111

Self-intoxication with morphine obtained from an infusion pump.  

PubMed

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

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

1999-01-01

112

Review of bilayer tablet technology.  

PubMed

Therapeutic strategies based on oral delivery of bilayer (and multilayer) tablets are gaining more acceptance among brand and generic products due to a confluence of factors including advanced delivery strategies, patient compliance and combination therapy. Successful manufacturing of these ever more complex systems needs to overcome a series of challenges from formulation design to tablet press monitoring and control. This article provides an overview of the state-of-the-art of bilayer tablet technology, highlighting the main benefits of this type of oral dosage forms while providing a description of current challenges and advances toward improving manufacturing practices and product quality. Several aspects relevant to bilayer tablet manufacturing are addressed including material properties, lubrication, layer ordering, layer thickness, layer weight control, as well as first and final compression forces. A section is also devoted to bilayer tablet characterization that present additional complexities associated with interfaces between layers. The available features of the manufacturing equipment for bilayer tablet production are also described indicating the different strategies for sensing and controls offered by bilayer tablet press manufacturers. Finally, a roadmap for bilayer tablet manufacturing is advanced as a guideline to formulation design and selection of process parameters and equipment. PMID:24370841

Abebe, Admassu; Akseli, Ilgaz; Sprockel, Omar; Kottala, Niranjan; Cuitiño, Alberto M

2014-01-30

113

Evaluation of the bioequivalence and pharmacokinetics of two tablet formulations of isosorbide-5-mononitrate after single oral administration in healthy volunteers.  

PubMed

The pharmacokinetic parameters of two oral formulations of 20 mg tablets of isosorbide-5-mononitrate (CAS 16051-77-7, Dilavenil as test and another commercially available preparation as reference) were compared in an open-label, randomized, single oral dose, two-period cross-over design in 20 healthy volunteers under fasting conditions. Plasma concentrations of isosorbide-5-mononitrate were measured by a validated gas chromatographic assay. The parametric 90% confidence intervals of the geometric mean values of the test/reference ratios were 101.2% to 108.5% (point estimate: 104.7%) for AUC0-variation of, 101.6% to 110.7% (point estimate: 106.2%) for AUC0-t, and 98.1% to 115.5% (point estimate: 106.1%) for Cmax, within the acceptance criteria for bioequivalence (80%-125%). Tmax values were analyzed by the nonparametric Wilcoxon test and the difference was not statistically significant. Therefore, it is concluded that the test and reference isosorbide-5-mononitrate formulations are bioequivalent for both the extent and the rate of absorption. PMID:11963645

Niopas, Ioannis; Daftsios, Athanasios C; Nikolaidis, Nicolaos

2002-01-01

114

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

PubMed

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

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

2013-10-15

115

Bioequivalence study of two oral tablet formulations containing saquinavir mesylate boosted with ritonavir in healthy male subjects.  

PubMed

Saquinavir (SAQ) mesylate (CAS 149845-06-7) is a potent inhibitor of the HIV-1 protease indicated in combination with other antiretrovirals for the management of HIV-1 infection. The objective of this study was to compare rate and extent of absorption and to assess the bioequivalence between a new pharmaceutical equivalent tablet formulation containing 500 mg of SAQ mesylate and the innovator film coated tablet formulation. A randomized, single-center, open-label, two-treatment, two-sequence, three-period, replicated crossover bioequivalence study in 40 healthy male subjects was conducted. All subjects received 100 mg ritonavir (CAS 155213-67-5) twice daily for a run-in period of 3 days before treatment. Dosing was separated by a wash-out period of 14 days. Blood samples were collected over 72 h and plasma levels of SAQ were determined by a validated HPLC/UV assay. The 90% confidence interval (CI) of the ratio of the geometric means for log-transformed C(max), AUC(last) and AUC(inf) values were used to assess bioequivalence using the equivalence interval of 80-125%. Point estimate and 90% CI of the ratios of C(max), AUC(last) and AUC(inf) values were 94.9 (80.9-111.3), 97.4 (82.4-115.4) and 97.4 (82.5-115.0), respectively. Both treatments exhibited similar tolerability and safety. It was concluded that the new pharmaceutical product was bioequivalent to the innovator. PMID:21950153

Yerino, Gustavo A; Halabe, Emilia K; Zini, Elvira; Feleder, Ethel C

2011-01-01

116

Pharmacokinetic profiling and bioequivalence evaluation of 2 lamivudine tablet formulations after single oral administration in healthy human Indian volunteers.  

PubMed

The present study compared pharmacokinetic (PK) profile and single-dose tolerability of 2 marketed brands of lamivudine (3TC) 150-mg tablets, Lamivir (Cipla, Mumbai, India) and Epivir (GSK, Basingstoke, UK). The randomized, 2-treatment study was conducted in 24 fasting, healthy, Indian male subjects. Each subject received Epivir and Lamivir formulation separated by 7 days of drug-free washout period. Plasma concentrations of 3TC were used to estimate PK parameters such as maximum observed plasma concentration (Cmax) and area under plasma concentration-time curve (AUCinfinity). Geometric mean ratios (relative to Epivir) and resultant 90% CI of 3TC for Cmax and AUCinfinity were 1.00 (0.89-1.12) and 1.01 (0.94-1.07), respectively. As 90% CIs were entirely within 0.80-1.25 for log-transformed data, the 2 formulations were considered bioequivalent in the extent (AUCinfinity) and rate of absorption (Cmax and time to Cmax [tmax]). The means of primary PK parameters of 3TC, Cmax, and AUCinfinity in Indian subjects were comparable to those previously reported in the literature. Both formulations exhibited similar tolerability under fasting conditions. PMID:15793367

Narang, Vishal S; Lulla, Amar; Malhotra, Geena; Purandare, Shrinivas

2005-04-15

117

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

PubMed

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

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

2013-01-01

118

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

PubMed

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

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

2009-04-01

119

Microporous bilayer osmotic tablet for colon-specific delivery  

Microsoft Academic Search

Microporous bilayer osmotic tablet bearing dicyclomine hydrochloride and diclofenac potassium was developed using a new oral drug delivery system for colon targeting. The tablets were coated with microporous semipermeable membrane and enteric polymer using conventional pan-coating process. The developed microporous bilayer osmotic pump tablet (OPT) did not require laser drilling to form the drug delivery orifice. The colon-specific biodegradation of

Anil Chaudhary; Neha Tiwari; Vikas Jain; Ranjit Singh

2011-01-01

120

Some effects of morphine on habit function  

Microsoft Academic Search

In 2 experiments the morphine habit is compared with a food habit under various conditions of deprivation and satiation. In contrast to the food habit, both injection of morphine and the deprivation of morphine would appear to produce drive. Continuing effects of morphine may lead to learning without drive reduction. And, an injection of morphine counteracts the effect of food

H. D. Beach

1957-01-01

121

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

PubMed Central

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

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

2014-01-01

122

Increased calcium/calmodulin-dependent protein kinase II activity by morphine-sensitization in rat hippocampus.  

PubMed

Repeated exposure to drugs of abuse, such as morphine, elicits a progressive enhancement of drug-induced behavioral responses, a phenomenon termed behavioral sensitization. These changes in behavior may reflect long-lasting changes in some of the important molecules involved in memory processing such as calcium/calmodulin-dependent protein kinase II (CaMKII). In the present study, we investigated the effect of morphine sensitization on mRNA expression of ? and ? isoforms and activity of CaMKII in the hippocampus of male rats. Animals were treated for 3 days with saline or morphine (20mg/kg) and following a washout period of 5 days, a challenge dose of morphine (5mg/kg) were administered. The results indicate that morphine administration in pre-treated animals produces behavioral sensitization, as determined by significant increase in locomotion and oral stereotypy behavior. In addition, repeated morphine treatment increased mRNA expression of both ? and ? isoforms of CaMKII in the hippocampus. The present study also showed that induction of morphine sensitization significantly increased both Ca2+/calmodulin-independent and Ca2+/calmodulin-dependent activities of CaMK II in the rat hippocampus. However, acute administration of morphine (5mg/kg) did not alter either ? and ? CaMKII mRNA expression or CaMKII activity in the hippocampus. The stimulation effects of morphine sensitization on mRNA expression and activity of CaMKII were completely abolished by administration of naloxone, 30min prior to s.c. injections of morphine (20mg/kg/day×3 days). Our data demonstrated that induction of morphine sensitization could effectively modulate the activity and the mRNA expression of CaMKII in the hippocampus and this effect of morphine was exerted by the activation of opioid receptors. PMID:24675163

Kadivar, Mehdi; Farahmandfar, Maryam; Ranjbar, Faezeh Esmaeli; Zarrindast, Mohammad-Reza

2014-07-01

123

Formulation and evaluation of lactoferrin bioadhesive tablets.  

PubMed

For the treatment of chronic inflammation in the oral cavity, we attempted to develop bioadhesive tablets of bovine lactoferrin (B-LF) which has antibacterial properties and immune regulatory functions. B-LF tablets containing pectin, tamarind gum or carboxymethylcellulose (CMC) were prepared by direct compression. Tablets consisting of B-LF, pectin and xylitol passed through 60- or 100-mesh sieves were also prepared. The tablets containing CMC had insufficient bioadhesive force. Although the tablets containing tamarind gum showed the longest residence time in the oral cavity, an unpleasant taste gradually developed. The tablets containing pectin showed the highest value of bioadhesive force and the taste was acceptable. The characteristics of the B-LF tablets were improved by adding an appropriate amount of xylitol and using the ingredients sieved by a 100-mesh sieve. The therapeutic effect was evaluated by using rats with an ulcer on the oral mucosa. In the present study, swelling on the periphery of the ulcer was observed after administration of the B-LF tablets, and then the ulcer has reduced overall. PMID:17600641

Takahashi, Y; Takeda, C; Seto, I; Kawano, G; Machida, Y

2007-10-01

124

The pharmacokinetics of ibuprofen suspension, chewable tablets, and tablets in children with cystic fibrosis  

Microsoft Academic Search

Objectives: The objectives of this study were to compare the pharmacokinetic parameters of ibuprofen administered as a suspension, chewable tablet, or tablet in children with cystic fibrosis and to determine the optimal blood sampling times for measuring ibuprofen peak concentrations. Study design: A single oral 20 mg\\/kg dose of ibuprofen was administered, and blood samples were obtained at 15, 30,

Christy S. Scott; George Z. Retsch-Bogart; Robert P. Kustra; Katie M. Graham; Bradley J. Glasscock; Philip C. Smith

1999-01-01

125

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

PubMed Central

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

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

2013-01-01

126

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

PubMed

A rapid, sensitive and reliable high-performance liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous quantification of the five main bioactive components, calycosin, calycosin-7-O-?-d-glucoside, formononetin, astragaloside IV and schisandrin in rat plasma after oral administration of Shenqi Wuwei chewable tablets. Plasma samples were extracted using solid-phase extraction separated on a CEC18 column and detected by MS with an electrospray ionization interface in multiple-reaction monitoring mode. Calibration curves offered linear ranges of two orders of magnitude with r?>?0.995. The method had a lower limit of quantitation of 0.1, 0.02, 0.1, 1 and 0.1?ng/mL for calycosin, calycosin-7-O-?-d-glucoside, formononetin, astragaloside IV and schisandrin, respectively. Intra- and inter-day precisions (relative standard deviation) for all analytes ranged from 0.97 to 7.63% and from 3.45 to 10.89%, respectively. This method was successfully applied to the pharmacokinetic study of the five compounds in rats after oral administration of Shenqi Wuwei chewable tablets. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24652759

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

2014-08-01

127

Mucoadhesive tablets for controlled release of acyclovir.  

PubMed

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

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

2012-01-01

128

Should vitamin B12 tablets be included in more Canadian drug formularies? An economic model of the cost-saving potential from increased utilisation of oral versus intramuscular vitamin B12 maintenance therapy for Alberta seniors  

PubMed Central

Objective The aim of this study was to estimate the cost-savings attainable if all patients aged ?65 years in Alberta, Canada, currently on intramuscular therapy were switched to oral therapy, from the perspective of a provincial ministry of health. Setting Primary care setting in Alberta, Canada. Participants Seniors of age 65 years and older currently receiving intramuscular vitamin B12 therapy. Intervention Oral vitamin B12 therapy at 1000??g/day versus intramuscular therapy at 1000??g/month. Primary and secondary outcome measures Cost saving from oral therapy over intramuscular therapy, from the perspective of the Alberta Ministry of Health, including drug costs, dispensing fees, injection administration fees, additional laboratory monitoring and physician visit fees. Results Over 5?years, if all Albertans aged 65 years and older who currently receive intramuscular B12 are switched to oral therapy, our model found that $C13?975?883 can be saved. Even if no additional physician visits are billed for among patients receiving intramuscular therapy, $C8?444?346 could be saved from reduced administration costs alone. Conclusions Oral B12 therapy has been shown to be an effective therapeutic option for patients with vitamin B12 deficiency, yet only three provinces and the Non-Insured Health Benefits program include oral tablets on their formulary rather than the parenteral preparation. To ensure judicious use of limited health resources, clinicians and formulary committees are encouraged to adopt oral B12 therapy as a clinically and cost-effective first-line therapy for vitamin B12 deficiency.

Houle, Sherilyn K D; Kolber, Michael R; Chuck, Anderson W

2014-01-01

129

Secure tracking of tablets  

US Patent & Trademark Office Database

The present invention relates to a verification method for tracking and tracing tablets, particularly pharmaceutical tablets. It further relates to a visible secure marking or information that is a part of such tablet (10). The invention further relates to tablets suitable for such verification method, processes for manufacturing such tablets, and methods for reading the information.

2014-05-06

130

Peripheral postmortem redistribution of morphine.  

PubMed

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

Hargrove, Veronica M; Molina, D Kimberley

2014-06-01

131

Investigation of the bioavailability of hypericin, pseudohypericin, hyperforin and the flavonoids quercetin and isorhamnetin following single and multiple oral dosing of a hypericum extract containing tablet.  

PubMed

The objective of these two open phase I clinical trials was the investigation of the bioavailability of five constituents from a hypericum extract containing tablet, which are discussed as the components contributing to the antidepressant action. Each trial included 18 healthy male volunteers who received the test preparation, containing 612 mg dry extract of St John's wort (STW-3, Laif 600), either as a single oral dose or as a multiple once daily dose over a period of 14 days. Concentration/time curves were determined for hypericin, pseudohypericin, hyperforin, the flavonoid aglycone quercetin, and its methylated form isorhamnetin for 48 h after single dosing and for 24 h on day 14 at the end of 2 weeks of continuous daily dosing. After single dose intake, the key pharmacokinetic parameters were determined as follows: hypericin: area under the curve (AUC(0-infinity)) = 75.96 h x ng/ml, maximum plasma concentration (Cmax) = 3.14 ng/ml, time to reach Cmax (t(max)) = 8.1 h, and elimination half-life (t1/2) = 23.76 h; pseudohypericin: AUC(0-infinity) = 93.03 h x ng/ml, Cmax = 8.50 ng/ml, t(max) = 3.0 h, t1/2 = 25.39 h; hyperforin: AUC(0-max) = 1009.0 h x ng/ml, Cmax = 83.5 nglml, t(max) = 4.4 h, t1/2 = 19.64 h. Quercetin and isohamnetin showed two peaks of maximum plasma concentration separated by about 4 h. Quercetin: AUC(0-infinity) = 318,7 h x ng/ml, Cmax (1) = 47.7 ng/ml, t(max) (1) = 1.17 h, Cmax (2) = 43.8 ng/ml, t(max) (2) = 5.47 h, t1/2 = 4.16 h; isorhamnetin: AUC(0-infinity) = 98.0 h x ng/ml, Cmax (1) = 7.6 ng/ml, t(max) (1) = 1.53 h, Cmax (2) = 9.0 ng/ml, t(max), (2) = 6.42 h, t1/2 = 4.45 h. Under steady state conditions reached during multiple dose administration similar results were obtained. Further pharmacokinetic characteristics calculated from the obtained data were the mean residence time (MRT), the lag-time, the peak-trough fluctuation (PTF), the lowest observed plasma concentration (Cmin), and the average plasma concentration (Cav). The data obtained for hypericin, pseudohypericin and hyperforin generally corresponded well with values previously published, with some deviations observed for the extent of absorption of hypericin and the time course of absorption and elimination of hyperforin. The kinetic characteristics of the hypericum flavonoids are reported here for the first time. The trial preparation was well tolerated. PMID:15727160

Schulz, Hans-Ulrich; Schürer, Michael; Bässler, Dagmar; Weiser, Dieter

2005-01-01

132

tablet excipients  

Microsoft Academic Search

\\u000a In addition to the active drug, medicinal products often contain a number of other substances, e.g. for improving bioavailability such as disintegrants (e.g. starch), for taste masking and lubrication to ease swallowing (e.g. coats of sugar, cellulose,\\u000a polymers in film-coated tablets), or simply substances which facilitate production such as binders (e.g. cellulose derivatives),\\u000a glidants (colloidal silica) or diluents (lactose, crystalline

Gerhard Nahler

133

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

PubMed Central

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

2014-01-01

134

Intra-articular Morphine versus Lidocaine for Acute Knee Pain.  

PubMed

Objective: The authors conducted an unfunded randomized controlled trial approved by the Brooke Army Medical Center (BAMC) Institutional Review Board (IRB) to determine the possible efficacy of intra-articular morphine for pain in acute knee injuries. Methods: Patients presenting to the emergency department at San Antonio Military Medical Center (SAMMC) from May 2012 to August 2013 with knee pain due to an acute injury were consented and then enrolled based on a convenience sample. Patients were randomized to one of three intervention arms (morphine, lidocaine, or morphine and lidocaine) and were blinded to the intervention. The respective solution was injected into the knee joint using standard techniques. The patients self-reported their levels of knee pain via a standard 100mm visual analogue scale (VAS) at the time of injection and 30 minutes, 60 minutes, 90 minutes, 2 hours, 6 hours, and 24 hours postinjection. At 24 hours, the patients also reported the estimated amount of time they applied ice to the knee and the amount of oral analgesia consumed in the previous 24 hours. Results: The primary outcome was relative pain reduction as measured by the VAS. Secondary outcomes were the total cumulative use of ice and analgesics during the first 24 hours. Although this was a small study, the results showed a possible trend toward better pain control at all time intervals with injections containing morphine compared with lidocaine-only injections. Ice and oral analgesia usage was equivalent between the three intervention arms. Conclusion: Further investigation with a larger sample is required to explore whether these results are statistically significant and the possible superiority of intra-articular morphine to lidocaine for acute knee pain. PMID:24952044

Graham, Ross F; Hughes, John; Johnson, Anthony; Cuenca, Peter; Mosley, Trey

2014-01-01

135

Analgesia and central side-effects: two separate dimensions of morphine response  

PubMed Central

Aims To present a statistical model for defining interindividual variation in response to morphine and to use this model in a preliminary hypothesis-generating multivariate genetic association study. Methods Two hundred and sixty-four cancer patients taking oral morphine were included in a prospective observational study. Pain and morphine side-effect scores were examined using principal components analysis. The resulting principal components were used in an exploratory genetic association study of single nucleotide polymorphisms across the genes coding for the three opioid receptors, OPRM1, OPRK1 and OPRD1. Associations in multivariate models, including potential clinical confounders, were explored. Results Two principal components corresponding to residual pain and central side-effects were identified. These components accounted for 42 and 18% of the variability in morphine response, respectively, were independent of each other and only mildly correlated. The genetic and clinical factors associated with these components were markedly different. Multivariate regression modelling, including clinical and genetic factors, accounted for only 12% of variability in residual pain on morphine and 3% of variability in central side-effects. Conclusions Although replication is required, this data-driven analysis suggests that pain and central side-effects on morphine may be two separate dimensions of morphine response. Larger study samples are necessary to investigate potential genetic and clinical associations comprehensively.

Droney, Joanne M; Gretton, Sophy K; Sato, Hiroe; Ross, Joy R; Branford, Ruth; Welsh, Kenneth I; Cookson, William; Riley, Julia

2013-01-01

136

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

Microsoft Academic Search

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

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

137

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

PubMed

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

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

2013-01-16

138

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

PubMed

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

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

2009-01-01

139

Epilepsy and Oral Contraception  

PubMed Central

A controlled cross-over trial in 20 epileptic women, receiving regular anticonvulsant therapy showed that an oral contraceptive with a low oestrogen/ progestogen content had no significant effect on the average frequency of fits compared with identical dummy tablets.

Espir, Michael; Walker, M. E.; Lawson, June P.

1969-01-01

140

Comparison of the Time Course of Morphine??s Analgesic and Immunologic Effects  

Microsoft Academic Search

Morphine, an opioid analgesic commonly prescribed and abused, produces immune-altering effects. Whether morphine's antinociceptive and immunologic effects occur concurrently is unknown. Therefore, we investigated the time course of morphine's immuno- logic and antinociceptive effects. Rats were given a 15- mg\\/ kg morphine injection (subcutaneously), and ex- perimental assessments were taken at 30 min, 1 h, 2 h, 6 h, 12

Christina J. Nelson; Linda A. Dykstra; Donald T. Lysle

1997-01-01

141

Effect of morphine and beta-endorphin on human Fc receptor-dependent and natural killer cell functions.  

PubMed

Interactions between opiates and the human immune system have important clinical implications. To further evaluate these interactions, we studied in vitro and in vivo effects of morphine sulfate (morphine) and beta-endorphin (Bend) on antibody-dependent cell cytotoxicity (ADCC), natural killer cell cytotoxicity (NKCC), and effector cell expression of antibody Fc receptors. Morphine and Bend had no potent in vivo or in vitro effect on FcR expression nor did they have a significant in vitro effect on ADCC by monocytes or polymorphonuclear cells. Bend enhancement of NKCC in vitro was inhibited by coincubation of effector cells with morphine. After taking 90 to 150 mg of oral morphine, study volunteers demonstrated a significant decrease in ADCC by peripheral blood mononuclear cells. The same individuals demonstrated a consistent increase in NKCC and no change in the expression of Fc receptors. Effector cells from these individuals responded normally to in vitro incubation with interferon-gamma (IFN-gamma). PMID:1541057

Yeager, M P; Yu, C T; Campbell, A S; Moschella, M; Guyre, P M

1992-03-01

142

Bioequivalence of Clozapine Tablets  

Microsoft Academic Search

Objective To perform a bioequivalence study of clozapine tablets between Clozaril ? tablet (Novartis), the innovator product, and Clopaze ? tablet (Pharminar, Thailand). Method The study was performed in 12 healthy male volunteers for a single 100 mg dose of clozapine tablet. Randomized cross over design was used. Blood samples were collected before and after drug administration for 24 hours

Wandee Taesotikul; Sayam Kaewvichit; Chokchai Wongsinsup; Kittipong Sanichwankul; Wanida Pumpaisalchai

2000-01-01

143

Bronchoscopic and histological changes over time following acute ferrous sulphate tablet aspiration.  

PubMed

An 84-year-old woman accidentally aspirated an iron tablet. She was successfully treated with early endobronchial removal of the iron tablet remnants, oral corticosteroids and antibiotics. We describe the bronchoscopic and histological changes over time following acute iron tablet aspiration and highlight the importance of early intervention to avoid complications. PMID:23257641

Maw, Matthew; Chiu, Robert; Lim, Albert Yick Hou

2012-01-01

144

Miconazole mucoadhesive tablet for oropharyngeal candidiasis  

PubMed Central

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

Lalla, Rajesh V; Bensadoun, Rene-Jean

2011-01-01

145

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

PubMed Central

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

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

2011-01-01

146

Muscimol antagonism of morphine analgesia in rats.  

PubMed Central

1 Muscimol, a gamma-aminobutyric acid (GABA) receptor agonist, when injected intraventricularly antagonizes the antinociceptive effect of morphine given either subcutaneously or intraventricularly. The antagonistic effect of muscimol on morphine analgesia appears to be linearly related. 2 This finding provides support for the view that a GABA-ergic system is involved in morphine analgesia.

Mantegazza, P.; Tammiso, R.; Vicentini, L.; Zambotti, F.; Zonta, N.

1979-01-01

147

Intrathecal morphine for pediatric renal transplant recipients  

Microsoft Academic Search

Many pediatric renal transplant recipients have significant discomfort in the early postoperative period despite opioid administration. Intrathecal morphine is safe and effective for pain control in children. We examined our results with the use of intrathecal morphine for postoperative analgesia in renal transplant recipients at our institution. The morphine was administered while the patients were under general anesthesia. Seventeen of

R. E. Schwartz; C. A. Pasquariello; C. Schlichting

1994-01-01

148

Morphine Synthesis and Biosynthesis-An Update  

Microsoft Academic Search

This review covers recent developments in the area of morphine synthesis and biosynthesis. Literature is reviewed since the publication of the last major review. The first part of the chapter discusses recent advancements in biosynthesis of morphine alkaloids. Total syntheses published since 1996 are reviewed next and the third section discusses all published approaches to morphine skeleton. At the end

Bennett H. Novak; Tomas Hudlicky; Josephine W. Reed; Johann Mulzer; Dirk Trauner

2000-01-01

149

Influence of food on the oral bioavailability of rupatadine tablets in healthy volunteers: A single-dose, randomized, open-label, two-way crossover study  

Microsoft Academic Search

Background:Rupatadine is an oral active antihistamine for the management of diseases with allergic inflammatory conditions, such as perennial and seasonal rhinitis and chronic idiopathic urticaria. Oral rupatadine has been approved for the treatment of allergic rhinitis and chronic urticaria in adults and adolescents in several European countries.

Anna Solans; Juana Peña; Teresa Nadal; Iñaki Izquierdo; Manuel Merlos

2007-01-01

150

Evaluation of menstrual cycle effects on morphine and pentazocine analgesia  

PubMed Central

Studies have demonstrated menstrual cycle influences on basal pain perception, but direct evidence of menstrual cycle influences on analgesic responses has not been reported in humans. Our aim was to determine whether the magnitude of morphine and pentazocine analgesia varied across the menstrual cycle. Sixty-five healthy women, 35 taking oral contraceptives (OC) and 30 normally cycling (NOC), underwent experimental pain assessment both before and after intravenous administration morphine (0.08 mg/kg) or pentazocine (0.5 mg/kg) compared to saline placebo. Both active drug and placebo were administered once during the follicular phase and once during the luteal phase. Measures of heat, ischemic and pressure pain sensitivity were obtained before and after drug administration. Change scores in pain responses were computed to determine morphine and pentazocine analgesic responses, and medication side effects were recorded. The data were analyzed using mixed-model ANOVAs. NOC women showed slightly greater heat pain sensitivity in the follicular vs. luteal phase, while the reverse pattern emerged for OC women (p=0.046). Also, OC women showed lower pressure pain thresholds compared to NOC women (p < .05). Regarding analgesic responses, NOC women showed greater morphine analgesia for ischemic pain during the follicular vs. the luteal phase (p=0.004). Likewise, side effects for morphine were significantly higher in NOC women in the follicular phase than in the luteal phase (p=0.02). These findings suggest that sex hormones may influence opioid responses; however, the effects vary across medications and pain modalities and are likely to be modest in magnitude.

Ribeiro-Dasilva, MC; Shinal, RM; Glover, T; Williams, RS; Staud, R; Riley, JL; Fillingim, RB

2011-01-01

151

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

PubMed Central

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

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

2008-01-01

152

Fast dispersible/slow releasing ibuprofen tablets.  

PubMed

Eight formulations were developed containing ibuprofen in the form of orally disintegrating tablets. To prevent bitter taste and side effects of the drug, the drug was associated with Phospholipon 80H, a saturated lecithin, by wet granulation. The granules were then coated using different film forming agents (Kollicoat SR 30, Amprac 01, Kollidon 90F, Eudragit RD 100) obtaining four lots 1-4. Coated granules were then formulated with a sweetener (Aspartame), a mannitol-based diluent (Pearlitol SD 200) and Kollidon CL (1-4K) or Explotab (1-4E) were added as superdisintegrants and compacted under low compression force. The eight lots of tablets, 1-4K and 1-4E, were assessed if suitable as oral disintegrating tablets by determination of a range of technological parameters. Wetting and disintegregation time matched with the requirements of EP IV Ed., for almost all these formulations. Dissolution profiles suggested that the combined action of the hydrophobic lecithin and the coating delay the release of the drug from tablets with respect to when it is free or in the form of simple granules. By an appropriate combination of excipients it was thus possible to obtain orally disintegrating tablets and a delayed release of ibuprofen using simple and conventional techniques. PMID:18182280

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

2008-05-01

153

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

PubMed

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. PMID:22820648

Tolia, Gaurav; Li, S Kevin

2012-11-01

154

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

PubMed

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

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

2013-09-23

155

Effect of caffeine and morphine on the developing pre-mature brain.  

PubMed

Apnea of pre-maturity is common, occurring in 85% of infants born less than 34 week gestation. Oral caffeine is the most frequent form of therapy, often in conjunction with the use of intubation and intermittent ventilation. Morphine is used to reduce the pain believed to be associated with the latter. Little information is available on the effects of caffeine, morphine or their combination, on the developing brain. We determined the effect of caffeine and morphine alone and in combination of cell death on the developing brain of the rat. Cell death, measured by Fluoro-jade B and activated caspase-3, was significantly increased at 12 and 24 hour post-caffeine injection (P < 0.05) in the cortex, caudate, nucleus accumbens, hypothalamus, hippocampus and superior colliculus. No alterations were seen following morphine injection alone. However, in the thalamus, the combination of caffeine and morphine did increase cell death to a significantly greater extent than caffeine alone. Further research is required to determine the long-term pathologic and functional effects of caffeine and the combination of caffeine and morphine on the developing immature brain. PMID:18547548

Black, Amy M; Pandya, Shawna; Clark, Darren; Armstrong, Edward A; Yager, Jerome Y

2008-07-11

156

TASTE CONDITIONING EFFECTS OF BUPRENORPHINE IN MORPHINE-NAIVE AND MORPHINE-EXPERIENCED RATS  

Microsoft Academic Search

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

M. GAIARDI; C. GUBELLINI; M. BARTOLETTI

1998-01-01

157

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

PubMed Central

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

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

2013-01-01

158

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

PubMed

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

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

2012-12-27

159

Radioimmunoassay of morphine and morphine-like substances in biological fluids and human tissues  

Microsoft Academic Search

Summary  A radioimmunoassay is described for the determination of morphine and morphine-like substances in plasma, serum, biological\\u000a fluids and tissue homogenates using an antiserum to morphine-6-hemisuccinyl-BSA and125I-morphine as the labelled tracer. In the B\\/F separation with ammonium sulphate, calcium sulphate was added to make the precipitate\\u000a more compact. Some parameters related to the use of this method in direct assay on

Sergio Lafisca; Gianfranco Bolelli; Renata Mosca; Clementina Zanon

1977-01-01

160

An investigation into the influence of experimental conditions on in vitro drug release from immediate-release tablets of levothyroxine sodium and its relation to oral bioavailability.  

PubMed

The aim of this study was to investigate the influence of experimental conditions on levothyroxine sodium release from two immediate-release tablet formulations which narrowly passed the standard requirements for bioequivalence studies. The in vivo study was conducted as randomised, single-dose, two-way cross-over pharmacokinetic study in 24 healthy subjects. The in vitro study was performed using various dissolution media, and obtained dissolution profiles were compared using the similarity factor value. Drug solubility in different media was also determined. The in vivo results showed narrowly passing bioequivalence. Considering that levothyroxine sodium is classified as Class III drug according to the Biopharmaceutics Classification System, drug bioavailability will be less sensitive to the variation in its dissolution characteristics and it can be assumed that the differences observed in vitro in some of investigated media probably do not have significant influence on the absorption process, as long as rapid and complete dissolution exists. The study results indicate that the current regulatory criteria for the value of similarity factor in comparative dissolution testing, as well as request for very rapid dissolution (more than 85% of drug dissolved in 15 min), are very restricted for immediate-release dosage forms containing highly soluble drug substance and need further investigation. The obtained results also add to the existing debate on the appropriateness of the current bioequivalence standards for levothyroxine sodium products. PMID:21748540

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

2011-09-01

161

Morphine Enhances HIV Infection of Neonatal Macrophages  

PubMed Central

Perinatal transmission of HIV accounts for almost all new HIV infections in children. There is an increased risk of perinatal transmission of HIV with maternal illicit substance abuse. Little is known about neonatal immune system alteration and subsequent susceptibility to HIV infection after morphine exposure. We investigated the effects of morphine on HIV infection of neonatal monocyte-derived macrophages (MDM). Morphine significantly enhanced HIV infection of neonatal MDM. Morphine-induced HIV replication in neonatal MDM was completely suppressed by naltrexone, the opioid receptor antagonist. Morphine significantly up-regulated CCR5 receptor expression and inhibited the endogenous production of macrophage inflammatory protein-1? in neonatal MDM. Thus, morphine, most likely through alteration of ?-chemokines and CCR5 receptor expression, enhances the susceptibility of neonatal MDM to HIV infection, and may have a cofactor role in perinatal HIV transmission and infection.

Li, Yuan; Merrill, Jeffrey D.; Mooney, Kathy; Song, Li; Wang, Xu; Guo, Chang-Jiang; Savani, Rashmin C.; Metzger, David S.; Douglas, Steven D.; Ho, Wen-Zhe

2014-01-01

162

Comparison of the absorption of micronized (Daflon 500 mg) and nonmicronized 14C-diosmin tablets after oral administration to healthy volunteers by accelerator mass spectrometry and liquid scintillation counting.  

PubMed

Daflon 500 mg, is a micronized purified flavonoid fraction, containing 90% w/w diosmin and 10% w/w of flavonoids expressed as hesperidin, used clinically in the treatment of chronic venous insufficiency and hemorrhoidal disease. This study was designed to investigate the influence of particle size on the overall absorption of diosmin after oral administration of micronized (mean particle size = 1.79 microm, with 80% of particles having a size lower than 3.45 microm) and nonmicronized diosmin (mean particle size = 36.5 microm, with 80% of particles comprised between 19.9 and 159 microm). In a double blinded, cross-over study design, 500 mg tablets containing trace amounts (approximately 25 nCi) of (14)C-diosmin were administered to 12 healthy male volunteers as a single oral dose. Accelerator mass spectrometry and liquid scintillation counting were used for the measurement of (14)C-diosmin in urine and feces. Absorption of (14)C-diosmin from the gastrointestinal tract, measured by the urinary excretion of total radioactivity, was significantly improved with the micronized (57.9 +/- 20.2%) compared with the nonmicronized material (32.7 +/- 18.8%). Statistical comparison of the urinary excretion of the two pharmaceutical formulations showed this difference to be highly significant (p = 0.0004, analysis of variance). The overall excretion of the radiolabeled dose was 100% with mean +/- SD of 109 +/- 23% and 113 +/- 20% for the micronized and nonmicronized forms, respectively. The results of this study show: 1. the impact of a reduction of particle size on the extent of absorption of diosmin, giving a pharmacokinetic explanation to the better clinical efficacy observed with the micronized formulation, and 2. the use of accelerator mass spectrometry in conjunction with liquid scintillation counting in measurement of bioavailability in a human cross-over study comparing two drug formulations containing trace amounts of radioactivity. PMID:11782895

Garner, R C; Garner, J V; Gregory, S; Whattam, M; Calam, A; Leong, D

2002-01-01

163

Characterization of the constituents in rat biological fluids after oral administration of Fufang Danshen tablets by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry.  

PubMed

An ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry method was established to detect as many constituents in rat biological fluids as possible after oral administration of Fufang Danshen tablets (FDTs). A C18 column (1.8microm particle size) was adopted to separate the samples, and mass spectra were acquired in both negative and positive modes. First, the fingerprints of FDTs were established, resulting in 43 components being detected within 25min. Among these compounds, 37 were tentatively identified by comparing the retention times and mass spectral data with those of reference standards and the reference literature; the other 6 components were tentatively assigned solely based on the MS data. In vivo, 14 components and 8 metabolites of FDT were observed in plasma, and 12 components of FDT were detected in urine. Tanshinaldehyde, danshexinkun B, a glycine conjugate of danshensu and a methylated conjugate of danshexinkun B were newly detected in rat biological fluids. This study developed a high-speed and sensitive method that was successfully utilized for screening the active ingredients of a Chinese medical formula and provided helpful chemical information for further pharmacology and active mechanism research on Chinese medicine. PMID:20060253

Lv, Yonghai; Zhang, Xi; Liang, Xu; Liu, Xinru; Dai, Weixing; Yan, Shikai; Zhang, Weidong

2010-05-01

164

Morphine-induced impairment of spatial memory acquisition reversed by morphine sensitization in rats.  

PubMed

In the present study, the effects of systemic administration of morphine on spatial memory acquisition of a Morris water maze (MWM) task have been investigated in morphine-sensitized rats. Sensitization was obtained by subcutaneous (s.c.) injection of morphine, once daily for 3 days followed by 5 days free of the opioid before training. Then the rats were trained in the water maze task which was consisted of single training session of 8 trials and 24 h later a probe trial consist of 60 s free swim period without a platform and then non-spatial visual discrimination task was done. Our data indicated that pre-training single administration of morphine (2.5, 5 and 7.5 mg/kg) decreased the spatial memory acquisition in Morris water maze task with a maximum effect of 5 mg/kg of morphine. Amnesia induced by pre-training morphine was significantly reversed in morphine-sensitized (15 and 20 mg/kg) rats. The inhibition of morphine-induced amnesia in morphine-sensitized rats was decreased by once daily administration of naloxone (1 and 2 mg/kg) 30 min prior to injection of morphine during sensitization. The results suggest that morphine sensitization reverses the impairment of spatial memory acquisition induced by morphine and it is postulated that opioid receptors may play an important role in this effect. PMID:20226816

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

2010-08-25

165

Preparation of highly porous gastroretentive metformin tablets using a sublimation method.  

PubMed

The present investigation is aimed to formulate floating gastroretentive tablets containing metformin using a sublimation material. In this study, the release of the drug from a matrix tablet was highly dependent on the polymer concentrations. In all formulations, initial rapid drug release was observed, possibly due to the properties of the drug and polymer. The effect of the amount of PEO on swelling and eroding of the tablets was determined. The water-uptake and erosion behavior of the gastroretentive (GR) tablets were highly dependent on the amount of PEO. The water-uptake increased with increasing PEO concentration in the tablet matrix. The weight loss from tablets decreased with increasing amounts of PEO. Camphor was used as the sublimation material to prepare GR tablets that are low-density and easily floatable. Camphor was changed to pores in the tablet during the sublimation process. SEM revealed that the GR tablets have a highly porous morphology. Floating properties of tablets and tablet density were affected by the sublimation of camphor. Prepared floating gastroretentive tablets floated for over 24 h and had no floating lag time. However, as the amount of camphor in the tablet matrix increased, the crushing strength of the tablet decreased after sublimation. Release profiles of the drug from the GR tablets were not affected by tablet density or porosity. In pharmacokinetic studies, the mean plasma concentration of the GR tablets after oral administration was greater than the concentration of glucophase XR. Also, the mean AUC(0-?) values for the GR tablets were significantly greater than the plasma concentrations of glucophase XR. PMID:23246798

Oh, Tack-Oon; Kim, Ju-Young; Ha, Jung-Myung; Chi, Sang-Cheol; Rhee, Yun-Seok; Park, Chun-Woong; Park, Eun-Seok

2013-04-01

166

Co-administration of calcium gluconate and magnesium acetate effectively blocks the signs of morphine withdrawal in mice.  

PubMed

The present study was conducted to investigate the effect of oral administration of calcium gluconate and magnesium acetate on morphine withdrawal syndrome. Mice were rendered dependent on morphine by subcutaneous injection of increasing doses of morphine. Mice were observed for 30 minutes for the withdrawal signs (jumping or standing events, diarrhea, piloerection, tremor and ptosis). Separate oral administration of magnesium (50, 75 and 100 mg/kg) and calcium (500, 750 and 1,000 mg/kg) significantly decreased the jumping, without affecting standing in animals withdrawn from morphine. Co-administration of magnesium (at a fixed dose of 100 mg/kg) and calcium (at a range of doses from 250 to 1,000 mg/kg) resulted in a significant reduction in jumping and standing events (P<0.05). In a similar fashion, the qualitative signs of withdrawal were also reduced when the above combination of calcium and magnesium was administered. Co-administration of calcium/magnesium at 500/50, 750/75 and 1,000/100 mg/kg significantly reduced the number of jumps in morphine-dependent animals without affecting the number of standing events. This study demonstrates the potential activity of the co-administration calcium and magnesium in preventing the signs associated with morphine withdrawal syndrome. PMID:22429988

Rabbani, Mohammed; Hajhashemi, Valiollah; Vadizadeh, Ali

2012-03-01

167

Dose related changes in tissue morphine concentration.  

PubMed

Rats were injected with morphine-6(3)H diluted with increasing amounts of non-radiolabelled morphine. The entry of the isotope into the brain and various tissues was measured by combustion in a tissue oxidizer. The relative distribution of morphine between the blood and brain remained constant at about 5.5:1 over the range of doses studied (0.07 - 10.0 mg/kg). No dose related differential effects on morphine uptake were evident in central tissues, with the exception of the hypothalamus which exhibited a disproportionately greater uptake. Among the noncentral tissues, kidney and liver showed the greatest dose related increases in uptake. PMID:1265337

Hahn, E F; Norton, B I; Fishman, J

1976-04-01

168

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

PubMed

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. PMID:22414810

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

2012-05-15

169

Randomized, Crossover and Single-Dose Bioquivalence Study of Two Oral Desogestrel Formulations (Film-Coated Tablets of 75 ?g) in Healthy Female Volunteers  

PubMed Central

Despite the increase in the substitution of branded medicinal product with generic drugs, this is a controversial issue for some pharmacological groups (such as contraceptives). The aim of the present clinical trial was to assess the bioequivalence and tolerability of two oral formulations of desogestrel. Thirty-three healthy female volunteers participated in this randomized and two-way crossover study. During two separate experimental periods, with at least four weeks of washout period, women received a single oral dose of 75 ?g of desogestrel from each of the formulations (test formulation and reference formulation). Desogestrel bioavailability was determined by the measurement of 3-ketodesogestrel plasma concentration. Pharmacokinetic parameters were comparable and the 90% CI for the ratio of Cmax (96.14–114.53%) and AUC0–t (105.73–123.83%) values for the test and reference formulations fell within the established regulatory interval (80–125%). Both formulations were also comparable in terms of tolerability. From the results of this study it can be concluded that test formulation (desogestrel 75 ?g, Cyndea PHARMA S.L.) is bioequivalent to the reference formulation (Cerazet® 75 ?g, Organon Española S.A.).

Pena, Maria Angeles; Sanz, Emilio; Francisco, Silvia; Alonso, Ainhara; Abajo, Zurine; Felipe, Izaskun; Pascual, Jaume; Tost, Digna; Bailac, Sandra

2012-01-01

170

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

PubMed Central

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.

Beyaz, Serbulent Gokhan

2012-01-01

171

Midazolam exacerbates morphine tolerance and morphine-induced hyperactive behaviors in young rats with burn injury.  

PubMed

Midazolam and morphine are often used in pediatric intensive care unit (ICU) for analgesia and sedation. However, how these two drugs interact behaviorally remains unclear. Here, we examined whether (1) co-administration of midazolam with morphine would exacerbate morphine tolerance and morphine-induced hyperactive behaviors, and (2) protein kinase C (PKC) would contribute to these behavioral changes. Male rats of 3-4 weeks old were exposed to a hindpaw burn injury. In Experiment 1, burn-injured young rats received once daily saline or morphine (10mg/kg, subcutaneous, s.c.), followed 30min later by either saline or midazolam (2mg/kg, intraperitoneal, i.p.), for 14 days beginning 3 days after burn injury. In Experiment 2, young rats with burn injury were administered with morphine (10mg/kg, s.c.), midazolam (2mg/kg, i.p.), and chelerythrine chloride (a non-specific PKC inhibitor, 10nmol, intrathecal) for 14 days. For both experiments, cumulative morphine anti-nociceptive dose-response (ED50) was tested and hyperactive behaviors such as jumping and scratching were recorded. Following 2 weeks of each treatment, ED50 dose was significantly increased in rats receiving morphine alone as compared with rats receiving saline or midazolam alone. The ED50 dose was further increased in rats receiving both morphine and midazolam. Co-administration of morphine and midazolam also exacerbated morphine-induced hyperactive behaviors. Expression of the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor and PKC? in the spinal cord dorsal horn (immunohistochemistry; Western blot) was upregulated in burn-injured young rats receiving morphine alone or in combination with midazolam, and chelerythrine prevented the development of morphine tolerance. These results indicate that midazolam exacerbated morphine tolerance through a spinal NMDA/PKC-mediated mechanism. PMID:24713351

Song, Li; Wang, Shuxing; Zuo, Yunxia; Chen, Lucy; Martyn, Jeevendra A; Mao, Jianren

2014-05-20

172

In vitro antioxidant properties of morphine  

Microsoft Academic Search

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

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

2004-01-01

173

Morphine promotes apoptosis in Jurkat cells  

Microsoft Academic Search

Patients with intravenous heroin addic- tion are prone to recurrent infections and at times these infections are fatal. We evaluated the effect of morphine on the apoptosis of Jurkat cells and freshly isolated human T lymphocytes. Morphine promoted apoptosis of both the Jurkat cells and the freshly isolated T lymphocytes in a dose-dependent manner. DAGO, a specific µ receptor agonist,

Pravin C. Singhal; Aditi A. Kapasi; Krishna Reddy; Nicholas Franki; Nora Gibbons; Guohua Ding

1999-01-01

174

Mucoadhesive bilayered tablets for buccal sustained release of flurbiprofen  

Microsoft Academic Search

The aim of this work was the design of sustained-release mucoadhesive bilayered tablets, using mixtures of mucoadhesive polymers\\u000a and an inorganic matrix (hydrotalcite), for the topical administration of flurbiprofen in the oral cavity. The first layer,\\u000a responsible for the tablet retention on the mucosa, was prepared by compression of a cellulose derivative and polyacrylic\\u000a derivative blend. The second layer, responsible

Luana Perioli; Valeria Ambrogi; Stefano Giovagnoli; Maurizio Ricci; Paolo Blasi; Carlo Rossi

2007-01-01

175

A randomised trial of glucose tablets to aid smoking cessation  

Microsoft Academic Search

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

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

2009-01-01

176

Femara Tablets.doc  

Cancer.gov

____________________________________________________________________________________________________ Femara® Tablets, 2.5 mg Page 1 of 7 Approval Date: 28 Oct 03 1 0 0 MATERIAL SAFETY DATA SHEET NOVARTIS PHARMACEUTICALS CORPORATION One Health Plaza

177

Intravenous morphine pharmacokinetics in pediatric patients with sickle cell disease  

Microsoft Academic Search

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

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

1995-01-01

178

Endogenous formation of morphine in human cells  

PubMed Central

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

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

2004-01-01

179

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

PubMed

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

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

2013-01-01

180

Morphine withdrawal increases intrinsic excitability of oxytocin neurons in morphine-dependent rats.  

PubMed

To determine whether intrinsic mechanisms drive supraoptic nucleus oxytocin neuron excitation during morphine withdrawal, we calculated the probability of action potential (spike) firing with time after each spike for oxytocin neurons in morphine-naive and morphine-dependent rats in vivo and measured changes in intrinsic membrane properties in vitro. The opioid receptor antagonist, naloxone, increased oxytocin neuron post-spike excitability in morphine-dependent rats; this increase was greater for short interspike intervals (<0.1 s). Naloxone had similar, but smaller (P=0.04), effects in oxytocin neurons in morphine-naive rats. The increased post-spike excitability for short interspike intervals was specific to naloxone, because osmotic stimulation increased excitability without potentiating excitability at short interspike intervals. By contrast to oxytocin neurons, neither morphine dependence nor morphine withdrawal increased post-spike excitability in neighbouring vasopressin neurons. To determine whether increased post-spike excitability in oxytocin neurons during morphine withdrawal reflected altered intrinsic membrane properties, we measured the in vitro effects of naloxone on transient outward rectification (TOR) and after-hyperpolarization (AHP), properties mediated by K+ channels and that affect supraoptic nucleus neuron post-spike excitability. Naloxone reduced the TOR and AHP (by 20% and 60%, respectively) in supraoptic nucleus neurons from morphine-dependent, but not morphine-naive, rats. In vivo, spike frequency adaptation (caused by activity-dependent AHP activation) was reduced by naloxone (from 27% to 3%) in vasopressin neurons in morphine-dependent, but not morphine-naive, rats. Thus, multiple K+ channel inhibition increases post-spike excitability for short interspike intervals, contributing to the increased firing of oxytocin neurons during morphine withdrawal. PMID:15673449

Brown, Colin H; Stern, Javier E; Jackson, Keshia L M; Bull, Philip M; Leng, Gareth; Russell, John A

2005-01-01

181

Morphine sulphate induced histopathological and histochemical changes in the rat liver.  

PubMed

In this study, the histopathological and histochemical changes due to chronic usage of morphine sulphate in liver were assessed in rats with both light and electron microscopes. Twenty male albino rats (Rattus norvegicus) (130-150 g) were included and divided into four groups. Normal saline (5 ml) was given orally as placebo in the control group (N=5). Morphine groups (N=5) received morphine orally at a single dose of 5 ml/kg/day for 10, 20 and 30 days (groups II, III and IV), respectively. Liver specimens from all groups were evaluated for histopathological and histochemical changes. Light microscopy revealed severe centrilobular congestion, portal fibrosis with bile ductal proliferation and an increased inflammatory infiltration and focal parenchymal necrosis. Histochemical study revealed a progressive depletion of general carbohydrates and an increase in total protein contents. These changes were confirmed at ultrastructural level, including the presence of accumulated lipid in the hepatocytes; deposits of a collagen-like fibrous material were seen in the space of Disse and a reduction in the number of endothelial cell fenestrations. Our findings pointed out the risk of increased lipid fibrosis and hepatic damage due to long-term use of morphine. Although opioids are reported to be effective in pain management, their toxic effects should be kept in mind during chronic usage. PMID:20655561

Bekheet, Souad H M

2010-08-01

182

[Formulation of calcium acetate tablets].  

PubMed

The results of the testing of calcium acetate tablets, produced by direct compression and by wet granulation (Ph. Jug. IV) are presented. Tablet hardness, friability and disintegration were determined. The best properties were observed in the tablets produced with maize starch. This procedure is fast and simple, and compound tablets of calcium acetate fulfill the current requirements for this type of preparation. PMID:11521467

Obrenovic, D; Gazikalovic, E; Ognjanovic, J; Nidzovic Z, Z

2000-01-01

183

Mucoadhesive bilayer tablets of propranolol hydrochloride.  

PubMed

The purpose of this research was to study mucoadhesive bilayer buccal tablets of propranolol hydrochloride using the bioadhesive polymers sodium alginate (Na-alginate) and Carbopol 934P (CP) along with ethyl cellulose as an impermeable backing layer. The tablets were evaluated for weight variation, thickness, hardness, friability, surface pH, mucoadhesive strength, swelling index, in vitro drug release, ex vivo drug permeation, ex vivo mucoadhesion, and in vivo pharmacodynamics in rabbits. Tablets containing Na-alginate and CP in the ratio of 5:1 (F2) had the maximum percentage of in vitro drug release without disintegration in 12 hours. The swelling index was proportional to Na-alginate content and inversely proportional to CP content. The surface pH of all tablets was found to be satisfactory (7.0 +/- 1.5), close to neutral pH; hence, buccal cavity irritation should not occur with these tablets. The mechanism of drug release was found to be non-Fickian diffusion and followed zero-order kinetics. The formulation F4 was optimized based on good bioadhesive strength (28.9 +/- 0.99 g) and sustained in vitro drug permeation (68.65% +/- 3.69% for 12 hours). The behavior of formulation F4 was examined in human saliva, and both the drug and the buccal tablet were found to be stable. The formulation F4 was applied to rabbit oral mucosa for in vivo studies. The formulation inhibited isoprenaline-induced tachycardia. The studies conducted in rabbits confirmed the sustained release as compared with intravenous administration. PMID:17915827

Patel, Vishnu M; Prajapati, Bhupendra G; Patel, Harsha V; Patel, Karshanbhi M

2007-01-01

184

Calcification prevention tablets  

NASA Technical Reports Server (NTRS)

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

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

1991-01-01

185

Development and Evaluation of Buccoadhesive Controlled Release Tablets of Lercanidipine  

PubMed Central

The purpose of this research was to develop and evaluate buccal mucoadhesive controlled release tablets of lercanidipine hydrochloride using polyethylene oxide and different viscosity grades of hydroxypropyl methylcellulose individually and in combination. Effect of polymer type, proportion and combination was studied on the drug release rate, release mechanism and mucoadhesive strength of the prepared formulations. Buccal mucoadhesive tablets were made by direct compression and were characterized for content uniformity, weight variation, friability, surface pH, thickness and mechanism of release. In order to estimate the relative enhancement in bioavailability one optimized formulation was evaluated in rabbits. Further, placebo tablets were also evaluated for acceptability in human subjects. Results indicated acceptable physical characteristics of designed tablets with good content uniformity and minimum weight variation. Drug release and mucoadhesive strength were found to depend upon polymer type, proportion and viscosity. The formulations prepared using poly ethylene oxide gave maximum mucoadhesion. The release mechanism of most formulations was found to be of anomalous non-Fickian type. In vivo studies of selected formulation in rabbits demonstrated significant enhancement in bioavailability of lercanidipine hydrochloride relative to orally administered drug. Moreover, in human acceptability studies of placebo formulations, the designed tablets adhered well to the buccal mucosa for more than 4 h without causing any discomfort. It may be concluded that the designed buccoadhesive controlled release tablets have the potential to overcome the disadvantage of poor and erratic oral bioavailability associated with the presently marketed formulations of lercanidipine hydrochloride.

Mudgal, Madri; Kumar, Lajwinder; Saha, Ranendra

2008-01-01

186

Development and evaluation of buccoadhesive controlled release tablets of lercanidipine.  

PubMed

The purpose of this research was to develop and evaluate buccal mucoadhesive controlled release tablets of lercanidipine hydrochloride using polyethylene oxide and different viscosity grades of hydroxypropyl methylcellulose individually and in combination. Effect of polymer type, proportion and combination was studied on the drug release rate, release mechanism and mucoadhesive strength of the prepared formulations. Buccal mucoadhesive tablets were made by direct compression and were characterized for content uniformity, weight variation, friability, surface pH, thickness and mechanism of release. In order to estimate the relative enhancement in bioavailability one optimized formulation was evaluated in rabbits. Further, placebo tablets were also evaluated for acceptability in human subjects. Results indicated acceptable physical characteristics of designed tablets with good content uniformity and minimum weight variation. Drug release and mucoadhesive strength were found to depend upon polymer type, proportion and viscosity. The formulations prepared using poly ethylene oxide gave maximum mucoadhesion. The release mechanism of most formulations was found to be of anomalous non-Fickian type. In vivo studies of selected formulation in rabbits demonstrated significant enhancement in bioavailability of lercanidipine hydrochloride relative to orally administered drug. Moreover, in human acceptability studies of placebo formulations, the designed tablets adhered well to the buccal mucosa for more than 4 h without causing any discomfort. It may be concluded that the designed buccoadhesive controlled release tablets have the potential to overcome the disadvantage of poor and erratic oral bioavailability associated with the presently marketed formulations of lercanidipine hydrochloride. PMID:18446480

Charde, Shrikant; Mudgal, Madri; Kumar, Lajwinder; Saha, Ranendra

2008-01-01

187

A highly toxic morphine-3-glucuronide derivative.  

PubMed

By the coupling of octylamine to the uronic acid function of morphine-3-glucuronide (M3G) a new glycoconjugate (morphine-3-octylglucuronamide, M3GOAM) was prepared. When assayed in both rats and mice up to ng/kg (i.p.) doses none of the animals survived. The aliphatic octyl chain may be the lethal factor since a closely related derivative (M3GNH2), was not toxic and showed similar opioid antagonist properties than naloxone. PMID:15012991

Salvatella, Mariona; Arsequell, Gemma; Valencia, Gregorio; Rodríguez, Raquel E

2004-02-23

188

21 CFR 520.1805 - Piperazine phosphate with thenium closylate tablets.  

Code of Federal Regulations, 2013 CFR

... â(1) Amount. Administer orally to dogs as follows: Number of Tablets at Each...Toxocara canis ) from weaned pups and adult dogs. (3) Limitations. Do not use this product to treat dogs weighing less than 2 pounds,...

2013-04-01

189

REGULATION OF NEURONAL PLC? BY CHRONIC MORPHINE  

PubMed Central

Alterations in neurotrophic signaling pathways may contribute to the changes in the mesolimbic dopamine system induced by chronic morphine exposure. In a rat model of morphine dependence, we previously identified increased levels of phospholipase C gamma-1 (PLC?1) immunoreactivity specifically within the ventral tegmental area (VTA) following chronic morphine treatment. Using an antibody specific for the tyrosine-phosphorylated, activated form of PLC?1, we now show that chronic morphine also significantly upregulates PLC?1 activity in the VTA, as well as in the nucleus accumbens and hippocampus, regions which are also implicated in the reinforcing properties of morphine. In contrast, no increase in PLC?1 activity was found in the substantia nigra or dorsal striatum. HSV-mediated overexpression of PLC?1 in PC12 cells induced ERK activation via a mechanism dependent, in part, on both MAP-ERK kinase (MEK) and protein kinase C. PLC?1 overexpression in the VTA similarly induced ERK activation in the VTA in vivo. As chronic morphine treatment has been shown to increase ERK activity within the VTA, the current results suggest that increased PLC?1 activity may be an upstream mediator of this effect.

Wolf, Daniel H.; Nestler, Eric J.; Russell, David S.

2007-01-01

190

In vivo evidence for an increase in 5alpha-reductase activity in the rat central nervous system following morphine exposure.  

PubMed

In the present study, the effects of acute and chronic morphine exposure on testosterone concentrations in the central nervous system (CNS) and serum were investigated in rats. Acute morphine administration (5 mg/kg, s.c.) reduced significantly testosterone levels in serum and spinal cord but not in the brain. Following chronic morphine administration (orally for 21 days), the brain testosterone was also significantly reduced as well as serum and spinal cord. Since, the decrease in testosterone levels following morphine exposure was more obvious in the CNS than serum, we suggested that it cannot be caused by only a direct decline in testosterone levels in periphery, and an increased local metabolism of testosterone in the CNS might be attributed in these effects. This hypothesis was supported with the findings that pretreatment with finasteride, a 5alpha-reductase inhibitor (5 mg/kg, s.c.) blocked testosterone elimination from the CNS following morphine exposure. Moreover, the serum concentration of 5alpha-reduced metabolites of testosterone, dihydrotestosterone and 3alpha-diol glucuronide was increased significantly following chronic morphine exposure, but not after co-treatment with finasteride. These results suggest that morphine exposure increase the CNS activity of 5alpha-reductase, which is an important metabolizing enzyme for testosterone. PMID:16143488

Amini, Hossein; Ahmadiani, Abolhassan

2005-11-01

191

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

PubMed

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

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

2013-09-01

192

Comparison of Echinacea alkylamide pharmacokinetics between liquid and tablet preparations.  

PubMed

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

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

2007-09-01

193

Fast disintegrating tablets: Opportunity in drug delivery system  

PubMed Central

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

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

2011-01-01

194

Fast disintegrating tablets: Opportunity in drug delivery system.  

PubMed

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

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

2011-10-01

195

Postmortem distribution pattern of morphine and morphine glucuronides in heroin overdose  

Microsoft Academic Search

The postmortem distribution of morphine and its metabolites was investigated in four cases of heroin overdose to evaluate some of the factors that influence intravasal blood concentrations. Variables included were the chemical stability of morphine conjugates, hemoconcentration, incomplete distribution of the drug and diffusion processes. Blood samples from different sampling sites including the aorta, the infra- and suprarenal portion of

G. Skopp; B. Ganßmann; R. Mattern; R. Aderjan

1996-01-01

196

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

PubMed

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

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

2014-08-01

197

Pharmaceutical development of ondansetron tablets.  

PubMed

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

Leak, R E; Woodford, J D

1989-01-01

198

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

PubMed

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

Luong, Susan; Fu, Shanlin

2014-03-01

199

Influence of Tablet Dissolution on Furosemide Bioavailability: A Bioequivalence Study  

Microsoft Academic Search

In order to evaluate the in vitro dissolution and in vivo bioavailability relationship for furosemide, a bioequivalence study was carried out. Furosemide (40 mg) was administered orally to 12 normal volunteers in a 6 × 6 crossover design using six products (five tablets and one solution) obtained from three pharmaceutical companies. Plasma and urine concentrations of furosemide were quantitated by

Patrick J. McNamara; Thomas S. Foster; George A. Digenis; Rajani B. Patel; William A. Craig; Peter G. Welling; Rao S. Rapaka; Vadlamani K. Prasad; Vinod P. Shah

1987-01-01

200

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

PubMed Central

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

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

2013-01-01

201

The Role of GABAB Receptors in Morphine Self-Administration  

PubMed Central

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.

Ramshini, Effat; Alaei, Hojjatallah; Reisi, Parham; Alaei, Samaneh; Shahidani, Somaye

2013-01-01

202

Magnesium Sulfate Potentiates Morphine Antinociception at the Spinal Level  

Microsoft Academic Search

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

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

2000-01-01

203

Presence and Formation of Codeine and Morphine in the Rat  

Microsoft Academic Search

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

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

1986-01-01

204

Morphine stimulates nitric oxide release from invertebrate microglia  

Microsoft Academic Search

Morphine stimulates nitric oxide (NO) release in human endothelial cells. To determine whether this mechanism also occurs in invertebrates, the musselMytilus edulis was studied. Exposure of excised ganglia to morphine for 24 h resulted in a significant dose-dependent decrease in rnicroglial egress that was naloxone sensitive. In coincubating the excised ganglia with morphine and the nitric oxide synthase inhibitor, N

Yu Liu; David Shenouda; Thomas V. Bilfinger; Michelle L. Stefano; Harold I. Magazine; George B. Stefano

1996-01-01

205

Vindolanda Tablets Online  

NSDL National Science Digital Library

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

206

Relative abuse liability of prescription opioids compared to heroin in morphine-maintained heroin abusers  

PubMed Central

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

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

2013-01-01

207

In vivo bioavailability studies of sumatriptan succinate buccal tablets  

PubMed Central

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

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

2011-01-01

208

Preparation, characterization and tableting of cilnidipine solid dispersions.  

PubMed

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

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

2013-05-01

209

Tablet Process Simulator  

NSDL National Science Digital Library

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

2013-07-23

210

Plaque-inhibiting effect of bioadhesive mucosal tablets containing chlorhexidine in a 4-day plaque regrowth model  

Microsoft Academic Search

Background and aim. Compliance in the use of daily oral antiseptics can probably be enhanced by prescribing easily-applied bioadhesive tablets which slowly release chlorhexidine (CHX). This could also be of use in patients with difficulties in rinsing or performing mechanical plaque control. The aim of the present study was to evaluate the capacity of bioadhesive tablets containing either 30 mg

P. Coessens; F. Herrebout; De J. Boever; J. Voorspoels; J. Remon

2002-01-01

211

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

PubMed

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. PMID:23791737

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

2013-09-10

212

Obtaining fast dissolving disintegrating tablets with different doses of melatonin.  

PubMed

Fast dissolving disintegrating tablets (FDDTs) containing different dosages of melatonin have been manufactured for administration to a specific target population: pediatric patients, having potential difficulties taking other oral forms. The lower dosages (3 and 5mg) are intended for epileptic children, migraine prevention, neurodevelopmental disability, sleep disorders and blindness. Dosages of 10 and 60 mg are intended for Duchenne muscular dystrophy. Two FDDT groups have been designed, one which has excipients for direct compression and others having direct compression and effervescent excipients. Tablets have been produced having disintegration times of less than 25s and with friability and hardness values that require no special storage or packaging conditions. PMID:24699354

Muñoz, H; Castan, H; Clares, B; Ruiz, M A

2014-06-01

213

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

Microsoft Academic Search

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

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

1987-01-01

214

CES 2011: Tablet Crazy  

ERIC Educational Resources Information Center

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

Rapp, David

2011-01-01

215

Bioavailability of prednisolone tablets  

Microsoft Academic Search

Two fourtreatment crossover studies were performed using 12 adult male volunteers in each with seven different commercially available prednisolone tablets. Plasma samples were assayed for prednisolone by a radioimmunoassay method. Statisacal analyses of the data, by analysis of variance for crossover design (ANOVA), showed no significant differences among the treatment averages at any of the sampling times except at 0.25

Aubrey V. Tembo; Margarette R. Hallmark; Ermelinda Sakmar; Hannelore G. Bachmaan; Donald J. Weidler; John G. Wagner

1977-01-01

216

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

PubMed

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

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

2013-09-01

217

Pediatric drugs--a review of commercially available oral formulations.  

PubMed

Pediatric oral formulations can be quite scientifically challenging to develop and the prerequisites for both a measurable dosage form to administer based upon bodyweight, and also taste-masking are two of the challenges unique for pediatric oral formulations. The physicochemical and organoleptic properties of the active drug substance such as solubility, chemical stability, and taste along with the intended dose can determine which formulations are feasible to develop. Oral pediatric formulations are available in 17 different varieties and can be either a ready-to-use formulation such as a solution, syrup, suspension, tablet, scored tablet, chewable tablet, orally disintegrating tablet, or thin strip, or can also be a formulation that requires manipulation such as a powder for constitution to a suspension, tablet for constitution to a suspension, powder for constitution to a solution, drops for reconstitution to a suspension, concentrated solution for dilution, effervescent tablet, bulk oral granules, bulk oral powder, or solid in a capsule to mix with food or drink. Recently there has been an increase in pediatric formulation development inspired by increased regulatory incentives. The intent of this review is to educate the reader on the various types of formulations administered orally to pediatrics, the rationale in deciding which type of formulation to develop, the excipients used, development challenges, the in-use handling of oral pediatric formulations, and the regulatory incentives. PMID:17823956

Strickley, Robert G; Iwata, Quynh; Wu, Sylvia; Dahl, Terrence C

2008-05-01

218

Patient-controlled epidural analgesia with morphine or morphine plus ketamine for post-operative pain relief.  

PubMed

Sixty patients were randomly assigned to two equal groups. Group I received epidural morphine 1 mg after surgery and used a patient-controlled analgesia device programmed to deliver morphine 0. 2 mg h-1, 0.2 mg per bolus. Group II received an epidural loading dose of morphine 1 mg plus ketamine 5 mg and used a patient-controlled analgesia device programmed to deliver morphine 0. 2 mg+ketamine 0.5 mg h-1, morphine 0.2 mg+ketamine 0.5 mg per bolus with a lockout time of 10 min. The mean morphine consumption was 8. 6+/-0.7 mg for group I and 6.2+/-0.2 mg for group II. Although group II utilized significantly less morphine (P < 0.05), pain relief was significantly better in group II than in group I (P < 0.05) in the first 3 h. Vomiting occurred more frequently in group I (26%) than in group II (13%). The frequency and severity of pruritus and level of sedation were similar in the two groups. These findings suggest that patient-controlled epidural analgesia with morphine plus ketamine may provide effective analgesia with a lesser dose of morphine and fewer subsequent side effects, compared with patient-controlled epidural analgesia with morphine alone after lower abdominal surgery. PMID:10747210

Tan, P H; Kuo, M C; Kao, P F; Chia, Y Y; Liu, K

1999-12-01

219

(+)-Morphine attenuates the (-)-morphine-produced tail-flick inhibition via the sigma-1 receptor in the mouse spinal cord  

PubMed Central

Aims We have previously demonstrated that pretreatment with (+)-morphine given intrathecally attenuates the intrathecal (?)-morphine-produced tail-flick inhibition. The phenomenon has been defined as antianalgesia against (?)-morphine-produced analgesia. Present experiments were then undertaken to determine if the antianalgesic effect induced by (+)-morphine given spinally is mediated by the stimulation of the sigma-1 receptor in the mouse spinal cord. Main methods Sigma-1 receptor ligands, N-[2-(3,4-Dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine dihydrobromide (BD1047) and (+)-pentazocine were used to determine if (+)-morphine-induced antianalgesia is mediated by the stimulation of sigma-1 receptors in the mouse spinal cord. Tail-flick test was employed to measure the nociceptive response. All compounds were given intrathecally. Key findings Pretreatment with BD1047 (1–10 ?g) or (+)-pentazocine (0.1–10 ?g) dose-dependently reversed the attenuation of the (?)-morphine-produced tail-flick inhibition induced by (+)-morphine (10 pg). BD1047 and (+)-pentazocine injected alone did not affect (?)-morphine-produced tail-flick inhibition. Significance The finding indicates that (+)-morphine attenuates the (?)-morphine-produced tail-flick inhibition via the activation of the sigma-1 receptors in the mouse spinal cord. Sigma-1 receptors may play an important role in opioid analgesia in the mouse spinal cord.

Tseng, Leon F.; Hogan, Quinn H.; Wu, Hsiang-En

2011-01-01

220

Tableting and tablet properties of alginates: characterisation and potential for Soft Tableting.  

PubMed

The aim of the study was to evaluate the suitability of alginates for Soft Tableting. For this purpose the compaction properties of alginates, varying in molecular weight, guluronic acid/mannuronic acid ratio and salt, were investigated and compared to MCC. Based on the mechanical properties, the suitability of the tested excipients for Soft Tableting was predicted. In order to test the prediction the tested materials were used to tablet enteric coated pellets, which served as a pressure sensitive material. The tableting behaviour was analysed by the 3-D modeling technique. The tablet properties were analysed by determining the elastic recovery and the compactibility. Alginates in general deformed elastically. The compression behaviour depended on the chemical composition of the alginates with sodium alginates being more elastic than potassium alginates. Tablets containing alginates with low guluronic acid content exhibited higher elasticity than tablets with alginates having a low mannuronic acid content. The plasticity of potassium alginates was higher than for sodium alginates. However, the plasticity of all tested alginates was lower than the plasticity of MCC. The compactibility of the tested alginates was sufficient. The proposed prediction, which states that tableting excipients with higher elasticity are more suitable for tableting sensitive materials than plastic excipients, was valid for the tested materials. The elastic alginates inflicted less damage on the pellets than the plastic MCC. Thus, all alginates were more appropriate for tableting pressure sensitive materials than MCC. PMID:18992337

Schmid, Wolfgang; Picker-Freyer, Katharina M

2009-05-01

221

21 CFR 520.928 - Firocoxib tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Firocoxib tablets. 520.928 Section 520...FORM NEW ANIMAL DRUGS § 520.928 Firocoxib tablets. (a) Specifications ...tablet contains 57 or 227 milligrams (mg) firocoxib. (b) Sponsor . See No....

2010-04-01

222

21 CFR 520.928 - Firocoxib tablets.  

Code of Federal Regulations, 2010 CFR

...2009-04-01 2009-04-01 false Firocoxib tablets. 520.928 Section 520...FORM NEW ANIMAL DRUGS § 520.928 Firocoxib tablets. (a) Specifications ...tablet contains 57 or 227 milligrams (mg) firocoxib. (b) Sponsor . See No....

2009-04-01

223

Pharmacological analysis of certain mechanisms of morphine addiction.  

PubMed

The effects of L-Dopa, Methysergid, Diphenhydramine hydrochloride and LSD on the development of morphine dependence and the abstience syndrome after its withdrawal, were tested in experiments on 200 male Wistar albino rats. L-Dopa had no efect on the development of physical morphine dependence, while Methysergid prevented its development. Applied in rats during the abstinence syndrome, LSD intensified their aggressivity with no influence on the analgesic effect of morphine. Diphenhydramine reduced the aggressiveness of the rats during the abstinence syndrome. Biochemical tests show that in morphine-tolerant rats there was an increase in the content of brain serotonin, less of dopamine and no changes in noradrenaline. The significance of the brain levels of serotonin, dopamine and noradrenaline for the development of physical morphine-dependence is discussed. It is pointed out that serotonin and dopamine play an important role both for the origin of the physical morphine dependence, and in the abstinence syndrome after its withdrawal. PMID:1035029

Ovcharov, R; Bantoutova, I; Kobourova, K

1976-01-01

224

A comparison of ibuprofen arginine with morphine sulphate for pain relief after orthopaedic surgery.  

PubMed

In a randomized, double-blind, double-dummy, single-dose, parallel-group study, oral ibuprofen arginine (400 mg) was compared with intramuscular (i.m.) morphine sulphate (5 or 10 mg) for post-operative pain relief after orthopaedic surgery in 120 patients. The study medication was administered post-operatively at the time when each patient first requested pain relief for moderate to severe pain. Assessment of pain intensity and pain relief was made using standard visual analogue scales and verbal rating scores. In all three groups, there was a reduction in pain compared with baseline, measured by visual analogue scales and verbal rating scores, at all time points up to completion of the study at 240 min. For example, visual analogue scales decreased by 35 (10-52) mm at 1 h in the morphine 5 mg group, 24 (12-39) mm in morphine 10 mg group and 21 (8-38) mm in the ibuprofen arginine group (median and inter-quartile range). Verbal rating scores showed a similar pattern. Comparing the groups over the whole study period using the sum of pain intensity differences showed no significant differences in pain experience between the groups. Assessment of total pain relief also showed no significant differences. The incidence and types of side effect seen were similar in the three groups. PMID:8889425

Mansfield, M; Firth, F; Glynn, C; Kinsella, J

1996-09-01

225

Comparison of Preference for Rizatriptan 10-mg Wafer versus Sumatriptan 50-mg Tablet in Migraine  

Microsoft Academic Search

Rizatriptan (MAXALTTM, a registered trademark of Merck & Co. Inc.) is a selective 5-HT1B\\/1D receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized, open-label, crossover outpatient study assessed the preference of 481 patients for rizatriptan 10-mg rapidly disintegrating tablets versus sumatriptan (IMIGRANTM, a registered trademark of GlaxoWellcome PLC) 50-mg tablets

Julio Pascual; Gennaro Bussone; Jose Fernando Hernandez; Christopher Allen; Krupa Patel

2001-01-01

226

Preparation and evaluation of buccal bioadhesive tablets containing clotrimazole.  

PubMed

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

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

2008-04-01

227

The role of morphine in regulation of cancer cell growth  

Microsoft Academic Search

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

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

228

Sedation in intensive care: morphine and renal function  

Microsoft Academic Search

Intravenous morphine infusions have been administered to 12 critically-ill patients during controlled ventilation. Acute oliguric renal failure was present in 4 patients, who were treated with a combination of haemofiltration and haemodialysis. Severity of physiological disturbance was assessed using a modified APACHE Score, level of sedation by a linear-analogue scale, and blood morphine levels by high-pressure liquid chromatography. Morphine clearance

J. F. Bion; B. K. Logan; P. M. Newman; M. J. Brodie; J. S. Oliver; T. C. Aitchison; I. Mc A. Ledingham

1986-01-01

229

Effects of morphine on the human sphincter of Oddi  

Microsoft Academic Search

The effects of morphine on intraluminal pressures recorded from the sphincter of Oddi (SO) at endoscopic retrograde cholangiopancreatography in 19 patients who were without evidence of biliary or pancreatic disease were studied. Morphine was given in four successive doses of 2.5, 2.5, 5, and 10 micrograms\\/kg iv at five minute intervals. Morphine in subanalgesic doses increased the frequency of SO

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

1988-01-01

230

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

PubMed

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

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

2014-09-10

231

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

PubMed Central

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

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

2012-01-01

232

Cingulate metabolites during pain and morphine treatment as assessed by magnetic resonance spectroscopy  

PubMed Central

Background Experimental investigation of cerebral mechanisms underlying pain and analgesia are important in the development of methods for diagnosis and treatment of pain. The aim of the current study was to explore brain metabolites in response to pain and treatment with morphine. Methods Proton magnetic resonance spectroscopy of the anterior cingulate cortex was performed in 20 healthy volunteers (13 males and seven females, aged 24.9±2.6 years) during rest and acute pain before and during treatment with 30 mg of oral morphine or placebo in a randomized, double-blinded, cross-over study design. Pain was evoked by skin stimulation applied to the right upper leg using a contact heat-evoked potential stimulator. Results Data from 12 subjects were valid for analysis. Painful stimulation induced an increase in N-acetylaspartate/creatine compared with rest (F=5.5, P=0.04). During treatment with morphine, painful stimulation induced decreased glutamate/creatine (F=7.3, P=0.02), myo-inositol/creatine (F=8.38, P=0.02), and N-acetylaspartate/creatine (F=13.8, P=0.004) concentrations, whereas an increase in the pain-evoked N-acetylaspartate/creatine concentration (F=6.1, P=0.04) was seen during treatment with placebo. Conclusion This explorative study indicates that neuronal metabolites in the anterior cingulate cortex, such as N-acetylaspartate, glutamate, and myo-inositol, could be related to the physiology of pain and treatment with morphine. This experimental method has the potential to enable the study of brain metabolites involved in pain and its treatment, and may in the future be used to provide further insight into these mechanisms.

Hansen, Tine Maria; Olesen, Anne Estrup; Simonsen, Carsten Wiberg; Drewes, Asbj?rn Mohr; Fr?kjaer, Jens Br?ndum

2014-01-01

233

The Neurodevelopmental Impact of Neonatal Morphine Administration  

PubMed Central

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.

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

2014-01-01

234

The neurodevelopmental impact of neonatal morphine administration.  

PubMed

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

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

2014-01-01

235

Pharmacokinetics study of bio-adhesive tablet of Panax notoginseng saponins  

PubMed Central

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

2011-01-01

236

Morphine and tumor growth and metastasis  

Microsoft Academic Search

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

Banafsheh Afsharimani; Peter Cabot; Marie-Odile Parat

2011-01-01

237

A therapeutic strategy to prevent morphine dependence and tolerance by coadministration of cAMP-related reagents with morphine.  

PubMed

Morphine is the most potent opioid analgesic currently available and its use is increasing for treatment of severe pain, however, long-term morphine exposure induces physical dependence/tolerance. Although the mechanisms underlying this phenomenon have not been established, several biochemical changes including intracellular cAMP systems and Ca2+ mobilization have been suggested. To evaluate the contribution of cAMP, we investigated the effects of nefiracetam [N-(2,6-dimethyl-phenyl)-2(2-oxo-1-pyrrolidinyl)acetamide] and phosphodiesterase inhibitors (theophylline, enprofylline and rolipram) on the development of morphine dependence/tolerance. Mice administered morphine (6 or 10 mg/kg, s.c.) twice daily for 5 days, showed withdrawal signs (jumping, diarrhea and body weight loss) after naloxone challenge (5 mg/kg, i.p.), indicating the physical dependence to morphine. Further, the tolerance to antinociceptive effect of morphine was observed in these mice on the tail-flick test. However, coadministration of nefiracetam (5 or 10 mg/kg, p.o.), enprofylline (30 mg/kg, p.o.) and rolipram (0.3 or 1 mg/kg, i.p.) with morphine during the pretreatment period, significantly reduced the withdrawal signs, moreover, the tolerance was significantly attenuated. Acute administration of nefiracetam failed to reduce the withdrawal signs and did not affect the antinociceptive effect of morphine in morphine-naive mice. Theophylline (3 or 10 mg/kg, p.o.) tended to attenuate the development of morphine dependence/tolerance. The present findings suggest that coadministration of compounds which increase cAMP level with morphine may be a useful strategy to attenuate the development of morphine dependence/tolerance in the clinic. PMID:9819808

Itoh, A; Noda, Y; Mamiya, T; Hasegawa, T; Nabeshima, T

1998-09-01

238

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

PubMed

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

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

2013-01-01

239

Optimisation of floating matrix tablets and evaluation of their gastric residence time.  

PubMed

The present investigation concerns the development of the floating matrix tablets, which after oral administration are designed to prolong the gastric residence time, increase the drug bioavailability and diminish the side effects of irritating drugs. The importance of the composition optimisation, the technological process development for the preparation of the floating tablets with a high dose of freely soluble drug and characterisation of those tablets (crushing force, floating properties in vitro and in vivo, drug release) was examined. Tablets containing hydroxypropyl methylcellulose (HPMC), drug and different additives were compressed. The investigation shows that tablet composition and mechanical strength have the greatest influence on the floating properties and drug release. With the incorporation of a gas-generating agent together with microcrystalline cellulose, besides optimum floating (floating lag time, 30 s; duration of floating, >8 h), the drug content was also increased. The drug release from those tablets was sufficiently sustained (more than 8 h) and non-Fickian transport of the drug from tablets was confirmed. Radiological evidence suggests that, that the formulated tablets did not adhere to the stomach mucus and that the mean gastric residence time was prolonged (>4 h). PMID:10675690

Baumgartner, S; Kristl, J; Vrecer, F; Vodopivec, P; Zorko, B

2000-02-15

240

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

PubMed

1. Morphine 6-glucuronide (M6G) is a metabolite of morphine with analgesic activity. A double-blind, randomised comparison of the effects of morphine and M6G on respiratory function was carried out in 10 normal subjects after i.v. morphine (10 mg 70 kg-1) or M6G (1, 3.3 and 5 mg 70 kg-1). Analgesic potency was also assessed using an ischaemic pain test and other toxic effects were monitored. 2. Following morphine there was a significant increase in arterial PCO2, as measured by blood gases 45 min post dose (0.54 +/- 0.24 (s.d.) kPa, P < 0.001), and in transcutaneous PCO2 from 15 min post dose until the end of the study period (4 h), whereas blood gas and transcutaneous PCO2 were unchanged after M6G at 1.0, 3.3 and 5.0 mg 70 kg-1. This increased PCO2 following morphine was associated with an increase in expired CO2 concentration (FECO2) (0.20 +/- 0.14% expired air at 15 min post dose, P = 0.002), compared with small but significant reductions in FECO2 following morphine 6-glucuronide (-0.15 +/- 0.17% at 1 mg 70 kg-1 P = 0.030, -0.14 +/- 0.15% at 3.3 mg 70 kg-1 P = 0.017, -0.18 +/- 0.11% at 5 mg 70 kg-1 P = 0.024). Maximum transcutaneous PCO2 was significantly increased after morphine (0.63 +/- 0.28 kPa P = 0.009), but was not changed after M6G at 1 mg (0.10 +/- 0.34 kPa P = 0.11) 3.3 mg (0.06 +/- 0.37 kPa P = 0.34) or 5 mg (0.26 +/- 0.07 kPa P = 0.10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8562297

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

1995-08-01

241

Bioequivalence testing of a new tablet formulation of generic fluoxetine  

Microsoft Academic Search

Summary  The pharmacokinetics and relative bioavailability of fluoxetine capsules (reference) and tablets (test) were compared in 24\\u000a healthy subjects of both sexes after a single 20 mg oral dose of fluoxetine (as a hydrochloride salt).\\u000a \\u000a \\u000a A randomized, crossover design with a 2-week wash-out period between each dose was applied. Serum samples, obtained before\\u000a dosing and at various appropriate time points up

D. Jovanovi?; V. KILIBARDAI; S. DORDEVICI; M. JOVANOVICz; J. JOVIC-STOSICz; D. Srdi?; T. Kneževi?

2006-01-01

242

Morphine and alternative opioids in cancer pain: the EAPC recommendations  

Microsoft Academic Search

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

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

2001-01-01

243

Tests for addiction (chronic intoxication) of morphine type  

PubMed Central

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

Halbach, H.; Eddy, Nathan B.

1963-01-01

244

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

Microsoft Academic Search

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

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

1996-01-01

245

21 CFR 520.1510 - Nitenpyram tablets.  

Code of Federal Regulations, 2010 CFR

...nitenpyram tablets and flavored milbemycin/lufenuron tablets as in paragraph (d)(1...of this section with either flavored lufenuron tablets as in § 520.1288(c)(1) of this chapter or flavored milbemycin and lufenuron tablets as in §...

2010-04-01

246

21 CFR 520.1510 - Nitenpyram tablets.  

Code of Federal Regulations, 2010 CFR

...nitenpyram tablets and flavored milbemycin/lufenuron tablets as in paragraph (d)(1...of this section with either flavored lufenuron tablets as in § 520.1288(c)(1) of this chapter or flavored milbemycin and lufenuron tablets as in §...

2009-04-01

247

Continuous morphine produces more tolerance than intermittent or acute treatment.  

PubMed

Dosing protocol and analgesic efficacy have been proposed to be important determinants of the magnitude of opioid tolerance. The present study examined the effect of acute, intermittent and continuous treatment with the low analgesic efficacy agonist morphine on analgesic tolerance. Mice were implanted s.c. with a 25 mg morphine pellet for 1-7 days. Other mice were implanted s.c. with two 25 mg, or one 75 mg morphine pellet for 7 days. The release of morphine from subcutaneous implanted pellets was quantitated using a spectrophotometric assay. In other studies, mice were injected with morphine once (18.5-185 mg/kg/day; approximately 10-100 times ED(50) for morphine analgesia) or once/day for 7 days. Controls were implanted with a placebo pellet or injected with saline. Analysis of drug release from a 25 mg pellet indicated that release was greatest during the first 24 h, declined and then remained relatively constant. The amount of morphine released over 7 days by a 75 mg pellet (23.9 mg) was more than that of a single 25 mg pellet (15.4 mg) but less than two 25 mg pellets (30.8 mg). Following treatment, morphine cumulative dose-response studies were conducted (tail flick). Continuous treatment with morphine using pellet implantation produced a dose-dependent shift in the morphine ED(50) by 3.3, 5.8 and 8.5 fold for one 25 mg pellet, one 75 mg pellet and two 25 mg pellets, respectively. Acute and intermittent morphine administration produced substantially less analgesic tolerance than continuous release of morphine by implant pellets. The maximum shift in the ED(50) was 1.6 for acute treatment and 2.7 for 7 day intermittent treatment; despite a larger total daily dose. The present results indicate that continuous treatment with morphine results in greater analgesic tolerance than acute or intermittent morphine treatment even at comparable daily doses. These results are consistent with the suggestion that intermittent dosing has reduced risk of producing opioid tolerance. PMID:19248799

Dighe, Shveta V; Madia, Priyanka A; Sirohi, Sunil; Yoburn, Byron C

2009-05-01

248

[Research progress on the oral solid rapidly disintegrating dosage form].  

PubMed

Oral solid rapidly-disintegrating dosage form has aroused general concern increasingly because of its characteristics about convenient taking, rapid absorption, high bioavailability and not serious adverse drug reaction. This article introduced its mechanism, which was rapid disintegration, fast dissolution or the promoting dissolving action of supplementary material. This dosage form included dispersible tablets, fast dissolving tablets, fast releasing tablets, droppills, granules and tablets by solid dispersible technology, quick-liquefying chewable tablets and dry elixir. It will become a new way for promoting bioavailability in traditional Chinese medicine difficultly-dissolving composition, create up a new dosage form for treating emergency case by traditional Chinese medicine and give a new thinking for studying new supplementary materials. In brief, oral solid rapidly-disintegrating dosage form will have good prospect in the field of traditional Chinese medicine. PMID:15714807

Shen, Lan; Lin, Xiao; Xu, De-sheng; Feng, Yi

2005-01-01

249

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

Code of Federal Regulations, 2013 CFR

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

2013-04-01

250

21 CFR 520.623 - Diethylcarbamazine citrate, oxibendazole chewable tablets.  

Code of Federal Regulations, 2013 CFR

...false Diethylcarbamazine citrate, oxibendazole chewable tablets. 520.623 Section 520.623 Food and Drugs...623 Diethylcarbamazine citrate, oxibendazole chewable tablets. (a) Specifications. Each tablet...

2013-04-01

251

21 CFR 520.623 - Diethylcarbamazine citrate, oxibendazole chewable tablets.  

Code of Federal Regulations, 2010 CFR

...false Diethylcarbamazine citrate, oxibendazole chewable tablets. 520.623 Section 520.623 Food and Drugs...623 Diethylcarbamazine citrate, oxibendazole chewable tablets. (a) Specifications. Each tablet...

2009-04-01

252

Experimental mononeuropathy reduces the antinociceptive effects of morphine: implications for common intracellular mechanisms involved in morphine tolerance and neuropathic pain  

Microsoft Academic Search

Recent evidence suggests that hyperalgesia and morphine tolerance, two seemingly unrelated phenomena, have in common certain neural substrates such as activation of the N-methyl-d-aspartate (NMDA) receptor and the subsequent intracellular activation of protein kinase C and nitric oxide. Should common cellular elements be involved in hyperalgesia and morphine tolerance, these cellular and intracellular commonalities might be expected to result in

Jianren Mao; Donald D. Price; David J. Mayer

1995-01-01

253

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

PubMed

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

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

2011-01-01

254

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

PubMed Central

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

Wallace, Mark; Yaksh, Tony L.

2012-01-01

255

Effects of morphine on the turnover of brain catecholamines and serotonin in rats-acute morphine administration.  

PubMed

Morphine increased the rate of brain dopamine (DA) depletion when given before alpha-methyl-p-tyrosine (AMT) or alpha-propyl-dopacetamide, but not when given after AMT. No effect of morphine was found on the rate of depletion of brain noradrenaline (NA) or serotonin (5-HT) after the two synthesis inhibitors. The accumulation of homovanillic acid and 5-hydroxy-indoleacetic acid induced by probenecid was significantly increased by morphine pretreatment, whereas the accumulation of 3-methoxy-4-hydroxy-phenylglycol sulphate was not changed. These findings can be best explained by the hypothesis that morphine increases the non-functional intraneuronal catabolism of newly synthesized DA and 5-HT, without much effect on the monoamines already taken up in the synaptic vesicles. NA turnover does not seem to be changed by acute morphine administration. PMID:791658

Papeschi, R; Theiss, P; Herz, A

1975-12-01

256

PolyMorphine: an innovative biodegradable polymer drug for extended pain relief  

PubMed Central

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

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

2012-01-01

257

Alkaloids; Strychnine, Codeine, Heroin, and Morphine  

NSDL National Science Digital Library

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

258

Formulation, Characterization and Physicochemical Evaluation of Ranitidine Effervescent Tablets  

PubMed Central

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

Aslani, Abolfazl; Jahangiri, Hajar

2013-01-01

259

Formulation, characterization and physicochemical evaluation of ranitidine effervescent tablets.  

PubMed

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

Aslani, Abolfazl; Jahangiri, Hajar

2013-01-01

260

Risedronate-loaded Eudragit S100 microparticles formulated into tablets.  

PubMed

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

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

2014-05-01

261

Morphine suppresses intracellular interferon-? expression in neuronal cells?  

PubMed Central

Interferon alpha (IFN-?) not only plays a key role in innate host immunity against infections but also is involved in the cellular functions of the central nervous system (CNS). In this study, we examined the impact of morphine on IFN-? expression in human neuronal cells (NT2-N). Similar to human immune cells, NT2-N cells also expressed IFN-? at both mRNA and protein levels. IFN-? expression in NT2-N cells, however, was inhibited by morphine. Naltrexone antagonized the inhibitory effect of morphine on IFN-? expression in NT2-N cells. The specific mu opioid receptor antagonist, Cys2, Tyr3, Arg5, Pen7-amide (CTAP), also blocked the morphine action on intracellular IFN-? expression. Investigation of the mechanisms involved in the morphine action showed that although morphine had little effect on the expression of key IFN regulatory factors (IRFs), morphine inhibited IFN-? promoter activation and suppressed the expression and phosphorylation of signal transducer and activator of transcription 1 (STAT1) in the neuronal cells. These findings provide direct in vitro evidence that opioids may impair neuronal cell-mediated innate protection in the CNS.

Wan, Qi; Wang, Xu; Wang, Yan-Jian; Song, Li; Wang, Shi-Hong; Ho, Wen-Zhe

2008-01-01

262

Micturition in naive and morphine-dependent rats.  

PubMed Central

Voiding responses were recorded in conscious water-loaded rats. Morphine sulphate (5 mg kg-1) elevated the volume threshold for micturition (MV); the group mean MV of 16 rats after morphine was 40% larger than control. Micturition was nevertheless complete since no urine remained in the bladder afterwards. The implantation of 2 or 4 morphine-base pellets (150 or 300 mg morphine) elevated for 12 days the MV in water-loaded rats. On the 3rd to the 10th day following implantation the group mean was approximately twice that of untreated controls. After micturition was over no residual urine was found in the bladder. Within 3 days the rats became tolerant to the antinociceptive action of the morphine-base pellets but little apparent tolerance developed to their action on micturition. On the 1st day after the pellets were removed, the mean MV was reduced. When withdrawal was precipitated by the administration of naloxone the MV was often too small to measure. This component of a withdrawal syndrome could be elicited in the rats throughout the 12 days of morphine pellet implantation. The administration of 20 mg kg-1 morphine sulphate to anaesthetized rats did not decrease the contractions of the urinary bladder to repetitive stimulation of its motor nerves at 1 and 20 Hz.

Carpenter, F. G.

1986-01-01

263

Powerful Behavioral Interactions Between Methamphetamine and Morphine  

PubMed Central

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

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

2011-01-01

264

Bioequivalence study of ranitidine tablet  

Microsoft Academic Search

A bioequivalence study of ranitidine tablets was conducted according to the Korean Guidline for the Bioequivalence Test using\\u000a twelve healthy male subjects. The plasma concentration-time curves of ranitidine from the test and reference tablets showed\\u000a profound multiple peak phenomenon in each, subject as reported earlier. However, the area under the plasma concentration-time\\u000a curve (AUC) and the maximum plasma concentration at

Chang-Koo Shimw; Jae-Sun Hong; Chang-Ki Lee; Ik-Soo Han; Kwang-Sik Choi

1990-01-01

265

Effects of morphine and naloxone on feline colonic transit  

SciTech Connect

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

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

1989-01-01

266

Stress antagonizes morphine-induced analgesia in rats  

NASA Technical Reports Server (NTRS)

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

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

1981-01-01

267

Recent Advances in the Synthesis of Morphine and Related Alkaloids  

NASA Astrophysics Data System (ADS)

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

Chida, Noritaka

268

Methamphetamine and Amphetamine Pharmacokinetics in Oral Fluid and Plasma after Controlled Oral Methamphetamine Administration to Human Volunteers  

Microsoft Academic Search

Background: Methamphetamine (METH) and amphet- amine (AMP) concentrations in 200 plasma and 590 oral fluid specimens were used to evaluate METH pharma- cokinetics and pharmacodynamics after oral administra- tion of sustained-release METH. Methods: Eight participants received four oral 10-mg S-()-METH hydrochloride sustained-release tablets within 7 days. Three weeks later, five participants received four oral 20-mg doses. Blood samples were collected

Raf J. F. Schepers; Jonathan M. Oyler; Robert E. Joseph; Edward J. Cone; Eric T. Moolchan; Marilyn A. Huestis

269

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

PubMed Central

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

Eidson, Lori N.

2013-01-01

270

Mechanical property characterization of bilayered tablets using nondestructive air-coupled acoustics.  

PubMed

A noncontact/nondestructive air-coupled acoustic technique to be potentially used in mechanical property determination of bilayer tablets is presented. In the reported experiments, a bilayer tablet is vibrated via an acoustic field of an air-coupled transducer in a frequency range sufficiently high to excite several vibrational modes (harmonics) of the tablet. The tablet vibrational transient responses at a number of measurement points on the tablet are acquired by a laser vibrometer in a noncontact manner. An iterative computational procedure based on the finite element method is utilized to extract the Young's modulus, the Poisson's ratio, and the mass density values of each layer material of a bilayer tablet from a subset of the measured resonance frequencies. For verification purposes, a contact ultrasonic technique based on the time-of-flight data of the longitudinal (pressure) and transverse (shear) acoustic waves in each layer of a bilayer tablet is also utilized. The extracted mechanical properties from the air-coupled acoustic data agree well with those determined from the contact ultrasonic measurements. The mechanical properties of solid oral dosage forms have been shown to impact its mechanical integrity, disintegration profile and the release rate of the drug in the digestive tract, thus potentially affecting its therapeutic response. The presented nondestructive technique provides greater insight into the mechanical properties of the bilayer tablets and has the potential to identify quality and performance problems related to the mechanical properties of the bilayer tablets early on the production process and, consequently, reduce associated cost and material waste. PMID:20063078

Akseli, Ilgaz; Dey, Dipankar; Cetinkaya, Cetin

2010-03-01

271

Chronic Morphine’s Role on Innate Immunity, Bacterial Susceptibility and Implications in Wound Healing  

Microsoft Academic Search

\\u000a Opioids are considered the gold standard in treating pain. Patients who are prescribed morphine for the management of chronic\\u000a pain also present themselves with complications such as increased susceptibility to opportunistic infections and inadequate\\u000a healing of wounds. Yet, an in vivo model useful in elucidating mechanisms’ underlying this phenomenon has not been established.\\u000a \\u000a \\u000a Through the standardization of an in vivo

Josephine Martin; Sabita Roy

272

Comparative study of epidural application of morphine versus gelfoam soaked in morphine for lumbar laminectomy  

PubMed Central

Background: Epidural application of morphine has been used for postoperative analgesia following spine surgery but short duration of action of single application limits its widespread use. Materials and Methods: One hundred and fifty patients undergoing lumbar laminectomy were randomly allocated to two groups of 75 patients each. Anesthetic technique was standardized in both the groups. In Group I, at the completion of laminectomy, a 5 × 1-cm strip of gelfoam soaked in 5 mg morphine (1 mg/ml) was contoured to be placed in the epidural space whereas, in group II, gelfoam soaked in saline was placed in the epidural space and 5 mg morphine (1mg/ml) was instilled over the intact epidural space. Analgesic consumption for 48 hours, time-of first analgesic request, time of ambulation, time of discharge from post anesthesia care unit (PACU) and hospital and adverse effects were recorded. The data was analyzed using appropriate statistical tests. Results: Mean analgesic consumption in 48 hours was significantly less in group I (8.47 ± 3.674 mg) as compared to group II (24.80 ± 6.009 mg). Supplemental analgesia was requested at 30.03 ± 6.796 hours in Group I, vs 10.25 ± 2.243 in group II (P < 0.001). Group I patients were discharged earlier from PACU as compared to group II (P < 0.001) though time of discharge from hospital was similar in both the groups. There were no major adverse effects except pruritis, which was observed in 30.6% patients in group I and 37.3% in group II (statistically insignificant (P > 0.01)). Conclusion: Epidural application of morphine soaked in gelfoam is an effective method for prolonging the postoperative analgesia after spine surgery.

Kundra, Sandeep; Gupta, Vishnu; Bansal, Hanish; Grewal, Anju; Katyal, Sunil; Choudhary, Ashwini Kumar

2014-01-01

273

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

Microsoft Academic Search

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

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

2010-01-01

274

Disintegration of magnetic tablets in human stomach evaluated by alternate current Biosusceptometry  

Microsoft Academic Search

Oral administration is the most convenient route for drug therapy. The knowledge of the gastrointestinal transit and specific site for drug delivery is a prerequisite for development of dosage forms. The aim of this work was to demonstrate that is possible to monitor the disintegration process of film-coated magnetic tablets by multi-sensor alternate current Biosusceptometry (ACB) in vivo and in

Luciana A. Corá; Madileine F. Américo; Ricardo Brandt Oliveira; Oswaldo Baffa; Rogério Moraes; Fernando G. Romeiro; José Ricardo A. Miranda

2003-01-01

275

Intraarticular morphine administration provides pain relief after knee arthroscopy.  

PubMed

This present study investigated the effects of intraarticular morphine administration in 1 mg and 5 mg doses on post-operative pain relief and analgesic requirements for patients undergoing arthroscopic procedures. At the end of the operation patients were randomly allocated in a double-blinded fashion into three groups. The control group (Group 1) received normal saline 20 mL intraarticularly. The patients in the second and third groups received intraarticular morphine sulphate 1 and 5 mg in saline 20 mL, respectively. Post-operative pain was assessed on the 1st, 6th and 24th hour by visual analogue scale (VSA). Supplementary analgesic requirement and possible complications were also followed. The intensity of pain and analgesic requirement were reduced more in the morphine 5 mg group than in the control group. It is concluded, that the administration of intraarticular morphine 5 mg provides long-lasting and effective analgesia after knee arthroscopy. PMID:9088813

Kanbak, M; Akpolat, N; Ocal, T; Doral, M N; Ercan, M; Erdem, K

1997-03-01

276

Physical dependence to morphine diminishes the interferon response in mice.  

PubMed

Morphine pellet implantation in mice was demonstrated to diminish resistance to encephalomyocarditis virus infections. The variations in the response to three different interferon (IFN) inducers--Newcastle disease virus, Escherichia coli lipopolysaccharide and a tilorone analogue--were evaluated. A close relationship between morphine dependence and IFN response was detected. A clear inhibition in IFN induction appeared as a concomitant phenomenon with the syndrome of morphine dependence. In the response intensity, the mice strain tested was more important than the total drug dose in the pellet. This effect of morphine on IFN responses presented a characteristic age-related pattern and, perhaps, may also be influenced by the H-2 murine phenotype. PMID:2448267

Lorenzo, P; Portolés, A; Beneit, J V; Ronda, E; Portolés, A

1987-01-01

277

[Detection of morphine after ingestion of poppy seeds].  

PubMed

The aim of this study was to investigate whether morphine can be detected in urine after the ingestion of poppy seeds bought in Denmark. Morphine and codeine were determined in 10 different poppy seed specimens bought in Denmark. Ten and 25 g of the specimens containing the highest amount of morphine and codeine were consumed by respectively six and seven volunteers. Urine samples were collected for analysis at intervals up to 24 h. All samples were found positive by radioimmunoassay up to 24 h after ingestion. Using the less sensitive thin layer chromatography method, one of six and two of seven were positive, two to four hours after intake of respectively 10 and 25 g of the specimens. We conclude that the detection of morphine in urine does not necessarily indicate an illegal drug use. PMID:8273217

Angelo, H R; Kaa, E

1993-12-01

278

Herpes - oral  

MedlinePLUS

... HSV-2 is spread to the mouth during oral sex, causing oral herpes. Herpes viruses spread easily. You ... if someone has oral herpes. Do not have oral sex if you have oral herpes, especially if you ...

279

Morphine glucuronidation in human fetal and adult liver  

Microsoft Academic Search

Summary  The glucuronyltransferase activity towards morphine was measured in microsomes isolated from liver specimens obtained from\\u000a human fetuses and cancer patients. All the fetal livers investigated had measurable UDP-glucuronyltransferase activity towards\\u000a morphine. There was no correlation between the gestational age (15 to 27 weeks) and the glucuronidation rate. The mean value\\u000a of the enzymatic activities was higher in fetal livers obtained

G. M. Pacifici; J. Säwe; L. Kager; A. Rane

1982-01-01

280

Epidural morphine for outpatients with severe anginal pain.  

PubMed Central

Seven patients who had chronic coronary artery disease and had undergone coronary artery bypass surgery still suffered from anginal attacks several times daily despite optimal medical treatment. An epidural system of analgesia was implanted subcutaneously and treatment with epidural morphine started. The morphine was administered by the patients themselves or members of their family. During a median observation time of four months (range three to 11) all patients were free of pain while receiving this treatment. Images p476-a

Clemensen, S E; Thayssen, P; Hole, P

1987-01-01

281

E-Books and the Tablet PC.  

ERIC Educational Resources Information Center

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

Goodwin-Jones, Bob

2003-01-01

282

21 CFR 520.1310 - Marbofloxacin tablets.  

Code of Federal Regulations, 2010 CFR

...2009-04-01 2009-04-01 false Marbofloxacin tablets. 520.1310 Section 520...FORM NEW ANIMAL DRUGS § 520.1310 Marbofloxacin tablets. (a) Specifications ...50, 100, or 200 milligrams (mg) marbofloxacin. (b) Sponsor. See No....

2009-04-01

283

21 CFR 520.1310 - Marbofloxacin tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Marbofloxacin tablets. 520.1310 Section 520...FORM NEW ANIMAL DRUGS § 520.1310 Marbofloxacin tablets. (a) Specifications ...50, 100, or 200 milligrams (mg) marbofloxacin. (b) Sponsor. See No....

2010-04-01

284

21 CFR 520.1380 - Methocarbamol tablets.  

Code of Federal Regulations, 2013 CFR

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

2013-04-01

285

[Technology and analysis of "Askoeziuofito" tablets].  

PubMed

The objective of this work is to produce chewable tablets out of Echinacea purpurea liquid extract (1:1) and ascorbic acid: to create the technology, to select methods of analysis and to examine stability. The paper describes the technology of tablets: a method of condensation is chosen; the influence of additional substances over tableting is established; pressing characteristics of tableting mixtures are examined. The quality of tablets is evaluated in terms of appearance and technological rates: average tablet mass, hardness against pressure, hardness against wearing, time of disintegration, and speed of ascorbic acid secretion. The identity of ascorbic acid, ferments and hydroxycinamon acid was established. Quantities of ascorbic and chicory acids were defined. The tablets produced were named "Askoeziuofito" tablets. The name consists of abbreviated terms of ascorbic acid, Echinacea plant and phytochemical preparation. PMID:14617854

Bernatoniene, Jurga; Savickiene, Nijole; Savickas, Ar?nas; Bernatonis, Domininkas

2003-01-01

286

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

PubMed

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

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

2013-03-13

287

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

PubMed

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. PMID:22252547

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

2012-10-01

288

Galileo's Telescopy and Jupiter's Tablet  

NASA Astrophysics Data System (ADS)

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

Usher, P. D.

2003-12-01

289

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

PubMed Central

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

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

2014-01-01

290

Topographic Characterization of Cellulose Bilayered Tablets Interfaces  

Microsoft Academic Search

The introduction of bilayer tablets into the pharmaceutical industry has enabled the development of pre-determined release profiles of active ingredients. During production, however, these bilayer tablets have the tendency to fracture by capping, thought to be caused by internal tensile stresses normal to the plane of fracture. Bi-layered tablets of the widely used excipient microcrystalline cellulose (MCC) have been manufactured

S. J. Inman; B. J. Briscoe; K. G. Pitt

2007-01-01

291

Mathematics Instruction and the Tablet PC  

ERIC Educational Resources Information Center

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

Fister, K. Renee; McCarthy, Maeve L.

2008-01-01

292

Tablet - next generation sequence assembly visualization  

Microsoft Academic Search

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

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

2010-01-01

293

Scaffolding Equals Success in Teaching Tablet PCs  

ERIC Educational Resources Information Center

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

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

2009-01-01

294

Fast Dissolving Tablets of Aloe Vera Gel  

Microsoft Academic Search

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

Jyotsana Madan; AK Sharma; Ramnik Singh

295

Augmentation of Morphine-Induced Sensitization but Reduction in Morphine Tolerance and Reward in Delta-Opioid Receptor Knockout Mice  

PubMed Central

Studies in experimental animals have shown that individuals exhibiting enhanced sensitivity to the locomotor-activating and rewarding properties of drugs of abuse are at increased risk for the development of compulsive drug-seeking behavior. The purpose of the present study was to assess the effect of constitutive deletion of delta-opioid receptors (DOPr) on the rewarding properties of morphine as well as on the development of sensitization and tolerance to the locomotor-activating effects of morphine. Locomotor activity testing revealed that mice lacking DOPr exhibit an augmentation of context-dependent sensitization following repeated, alternate injections of morphine (20 mg/kg; s.c.; 5 days). In contrast, the development of tolerance to the locomotor-activating effects of morphine following chronic morphine administration (morphine pellet: 25 mg: 3 days) is reduced relative to WT mice. The conditioned rewarding effects of morphine were reduced significantly in DOPrKO mice as compared to WT controls. Similar findings were obtained in response to pharmacological inactivation of DOPr in WT mice, indicating that observed effects are not due to developmental adaptations that occur as a consequence of constitutive deletion of DOPr. Together, these findings indicate that the endogenous DOPr system is recruited in response to both repeated and chronic morphine administration and that this recruitment serves an essential function in the development of tolerance, behavioral sensitization, and the conditioning of opiate reward. Importantly, they demonstrate that DOPr has a distinct role in the development of each of these drug-induced adaptations. The anti-rewarding and tolerance-reducing properties of DOPr antagonists may offer new opportunities for the treatment and prevention of opioid dependence as well as for the development of effective analgesics with reduced abuse liability.

Chefer, VI; Shippenberg, TS

2008-01-01

296

Finasteride, a 5alpha-reductase inhibitor, potentiates antinociceptive effects of morphine, prevents the development of morphine tolerance and attenuates abstinence behavior in the rat.  

PubMed

It has been shown that morphine increases 5alpha-reductase enzyme activity in the rat central nervous system; however importance of this finding on morphine analgesia, tolerance and dependence has not been reported. In the present study, we investigated inhibition of 5alpha-reductase enzyme on morphine effects using finasteride. To determine whether the 5alpha-reductase enzyme interact with morphine analgesia, finasteride (5 mg/kg, i.p.) was administrated with morphine (5 and 7 mg/kg, i.p.). The tail-flick test was used to assess the nociceptive threshold, before and 15, 30, 45, 60 and 90 min after drug administration. In tolerance experiments, morphine 20 mg/kg was injected i.p., twice daily for 4 days. The development and expression of dependence were assessed in the naloxone precipitation test 5 days after the morphine (20-30 mg/kg, i.p.) administration. We found that finasteride could potentiate the antinociceptive effect of morphine. In addition, chronic finasteride administration effectively blocked development of tolerance and dependence to morphine. Following chronic morphine administration, single dose injection of finasteride failed to reverse tolerance but prevented naloxone precipitate withdrawal syndrome. Therefore, it was concluded that there is a functional relationship between 5alpha-reductase enzyme and morphine. PMID:17428486

Verdi, Javad; Ahmadiani, Abolhassan

2007-05-01

297

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

PubMed

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

Abdelbary, Ghada; Amin, Maha; Salah, Salwa

2013-01-01

298

Esophageal transit of risedronate cellulose-coated tablet and gelatin capsule formulations.  

PubMed

Risedronate sodium is an orally active antiresorptive agent and a member of the pyridinyl class of bisphosphonates. It has been approved for the treatment of Paget's disease of the bone and is under development as a chronic therapy for the treatment and prevention of osteoporosis. A novel cellulose film-coated tablet formulation was developed to optimize esophageal transit of this bisphosphonate. The aim of the present study was to compare the esophageal transit of the film-coated tablet formulation of risedronate with its original gelatin capsule dose form. A total of 25 elderly, healthy volunteers (mean 66 years), who were dysphagia-free, participated in this randomized cross-over study. On separate occasions, volunteers swallowed radiolabeled placebo formulations with 50 ml water. Dynamic images with participants in a sitting position were recorded for 10 min using a gamma camera. Scintigraphic imaging showed a delay in esophageal transit (greater than 15 s) in 28% of patients in the capsule group but in none of the tablet group (P<0.05). The mean transit times of the capsules and tablets were 23.8 and 3.3 s, respectively. Esophageal transit of film-coated tablets was faster than gelatin capsules, suggesting that film-coated tablets would be the appropriate formulation for all pivotal trials with risedronate and for subsequent commercialization. PMID:10486435

Perkins, A C; Wilson, C G; Frier, M; Vincent, R M; Blackshaw, P E; Dansereau, R J; Juhlin, K D; Bekker, P J; Spiller, R C

1999-09-20

299

Formulation and evaluation of sustained release bioadhesive tablets of ofloxacin using 32 factorial design  

PubMed Central

Background: Oral sustained release gastroretentive dosage forms offer many advantages for drugs having absorption from upper gastrointestinal tract and improve the bioavailability of medications that are characterized by narrow absorption window. The aim of current study was to design sustained release bioadhesive gastroretentive dosage form of ofloxacin. Materials and Methods: A 32 full factorial design was employed to systematically study the drug release profile and bioadhesive strength. Carbopol 934P and HPMC K100M were selected as the independent variables. Compatibility between drug and polymer was tested by fourier transform infrared (FTIR) and X-ray diffraction (XRD) techniques. Tablets were prepared by direct compression and were evaluated for tablet characteristics, swelling study, adhesion strength, percent drug released, radiographic imaging study and stability study. The optimized formulation was then compared with marketed formulation (Oflin OD®). Results: Tablets prepared showed good tablet characteristics, optimum swelling property, and good adhesion strength with high detachment force. Most of the formulations including the optimized formulation followed Higuchi kinetics and the drug release mechanism was found to be anomalous. Radiographic image proved that tablet remains intact in its structural integrity and shape in stomach up to 24 h. The short-term accelerated stability testing was carried out for the optimized formulation, and results revealed that drug content, in-vitro dissolution and all other parameters were within acceptable limits. Conclusion: Thus, the prepared bioadhesive gastroretentive ofloxacin tablet may prove to be a potential candidate which increases the bioavailability of ofloxacin for any intragastric condition.

Gangurde, Hemant H; Chordiya, Mayur A; Tamizharasi, S; Senthilkumaran, K; Sivakumar, T

2011-01-01

300

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

PubMed Central

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

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

2014-01-01

301

Rapid simultaneous determination of codeine and morphine in plasma using LC-ESI-MS/MS: application to a clinical pharmacokinetic study.  

PubMed

A rapid and sensitive high-performance LC-MS/MS method was developed and validated for the simultaneous quantification of codeine and its metabolite morphine in human plasma using donepezil as an internal standard (IS). Following a single liquid-liquid extraction with ethyl acetate, the analytes were separated using an isocratic mobile phase on a C(18 )column and analyzed by MS/MS in the selected reaction monitoring mode using the respective [M+H](+ )ions, mass-to-charge ratio (m/z) 300/165 for codeine, m/z 286/165 for morphine and m/z 380/91 for IS. The method exhibited a linear dynamic range of 0.2-100/0.5-250 ng/mL for codeine/morphine in human plasma, respectively. The lower LOQs were 0.2 and 0.5 ng/mL for codeine and its metabolite morphine using 0.5 mL of human plasma. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.0 min for each sample made it possible to analyze more than 300 human plasma samples per day. The validated LC-MS/MS method was applied to a pharmacokinetic study in which healthy Chinese volunteers each received a single oral dose of 30 mg codeine phosphate. PMID:19156643

Liao, Qiongfeng; Deng, Yating; Xie, Zhiyong; Pan, Biyan; Zhang, Lei

2009-01-01

302

The effect of prolonged exposure to morphine on canine cerebral 5-HT2A receptors measured with (123)I-R91150 SPECT.  

PubMed

Down-stream neuronal alterations, including changes in the 5-HT-2A receptor system, play an important role in the etiology and treatment of depression. The present study examined the effect of prolonged opioid treatment on cerebral 5-HT2A receptors. Cerebral 5-HT2A receptor availability was estimated in seven healthy five-year-old female neutered Beagle dogs pre and post 10-day morphine treatment (oral sustained release morphine 20mg twice daily for 10 days) with (123)I-R-91150, a 5-HT2A selective radioligand, and SPECT. 5-HT2A receptor binding indices (BI) for the frontal, parietal, temporal and occipital cortex and the subcortical region were calculated. Statistical analysis was performed using a linear mixed-effect model with treatment as fixed effect and dog as random effect. Morphine treatment significantly (P?0.05) lowered 5-HT2A BIs in the right and left frontal cortex, the right and left temporal cortex, the right and left parietal cortex, and the subcortical region. The decreased cerebral 5-HT2A receptor availability following prolonged morphine exposure provides further evidence for an interaction between the opioid and serotonergic system. PMID:24726581

Adriaens, Antita; Polis, Ingeborgh; Vermeire, Simon; Waelbers, Tim; Croubels, Siska; Duchateau, Luc; Van Dorpe, Sylvia; Eersels, Jos; De Spiegeleer, Bart; Peremans, Kathelijne

2014-07-01

303

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

PubMed

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

Schmidt, P C; Herzog, R

1993-06-18

304

Ciprofloxacin Absorption Is Impaired in Patients Given Enteral Feedings Orally and via Gastrostomy and Jejunostomy Tubes  

Microsoft Academic Search

Twenty-six hospitalized patients participated in a randomized crossover study to evaluate the effect of enteral feedings on ciprofloxacin absorption when given orally or via gastrostomy or jejunostomy tubes. Patients in the oral group received an intact 500-mg ciprofloxacin tablet alone or ciprofloxacin plus three oral doses of Sustacal (240 ml given 8 h before, with, and 4 h after ciprofloxacin

DANIEL P. HEALY; MARY C. BRODBECK; ANDCHRIS E. CLENDENING

1996-01-01

305

Intrathecal ketorolac enhances intrathecal morphine analgesia following total knee arthroplasty  

PubMed Central

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

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

2013-01-01

306

Asymmetrical Cross-Tolerance Between Morphine- and Scopolamine-Induced Antinociception in the Primate.  

National Technical Information Service (NTIS)

Two experiments were designed to explore further the role of the cholinergic system in mediating morphine-induced analgesia in the Rhesus monkey. Experiment 1 tested for cross-tolerance between morphine and scopolamine using the shock titration technique....

A. Pert G. Maxey

1975-01-01

307

Action of Reserpine in Morphine Tolerant Rats: Absence of an Antagonism of Catecholamine Depletion.  

National Technical Information Service (NTIS)

The mechanism of resistance to the catecholamine depleting effects of reserpine in morphine tolerant rats was examined. In vitro, morphine did not alter reserpine inhibition of 3H-norepinephrine uptake by synaptic vesicles. Similarly, uptake by vesicles i...

J. C. Blosser G. N. Catravas

1974-01-01

308

Investigation of Fluorescence Based Systems for Detection of Morphine in Urine.  

National Technical Information Service (NTIS)

Conditions for extraction of morphine free base from urine were optimized. Procedures for derivatization of the morphine extracted from urine with dansyl chloride and also with isatoic anhydride were developed. Methods for separation of the fluorescent mo...

D. A. Knowlton M. B. Neher

1974-01-01

309

Preparation and in-vivo pharmacokinetic study of a novel extended release compression coated tablets of fenoterol hydrobromide.  

PubMed

The aim of this study was to formulate extended release compression coated core tablets of fenoterol hydrobromide, a selective beta(2) adrenergic receptor agonist, in an attempt to prevent nocturnal asthma. Two hydrophilic polymers viz Kollidon SR, Polyox WSR 303 and a hydrophobic one (Precirol ATO5) were employed. Compression coated tablets were formulated by preparing a core tablet containing 7.5 mg drug and various amounts of polymer and Emcompress then compressed coated with the same polymeric materials. For comparison purpose different matrix tablets were also prepared employing the same polymers. In-vitro release studies were carried out at different pH (1.2 and 6.8). Pharmacokinetics of extended release tablets as well as commercially available immediate release tablets (Berotec) were studied after oral administration to beagle dogs using a new developed LC-MS/MS method with a lower limit of quantification of 1 ng/ml. Fenoterol release from compression coated tablets was significantly lower than matrix tablets. The mechanism of release was changed with the nature and content of polymer. The release pattern of drug from F16 containing 40 mg Kollidon SR divided in the core tablet (15 mg) and the rest in the compressed coat (25 mg) showed a typical zero order release kinetic that could extend drug release >10 h and reasonable time for 75% to be released (t(75)) (8.92 h). When compared to immediate release Berotec tablet the MRT was significantly extended from 7.03 +/- 0.76 to 10.93 +/- 1.25 h (P < 0.001) and HVD(t 50%Cmax) was also significantly extended from 2.71 +/- 0.68 to 6.81 +/- 0.67 h with expected prevention of nocturnal asthma. PMID:18770048

Elshafeey, Ahmed H; Sami, Elshaimaa I

2008-01-01

310

Preparation and In-vivo Pharmacokinetic Study of a Novel Extended Release Compression Coated Tablets of Fenoterol Hydrobromide  

PubMed Central

The aim of this study was to formulate extended release compression coated core tablets of fenoterol hydrobromide, a selective ?2 adrenergic receptor agonist, in an attempt to prevent nocturnal asthma. Two hydrophilic polymers viz Kollidon® SR, Polyox® WSR 303 and a hydrophobic one (Precirol® ATO5) were employed. Compression coated tablets were formulated by preparing a core tablet containing 7.5 mg drug and various amounts of polymer and Emcompress® then compressed coated with the same polymeric materials. For comparison purpose different matrix tablets were also prepared employing the same polymers. In-vitro release studies were carried out at different pH (1.2 and 6.8). Pharmacokinetics of extended release tablets as well as commercially available immediate release tablets (Berotec®) were studied after oral administration to beagle dogs using a new developed LC-MS/MS method with a lower limit of quantification of 1 ng/ml. Fenoterol release from compression coated tablets was significantly lower than matrix tablets. The mechanism of release was changed with the nature and content of polymer. The release pattern of drug from F16 containing 40 mg Kollidon® SR divided in the core tablet (15 mg) and the rest in the compressed coat (25 mg) showed a typical zero order release kinetic that could extend drug release >10 h and reasonable time for 75% to be released (t75) (8.92 h). When compared to immediate release Berotec® tablet the MRT was significantly extended from 7.03?±?0.76 to 10.93?±?1.25 h (P?

Sami, Elshaimaa I.

2008-01-01

311

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

Microsoft Academic Search

Introduction: There is considerable and unexplained individual variability in the morphine dose-effect relationship. The efflux pump P-glycoprotein regulates brain access and intestinal absorption of numerous drugs. Morphine is a P-glycoprotein substrate in vitro, and P-glycoprotein affects morphine brain access and pharmacodynamics in animals. However, the role of P-glycoprotein in human morphine disposition and clinical effects is unknown. This investigation tested

Evan D. Kharasch; Christine Hoffer; Dale Whittington; Pam Sheffels

2003-01-01

312

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

PubMed Central

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

Balch, Robert J; Trescot, Andrea

2010-01-01

313

The strength of bilayered tablets  

Microsoft Academic Search

The tensile strength of model materials (dicalcium phosphate dihydrate, microcrystalline cellulose and pregelatinised starch) compacted to form tablets in the form of beams consisting of two layers of equal thickness has been determined by three-point loading. The values of the tensile strength of the materials were sometimes higher and sometimes lower than the tensile strength of beams of the same

F. Podczeck; K. R. Drake; J. M. Newton; I. Haririan

2006-01-01

314

Identification of Morphine Accumulation in the Rat Embryo Central Nervous System: A C14-Morphine Administration Study  

PubMed Central

Background: Previous studies have shown that morphine consumption during pregnancy may cause delay or defect of embryo development or abnormal nervous system function in the human and animal models. In the present study, the highest density of morphine accumulation in the central nervous system of rat embryos was evaluated using C14-morphine. Methods: Female Wistar rats (W 170-200 g) used and were crossed with male rats and coupling time was recorded (Embryonic day 0-E0). Experimental groups received 0.05 mg/ml of C14-morphine in drinking water daily. On the 10th and 17th days of pregnancy, pregnant rats were anesthetized and the embryos with these uterus and placenta were surgically removed and were fixed in formalin 10% for 4 week. Then the embryos were processed, sectioned in 25 ?m and 5 ?m thicknesses, fixed on the glasses for further evaluations. The sectioned in 25, the glasses were fixed on the Blanc black and white film for 6 h. Then, the films were appeared and their negatives were prepared. The sectioned in five staining hematoxylin and eosin by light microscope and MOTIC software. Results: Our results indicated that the highest C14-morphine accumulation was observed in the vesicles and the ventricular choroid plexus (CP) of (E17) embryos, whereas, in the (E10) embryos. Highest concentration was observed in the brain vesicles and the ventricular CP. In addition, this study showed the surface area of lateral, 3rd and 4th ventricular CP in the experimental groups were increased in compared to control groups. Conclusions: Our results indicated that effects of morphine on reduction of embryos brain development may be due to the highest accumulation of C14-morphine in the CP and brain vesicles.

Sahraei, Hedayat; Rostamkhani, Fatemeh; Tekieh, Elaheh; Dehghani, Leila; Poorazizi, Elahe; Meamar, Rokhsareh; Kazemi, Masoomeh

2013-01-01

315

Effects of morphine on the turnover of brain catecholamines and serotonin in rats-chronic morphine administration.  

PubMed

The turnover of brain monoamine was studied in rats in which different degrees of tolerance to and dependence on morphine were induced by pellet implantation. The degree of tolerance to morphine was assessed by measuring the increase in effective dose for an antinociceptive effect (vocalization test). The rate of depletion of brain dopamine (DA) and serotonin (5-ht) after alpha-methyl-p-tyrosine (AMT) or alpha-propyl-dopacetamide (dopacetamide) was not changed by chronic morphine treatment. In contrast, the accumulation of brain homovanillic acid HVA) and 5-hydroxyindoleacetic acid (5-HIAA) after probenecid was significantly increased, but there was no correlation between the biochemical changes and the degree of tolerance/dependence of the animals; at a very high degree of dependence 5-HIAA accumulation even became normal. In rats in which smaller amounts of morphine were repeatedly injected every 8 hr for 1 week the increased accumulation of HVA and 5-HIAA persisted in spite of complete tolerance to the antinociceptive effect. The rate of depletion of brain noradrenaline (NA) after AMT or dopacetamide was not changed and the accumulation of brain 3-methoxy-4-hydroxy-phenylglycol sulphate (MHPG-SO4) after probenecid was not affected in most chronic morphine groups. In the group with the highest degree of tolerance/dependence NA depletion after AMT was even retarded. The results suggest that chronic morphine treatment increases the synthesis and the intraneuronal destruction of newly synthesized DA and 5-HT without changing the rate of functional utilization of the monoamines. It is unlikely that the changes in monoamine metabolism are causally related to processes leading to morphine tolerance/dependence. PMID:791659

Theiss, P; Papeschi, R; Herz, A

1975-12-01

316

[Analgesic effect of morphine and its metabolites administered by an intracerebroventricular route].  

PubMed

Intraventricular morphine administration is indicated, in some selected cases, to alleviate intractable cancer pain. Our pharmacokinetics data in cerebro-spinal fluid allowed us to formulate the theory of "Front de Recrutement". Then we were able to determine in cisternal and ventricular cerebrospinal fluid the morphine 6-glucuronide concentrations. Morphine 6-glucuronide is the main analgesic metabolite of morphine and its presence in cerebro-spinal fluid could be due to a metabolism of morphine in the central nervous system. Our animal studies showed that the analgesic activity of morphine 6-glucuronide was 27 to 67 times higher than that of morphine. By demonstrating the 6-monoacetyl morphine potency (analgesic metabolite of heroin that is 20 times more potent than morphine), we showed the involvement of the 6 position in the analgesic effect of these opioids. When we compared the morphine-6 concentrations in human cerebro-spinal fluid with the analgesic potency of this metabolite, the morphine-6 glucuronide was responsible of 33% to 67% of the supra-spinal analgesic effect. As heroin, morphine must be considered as a precursor whose metabolites have pharmacologic effects. PMID:8542351

Serrié, A

1995-06-01

317

Pharmacokinetic Drug Interactions of Morphine, Codeine, and Their Derivatives: Theory and Clinical Reality, Part I  

Microsoft Academic Search

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

SCOTT C. ARMSTRONG; KELLY L. COZZA

2003-01-01

318

Transformation of Thebaine to Oripavine, Codeine, and Morphine by Rat Liver, Kidney, and Brain Microsomes  

Microsoft Academic Search

Thebaine, an intermediate of morphine biosynthesis in the poppy plant, Papaver somniferum, was transformed to oripavine, codeine, and morphine by rat liver, kidney, and brain microsomes in the presence of an NADPH-generating system. The formation of morphine, codeine, and oripavine was identified by a specific RIA, HPLC, and GCMS. Thebaine also gave rise to four other compounds, which for the

Haruyoshi Kodaira; Sydney Spector

1988-01-01

319

Postoperative Analgesia for Outpatient Arthroscopic Knee Surgery with Intraarticular Clonidine and\\/or Morphine  

Microsoft Academic Search

Both clonidine, an a2 agonist, and morphine, an opioid agonist, provide enhanced patient analgesia after ar- throscopic knee surgery when administered via the in- traarticular (IA) route. Clonidine potentiates morphine analgesia in the animal model. We designed this study to determine whether clonidine or morphine results in better analgesia and whether their combination would provide superior analgesia to either drug

Wanda Joshi; Scott S. Reuben; Prasad R. Kilaru; Joseph Sklar; Holly Maciolek

2000-01-01

320

Lack of effect of inhaled morphine on exercise-induced breathlessness in chronic obstructive pulmonary disease  

Microsoft Academic Search

BACKGROUND--Inhaled nebulised morphine may reduce breathlessness in patients with lung disease, although the results of controlled trials are conflicting. A direct action of morphine on the lung has been postulated. This study aimed to investigate whether nebulised morphine reduced exercise-induced breathlessness in patients with chronic obstructive pulmonary disease (COPD) and to determine if this was a local pulmonary effect or

A R Masood; J W Reed; S H Thomas

1995-01-01

321

Evaluating the toxicity of novel Zn-DTPA tablet formulation in dogs and rats.  

PubMed

The purpose of this research work is to evaluate toxicity of diethylenetriamine pentaacetic acid zinc trisodium salt (Zn-DTPA) tablets, a novel oral solid dosage form containing permeation enhancers in beagle dogs and Sprague Dawley rats. (Zn-DTPA) in tablet dosage form was administered once daily for 7 days to beagle dogs at low (840?mg/dog/day), mid (2520?mg/dog/day), or high (7560?mg/dog/day). On day 8, all treated and control groups were necropsied. The novel Zn-DTPA tablet formulation showed rapid absorption with the T(max) at 1?h. Plasma concentrations as high as 270??g/mL were observed after 7 days of administration. Exposure to DTPA, based on area under the curve (AUC(last)) and maximum concentration (C(max)), was dose dependent but not dose proportional. No biologically relevant changes in hematology or clinical chemistry that were related to DTPA exposure were observed, and there were no changes in body weight in treated dogs compared with controls. Zn-DTPA was well tolerated, with minor toxicological effects of emesis and diarrhea, following oral tablet administration for 7 consecutive days. Based on the endpoints evaluated in this study, the maximum tolerated dose is considered to be greater than 7560?mg/dog/day (2535??mol/kg/day, 1325?mg/kg/day), and the no-observed-adverse-effect level (NOAEL) is considered to be approximately 1325?mg/kg/day per oral when given to male and female beagle dogs. For rats, the NOAEL was estimated to be greater than 1000?mg/kg/day when administered by oral gavage of the crushed Zn-DTPA tablets as suspension once daily (qd) to male and female Sprague Dawley rats. PMID:24648048

Shankar, Gita N; Potharaju, Suresh; Green, Carol E

2014-02-01

322

Reversal of morphine analgesic tolerance by ethanol in the mouse.  

PubMed

The chronic use of opioids in humans, accompanied by the development of tolerance, is a dangerous phenomenon in its own right. However, chronic opioid use is often made more dangerous by the coconsumption of other substances. It has been observed that the blood level of opioids in postmortem analyses of addicts, who consumed ethanol along with the opioid, was much less than that observed in individuals who died from opioids alone. This relationship between ethanol and opioids led us to investigate the hypothesis that ethanol alters tolerance to opioids. In the present study, we report that ethanol significantly and dose-dependently reduced the antinociceptive tolerance produced by morphine and the cross-tolerance between [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and morphine in the mouse tail-flick test. The reversal of morphine tolerance was partially blocked by both the gamma receptor blocker bicuculline and by the ?-aminobutyric acid (GABA)(B) receptor blocker phaclofen and the administration of both inhibitors completely reversed the effects of ethanol on morphine tolerance. Diazepam, like ethanol, decreased morphine tolerance. However, this inhibition was reversed by the GABA(A) antagonist bicuculline but not by the GABA(B) antagonist phaclofen. These findings have important implications for individuals who abuse opioids and ethanol as well as suggest a mechanism to reduce the amount of opioid needed in chronic pain treatment. PMID:23528610

Hull, L C; Gabra, B H; Bailey, C P; Henderson, G; Dewey, W L

2013-06-01

323

Effect of morphine on sympathetic nerve activity in humans  

NASA Technical Reports Server (NTRS)

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

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

2002-01-01

324

Reversal of Morphine Analgesic Tolerance by Ethanol in the Mouse  

PubMed Central

The chronic use of opioids in humans, accompanied by the development of tolerance, is a dangerous phenomenon in its own right. However, chronic opioid use is often made more dangerous by the coconsumption of other substances. It has been observed that the blood level of opioids in postmortem analyses of addicts, who consumed ethanol along with the opioid, was much less than that observed in individuals who died from opioids alone. This relationship between ethanol and opioids led us to investigate the hypothesis that ethanol alters tolerance to opioids. In the present study, we report that ethanol significantly and dose-dependently reduced the antinociceptive tolerance produced by morphine and the cross-tolerance between [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and morphine in the mouse tail-flick test. The reversal of morphine tolerance was partially blocked by both the gamma receptor blocker bicuculline and by the ?-aminobutyric acid (GABA)B receptor blocker phaclofen and the administration of both inhibitors completely reversed the effects of ethanol on morphine tolerance. Diazepam, like ethanol, decreased morphine tolerance. However, this inhibition was reversed by the GABAA antagonist bicuculline but not by the GABAB antagonist phaclofen. These findings have important implications for individuals who abuse opioids and ethanol as well as suggest a mechanism to reduce the amount of opioid needed in chronic pain treatment.

Hull, L. C.; Gabra, B. H.; Bailey, C. P.; Henderson, G.

2013-01-01

325

Managing chronic nonmalignant pain with continuous intrathecal morphine.  

PubMed

One alternative to traditional treatment modalities for chronic pain is continuous intrathecal administration of morphine via an implanted pump. However, relatively little is known about the benefits and long-term complications of this therapy for chronic nonmalignant pain. The purpose of this study was to describe patient responses to continuous intrathecal morphine over the course of one year with respect to morphine dosage used, complications and subjective assessments of pain. Data were obtained from twelve patients who completed one year of therapy. After one year, a 42% reduction in pain as measured by the McGill pain questionnaire had occurred (p < .01). A similar 41% reduction in pain was also present based on the Verbal Descriptor Scale (p < .01). A 35% reduction in the perceived hardship of pain was present (p < .01) accompanied by anecdotal comments that an improvement in the ability to manage activities of daily living had occurred. One patient was able to return to work. A statistically nonsignificant increase in the mean daily dosage of morphine occurred and few long-term adverse effects were present. Complications of implantation occurred in 33.3% of the patients and were successfully managed without discontinuing therapy. In selected patients with chronic pain, intrathecal administration of morphine via an implanted pump can reduce pain with minimal long-term adverse effects or complications. PMID:9791778

Valentino, L; Pillay, K V; Walker, J

1998-08-01

326

?-Opioid receptor desensitization: Is morphine different?  

PubMed Central

Opioid tolerance and dependence are important phenomena. The contribution of acute ?-opioid receptor regulatory mechanisms to the development of analgesic tolerance or physical dependence are unknown, and even the mechanisms underlying relatively rapid receptor desensitization in single cells are unresolved. To a large degree, the uncertainty surrounding the mechanisms and consequences of short-term regulation of ?-opioid receptors in single cells arises from the limitations in the experimental design in many of the studies that have investigated these events. Receptor overexpression and use of assays in which regulatory mechanisms are likely to blunt control determinations have led to measurements of opioid receptor activity that are likely to be insensitive to receptor uncoupling. Together with uncertainties concerning molecular details of ?-opioid receptor interactions with potential regulatory molecules such as G protein-coupled receptor kinases and arrestins, we are left with an incomplete picture crudely copied from the well-worked-out regulatory schema for ?2-adrenoceptors. As a consequence, suggestions that clinically relevant ?-opioid receptor agonists may have different propensities to produce tolerance and dependence that arise from their differential recruitment of regulatory mechanisms are premature, and have not yet been appropriately assessed, nor explained in the context of a thoroughly established regulatory scheme. In this commentary, we outline the experimental limitations that have given rise to conflicting ideas about how ?-opioid receptors are regulated, and identify the issues we feel still need to be addressed before we can understand why morphine promotes receptor trafficking differently to other opioids.

Connor, Mark; Osborne, Peregrine B; Christie, MacDonald J

2004-01-01

327

Mechanisms underlying morphine analgesic tolerance and dependence.  

PubMed

The mechanisms underlying opioid tolerance are not fully understood, but appear to be comprised of two types of plasticity or counter-adaptation, at the cellular level and through neuronal circuits. Current studies mostly emphasize the cellular adaptation mechanisms, which include altered gene expression and receptor desensitization due to phosphorylation and endocytosis. However, the mechanisms underlying opioid tolerance and dependence are not always explained by cellular adaptation mechanisms alone. This review focuses on the plasticity in neuronal circuits achieved through an enhancement of synaptic activities between glutamate and NMDA receptor due to up-regulation of receptor and racemase to produce D-serine, an allosteric NMDA receptor agonist, and down-regulation of glutamate transporter, all which contribute to the counterbalance of opioid actions or anti-opioid mechanisms underlying opioid tolerance. This anti-opioid system is supposed to be also augmented by altered expression of key molecules regulating through neuron-glial networks. This review also introduces a new approach using in vivo electroporation to identify the brain loci responsible for morphine tolerance and dependence. PMID:19482614

Ueda, Hiroshi; Ueda, Mutsumi

2009-01-01

328

Profiling of ecstasy tablets seized in iran.  

PubMed

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

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

2011-01-01

329

Profiling of Ecstasy Tablets Seized in Iran  

PubMed Central

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

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

2011-01-01

330

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

PubMed Central

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

2010-01-01

331

Reduction of human experimental muscle pain by alfentanil and morphine.  

PubMed

Musculoskeletal pain is a major clinical problem. By using various experimental models in humans, the understanding of the basic mechanisms behind muscle pain can increase, thereby giving hope for new and optimized treatment. Opioids are increasingly often used to treat muscle pain. There are, however, a limited number of previous studies on opioids and muscle pain, most of them using a relative low, single dose. Therefore, we wanted to further study the effect of two rather high doses of alfentanil (25 and 75ng/ml) and morphine (0.14 and 0.28mg/kg) in human volunteers. The study consisted of two parallel studies with morphine and alfentanil, respectively, and was conducted as randomized, double-blinded, placebo-controlled, 3-way cross-over. We used intramuscular infusion of hypertonic saline and intramuscular electrical stimulation to induce experimental pain. Visual analog scale (VAS)-score, intramuscular electrical pain thresholds and pain area (local and referred) were measured. Both alfentanil and morphine at their highest doses induced a 6 to 7-fold increase in pain thresholds to single and repetitive (5 stimulations, 2Hz) electrical stimulation. Alfentanil and morphine also reduced VAS score about 4 to 5-fold during suprathreshold electric stimulation and during infusion of hypertonic saline. None of the drugs decreased referred pain. There were no apparent differences between the drugs, in terms of effect or adverse reactions. In conclusion, this is the first study to compare two high doses of alfentanil and morphine on experimental muscle pain in humans. Both alfentanil and morphine reduced experimental muscle pain. There were no indications of any true pharmacodynamic differences between the two drugs. PMID:16414295

Schulte, Helène; Segerdahl, Märta; Graven-Nielsen, Thomas; Grass, Stefan

2006-11-01

332

A randomized, double-blind comparison of OROS® hydromorphone and controlled-release morphine for the control of chronic cancer pain  

PubMed Central

Background Long-acting opioid formulations are advocated for maintaining pain control in chronic cancer pain. OROS® hydromorphone is a sustained-release formulation of hydromorphone that requires dosing once daily to maintain therapeutic concentrations. The objective of this study was to demonstrate the clinical equivalence of immediate-release and sustained-release formulations of hydromorphone and morphine for chronic cancer pain. Methods 200 patients with cancer pain (requiring ? 540 mg/d of oral morphine) participated in this double-blind, parallel-group trial. Patients were randomized to receive hydromorphone or morphine (immediate-release for 2–9 days, sustained-release for 10–15 days). Efficacy was assessed with the Brief Pain Inventory (BPI), investigator and patient global evaluations, Eastern Cooperative Oncology Group performance status, and the Mini-Mental State Examination. The primary endpoint was the 'worst pain in the past 24 hours' item of the BPI, in both the immediate-release and sustained-release study phases, with treatments deemed equivalent if the 95% confidence intervals (CI) of the between-group differences at endpoint were between -1.5 and 1.5. No equivalence limits were defined for secondary endpoints. Results Least-squares mean differences (95% CI) between groups were 0.2 (-0.4, 0.9) in the immediate-release phase and -0.8 (-1.6, -0.01) in the sustained-release phase (intent-to-treat population), indicating that the immediate-release formulations met the pre-specified equivalence criteria, but that the lower limit of the 95% CI (-1.6) was outside the boundary (-1.5) for the sustained-release formulations. BPI 'pain now PM' was significantly lower with OROS® hydromorphone compared with controlled-release morphine (least-squares mean difference [95% CI], -0.77 [-1.49, -0.05]; p = 0.0372). Scores for other secondary efficacy variables were similar between the two sustained-release treatments. At endpoint, > 70% of investigators and patients rated both treatments as good to excellent. The safety profiles of hydromorphone and morphine were similar and typical of opioid analgesics. Conclusion Equivalence was demonstrated for immediate-release formulations of hydromorphone and morphine, but not for the sustained-release formulations of OROS® hydromorphone and controlled-release morphine. The direction of the mean difference between the treatments (-0.8) and the out-of-range lower limit of the 95% CI (-1.6) were in favor of OROS® hydromorphone. Trial registration ClinicalTrials.gov: NCT0041054

Hanna, Magdi; Thipphawong, John

2008-01-01

333

Effect of cinitapride in isolated ileum obtained from guinea-pigs treated with morphine.  

PubMed

1. Cinitapride enhanced the contractile response induced by electrical stimulation in the guinea-pig myenteric plexus-longitudinal muscle strip preparations. 2. The contractile force was significantly increased in strips pretreated with morphine "in vitro" and in tolerant strips. 3. However when tissues were obtained from tolerant guinea-pigs and morphine was not added to the organ bath (morphine-abstinence), the cinitapride effect was significantly decreased. 4. Although further work is required to explain the changes in the effect of cinitapride after acute morphine treatment and in morphine tolerant tissues, the changes observed suggest that some of the cinitapride effects could be linked with the peripheral opioid system. PMID:1662171

Colado, M I; Alfaro, M J; del Val, V L; Martín, M I

1991-01-01

334

Steady-State Pharmacokinetic Comparison of a New, Extended-Release, Once-Daily Morphine Formulation, Avinza™, and a Twice-Daily Controlled-Release Morphine Formulation in Patients with Chronic Moderate-to-Severe Pain  

Microsoft Academic Search

Extended-release morphine formulations are widely used in the management of chronic pain. Avinza™ (morphine sulfate extended-release [MSER, Morphelan™]) is a new, once-a-day, extended-release morphine formulation designed to reach target concentrations rapidly and maintain concentrations throughout a 24-hour period. The primary objective of this study was to compare the 24-hour steady-state pharmacokinetic (PK) profiles of morphine and its metabolites (morphine-6-glucuronide [M6G

Russell K. Portenoy; Andréa Sciberras; Lise Eliot; Gordon Loewen; Jackie Butler; John Devane

2002-01-01

335

Ketanserin and pirenperone attenuate acute morphine withdrawal in rats.  

PubMed

The involvement of serotonin2 (5-HT2) receptors in the expression of opiate withdrawal was examined using a behavioral test for acute morphine dependence. The 5-HT2 antagonists, ketanserin and pirenperone, injected shortly before naloxone, attenuated the naloxone-induced suppression of an autoshaped lever-touch response in rats treated 4 h earlier with a moderate dose of morphine. A low dose of pirenperone was also effective in blocking withdrawal-induced hypothermia. These data support the hypothesis that 5-HT is involved in the expression of opiate withdrawal. PMID:3816979

Neal, B S; Sparber, S B

1986-12-16

336

Digoxin Oral  

MedlinePLUS

Digoxin is used to treat heart failure and abnormal heart rhythms (arrhythmias). It helps the heart work ... Digoxin comes as a tablet, capsule, or pediatric elixir (liquid) to take by mouth. Digoxin is usually ...

337

Plasma levels and pharmacokinetics of norethindrone and ethinylestradiol administered in solution and as tablets to women.  

PubMed

Twenty-four normal adult female volunteers were dosed orally with a solution and tablet formulation containing the contraceptive combination of norethindrone (NET, 1.0 mg) and ethinylestradiol (EE2, 0.12 mg) in a crossover bioequivalence study. Blood was sampled sequentially following single oral doses and the plasma separated for analysis of NET and EE2 by specific radioimmunoassays. Comparisons of both drugs following a dose in solution and tablets were made with respect to the following parameters: (a) plasma concentrations at each sample time; (b) maximum plasma concentration (Cpmax); (c) time to maximum plasma concentration (Tmax); (d) total area under the plasma concentration vs. time curve (AUC), and (e) plasma half-life (t1/2). It was found that the tablet and solution doses were bioequivalent with respect to EE2 absorption. However, absorption of NET from solution and tablet doses exhibited significant differences with respect to plasma levels at certain time points as well as AUC (which were higher following the tablet dose), but Cpmax, Tmax and t1/2 were not significantly different. Pharmacokinetic analysis of both drugs following the tablet dose was carried out using a two-compartment open model. The absorption rate constant (ka) and peripheral to central compartment transfer rate constant (k21) were similar for NET and EE2, but statistically significant differences were observed with respect to the distribution rate constant (alpha), the central to peripheral transfer rate constant (k12), the overall elimination rate constant (ke1), and volume of distribution (V1/F). The elimination rate constant (beta) for both drugs showed a difference of borderline statistical significance. PMID:6641224

Stanczyk, F Z; Mroszczak, E J; Ling, T; Runkel, R; Henzl, M; Miyakawa, I; Goebelsmann, U

1983-09-01

338

21 CFR 520.1242e - Levamisole hydrochloride effervescent tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Levamisole hydrochloride effervescent tablets...FORM NEW ANIMAL DRUGS § 520.1242e Levamisole hydrochloride effervescent tablets...Each tablet contains 907 milligrams of levamisole hydrochloride. (b) Sponsor....

2010-04-01

339

21 CFR 520.2041 - Pyrantel pamoate chewable tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Pyrantel pamoate chewable tablets. 520.2041 Section 520.2041 Food and Drugs...NEW ANIMAL DRUGS § 520.2041 Pyrantel pamoate chewable tablets. (a) Specifications. Each tablet...

2010-04-01

340

21 CFR 520.2150b - Stanozolol chewable tablets.  

Code of Federal Regulations, 2010 CFR

... 2009-04-01 false Stanozolol chewable tablets. 520.2150b Section 520.2150b...ANIMAL DRUGS § 520.2150b Stanozolol chewable tablets. (a) Specifications. Each chewable tablet contains 2 milligrams of...

2009-04-01

341

21 CFR 520.2150b - Stanozolol chewable tablets.  

Code of Federal Regulations, 2010 CFR

... 2010-04-01 false Stanozolol chewable tablets. 520.2150b Section 520.2150b...ANIMAL DRUGS § 520.2150b Stanozolol chewable tablets. (a) Specifications. Each chewable tablet contains 2 milligrams of...

2010-04-01

342

Evidence of active transport involvement in morphine transport via MDCKII and MDCK-PGP cell lines  

PubMed Central

Several transporters appear to be important in transporting various drugs. Many patients, who receive morphine as analgesic medication, also receive other medications with potency of changing morphine transport by affecting P-glycoprotein (P-GP) and oatp2 transport system. This could influence morphine pharmacokinetics and pharmacodynamics. The aim of present study was to elucidate the transport mechanisms involved in transporting morphine via MDCKII and MDCK-PGP cells. Morphine permeability was examined in the presence of various compounds with ability in inhibiting different transport systems including: digoxin, probenecid and d- glucose. The effect of morphine concentration changes on its transport was also examined. Morphine concentration was measured using HPLC with electrochemical detector. Morphine permeability via a MDCK II cells was greater than sucrose permeability, and reduced when a P-GP expressed cell line was used. Its permeability was increased significantly in the presence of a strong P-GP inhibitor. Morphine permeability decreased significantly in the presence of digoxin but not in the presence of d-glucose or probenecid. These results showed that morphine was a P-GP substrate, and digoxin related transporters such as oatp2 were involved in its transport. Morphine was not substrate for glucose or probenecid-sensitive transporters.

Mashayekhi, S.O.; Sattari, M.R.; Routledge, P.A.

2010-01-01

343

Voluntary and forced exercises prevent the development of tolerance to analgesic effects of morphine in rats  

PubMed Central

Objective(s): Morphine is widely used to treat chronic pain. However, its utility is hindered by the development of tolerance to its analgesic effects. Despite the renowned beneficial effects of physical exercise on cognitive functions and signs of morphine withdrawal in morphine-dependent rats, little is known about the roles of voluntary and forced exercises in tolerance to analgesic effect of morphine in rats. Materials and Methods: In this study, rats were injected with 10 mg/kg of morphine, once daily, SC over a period of 8 days of either voluntary or treadmill exercise. Following these injections, the percent of maximum possible effect (%MPE) of morphine was measured on the 1st, 4th, and 8th days by hot plate test. Results: Both voluntary and forced exercises significantly increased pain threshold compared to the sedentary group (P<0.05). Voluntary and forced exercises also significantly increased potency of morphine compared to sedentary morphine group (P<0.05). Thus, we concluded that voluntary and forced exercises blocked the development of tolerance during 8 daily simultaneously treatments. When exercising rats were returned to sedentary conditions, sensitivity to the analgesic effects of morphine increased significantly and persisted during sedentary period in the exercising rats. In other words, %MPE of the exercising morphine-group increased significantly compared to saline group (P<0.05). Conclusion: Our results showed that voluntary and forced exercises may be possible methods for treating the development of tolerance to analgesic effect of morphine in rats.

Shokraviyan, Monireh; Miladi-Gorji, Hossein; Vaezi, Gholam Hassan

2014-01-01

344

Alleviation of Morphine Withdrawal Signs but Not Tolerance by the Essential Oil of Kelussia odoratissima Mozaff.  

PubMed Central

The aim of the present study was to assess the effects of chronic and acute treatment of the essential oil (EO) of Kelussia odoratissima Mozaff. on the development of morphine tolerance and dependence in mice. Mice were rendered tolerant to and dependent on morphine by subcutaneous injection of morphine over a period of 5 days. Tolerance was assessed using the tail-pinch test and withdrawal signs of morphine were precipitated by injecting naloxone 2?h after the final morphine injection. Repeated injection of the EO of K. odoratissima (5 and 10?mg/kg) for 4 days significantly suppressed morphine-withdrawal jumps, a sign of the development of dependence to opiate as assessed by naloxone precipitation withdrawal on day 5 of testing. A single injection (25, 50, 100?mg/kg) of the EO on day 5, 1?h prior to morphine failed to produce any significant change in morphine withdrawal signs. Neither the acute nor the chronic administration of EO of the K. odoratissima did significantly influence the development of tolerance to the analgesic effect of morphine. Alleviation in morphine signs of withdrawal after chronic injection with K. odoratissima is indicative of reversal of neuronal adaptation that takes place during morphine presence in the brain.

Rabbani, Mohammed; Sajjadi, Seyed Ebrahim; Izadi, Azadeh

2012-01-01

345

Acceptability of different oral formulations in infants and preschool children  

PubMed Central

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

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

2013-01-01

346

Effects of Shilajit on the development of tolerance to morphine in mice.  

PubMed

Effects of concomitant administration of Processed Shilajit (PS, 0.1 and 1 mg/kg, i.p.), in Swiss mice were evaluated on the development of tolerance to morphine induced analgesia in the hot plate test. Chronic administration of morphine (10 mg/kg, i.p., b.i.d.) to mice over a duration of 10 days resulted in the development of tolerance to the analgesic effect of morphine. Concomitant administration of PS with morphine, from day 6 to day 10, resulted in a significant inhibition of the development of tolerance to morphine (10 mg/kg, i.p.) induced analgesia. Processed Shilajit per se, in the doses used, did not elicit any significant analgesia in mice; nor did the chronic concomitant administration of Processed Shilajit alter the morphine-induced analgesia. These findings with Processed Shilajit indicate its potential as a prospective modifier of analgesic tolerance to morphine. PMID:11268125

Tiwari, P; Ramarao, P; Ghosal, S

2001-03-01

347

Bioequivalence study of nabumetone tablets in man  

Microsoft Academic Search

A nabumetone tablet in development (NabutonR) was tested for its bioequivalence to the reference tablet (UnitonR). Seventeen healthy Korean male subjects participated in this study. Each subject received a 1-g dose of nabumetone (2 tablets\\u000a each) in an unbalanced, randomized, two-way crossover investigation. Serum concentrations of 6-methoxy-2-naphthylacetic acid\\u000a (6-MNA), a major metabolite of nabumetone, were measured over 120 hr interval

Young-Joo Lee; Eun-Ju Jang; Jeong-Uk Lee; Yong-Hae Han; Suk-Jae Chung; Min-Hwa Lee; Chang-Koo Shim

1995-01-01

348

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

Microsoft Academic Search

Aim:To develop a novel gastroretentive drug delivery system based on a self-microemulsifying (SME) lipid mixture for improving the oral absorption of the immunosuppressant tacrolimus.Methods:Liquid SME mixture, composed of Cremophor RH40 and monocaprylin glycerate, was blended with polyethylene oxide, chitosan, polyvinylpyrrolidone and mannitol, and then transformed into tablets via granulation, with ethanol as the wetting agent. The tablets were characterized in

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

2011-01-01

349

In vitro release kinetics and bioavailability of gastroretentive cinnarizine hydrochloride tablet.  

PubMed

An oral sustained release dosage form of cinnarizine HCl (CNZ) based on gastric floating matrix tablets was studied. The release of CNZ from different floating matrix formulations containing four viscosity grades of hydroxypropyl methylcellulose, sodium alginate or polyethylene oxide, and gas-forming agent (sodium bicarbonate or calcium carbonate) was studied in simulated gastric fluid (pH 1.2). CNZ release data from the matrix tablets were analyzed kinetically using Higuchi, Peppas, Weibull, and Vergnaud models. From water uptake, matrix erosion studies, and drug release data, the overall release mechanism can be explained as a result of rapid hydration of polymer on the surface of the floating tablet and formation of a gel layer surrounding the matrix that controls water penetration into its center. On the basis of in vitro release data, batch HP1 (CNZ, HPMC-K100LV, SBC, LTS, and MgS) was subjected to bioavailability studies in rabbits and was compared with CNZ suspension. It was concluded that the greater bioavailability of HP1 was due to its longer retention in the gastric environment of the test animal. Batch no. HP1 of floating tablet in rabbits demonstrated that the floating tablet CNZ could be a 24-h sustained release formulation. PMID:20182827

Nagarwal, Ramesh C; Ridhurkar, Devendra N; Pandit, J K

2010-03-01

350

Responses to Oral ? 9Tetrahydrocannabinol in Frequent and Infrequent Marijuana Users  

Microsoft Academic Search

It is known that an individual’s drug use history affects the quality of subjective effects experienced following administration of several clinically used psychoactive drugs such as barbiturates, diazepam, and morphine. However, it is not known whether drug use history also affects responses to therapeutic cannabinoids such as ?9-THC. The current experiment compared the subjective and behavioral effects of oral ?9-THC

J. M Kirk; Harriet De Wit

1999-01-01

351

Increase in plasma concentrations of geranylgeranoic Acid after turmeric tablet intake by healthy volunteers.  

PubMed

Geranylgeranoic acid (GGA) is one of the most potent cancer-preventive acyclic retinoids. GGA has been shown to induce cell death in human hepatoma-derived HuH-7 cells. We have recently reported the natural occurrence of GGA and its related compounds in several medicinal herbs such as turmeric, basil, rosehip, cinnamon and others [Shidoji and Ogawa, J. Lipid Res., 45: 1092-1103, 2004]. In the present study, we performed oral administration of turmeric tablets to healthy volunteers in order to investigate bioavailability of natural GGA. By using liquid chromatography/mass spectrometry, authentic GGA was eluted at a retention time of around 18 min as a negative ion of m/z 303.4. With healthy volunteers, plasma GGA was detected prior to the tablet intake and its concentrations were increased at 2 h after its intake and maintained at higher level until 4 h, suggesting an efficient bioavailability of preformed GGA in the turmeric tablets through oral administration. These results indicated that GGA in the turmeric tablet was absorbed as an intact form from intestinal mucosa. The present study provides a clue to conduct a research for cancer preventive roles of GGA in a number of spices. PMID:20490321

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

2010-05-01

352

Comprehensive review on oral disintegrating films.  

PubMed

Fast-dissolving drug-delivery systems were first developed in the late 1970s as an alternative to tablets, capsules, and syrups for pediatric and geriatric patients who experience difficulties swallowing traditional oral solid dosage forms. In response to this need, a variety of orally disintegrating tablet (ODT) formats were commercialized, which disintegrate within 1 min when placed in the mouth without drinking water or chewing. Oral drug delivery technology has improved from conventional dosage forms to modified release dosage forms to ODT to the recent oral disintegrating films (ODF). Oral disintegrating film or strip that employs a water dissolving polymer which allows the dosage form to quickly hydrate by saliva, adhere to mucosa, and disintegrate within a few seconds, dissolve and releases medication for oromucosal absorption when placed on the tongue or oral cavity. Oral strip technology provides an alternate route for drugs with first pass metabolism. This review give details of materials used in ODF, manufacturing aspects, technologies, evaluation tests and marketed products. PMID:22920576

Nagaraju, T; Gowthami, R; Rajashekar, M; Sandeep, S; Mallesham, M; Sathish, D; Kumar, Y Shravan

2013-02-01

353

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

PubMed Central

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

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

2014-01-01

354

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

PubMed

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

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

2014-01-01

355

Polymers derived from Xanthomonas campesteris and Cyamopsis tetragonolobus used as retardant materials for the formulation of sustained release floating matrix tablet of atenolol.  

PubMed

The objective of the present study was to develop, optimize, in vitro, and in vivo evaluation of floating matrix tablet of atenolol using polymer blend derived from Xanthomonas campesteris and Cyamopsis tetragonolobus that are characterized by release requirements of sustained-release product and to improve the oral bioavailability of the drug. A 3(2) full factorial design was employed to optimize the tablets, where content of polymer blend (X1) and ratio of xanthan gum-to-guar gum (X2) were considered as independent variables. The effects of independent variables on dependent variables, i.e. floating time, diffusion exponent, and time to release 50% of atenolol were evaluated. The in vivo pharmacokinetic parameters of the optimized formulation were compared with the marketed sustained release formulation of atenolol (Aten(®)). The optimized formulation containing 20% (w/w) of polymer blend and 50:50 ratio of xanthan gum-to-guar gum was able to float more than 12h and showed the desired sustained drug release from the tablets. In vivo retention studies in rabbit stomach showed the gastric residence of tablet up to 6h. The in vivo study of optimized tablets illustrated significant improvement in the oral bioavailability of atenolol in rabbits. It can be concluded that floating matrix tablet of atenolol prepared by using xanthan gum and guar gum has potential for sustained release of the drug as well as improved oral bioavailability through enhanced gastric residence time of formulation in stomach. PMID:24472506

Dey, Sanjay; Mazumder, Bhaskar; Chattopadhyay, Sankha; Das, Malay Kanti; Sinha, Samarendu; Ganguly, Shantanu; De, Kakali; Mishra, Mridula

2014-04-01

356

Electroacupuncture, morphine and clonidine: a comparative study of analgesic effects.  

PubMed

This is a comparative study of the analgesic effects of the modified traditional method of analgesia, electroacupuncture (EA), a standard analgesic drug, morphine, a potential analgesic drug, clonidine and the combination of EA + morphine and EA + clonidine. In each case, the index of analgesia (IA) was determined by recording the tail flick latency (TFL) in 60 rats divided into 6 groups of 10 rats each. Group I rats served as control group while Group II-VI were subjected to EA for 20 min (at Zusanli and Kunlun points), morphine (5 mg/kg bw i.p.), clonidine (150 micrograms/kg bw i.p.), EA + morphine and EA + clonidine respectively. TFLs were recorded after the procedure and at 10 min intervals for 150 min or til the TFL returned to¿ the baseline. The IA, analyzed using the Kruskal-Wallis test and its significance determined by multiple comparison test (at 5% level), was found to be significantly different, at various time intervals, in the 6 groups studied. PMID:8950137

Shankar, N; Varshney, A; Bhattacharya, A; Sharma, K N

1996-07-01

357

Subcutaneous morphine pump for postoperative hemorrhoidectomy pain management  

Microsoft Academic Search

PURPOSE: Many anorectal procedures are currently being performed on an outpatient basis, hemorrhoidectomy being the exception because of the need for parenteral narcotics postoperatively. We investigated the effectiveness of a subcutaneous morphine pump (SQMP) for outpatient posthemorrhoidectomy pain control. METHODS: In Phase 1 of our study, 22 patients undergoing radical hemorrhoidectomy were started on an SQMP protocol postoperatively. Twenty-nine patients

Elsa T. Goldstein; Paul R. Williamson; Sergio W. Larach

1993-01-01

358

Morphine and endorphins modulate dopamine turnover in rat median eminence.  

PubMed Central

The is evidence that some of the actions of both endogenous and exogenous opioids (e.g., stimulation of prolactin release) are mediated by interaction with catecholaminergic systems. Morphine (1.67, 5, and 15 mg/kg of body weight, intraperitoneally) altered dopamine turnover as measured by the alpha-methyl-p-tyrosine method in the median eminence, neostriatum, and frontal cortex of male Sprague-Dawley rats. The turnover rate of dopamine was reduced in the median eminence and frontal cortex but accelerated in the neostriatum. In the frontal cortex all doses were effective in decreasing dopamine turnover; however, in the median eminence the lowest dose of morphine did not significantly alter dopamine turnover. All three doses accelerated dopamine turnover in the neostriatum. Naloxone effectively reversed the effects of morphine at all doses in all brain areas, whereas it had no effect on turnover when given alone. In the median eminence, neostriatum, and frontal cortex, intraventricular injection of [D-Ala2,D-Leu5]-enkephalin (25 micrograms) or beta-endorphin (15 micrograms) produced the same effects on dopamine turnover as morphine. The actions of these peptides were blocked by naloxone. It is hypothesized that opiates and opioid peptides increase prolactin release by reducing the activity of the tuberoinfundibular dopaminergic system.

Deyo, S N; Swift, R M; Miller, R J

1979-01-01

359

Morphine protects for head trauma induced cognitive deficits in mice.  

PubMed

Victims of minor traumatic brain injury (mTBI) can show long lasting cognitive, emotional and concentration difficulties, amnesia, depression, apathy and anxiety. The symptoms are generally known as a post-concussive syndrome without clear morphological brain defects. Endogenous opiates are released after impact to the brain, suggesting they may play a role in TBI pathophysiology. Furthermore, the administration of opiates to the brain of injured animals has been shown to affect the injury, induce cellular changes and also have protective qualities for neurological impairments. Here, we examined the protective properties of the opiate morphine on cognitive performances following minimal brain injury in mice. For this purpose, we have used our non-invasive closed-head weight drop model in mice, which closely mimics real life mTBI and examined mice performance in the Morris water maze. Our procedure did not cause visible structural or neurological damage to the mice. A single morphine injection administrated immediately after the induction of minimal TBI protected the injured mice from cognitive impairment, checked 30, 60 and 90 days post injury. However, mice injected with morphine that were examined 7 days after the injury did not show better performance than the saline injected mice. Our results indicate that morphine has long but not short-term effects on the cognitive ability of brain-injured mice. Although the exact nature of opioid neuroprotection is still unknown, its elucidation may lead to the much-needed treatment for traumatic brain injury. PMID:16356639

Zohar, Ofer; Getslev, Valery; Miller, Ayelet L; Schreiber, Shaul; Pick, Chaim G

2006-02-20

360

Exposure of consumers to morphine from poppy seeds in Hungary  

Microsoft Academic Search

Poppy seed-containing foods are popular dishes in Hungary and some other Central European countries. The alkaloids of poppy are used in the production of medicines. Poppy seeds used as food may also contain considerable amounts of alkaloids, which raises the question of food safety. Morphine, codeine, thebaine and noscapine concentrations of poppy seed samples from the period 2001–2010 and consumption

A. Zentai; J. Sali; M. Szeitzné-Szabó; I. J. Szabó; Á. Ambrus

2012-01-01

361

Exposure of consumers to morphine from poppy seeds in Hungary.  

PubMed

Poppy seed-containing foods are popular dishes in Hungary and some other Central European countries. The alkaloids of poppy are used in the production of medicines. Poppy seeds used as food may also contain considerable amounts of alkaloids, which raises the question of food safety. Morphine, codeine, thebaine and noscapine concentrations of poppy seed samples from the period 2001-2010 and consumption data from two Hungarian surveys, carried out in 2003 and 2009, were evaluated. Exposure calculations were made for morphine intake by both point estimate and probabilistic methods, and the uncertainty of the calculated values was estimated. The point estimate for the acute consumer exposure, calculated using the 97.5th percentiles of morphine concentration and of poppy seed consumption and taking into account the reduction of morphine content by processing, was 78.64?µg (kg?bw)?¹?day?¹ for adults, and 116.90?µg (kg?bw)?¹?day?¹ for children. Based on probabilistic estimations, the 97.5th and 99th percentile exposures ranged between 18.3-25.4 and 25.6-47.4?µg (kg?bw)?¹?day?¹ for adults, and between 32.9 and 66.4?µg (kg?bw)?¹?day?¹ for children, respectively. As a no observed effect level (NOEL) had not been established, the significance of exposure could not be assessed. PMID:22165856

Zentai, A; Sali, J; Szeitzné-Szabó, M; Szabó, I J; Ambrus, Á

2012-01-01

362

Exposure of consumers to morphine from poppy seeds in Hungary  

Microsoft Academic Search

Poppy seed-containing foods are popular dishes in Hungary and some other Central European countries. The alkaloids of poppy are used in the production of medicines. Poppy seeds used as food may also contain considerable amounts of alkaloids, which raises the question of food safety. Morphine, codeine, thebaine and noscapine concentrations of poppy seed samples from the period 2001–2010 and consumption

A. Zentai; J. Sali; M. Szeitzné-Szabó; I. J. Szabó; Á. Ambrus

2011-01-01

363

Systemic absorption of rifamycin SV MMX administered as modified-release tablets in healthy volunteers.  

PubMed

The new oral 200-mg rifamycin SV MMX modified-release tablets, designed to deliver rifamycin SV directly into the colonic lumen, offer considerable advantages over the existing immediate-release antidiarrheic formulations. In two pharmacokinetics studies of healthy volunteers, the absorption, urinary excretion, and fecal elimination of rifamycin SV after single- and multiple-dose regimens of the new formulation were investigated. Concentrations in plasma of >2 ng/ml were infrequently and randomly quantifiable after single and multiple oral doses. The systemic exposure to rifamycin SV after single and multiple oral doses of MMX tablets under fasting and fed conditions or following a four-times-a-day (q.i.d.) or a twice-a-day (b.i.d.) regimen could be considered negligible. With both oral regimens, the drug was confirmed to be very poorly absorbable systemically. The amount of systemically absorbed antibiotic excreted by the renal route is far lower than 0.01% of the administered dose after both the single- and multiple-dose regimens. The absolute bioavailability, calculated as the mean percent ratio between total urinary excretion amounts (?Xu) after a single intravenous injection and after a single oral dose under fasting conditions, was 0.0410±0.0617. The total elimination of the unchanged rifamycin SV with feces was 87% of the administered oral dose. No significant effect of rifamycin SV on vital signs, electrocardiograms, or laboratory parameters was observed. PMID:21402860

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

2011-05-01

364

Antinociceptive tolerance to morphine from repeated nociceptive testing in the rat.  

PubMed

Repeated morphine administration has been shown to produce tolerance to the antinociceptive effects of morphine. However, the degree to which repeated morphine administration decreases antinociception is exaggerated by repeated behavioral testing, a phenomenon known as behavioral tolerance. An important question is whether behavioral tolerance can be overcome by direct administration of morphine into the ventrolateral periaqueductal gray (vPAG), a key structure contributing to morphine antinociception. Rats were injected with morphine or saline into the vPAG (Experiment 1) or subcutaneously (Experiment 2) followed 20 min later with hot-plate testing. The control groups received the same drug administration, but no nociceptive testing. Repeated nociceptive testing or repeated morphine administration produced antinociceptive tolerance regardless of whether morphine was injected into the vPAG or systemically. Administration of a high dose of morphine (20 mg/kg, s.c.) was able to overcome the development of behavioral tolerance, but not pharmacological tolerance revealing separate mechanisms for these two types of tolerance. These data indicate that behavioral tolerance is independent of the route of morphine administration. PMID:15878767

Lane, Diane A; Morgan, Michael M

2005-06-14

365

Chronic psychostimulant exposure to adult, but not periadolescent rats reduces subsequent morphine antinociception.  

PubMed

Preweanling methylphenidate (MPH) exposure produces a long lasting enhanced sensitivity to opioids. Two important questions are whether this enhancement is specific to the age of psychostimulant exposure and the type of psychostimulant. To answer these questions periadolescent (PD 35) and adult (PD 55) rats received daily injections of saline, MPH, or methamphetamine (METH) for 10 consecutive days. Two weeks later, acute morphine antinociception was assessed on the hot plate using a cumulative dose response procedure. Following acute antinociceptive testing, morphine tolerance was induced in half the animals by administering morphine twice a day over 2 days. Rats pretreated with MPH and METH during the periadolescent period of ontogeny showed no change in acute morphine antinociception, but rats exposed to a relatively high METH dose (3 mg/kg) displayed enhanced morphine tolerance compared to saline pretreated controls. MPH and METH pretreatment during adulthood led to a reduction in morphine antinociceptive potency and an apparent reduction in morphine tolerance. When combined with our previously published findings, these data indicate that the developmental stage during which MPH and METH exposure occurs differentially alters adult morphine responsiveness. That is, psychostimulant exposure to preweanling rats enhances morphine antinociception and facilitates the development of tolerance, whereas psychostimulant exposure to adult rats reduces subsequent morphine antinociception and tolerance. These alterations indicate that it could be important for physicians to know about prior psychostimulant use when prescribing opioids for pain relief. PMID:22405777

Cyr, Michelle C; Ingram, Susan L; Aicher, Sue A; Morgan, Michael M

2012-06-01

366

Chronic psychostimulant exposure to adult, but not periadolescent rats reduces subsequent morphine antinociception  

PubMed Central

Preweanling methylphenidate (MPH) exposure produces a long lasting enhanced sensitivity to opioids. Two important questions are whether this enhancement is specific to the age of psychostimulant exposure and the type of psychostimulant. To answer these questions periadolescent (PD 35) and adult (PD 55) rats received daily injections of saline, MPH, or methamphetamine (METH) for 10 consecutive days. Two weeks later, acute morphine antinociception was assessed on the hot plate using a cumulative dose response procedure. Following acute antinociceptive testing, morphine tolerance was induced in half the animals by administering morphine twice a day over two days. Rats pretreated with MPH and METH during the periadolescent period of ontogeny showed no change in acute morphine antinociception, but rats exposed to a relatively high METH dose (3 mg/kg) displayed enhanced morphine tolerance compared to saline pretreated controls. MPH and METH pretreatment during adulthood led to a reduction in morphine antinociceptive potency and an apparent reduction in morphine tolerance. When combined with our previously published findings, these data indicate that the developmental stage during which MPH and METH exposure occurs differentially alters adult morphine responsiveness. That is, psychostimulant exposure to preweanling rats enhances morphine antinociception and facilitates the development of tolerance, whereas psychostimulant exposure to adult rats reduces subsequent morphine antinociception and tolerance. These alterations indicate that it could be important for physicians to know about prior psychostimulant use when prescribing opioids for pain relief.

Cyr, Michelle C; Ingram, Susan L.; Aicher, Sue A.; Morgan, Michael M

2012-01-01

367

The effect of morphine sensitization on extracellular concentrations of GABA in dorsal hippocampus of male rats.  

PubMed

Repeated, intermittent exposure to drugs of abuse, such as morphine results in response enhancements to subsequent drug treatments, a phenomenon referred to as behavioral sensitization. As persistent neuronal sensitization may contribute to the long-lasting consequences of drug abuse, characterizing the neurochemical mechanisms of sensitization is providing insights into addiction. Although it has been shown that GABAergic systems in the CA1 region of dorsal hippocampus are involved in morphine sensitization, the alteration of extracellular level of GABA in this area in morphine sensitization has not been investigated. In the present study, using the in vivo microdialysis technique, we investigated the effect of morphine sensitization on extracellular GABA concentration in CA1 region of dorsal hippocampus of freely moving rats. Sensitization was induced by subcutaneous (s.c.) injection of morphine, once daily for 3 days followed by 5 days free of the opioid treatment. The results showed that extracellular GABA concentration in CA1 was decreased following acute administration of morphine in non-sensitized rats. However, morphine-induced behavioral sensitization significantly increased the extracellular GABA concentration in this area. The enhancement of GABA in morphine sensitized rats was inhibited by administration of naloxone 30 min before each of three daily doses of morphine. These results suggest an adaptation of the GABAergic neuronal transmission in dorsal hippocampus induced by morphine sensitization and it is implied that opioid receptors may play an important role in this effect. PMID:21872582

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

2011-11-01

368

Increased morphine analgesia and reduced side effects in mice lacking the tac1 gene  

PubMed Central

Background and purpose: Although morphine is a very effective analgesic, its narrow therapeutic index and severe side effects limit its therapeutic use. Previous studies indicated that the pharmacological responses of opioids are modulated by genetic and pharmacological invalidation of tachykinin receptors. Here we address the role of substance P and neurokinin A, which are both encoded by the tachykinin 1 (tac1) gene, as modulators of opioid effects. Experimental approach: The analgesic and side effect potential of morphine was compared between wild-type and tac1 null mutant mice. Key results: Morphine was a more potent analgesic in tac1 null mutant mice, that is, in the absence of substance P/neurokinin A signalling. Interestingly, the most serious side effect of acute morphine, that is respiratory depression, was reduced in tac1?/? animals. Comparing the addictive potential of morphine in wild-type and knockout animals we found that morphine preference was similar between the genotypes. However, the aversive effect of withdrawal precipitated by naloxone in morphine-dependent animals was significantly reduced in tac1 knockout mice. Behavioural sensitization, the underlying mechanism of addiction, was also significantly lower in tac1?/? mice. Conclusion and implications: The analgesic potential of morphine was increased in tac1 knockout mice. In contrast, both the ventilatory suppressing effect and the addictive potential of morphine were reduced. These results suggest that reducing activity of the tachykinin system may be a possible strategy to improve the pharmacological potential of morphine.

Bilkei-Gorzo, A; Berner, J; Zimmermann, J; Wickstrom, R; Racz, I; Zimmer, A

2010-01-01

369

PKC-Mediated Potentiation of Morphine Analgesia by St. John's Wort in Rodents and Humans.  

PubMed

Our purpose was to combine the use of morphine with clinically available inhibitors of protein kinase C (PKC), finally potentiating morphine analgesia in humans. Thermal tests were performed in rodents and humans previously administered with acute or chronic morphine combined or not with increasing doses of the PKC-blocker St. John's Wort (SJW) or its main component hypericin. Phosphorylation of the ? subunit of PKC enzyme was assayed by western blotting in the periaqueductal grey matter (PAG) from rodents co-administered with morphine and hypericin and was prevented in rodent PAG by SJW or hypericin co-administration with morphine, inducing a potentiation of morphine analgesia in thermal pain. The score of pain assessment in healthy volunteers were decreased by 40% when morphine was co-administered with SJW at a dose largely below those used to obtain an antidepressant or analgesic effect in both rodents and humans. The SJW/hypericin potentiating effect lasted in time and preserved morphine analgesia in tolerant mice. Our findings indicate that, in clinical practice, SJW could reduce the dose of morphine obtaining the same analgesic effect. Therefore, SJW and one of its main components, hypericin, appear ideal to potentiate morphine-induced analgesia. PMID:24739262

Galeotti, Nicoletta; Farzad, Mersedeh; Bianchi, Enrica; Ghelardini, Carla

2014-01-01

370

In vitro evaluation of the potential role of sulfite radical in morphine-associated histamine release  

PubMed Central

Background Intravenous morphine use is associated with elevated histamine release leading to bronchoconstriction, edema and hemodynamic instability in some patients. This study evaluated the possibility that sulfite, which is present as a preservative in many morphine preparations, might contribute to histamine release in vitro. Results The human mast cell line, HMC-1, was exposed to various morphine concentrations, in the absence of sulfite, under cell culture conditions. Clinically attained concentrations of morphine (0.018?g/ml and 0.45?g/ml) did not cause increased histamine release from mast cells. There was a significant increase in histamine release when the morphine concentration was increased by 1184-fold (668?g/ml morphine). Histamine release from mast cells exposed to morphine and/or sulfite required the presence of prostaglandin H synthetase. Histamine release in experiments using sulfite-containing morphine solutions was not statistically different from that observed in morphine-only solutions. Conclusion Sulfite in sulfite-containing morphine solutions, at concentrations seen clinically, is not responsible for histamine release in in vitro experiments of the human mast cell line, HMC-1. This does not preclude the fact that sulfite may lead to elevation of histamine levels in vivo.

Gordon, Emma M; Myers, Carolyn; Blumer, Jeffrey

2004-01-01

371

C-Fos activation in the periaqueductal gray following acute morphine-3?-D-glucuronide or morphine administration.  

PubMed

Morphine-3?-D-glucuronide (M3G), a primary morphine metabolite, evokes hyperalgesia in mice and rats and putatively mediates hyperalgesia associated with morphine (MOR) administration. However, M3G does not act via opioid receptors and its locus of activity in the CNS is unknown. Here we assessed the density of neurons immunoreactive for c-Fos, an immediate early gene regulated by neuronal activity, in the periaqueductal gray (PAG), a midbrain region critical to pain modulation, in male CD-1 mice after MOR and M3G exposure. Mice were injected with acute doses of MOR or M3G following a pre-injection of saline (SAL) or the opioid antagonist naltrexone (NTX), perfused 3 h later, and labeled for c-Fos using immunohistochemistry. Labeled image stacks taken from the PAG were then analyzed on a confocal microscope for the number of neurons showing c-Fos expression. Relative to controls, significant but similar increases in the mean density of PAG c-Fos immunoreactive neurons were observed in mice pre-injected with SAL then M3G or morphine. However, NTX pre-injection blocked this increase in MOR but not M3G injected mice. The data demonstrate for the first time a CNS locus for M3G activity. Consistent with previous observations, this M3G activity is not mediated by opioid receptors. PMID:24631297

Arout, Caroline A; Caldwell, Megan; McCloskey, Daniel P; Kest, Benjamin

2014-05-10

372

Morphine desensitization and cellular tolerance are distinguished in rat locus ceruleus neurons.  

PubMed

?-Opioid receptor desensitization is considered an initial step in the development of tolerance. Curiously, the commonly used opioid morphine produces robust tolerance but minimal acute desensitization. This study was designed to test the hypothesis that desensitization is indeed present in morphine-treated animals and is distinguished from cellular tolerance by time course of recovery and mechanism. To induce tolerance, rats were treated with continuously released morphine for 1 week. Morphine-mediated activation of G protein-coupled inwardly rectifying potassium conductance was measured using voltage-clamp recordings from locus ceruleus neurons in brain slices from naive or morphine-treated rats. Cellular tolerance was observed as a decrease in morphine efficacy in slices from morphine-treated rats. This tolerance persisted for at least 6 h. An additional reduction in morphine-mediated current was observed when slices from morphine-treated rats were continuously maintained in morphine at approximately the circulating plasma concentration. This additional reduction recovered within 1 h after removal of morphine from the slice and represents desensitization that developed in the tolerant animal. Recovery from desensitization, but not long-lasting tolerance, was facilitated by protein phosphatase 1 (PP1) activity. Furthermore, desensitization, but not tolerance, was reversed by protein kinase C (PKC) inhibitor but not by an inhibitor of c-Jun N-terminal kinase. Therefore, morphine treatment leads to both long-lasting cellular tolerance and readily reversible desensitization, which are differentially dependent on PP1 and PKC activity and combine to result in a substantial decrease in morphine effectiveness. This PKC-mediated desensitization may contribute to the previously reported PKC-dependent reversal of behavioral tolerance. PMID:22914548

Levitt, Erica S; Williams, John T

2012-11-01

373

Effect of chronic morphine treatment on transmitter release from sympathetic varicosities of the mouse vas deferens.  

PubMed Central

1 Transmitter release from sympathetic varicosities of mouse vasa deferentia removed from animals which were chronically treated with morphine for 7 to 9 days has been evaluated. 2 In control preparations increasing the extracellular calcium concentration ([Ca2+]o) from 1 to 2 mM increased transmitter release by 3 fold while increasing [Ca2+]o from 6 to 8 mM increased transmitter release by about 0.9 fold. Introduction of morphine (1.0 microM) produced a uniform decrease in transmitter release, shifting the relationship between transmitter release and [Ca2+]o to the right. 3 Only sympathetic varicosities with probabilities of transmitter release greater than 0.01 were chosen for this study. In these varicosities the decrease in transmitter release induced by morphine in control preparations (bathed in [Ca2+]o 2.0 mM) was not observed following 7 to 9 days of morphine treatment. When the morphine was acutely withdrawn from these preparations transmitter release was more than 6 times the average level of transmitter release from control preparations. 4 The morphine induced increase in facilitation of transmitter release while stimulating with short trains of nerve impulses was not observed when the preparations were removed from animals which had been exposed to morphine for 7 to 9 days. When these preparations were acutely withdrawn from morphine there was a further decrease in the level of facilitation and a significant increase in depression of transmitter release when compared to control. 5 The morphine induced decrease in probability of transmitter release when naive sympathetic varicosities in vitro were bathed with morphine (1 microM) was not observed following chronic morphine treatment of the animals for 7 to 9 days. When the morphine was acutely withdrawn from chronically morphine treated preparations the underlying increase in probabilities of transmitter release of sympathetic varicosities was unmasked. Images Figure 1

Lavidis, N. A.

1995-01-01

374

PERIAQUEDUCTAL GRAY NEUROPLASTICITY FOLLOWING CHRONIC MORPHINE VARIES WITH AGE: ROLE OF OXIDATIVE STRESS  

PubMed Central

The development of tolerance to the antinociceptive effects of morphine has been associated with networks within ventrolateral periaqueductal gray (vlPAG) and separately, nitric oxide signaling. Furthermore, it is known that the mechanisms that underlie tolerance differ with age. In this study, we used a rat model of antinociceptive tolerance to morphine at two ages, postnatal day (PD) 7 and adult, to determine if changes in the vlPAG related to nitric oxide signaling produced by chronic morphine exposure were age-dependent. Three pharmacological groups were analyzed: control, acute morphine, and chronic morphine group. Either morphine (10 mg/kg) or equal volume of normal saline was given subcutaneously twice daily for 6 ½ days. Animals were analyzed for morphine dose-response using Hot Plate test, and for the expression of several genes associated with nitric oxide metabolism was evaluated using rtPCR. In addition, the effect of morphine exposure on immunohistochemistry for Fos, and nNOS as well as nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) reaction at the vlPAG were measured. In both age groups acute morphine activated Fos in the vlPAG, and this effect was attenuated by chronic morphine, specifically in the vlPAG at the level of the laterodorsal tegmental nucleus (LDTg). In adults, but not PD7 rats, chronic morphine administration was associated with activation of nitric oxide function. In contrast, changes in the gene expression of PD7 rats suggested superoxide and peroxide metabolisms may be engaged. These data indicate that there is supraspinal neuroplasticity following morphine administration as early as PD7. Furthermore, oxidative stress pathways associated with chronic morphine exposure appear age-specific.

Bajic, Dusica; Berde, Charles B.; Commons, Kathryn G.

2012-01-01

375

21 CFR 520.812 - Enrofloxacin tablets.  

Code of Federal Regulations, 2010 CFR

...2009-04-01 2009-04-01 false Enrofloxacin tablets. 520.812 Section 520...FORM NEW ANIMAL DRUGS § 520.812 Enrofloxacin tablets. (a) Specifications...68.0, or 136.0 milligrams of enrofloxacin. (b) Sponsor. See No....

2009-04-01

376

21 CFR 520.812 - Enrofloxacin tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Enrofloxacin tablets. 520.812 Section 520...FORM NEW ANIMAL DRUGS § 520.812 Enrofloxacin tablets. (a) Specifications...68.0, or 136.0 milligrams of enrofloxacin. (b) Sponsor. See No....

2010-04-01

377

Tablet computers in the veterinary curriculum.  

PubMed

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

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

2005-01-01

378

21 CFR 520.1288 - Lufenuron tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Lufenuron tablets. 520.1288 Section 520...FORM NEW ANIMAL DRUGS § 520.1288 Lufenuron tablets. (a) Specifications ...204.9, or 409.8 milligrams (mg) lufenuron for use as in paragraphs...

2010-04-01

379

21 CFR 520.1288 - Lufenuron tablets.  

Code of Federal Regulations, 2010 CFR

...2009-04-01 2009-04-01 false Lufenuron tablets. 520.1288 Section 520...FORM NEW ANIMAL DRUGS § 520.1288 Lufenuron tablets. (a) Specifications ...204.9, or 409.8 milligrams (mg) lufenuron for use as in paragraphs...

2009-04-01

380

Enhancing Student Performance Using Tablet Computers  

ERIC Educational Resources Information Center

Tablet PCs have the potential to change the dynamics of classroom interaction through wireless communication coupled with pen-based computing technology that is suited for analyzing and solving engineering problems. This study focuses on how tablet PCs and wireless technology can be used during classroom instruction to create an Interactive…

Enriquez, Amelito G.

2010-01-01

381

Putting Tablet PCs to the Test  

ERIC Educational Resources Information Center

Like many educators, the author and her colleagues (five faculty members and two IT techs) in the department of Media Communications and Technology at East Stroudsburg University in Pennsylvania were interested to find out the status of tablet PCs in education. Microsoft listed 10 manufacturers of tablet PCs following two forms: the slate and the…

Amirian, Susan

2004-01-01

382

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

Microsoft Academic Search

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

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

383

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

Microsoft Academic Search

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

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

2003-01-01

384

Bioequivalence Study of 30 mg Pioglitazone Tablets in Thai Healthy Volunteers  

Microsoft Academic Search

Material and Method: A randomized, single dose, two-treatment, two-period, two-sequence crossover study was conducted. Twenty-four healthy volunteers were recruited at Siriraj Clinical Research Unit. Each subject received a 30 mg pioglitazone tablet of both formulations with at least a week washout period. Blood samples were collected over 48 h after the oral administration. The plasma fractions were analyzed for pioglitazone

Somruedee Chatsiricharoenkul; Piyapat Pongnarin

385

Comparative bioavailability of two immediate release tablets of enalapril\\/hydrochlorothiazide in healthy volunteers  

Microsoft Academic Search

Summary  A bioequivalence study of two oral formulations of 20\\/12.5 mg tablets of enalapril\\/hydrochlorothiazide was carried out in\\u000a 20 healthy male volunteers according to a single dose, two-sequence, crossover randomized design. One washout period of nine\\u000a days was observed between the two periods. Multiple samples were collected over 96 hours post-dosing. Bioavailability was\\u000a evaluated on the basis of plasma concentrations of

Manuela T. Maya; Nuno J. Goncalves; Nuno E. Silva; Augusto E. P. Filipe; José A. Morais; M. C. Caturla; M. Rovira

2002-01-01

386

A survey of patient preferences for a placebo orodispersible tablet  

PubMed Central

Aim 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.

Wade, Alan G; Crawford, Gordon M; Young, David

2012-01-01

387

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

PubMed

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

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

2010-09-01

388

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

PubMed

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

Marczy?ski, Zbigniew; Bodek, Kazimiera Henryka

2007-01-01

389

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

PubMed Central

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

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

2012-01-01

390

Oral hygiene products and acidic medicines.  

PubMed

Acidic or EDTA-containing oral hygiene products and acidic medicines have the potential to soften dental hard tissues. The low pH of oral care products increases the chemical stability of some fluoride compounds, favors the incorporation of fluoride ions in the lattice of hydroxyapatite and the precipitation of calcium fluoride on the tooth surface. This layer has some protective effect against an erosive attack. However, when the pH is too low or when no fluoride is present these protecting effects are replaced by direct softening of the tooth surface. Xerostomia or oral dryness can occur as a consequence of medication such as tranquilizers, anti-histamines, anti-emetics and anti-parkinsonian medicaments or of salivary gland dysfunction e.g. due to radiotherapy of the oral cavity and the head and neck region. Above all, these patients should be aware of the potential demineralization effects of oral hygiene products with low pH and high titratable acids. Acetyl salicylic acid taken regularly in the form of multiple chewable tablets or in the form of headache powder as well chewing hydrochloric acids tablets for treatment of stomach disorders can cause erosion. There is most probably no direct association between asthmatic drugs and erosion on the population level. Consumers, patients and health professionals should be aware of the potential of tooth damage not only by oral hygiene products and salivary substitutes but also by chewable and effervescent tablets. Additionally, it can be assumed that patients suffering from xerostomia should be aware of the potential effects of oral hygiene products with low pH and high titratable acids. PMID:16687890

Hellwig, E; Lussi, A

2006-01-01

391

Interactions between 3,4-methylenedioxymethamphetamine, methamphetamine, ketamine, and caffeine in human intestinal Caco-2 cells and in oral administration to rats  

Microsoft Academic Search

Amphetamine-type stimulants (ATSs) are often abused orally in the form of tablets for recreational purposes. The ATS tablets contain one or more active ingredients such as 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine (MA), ketamine (KA), and caffeine (CF). The aim of this work is to determine whether such components in tablets interact with each other in intestinal absorption. The interactions between MDMA, MA,

Kenji Kuwayama; Hiroyuki Inoue; Tatsuyuki Kanamori; Kenji Tsujikawa; Hajime Miyaguchi; Yuko Iwata; Seiji Miyauchi; Naoki Kamo; Tohru Kishi

2007-01-01

392

Dexamethasone mimics the inhibitory effect of chronic pain on the development of tolerance to morphine analgesia and compensates for morphine induced changes in G proteins gene expression.  

PubMed

It is previously reported that the HPA axis plays role in the inhibitory effect of pain on tolerance development to analgesic effect of opioids. The present study was designed to investigate whether the chronic co-administration of dexamethasone as a glucocorticoid is also able to prevent or reverse analgesic tolerance to morphine and to compare the expression of G(alphai/o) and G(beta) subunits of G proteins in the context of chronic dexamethasone, development of morphine tolerance and their combination. Analgesic tolerance to morphine was induced by chronic intraperitoneally (i.p.) administration of morphine 20 mg/kg to male Wistar rats weighing 200-240 g within 4 consecutive days and analgesia was assessed using tail-flick test. Chronic dexamethasone was applied using 4 daily i.p. injections. Lumbar spinal tissues were assayed for the expression of G(alphai/o) and G(beta) proteins using "semiquantitative PCR" normalized to beta-actin gene expression. Results showed that chronic administration of dexamethasone could reduce and reverse the development of tolerance in rats that received chronic i.p. injections of morphine. Chronic administration of dexamethasone significantly increased the expression of G(alphai/o), while chronic administration of morphine did not change its expression. The expression of G(beta), however, was increased after the chronic administration of morphine, but did not change after the administration of chronic dexamethasone. None of these increases were observed when morphine and dexamethasone were co-administered. We conclude that the development of tolerance to analgesic effect of morphine could be prevented and reversed by dexamethasone co-administration. The increase in G(alphai/o) genes expression produced by chronic dexamethasone may facilitate the opioid signaling pathway and compensate for morphine-induced tolerance. PMID:16828064

Javan, Mohammad; Kazemi, Bahram; Ahmadiani, Abolhassan; Motamedi, Fereshteh

2006-08-01

393

Chronic Morphine Treatment Inhibits LPS Induced Angiogenesis: Implications in Wound healing  

PubMed Central

Delayed wound healing is a chronic problem in opioid drug abusers. We investigated the role chronic morphine plays on later stages of wound healing events using an angiogenesis model. Our results show that morphine treatment resulted in a significant decrease in inflammation induced angiogenesis. To delineate the mechanisms involved we investigate the role of hypoxia inducible factor 1 alpha (HIF-1 alpha), a potent inducer of angiogenic growth factor. Morphine treatment resulted in a significant decrease in the expression and nuclear translocation of HIF-1 alpha with a concurrent suppression in vascular endothelial growth factor (VEGF) synthesis. Cells of the innate immune system play a dominant role in the angiogenic process. Morphine treatment inhibited early recruitment of both neutrophils and monocytes towards an inflammatory signal with a significant decrease in the monocyte chemoattractant MCP-1. Taken together, our studies show that morphine regulates the wound repair process on multiple levels. Morphine acts both directly and indirectly in suppressing angiogenesis.

Martin, Josephine L.; Charboneau, Richard; Barke, Roderick A.; Roy, Sabita

2010-01-01

394

New oral solid dosage form for furosemide oral administration.  

PubMed

Furosemide (FURO) is a drug labeled in class IV of the Biopharmaceutics Classification System (BCS) as it is both poor soluble and poor permeable. The aim of this work was to improve FURO biopharmaceutical properties by its formulation in a new solid oral dosage form. It consists in the realization of the composite MgAl-HTlc-FURO, obtained by FURO intercalation into the inorganic matrix hydrotalcite (MgAl-HTlc), and its successive formulation in tablets intended to be swallowed whole and to disintegrate rapidly in the stomach. These formulations were prepared by direct compression of a simple powder mixture constituted by MgAl-HTlc-FURO, a super disintegrant (Explotab, PolyplasdoneXL, PolyplasdoneXL-10, PolyplasdoneINF 10 or L-HPCLH-21) and a filler. The prepared formulations were submitted to disintegration time tests, and only those displaying the lowest disintegration time in gastric medium were submitted to in vitro release studies. Drug dissolution profiles from MgAl-HTlc-FURO tablets were compared with those containing crystalline FURO alone or physically mixed to MgAl-HTlc instead of MgAl-HTlc-FURO. The results revealed that tablets containing MgAl-HTlc-FURO give the best dissolution profile and that L-HPCLH-21 is able to promote the highest drug release in gastric medium, resulting in the most suitable super disintegrant in comparison with the other tested. PMID:22230797

Perioli, Luana; D'Alba, Giuseppina; Pagano, Cinzia

2012-04-01

395

Pharmacokinetics of pramiracetam in healthy volunteers after oral administration.  

PubMed

The pharmacokinetics of pramiracetam was assessed using an HPLC method after oral administration of two different formulations of 600 mg (a solution and a tablet) of pramiracetam to 11 fasting volunteers. The mean kinetic parameters were: t1 = 4.7 +/- 2.4 - 4.3 +/- 2.2 h, AUC = 57.6 +/- 43.6 - 47.2 +/- 33.9 micrograms h/ml, Cmax = 6.80 +/- 3.2 - 5.80 +/- 3.3 micrograms/ml for the solution and the tablet respectively. The plasma profile of pramiracetam proved to be not highly affected by the formulation, only that the absorption rate was faster after oral administration of the drug in solution than after administration as a tablet. The half-life was very variable between subjects [2-8 hours], but less variable within subjects and it was unaffected by the formulation. PMID:1473879

Auteri, A; Blardi, P; Celasco, G; Segre, G; Urso, R

1992-01-01

396

Development of Taste Masked Oral Formulation of Ornidazole  

PubMed Central

Taste masked microspheres of ornidazole were prepared using amino alkyl methacrylate copolymers (Eudragit E-100) by solvent evaporation technique. Taste assessment of these microspheres was done by both spectrophotometric taste evaluation technique and panel testing. Compressed tablets of taste masked ornidazole microspheres which rapidly disintegrated in the oral cavity were prepared using microcrystalline cellulose as directly compressible filler and sodium starch glycolate as a super-disintegrant. These were subsequently evaluated for various pharmacopoeial tests, drug release, and disintegration time in the oral cavity. Sensory taste evaluation was carried by panel testing in 20 healthy human volunteers. Results indicate successful formulation of oral fast disintegrating tablets which disintegrated in the oral cavity in about 30 s and possessed good taste.

Shishu; Kamalpreet; Kapoor, V. R.

2010-01-01

397

Repeated cannabinoid injections into the rat periaqueductal gray enhance subsequent morphine antinociception.  

PubMed

Cannabinoids and opiates inhibit pain, in part, by activating the periaqueductal gray (PAG). Evidence suggests this activation occurs through distinct mechanisms. If the antinociceptive mechanisms are distinct, then cross-tolerance between opioids and cannabinoids should not develop. This hypothesis was tested by measuring the antinociceptive effect of microinjecting morphine into the ventrolateral PAG of rats pretreated with the cannabinoid HU-210 for two days. Male Sprague-Dawley rats were injected twice a day for two days with vehicle (0.4 microL), morphine (5 microg/0.4 microL), HU-210 (5 microg/0.4 microL), or morphine combined with HU-210 into the ventrolatera