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1

Long-term rectal administration of high-dose sustained-release morphine tablets  

Microsoft Academic Search

Two proprietary sustained-release morphine tablets for oral administration are available in the USA, and the authors have found that rectal administration of these provide excellent analgesia although their use by this route is not approved by the United States Food and Drug Administration. An illustrative case in a 72-year-old patient with prostate cancer is reported.

Declan Walsh; Pamela S. Tropiano

2002-01-01

2

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

Microsoft Academic Search

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

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

1990-01-01

3

Oral Clonidine Premedication Enhances Postoperative Analgesia by Epidural Morphine  

Microsoft Academic Search

This study was designed to evaluate the effects of oral clonidine premedication on postoperative analgesia by epidural morphine in a prospective, randomized, double- blinded design. Sixty consenting patients, scheduled for total abdominal hysterectomy, were randomly assigned to one of three groups (n 5 20 each); the clonidine- morphine group received oral clonidine 5 mg\\/kg 90 min before arriving in the

Toru Goyagi; Makoto Tanaka; Toshiaki Nishikawa

1999-01-01

4

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

PubMed Central

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

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

2008-01-01

5

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

Federal Register 2010, 2011, 2012, 2013

...FDA-2011-P-0822] Determination That AVALIDE (Hydrochlorothiazide and Irbesartan), Oral Tablets...has determined that AVALIDE (hydrochlorothiazide and irbesartan), oral tablets...drug applications (ANDAs) for hydrochlorothiazide and irbesartan, oral...

2012-01-11

6

Oral administration of dextromethorphan prevents the development of morphine tolerance and dependence in rats  

Microsoft Academic Search

Combined oral administration of morphine sulfate (MS) and the over-the-counter antitussive drug and N-methyl-d-aspartate receptor antagonist dextromethorphan (DM) prevented the development of tolerance to the antinociceptive effects of MS (15, 24, or 32 mg\\/kg) in rats. This combined oral treatment regimen also attenuated signs of naloxone-precipitated physical dependence on morphine in the same rats. A wide range of ratios of

Jianren Mao; Donald D. Price; Frank S. Caruso; David J. Mayer

1996-01-01

7

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

PubMed

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 (20 mg), morphine (30 mg), THC-morphine (20 mg THC+30 mg morphine), or placebo were given orally and as single doses. Twelve healthy volunteers were included in the randomized, placebo-controlled, double-blinded, crossover study. The experimental pain tests (order randomized) were heat, cold, pressure, single and repeated transcutaneous electrical stimulation. Additionally, reaction time, side-effects (visual analog scales), and vital functions were monitored. For the pharmacokinetic profiling, blood samples were collected. THC did not significantly reduce pain. In the cold and heat tests it even produced hyperalgesia, which was completely neutralized by THC-morphine. A slight additive analgesic effect could be observed for THC-morphine in the electrical stimulation test. No analgesic effect resulted in the pressure and heat test, neither with THC nor THC-morphine. Psychotropic and somatic side-effects (sleepiness, euphoria, anxiety, confusion, nausea, dizziness, etc.) were common, but usually mild. PMID:14499423

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

2003-09-01

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

Oral administration of dextromethorphan prevents the development of morphine tolerance and dependence in rats.  

PubMed

Combined oral administration of morphine sulfate (MS) and the over-the-counter antitussive drug and N-methyl-D-aspartate receptor antagonist dextromethorphan (DM) prevented the development of tolerance to the antinociceptive effects of MS (15, 24, or 32 mg/kg) in rats. This combined oral treatment regimen also attenuated signs of naloxone-precipitated physical dependence on morphine in the same rats. A wide range of ratios of MS to DM (2:1, 1:1, and 1:2) were effective for preventing the development of morphine tolerance and dependence. In addition, we provide evidence that under certain circumstances DM increases the acute antinociceptive effects of MS. All of these results indicate that oral treatment that combines DM with opiate analgesics may be a powerful approach for simultaneously preventing opiate tolerance and dependence and enhancing analgesia in humans. PMID:8951930

Mao, J; Price, D D; Caruso, F S; Mayer, D J

1996-10-01

10

Relative bioavailability of ofloxacin tablets in comparison to oral solution.  

PubMed

Single oral doses of solution and tablet preparations of 300 mg ofloxacin were given to 13 healthy male volunteers in an open, randomized crossover study. Concentrations of the unchanged drug were monitored at various times in serum and urine, over 28 hours and 48 hours, respectively. Each dose was followed by a 1-week washout period. Drug concentrations were measured both by a specific high pressure liquid chromatography (HPLC) method and a microbiological assay. A linear distribution independent regression analysis for method comparisons was calculated and good agreement between the two methods was found. Medians of maximum serum concentrations (Cmax) of ofloxacin after oral solution and tablet form were 5.0 mg/l and 3.5 mg/l, respectively. The times to maximal serum concentration (tmax) were 0.5 hr and 1.0 hr, respectively. The lower Cmax and later tmax after the tablet form were both statistically (p less than 0.05) different when compared to the corresponding values after the oral solution. However, the areas under the serum concentration-time curves (AUC0-28), as also the urinary recoveries did not differ significantly, showing that only the speed of absorption, but not the bioavailability of the tablet is changed in comparison to the oral solution form. Long-lasting, clinically relevant urine concentrations of ofloxacin were observed after both forms until the last collecting fraction (36 to 48 hours after medication). General tolerability was good; no side-effects were reported. PMID:3479296

Malerczyk, V; Verho, M; Korn, A; Rangoonwala, R

1987-01-01

11

Utilisation de la morphine orale pour les douleurs post-traumatiques de l'enfant  

Microsoft Academic Search

Objectives. – To study the compliance of prescription, the efficacity and the adverse events of oral morphine used in the pediatric emergency departement (ED) in traumatic pains.Method. – This prospective study was conducted in the ED from october 2002 to september 2003. Children aged six months to 16 years with a visual analogic scale (VAS) score higher than 70 or with

C. Wille; N. Bocquet; B. Cojocaru; A. Leis; G. Chéron

2005-01-01

12

Mucoadhesive tablet releasing iodine for treating oral infections.  

PubMed

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

Mizrahi, Boaz; Domb, Abraham J

2007-11-01

13

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

14

Stability of benzocaine formulated in commercial oral disintegrating tablet platforms.  

PubMed

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

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

2013-12-01

15

Oral pharmacokinetic comparison of different genistein tablets in beagle dogs.  

PubMed

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

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

2013-04-01

16

Further improvement of orally disintegrating tablets using micronized ethylcellulose.  

PubMed

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

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

2012-02-28

17

Maximal bioavailability of digoxin from tablets and oral solution in steady state.  

PubMed

Comparison has been made between the absorption of digoxin from Lanoxin tablets and the absorption of international chemical reference substance digoxin from an oral solution. Plasma levels, areas under 24-hour plasma concentration curves and urinary excretion were similar by both formulations in steady state. 78% of the digoxin administered was absorbed from the tablets and 76% from the solution. Rapid dissolution in the intestinal fluids accounts for the high digoxin bioavailability of the tablets. PMID:937075

Manninen, V; Reissell, P; Ojala, K

1976-01-01

18

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

PubMed

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

Adeoye, Oluwatomide; Alebiowu, Gbenga

2014-01-01

19

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

PubMed

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

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

2009-12-01

20

Morphine Oral  

MedlinePLUS

... through your tube.If you are unable to swallow the long-acting capsules (Avinza, Kadian), you can ... spoonful of cold or room temperature applesauce, and swallow the entire mixture immediately without chewing or crushing ...

21

Pharmacokinetic comparison of oral solution and tablet formulations of citalopram: a single-dose, randomized, crossover study  

Microsoft Academic Search

Background: Citalopram tablets fulfill most dosing needs in the treatment of depression, but some patients may have difficulty swallowing tablets and thus may be less likely to comply with their medication regimen. A liquid formulation of citalopram could be beneficial for such patients.Objective: This study was undertaken to compare the pharmacokinetic profiles of oral solution and tablet formulations of citalopram

Marcelo M. Gutierrez; Wattanaporn Abramowitz

2000-01-01

22

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

PubMed

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

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

2013-10-01

23

Oral mucosal ulceration due to ferrous sulphate tablets: report of a case.  

PubMed

Recurrent oral ulceration due to underlying iron-deficiency anaemia is already recognized. However, this case report describes a 78-year-old lady who developed severe ulceration of the tongue and floor of the mouth as a result of the treatment of iron-deficiency anaemia with ferrous sulphate tablets. Withdrawal of the ferrous sulphate tablets and replacement with ferrous fumarate syrup led to resolution of the lesion. PMID:17209540

Jones, Terry A; Parmar, Satyesh C

2006-12-01

24

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

25

Pharmacokinetics of naproxen after oral administration of two tablet formulations in healthy volunteers.  

PubMed

The pharmacokinetics of two naproxen tablet formulations were compared after oral administration. The 250-mg naproxen tablets, tablet I from AFI, Oslo, Norway, and tablet II Naprosyn, Astra-Syntex, were taken by 12 healthy volunteers in a randomized two-period crossover study. Plasma levels of naproxen were measured by a sensitive and specific HPLC method. The data were analyzed by means of two-way analysis of variance to test for significant differences between tablet formulation and differences between the first and second trial periods. Rapid absorption, with most Cmax values from 50-60 micrograms/ml reached within 1.5-3 h, was found for both tablet formulations. No significant difference was found in the rate and extent of absorption between the two formulations: the relative bioavailability of tablet I compared to tablet II was 1.05 +/- 0.21 (mean +/- SD). The naproxen concentration 2 h after ingestion and the Cmax were higher on the second occasion, regardless of preparation, suggesting that the subjects were clinically different on the two occasions. PMID:6885201

Aarbakke, J; Gadeholt, G; Høylandskjaer, A

1983-06-01

26

Effect of powder characteristics on oral tablet disintegration.  

PubMed

This report describes an investigation of the factors affecting disintegration time in the mouth (DTM) of rapidly disintegrating tablets. The relation between DTM and stationary time of upper punch displacement (STP) was examined using a tableting process analyzer (TabAll). Results indicated that the bulk density of mixed excipient powder used for tablet preparation affects both DTM and STP. As the value of bulk density increased, STP became longer and DTM shorter. The results of a combination of granules and powder with or without a drug showed liner relation between apparent volume (reciprocal of bulk density) and DTM (r(2)=0.7332). For a DTM less than 60 s, a formulation with a bulk density greater 0.5 g/mL should be chosen with a compression force of 5 kN. The hardness of tablets could be greater than 3 kg if at least one high-compressibility excipient was used in the formulation. PMID:18804156

Yamamoto, Yoshihisa; Fujii, Makiko; Watanabe, Ken-ichi; Tsukamoto, Masashi; Shibata, Yusuke; Kondoh, Masuo; Watanabe, Yoshiteru

2009-01-01

27

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

PubMed Central

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

Moghimipour, Eskandar; Aghel, Nasrin; Adelpour, Akram

2012-01-01

28

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

PubMed

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

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

2014-01-01

29

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

PubMed

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

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

2010-09-01

30

Levetiracetam: Relative Bioavailability and Bioequivalence of a 10% Oral Solution (750 mg) and 750-mg Tablets  

Microsoft Academic Search

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

René Coupez; Roel Straetemans; Geeta Sehgal; Armel Stockis

2003-01-01

31

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

PubMed

One of the promising approaches to predict in vivo disintegration time of orally disintegrating tablets (ODT) is the use of texture analyzer instrument. Once the method is able to provide good in vitro in vivo correlation (IVIVC) in the case of different tablets, it might be able to predict the oral disintegration time of similar products. However, there are many tablet parameters that influence the in vivo and the in vitro disintegration time of ODT products. Therefore, the measured in vitro and in vivo disintegration times can occasionally differ, even if they coincide in most cases of the investigated products and the in vivo disintegration times may also change if the aimed patient group is suffering from a special illness. If the method is no longer able to provide good IVIVC, then the modification of a single instrumental parameter may not be successful and the in vitro method must be re-set in a complex manner in order to provide satisfactory results. In the present experiment, an optimization process was developed based on texture analysis measurements using five different tablets in order to predict their in vivo disintegration times, and the optimized texture analysis method was evaluated using independent tablets. PMID:23558313

Szakonyi, G; Zelkó, R

2013-05-20

32

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

PubMed

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

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

2009-01-01

33

Clinical equivalence between deflazacort oral drops and tablets in active rheumatoid arthritis.  

PubMed

In order to assess the clinical equivalence between deflazacort oral drops and tablets, 18 patients with active rheumatoid arthritis were enrolled in an open, controlled, randomised ('tablets --> drops' sequence, or vice versa), two-period (21 days each) crossover trial (from tablets to drops, or vice versa). Individual dose titration of deflazacort drops or tablets was made weekly on the basis of clinical need. Primary outcome measures of efficacy were changes in the joint swelling count (JSC), erythrocyte sedimentation rate (ESR), hand-grip strength (HGS), joint pain (JP), duration of morning stiffness (MS), physician's global evaluation and patient's self-assessment. Sixteen patients were available by the end of the study. The formulations were equivalent with respect to HGS and improvement in duration of MS, and close to equivalence with respect to JSC and ESR decrease; the drops seemed to be more effective than tablets with respect to JP reduction. No differences between the two formulations were observed with respect to physician's and patient's assessment. The minimum effective dose of each preparation and the relative potency ratio were also established. Drops and tablets were found to have the same potency. PMID:10357120

Di Munno, O; Mazzantini, M; Milani, S; Pasero, G

1999-01-01

34

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

35

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

PubMed Central

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

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

2010-01-01

36

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

37

Preparation and evaluation of taste-masked dextromethorphan oral disintegrating tablet.  

PubMed

This study was aimed at preparing and evaluating oral disintegrating tablets (ODTs) using a strongly cationic resin, Amberlite(®) IRP-69, to mask the bitter taste of a delivered drug, i..e. dextromethorphan hydrobromide. The drug was loaded into the resin (referred to as resinate) or physically mixed with the resin (referred to as physical mixture), and was then incorporated into ODTs by direct compression. A variety of formulae was developed to acquire the optimal formulations of taste-masked ODTs that had acceptable hardness and mouth feel (grittiness). The optimized ODTs were further evaluated for thickness, diameter, weight, friability, disintegration time, wetting time, wetting rate, drug content, drug release and degree of bitter taste, respectively. The thickness, diameter, weight and friability of the tablet with resinate were slightly higher than those with physical mixture. The tablet with resinate had a longer disintegration time, corresponding with its slower wetting time and rate. Both tablets with resinate and physical mixture provided a sustained pattern of drug release. However, only tablets with resinate successfully masked the bitter taste of the drug. In conclusion, the combination of drug and ion exchange resin as resinate could increase the palatability and acceptability of ODTs containing bitter drugs. PMID:21142821

Samprasit, Wipada; Opanasopit, Praneet; Akkaramongkolporn, Prasert; Ngawhirunpat, Tanasait; Wongsermsin, Kaewnapa; Panomsuk, Suwannee

2012-01-01

38

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

39

Pulmonary Effects of IV Injection of Crushed Oral Tablets: "Excipient Lung Disease".  

PubMed

OBJECTIVE. When crushed oral tablets are injected IV, their filler material (excipient) can induce a potentially fatal foreign-body reaction in pulmonary arterioles, presenting as dyspnea and pulmonary hypertension with centrilobular nodules on CT. We will describe the imaging and pathologic features of "excipient lung disease." CONCLUSION. The radiologist has a critical role in recognizing and reporting excipient lung disease because the referring clinician may be unaware of the patient's IV drug abuse. PMID:25341165

Nguyen, Vicky T; Chan, Elaine S; Chou, Shinn-Huey S; Godwin, J David; Fligner, Corinne L; Schmidt, Rodney A; Pipavath, Sudhakar N J

2014-11-01

40

A Novel Multilayered Multidisk Oral Tablet for Chronotherapeutic Drug Delivery  

PubMed Central

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

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

2013-01-01

41

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

PubMed

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

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

2009-01-01

42

SLEEP AND GABA LEVELS IN THE ORAL PART OF RAT PONTINE RETICULAR FORMATION ARE DECREASED BY LOCAL AND SYSTEMIC ADMINISTRATION OF MORPHINE  

PubMed Central

Morphine, a ?-opioid receptor agonist, is a commonly prescribed treatment for pain. Although highly efficacious, morphine has many unwanted side effects including disruption of sleep and obtundation of wakefulness. One mechanism by which morphine alters sleep and wakefulness may be by modulating GABAergic signaling in brain regions regulating arousal, including the oral pontine reticular formation (PnO). This study used in vivo microdialysis in unanesthetized Sprague-Dawley rat to test the hypothesis that ?-opioid receptors modulate PnO GABA levels. Validation of the high performance liquid chromatographic technique used to quantify GABA was obtained by dialyzing the PnO (n=4 rats) with the GABA reuptake inhibitor nipecotic acid (500 ?M). Nipecotic acid caused a 185±20% increase in PnO GABA levels, confirming chromatographic detection of GABA and demonstrating the existence of functional GABA transporters in rat PnO. Morphine caused a concentration-dependent decrease in PnO GABA levels (n=25 rats). Coadministration of morphine (100 ?M) with naloxone (1 ?M), a ?-opioid receptor antagonist, blocked the morphine-induced decrease in PnO GABA levels (n=5 rats). These results show for the first time that ?-opioid receptors in rat PnO modulate GABA levels. A second group of rats (n=6) was used to test the hypothesis that systemically administered morphine also decreases PnO GABA levels. Intravenous morphine caused a significant (p<0.05) decrease (19%) in PnO GABA levels relative to control intravenous infusions of saline. Finally, microinjections followed by 2 h recordings of electroencephalogram and electromyogram tested the hypothesis that PnO morphine administration disrupts sleep (n=8 rats). Morphine significantly (p<0.05) increased the percent of time spent in wakefulness (65%) and significantly (p<0.05) decreased the percent of rapid eye movement (REM) sleep (-53%) and non-REM sleep (-69%). The neurochemical and behavioral data suggest that morphine may disrupt sleep, at least in part, by decreasing GABAergic transmission in the PnO. PMID:17055662

Watson, Christopher J.; Lydic, Ralph; Baghdoyan, Helen A.

2009-01-01

43

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

PubMed

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

Jones, Joseph; Tomlinson, Kimberly; Moore, Christine

2002-04-01

44

Evaluating the Effects of Oral Morphine on Embryonic Development of Cerebellum in Wistar Rats  

PubMed Central

In the present research, the effect of morphine consumption during pregnancy on the development of the embryo's spinal cord was studied in Wistar rat. Female Wistar rats (Wt: 250-300 g) were mated with males. The test group received morphine (0.01 mg/ml) in their drinking water. Pregnant rats were later killed with chloroform on the 12th, 13th and 14th days of pregnancy, and the embryos were taken out surgically. The embryos were fixed in formalin 10% for 2 weeks. Then, the weight of fixed embryos was calculated by a scale. In addition, several animals’ sizes including fronto-posterior and lateral length were measured by a caliper. Tissue processing, sectioning and hematoxylin and eosin (H&E) staining were applied for the embryos. The sections were examined for spinal cord development by light microscope and MOTIC software. Significant decrease was observed in the fronto-posterior and lateral length and the weight of the embryos in the test groups. The thickness of the white matter layer decreased on the 12th, 13th and 14th embryonic days. The thickness of the spine's grey layer was also less than the control group, on the same days. Increase in the length of the ependimal duct observed as well. Number of grey substance cells decreased compared to the control group within the same days. Meanwhile, thickness of the germinal layer reduced in comparison to the control group on the mentioned days. In conclusion, morphine consumption during pregnancy causes defects in growth and completion of the spinal cord. PMID:25337339

Niknam, Narges A.; Azarnia, Mahnaz; Bahadoran, Hossein; Kazemi, Masoomeh; Tekieh, Elaheh; Ranjbaran, Mina; Sahraei, Hedayat

2013-01-01

45

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

PubMed

Disintegration time is an important characteristic of orally disintegrating tablets (ODTs), and evaluation of disintegration time is a key step in formulation development, manufacturing, and clinical practice. In this study, we aimed to clarify the clinical disintegration time of ODTs that are currently used clinically, and to evaluate its correlation with the in vitro disintegration time of ODTs which was measured using Tricorptester, a newly developed disintegration testing apparatus. The clinical disintegration time of 17 ODT products was measured in healthy volunteers (n=9-10; age range, 21-28 years). A randomized single-blind trial was performed; each tablet was placed on the tongues of the participants, and it disintegrated in their oral cavities. No significant difference was observed in the clinical disintegration time of each ODT among the 3 groups to which the subjects were randomly assigned. The clinical disintegration time of the 17 ODT products was between 17.6 s and 33.8 s. The in vitro disintegration time of 26 clinically used ODT products measured using Tricorptester ranged between 4.40 s and 30.4 s. A significant positive correlation was observed between in vitro and clinical disintegration times (r=0.79; p<0.001). This study shows that all the tested products, which are clinically available in Japan, showed good disintegration and that the disintegration time varied according to the product. In addition, the in vitro disintegration time of ODTs measured using Tricorptester is a good reflection of the disintegration time in the oral cavity. PMID:23995661

Yoshita, Tomohiro; Uchida, Shinya; Namiki, Noriyuki

2013-01-01

46

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

PubMed Central

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

Tayebi, Hoda; Mortazavi, Seyed Alireza

2011-01-01

47

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

PubMed

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

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

2014-01-01

48

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

49

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

PubMed

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

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

2013-01-01

50

The Relative Potency between High Dose Oral Oxycodone and Intravenous Morphine  

Microsoft Academic Search

Oxycodone is an effective opioid analgesic for cancer pain. In the United States, it is available exclusively as an oral formulation, predominantly in fixed dose combination with acetaminophen or aspirin. The latter limits its use in cancer pain due to the potential toxicity of the nonopioid component. Oxycodone is now available as a single agent, controlled release formulation. The following

Donna S Zhukovsky; Declan Walsh; Marie Doona

1999-01-01

51

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

PubMed Central

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

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

2010-01-01

52

The ACTION study: a randomized, open-label, multicenter trial comparing once-a-day extended-release morphine sulfate capsules (AVINZA) to twice-a-day controlled-release oxycodone hydrochloride tablets (OxyContin) for the treatment of chronic, moderate to severe low back pain.  

PubMed

This large, open-label, randomized, parallel-group, multicenter study compared two oral sustained-release opioids (SROs)--AVINZA (A-MQD), morphine sulfate extended-release capsules given once a day, and OxyContin (O-ER), oxycodone modified-release tablets given twice a day--in SRO-naive subjects ages 30 to 70 with chronic, moderate to severe low back pain. Of the 392 subjects enrolled and randomized, 266 (132 in the A-MQD group and 134 in the O-ER group) completed the opioid dose titration phase and entered an eight-week evaluation phase. During the evaluation phase, A-MQD achieved significantly better pain control than O-ER, as demonstrated by a greater decrease from baseline in pain scores obtained four times daily during weeks one, four, and eight (p = 0.002). The number of breakthrough-pain rescue medication doses adjusted for the number of patient days was significantly lower in the A-MQD group (p < 0.0001). Better pain control with A-MQD was achieved with a significantly lower daily opioid dose than with O-ER (mean 69.9 mg and 91 mg morphine equivalents, respectively; p = 0.0125). Quality of sleep was significantly better with A-MQD for the entire evaluation phase (p = 0.0026). The incidence and severity of elicited opioid side effects were similar in the two groups. This trial demonstrated that once-daily A-MQD provides consistent around-the-clock pain relief in patients with low back pain. In patients who completed opioid dose titration, A-MQD was significantly better than O-ER for reducing pain and improving sleep, while requiring a lower daily opioid dose. PMID:17319449

Rauck, Richard L; Bookbinder, Stephen A; Bunker, Timothy R; Alftine, Christopher D; Ghalie, Richard; Negro-Vilar, Andres; de Jong, Egbert; Gershon, Steven

2006-01-01

53

Time-Dependent Effect of Oral Morphine Consumption on the Development of Cytotrophoblast and Syncytiotrophoblast Cells of the Placental Layers during the Three Different Periods of Pregnancy in Wistar Rats  

PubMed Central

Previous studies have shown that morphine abuse during pregnancy cancause a delay in the development of the placenta and embryo and also bring about birth defects. The present study investigates the effect of the duration of maternal morphine consumption during pregnancy, as well as the impacts of morphine abuse on the development of placental layers during the three different periods of pregnancy in Wistar rats. Materials and Methodology. Female Wistar rats have been used in the present study. Experimental groups received morphine (0.05?mg/mL of drinking water) after one night of coupling with male rats for mating. On 9th, 10th, and 14th days of pregnancy, pregnant animals were killed, and placentas were removed and fixed. The cells of the placentas layers were calculated by light microscope and MOTIC and SPSS software. Results. The maternal surface thickness of the placenta was significantly increased, whereasthe fetal surface thickness of placenta was significantly decreased with morphine consumption with a time-dependent manner in experimental groups, compared to control groups. Moreover, the number of trophoblast cells increased in both maternal and fetal surfaces of placenta with respect to the duration of morphine consumption which was overt in the experimental groups compared to the control groups. Conclusion. In general, the time-dependent effects of oral morphine consumption can inhibit the development and natural functioning of cytotrophoblast and syncytiotrophoblast cells of the placental layers. PMID:23533457

Dehghani, Leila; Sahraei, Hedayat; Meamar, Rokhsareh; Kazemi, Masoomeh

2013-01-01

54

Improved oral bioavailability of lopinavir in melt-extruded tablet formulation reduces impact of third trimester on lopinavir plasma concentrations.  

PubMed

Lopinavir exposure was reduced during the third trimester in pregnant women receiving standard dosing of the soft-gel capsule (SGC; 400/100 mg twice daily [b.i.d.]). Pharmacokinetic data on the lopinavir tablet in pregnancy are limited. On the basis of the tablet's improved bioavailability, standard dosing (400/100 mg b.i.d.) may provide adequate lopinavir exposure in pregnancy without a need for dose adjustment. Here we compared the total and unbound lopinavir pharmacokinetics throughout pregnancy in the second and third trimesters in HIV-infected women receiving standard dosing of the lopinavir SGC or tablet. Postpartum sampling was also performed in patients continuing therapy postdelivery. Blood samples were collected at 0 to 12 h postdosing, and lopinavir concentrations were determined by high-pressure liquid chromatography-tandem mass spectrometry. Nineteen patients were included: 8 received the SGC (cohort 1) and 11 received the tablet (cohort 2). Total lopinavir exposures in the third trimester were lower than those in the second trimester (35 and 28% for cohorts 1 and 2, respectively) and postpartum (35% for cohort 2). In the third trimester, the area under the concentration-time curve (AUC) from 0 to 12 h (AUC(0-12)) and maximum concentration were ?15% and 25% higher, respectively, for the lopinavir tablet than the SGC. One SGC patient had lopinavir concentrations of <1,000 ng/ml; all patients on the tablet had concentrations of >1,000 ng/ml. In cohort 2, the percentage of the AUC that was unbound was higher (nonsignificantly) in the second (1.28%) and third (1.18%) trimesters than postpartum (1.01%). Seventeen of 19 patients had an undetectable viral load at delivery. There were no HIV transmissions. Although lopinavir (tablet) exposures were reduced during the third trimester, the higher total and unbound concentrations achieved in women receiving the tablet than in women receiving the SGC suggest that the tablet's improved oral bioavailability may partly compensate for the reduction in lopinavir exposure during the later stages of pregnancy. PMID:22106215

Else, L J; Douglas, M; Dickinson, L; Back, D J; Khoo, S H; Taylor, G P

2012-02-01

55

Biopharmaceutical characterization of oral theophylline and aminophylline tablets. Quantitative correlation between dissolution and bioavailability studies.  

PubMed

Considering the narrow therapeutic index of theophylline and the low range between the safe and toxic serum concentrations of this drug, the study of its pharmacokinetic properties is necessary. However, considering the time consuming and expensive in vivo tests, quantitative correlation between in vivo bioavailability and in vitro dissolution tests can be used routinely in quality control tests of these drug products to predict the in vivo pharmacokinetic parameters. For this reason healthy human volunteers were used for in vivo studies and serum samples were analyzed by a fluorescence polarization immunoassay analysis (FPIA) method. The results showed that an open one compartmental model could best describe the pharmacokinetic properties of orally administered theophylline and aminophylline tablets. Linear regression analysis by least-square method showed a good correlation between some in vivo and in vitro parameters obtained from dissolution studies by rotating basket and paddle methods. D(30)% (percentage of drug dissolved in vitro after 30 min) and F(0.5)% (drug absorbed in vivo after half an hour calculated by Wagner-Nelson equation) showed best correlation (r=0. 99036). C(max) (maximum serum concentration) of this drug also correlates well with t(25%) (time required to dissolve 25% of the drug). The calculated correlation coefficients could best predict the actual values of some pharmacokinetic parameters; AUC(0-->infinity), AUC(0-->1), F(0.5)% and C(max). PMID:10962242

Varshosaz, J; Ghafghazi, T; Raisi, A; Falamarzian, M

2000-09-01

56

[Modernity in the treatment of erectile dysfunction: Levitra (vardenafil) in the form of oral dispersible tablet].  

PubMed

Due to high efficiency, prompt action and low incidence of side effects, phosphodiesterase type 5 inhibitors are the drugs of first choice in the treatment of erectile dysfunction (ED). One of the most widely used drugs in this group currently is vardenafil. Vardenafil has a number of properties that distinguish it from other drugs in this group: high selectivity and the highest inhibitory activity. Recently, new form of this drug, an oral-dispersible tablet (Levitra ODT) was developed. It dissolves in the mouth for a few seconds and does not required to drink water. This feature Levitra ODT enables easy administration of the drug, which provides the desired effect at any time and in any circumstances. Studies have shown that of simplicity of drug intake is one of the most important characteristics of the "ideal" treatment for erectile dysfunction from the point of view of patients. Currently, Levitra ODT is available at a dose of 10 mg. Two large, randomized, double-blind placebo-controlled studies, POTENT I and POTENT II, with participation of more than 700 patients with erectile dysfunction divided into 2 age groups, have shown a high efficacy and good tolerability of Levitra ODT in both groups. Thus, Levitra ODT is a new and promising form of the drug vardenafil, more convenient to use. There is no doubt that Levitra ODT will occupy an important place in the arsenal of modern methods of treatment of erectile dysfunction due to its high efficacy, good tolerability and usability. PMID:23987060

Gamidov, S I; Iremashvili, V V; Popova, A Iu

2013-01-01

57

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

PubMed Central

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

Nabais, Teresa; Leclair, Gregoire

2014-01-01

58

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

PubMed

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

Nabais, Teresa; Leclair, Grégoire

2014-01-01

59

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

60

Risperidone oral solution versus standard tablets for the acute treatment of patients with schizophrenia.  

PubMed

The time required to attain the maximum plasma level of risperidone (RIS) is shorter for RIS oral solution (OS) than for RIS standard tablets (ST), although both forms have equal bioavailability. The objective of this study was to clarify whether RIS-OS shows a faster onset of efficacy and lower adverse events than RIS-ST. The two forms of risperidone were compared with respect to effectiveness including a speed of response, efficacy and tolerability. An open-label, 24-week, multicentre, randomized, flexible-dose study comparing the RIS-OS (mean dose, 3.7 mg; N=44) to the RIS-ST (mean dose, 3.7 mg; N=37) in acutely ill patients with schizophrenia showed no differences. Outcome measures included psychopathology, tolerability (extrapyramidal symptoms and serum prolactin), and Drug Attitude Inventory. This study was conducted between October 2006 and October 2008. Both RIS-OS- and RIS-ST-treated patients showed statistically significant reductions from the baseline in the mean scores of the Positive and Negative Syndrome Scale (PANSS)-total and PANSS-excite component, with no statistically significant differences between the treatment groups. The accumulated treatment response ratio was similar between the two groups. There was no significant difference in the Drug-Induced Extrapyramidal Symptom Scale score or serum prolactin increase between the treatment groups, but RIS-OS appeared to induce less serum prolactin increase than RIS-ST in drug-naïve female patients. Because there is no theoretical reason why this should be so, these results will require confirmation from a double-blind study in a larger sample. No significant difference was observed in the subjective drug attitude between the two groups. The original hypothesis that RIS-OS shows an earlier onset of efficacy or less adverse events than RIS-ST was not supported in this study. Subsequent studies should carefully establish the differences among various forms of antipsychotic drugs. PMID:21168464

Kusumi, Ichiro; Honda, Minoru; Ito, Koichi; Uemura, Keiichi; Kumazawa, Yukie; Ishikane, Tomohito; Niide, Yasushi; Koyama, Tsukasa

2011-03-30

61

Comparative effects of different cellulosic-based directly compressed orodispersable tablets on oral bioavailability of famotidine  

Microsoft Academic Search

Famotidine is a potent H2-receptor antagonist most commonly used by elderly patients. Orodispersible tablets (ODT) are gaining popularity over conventional tablets due to their convenience and suitability for patients having dysphagia. The purpose of this study is to prepare famotidine ODT using the economic direct-compression method.A 32 full factorial design was used to evaluate the influence of different excipients on

A. Abdelbary; A. H. Elshafeey; G. Zidan

2009-01-01

62

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

PubMed

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

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

2014-07-01

63

Differential pharmacokinetics and the brain distribution of morphine and ephedrine constitutional isomers in rats after oral administration with Keke capsule using rapid-resolution LC-MS/MS.  

PubMed

Opioid and ephedra alkaloids known as the active ingredients for Keke capsule, which is used to treat coughs and bronchial asthma, could have potential adverse effects on the central nervous system. Therefore, an efficient, sensitive rapid-resolution LC-MS/MS method for the simultaneous determination of morphine, ephedrine, and pseudoephedrine in rat plasma and brain tissue homogenate has been developed. The method was validated in the plasma and brain tissue samples, showed good linearity over a wide concentration range (r(2) > 0.99). The intra- and interday assay variability was less than 15% for all analytes, and the accuracy was between -8.8 and 5.7%. The study provided the pharmacokinetics profiles and the brain regional distribution of the three active alkaloids after oral administration of Keke capsule. The results also indicated that significant difference in pharmacokinetics parameters of the epimers was observed between ephedrine and pseudoephedrine. PMID:24318005

Song, Yonggui; Su, Dan; Lu, Tulin; Mao, Chunqin; Ji, De; Liu, Yali; Wei, Binbin; Fan, Ronghua

2014-02-01

64

Urinary Excretion and Metabolism of Arbutin after Oral Administration of Arctostaphylos uvae ursi Extract as Film-Coated Tablets and Aqueous Solution in Healthy Humans  

Microsoft Academic Search

Bearberry leaves and preparations made from them are traditionally used for urinary tract infections. The urinary excretion of arbutin metabolites was examined in a randomized crossover design in 16 healthy volunteers after the application of a single oral dose of bearberry leaves dry extract (BLDE). There were two groups of application using either film-coated tablets (FCT) or aqueous solution (AS).

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

2002-01-01

65

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

66

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

PubMed

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

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

2005-05-30

67

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

68

Preparation and stability evaluation of extemporaneous oral suspension of valsartan using commercially available tablets.  

PubMed

The aim of this study was to develop an extemporaneous valsartan suspension (80 mg valsartan/5 mL) starting from commercial tablets (80-mg/ tablet). A high-performance liquid chromatographic system was used for the analysis and quantification of valsartan in the samples studied. Samples of valsartan suspension for analysis were prepared as reported by the validated high-performance liquid chromatographic method and the dissolution tests were performed according to the U.S. Food and Drug Administration's method. The high-performance liquid chromatographic assay indicated that the 80-mg/5-mL valsartan suspension was stable for 30 days when stored at long-term and accelerated storage conditions. Valsartan release profile showed that approximately 85% of valsartan dissolved after 10 minutes and, accordingly, the calculation of similarity factor was not necessary. It is possible for the pharmacist to crush valsartan 80-mg tablets and prepare a suspension which has dosage flexibility that can be calculated according to body-surface area, kidney, and liver functions, without affecting the chemical stability of the active ingredient nor its dissolution profile and also have a cost-effective dosage form. PMID:24881122

Zaid, Abdel Naser; Assali, Mohyeddin; Qaddomi, Aiman; Ghanem, Mashhour; Zaaror, Yara Abu

2014-01-01

69

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

PubMed Central

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

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

2014-01-01

70

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

PubMed Central

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

2014-01-01

71

A randomized cross-over study to evaluate the swallow-enhancing and taste-masking properties of a novel coating for oral tablets  

Microsoft Academic Search

Objective To explore the swallowing-enhancing and taste-masking effects of MedCoat, a new disposable device used to apply a coating\\u000a to tablets just before oral administration. Setting Kaunas Medical University Hospital in Lithuania. Method The study was performed as a randomized cross-over study. In total 41 subjects (20 male and 21 female) were enrolled in the\\u000a study. Subjects were healthy volunteers

Virgilijus UlozaIngrida Uloziene; Ingrida Uloziene; Egle Gradauskiene

2010-01-01

72

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

PubMed

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

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

2007-06-01

73

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

PubMed

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

Ono, Asami; Sugano, Kiyohiko

2014-11-20

74

Immediate or sustained-release morphine for dose finding during start of morphine to cancer patients: a randomized, double-blind trial  

Microsoft Academic Search

A titration procedure using immediate-release morphine given 4-hourly is recommended during start of oral morphine for cancer pain. This recommendation is not based on evidence from controlled studies, and many physicians start morphine treatment with controlled-release morphine. We included 40 patients with malignant disease and pain despite treatment with opioids for mild to moderate pain in a randomized, double-blind, double-dummy,

P Klepstad; Stein Kaasa; Åse Jystad; Bjørn Hval; Petter C Borchgrevink

2003-01-01

75

Comparative bioavailability of alpha-methyldopa normal and film tablet formulations after single oral administration in healthy volunteers  

Microsoft Academic Search

Summary  In a single dose, randomized, cross-over study, with one week of wash-out period, the relative bioavailability of Dopegyt®\\u000a tablets containing 250 mg alpha-methyldopa (AMD) and Presinol® film tablets with identical active ingredient content was examined\\u000a in 24 healthy volunteers.\\u000a \\u000a \\u000a Since technologically two completely different preparations (a film-tablet and a non-film-tablet) having significantly different\\u000a in vitro dissolution were to be compared,

K. Róna; K. Ary; G. Renczes; B. Gachályi; Gy. Grézal; S. Drabant; I. Klebovich

2001-01-01

76

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

77

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

PubMed Central

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

Gasperini, Claudio; Ruggieri, Serena; Pozzilli, Carlo

2010-01-01

78

A comparison of the bioavailability of digoxin in capsule, tablet, and solution taken orally with intravenous digoxin.  

PubMed

Six healthy volunteers were given five single-dose treatments of 0.40 mg digoxin either intravenously, in liquid form, in conventional tablet form (dissolution rate 76 per cent in 1-hour), or in new capsule preparations containing 0.05, 0.10, or 0.20 mg digoxin per capsule. Serum levels, area under the concentration-time curve, and daily urinary digoxin excretion were measured for six days. Higher serum digoxin levels were seen after ingestion of the capsules than after the tablets, with peak levels for the former being 2.2-2.8 times higher than after tablet digoxin. Bioavailability was assessed further by comparing the area under a six-hour concentration-time curve, and again the capsules gave a consistently higher value than the tablets. In addition, the absorption of 0.40 mg digoxin from any of the capsule preparations was much greater than 0.50 mg digoxin in commercially available tablets. The six-day cumulative urinary digoxin excretion was also greater for the capsules than for the 0.20-mg tablets. In comparison with intravenous digoxin, tablets provide 75 per cent maximum bioavailability, whereas the capsule preparations of digoxin improve the bioavailability of digoxin and the 0.20-mg digoxin capsule is absorbed better than 0.25-mg digoxin tablet. PMID:977789

Binnion, P F

1976-10-01

79

Nebulized Versus Subcutaneous Morphine for Patients with Cancer Dyspnea: A Preliminary Study  

Microsoft Academic Search

This study compared the effects of nebulized versus subcutaneous morphine on the intensity of dyspnea in cancer patients. Patients with a resting dyspnea intensity ?3 on a 0–10 scale (0=no dyspnea, 10=worst possible dyspnea) who received regular oral or parenteral opioids were included. On day 1, patients received either subcutaneous (SC) morphine plus nebulized placebo or nebulized morphine plus SC

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

2005-01-01

80

Quality assessment of morphine hydrochloride solutions.  

PubMed

The therapeutic substances in solution prepared in pharmaceutical laboratories (prescribed drugs) must preserve their activity. Therefore, they must be stable throughout the period of storage in home conditions. The maintenance of stability is particularly difficult for morphine hydrochloride solutions administered orally to cancer patients at the last stage of the disease being at home. This study, aiming at the assessment of stability of morphine hydrochloride solutions, was performed on samples of 0.5% water solutions of the drug alone, 0.25% and 0.5% solutions of the drug in water with chloroform as well as injection solutions (Morphinum hydrochloricum, 20 mg, Polfa Warsaw). All the samples were kept at 20 degrees C for six months. Throughout this time observations were made to detect changes in their appearence and pH values. Their qualitative composition was determined by TLC and the content of morphine was checked by UV spectrophotometry in an environment of 0.1 mol/l of hydrochloric acid at 285 nm. Results of the kinetic study permitted drawing conclusions as to the mechanism of the decomposition of morphine hydrochloride in the solutions studied - according to a simple first order reaction and determination of the rate constants (k, s(-1)) of the process. Results of the chromatographic and spectrophotometric study did not show differences in the stability of water and chloroform/water solutions of morphine hydrochloride studied after 4 weeks and 6 months. After that time the decrease of morphine content was 10 and 25%, respectively. PMID:15493291

P?otkowiak, Zyta; Popielarz-Brzezi?ska, Maria; Luczak, Jacek; Kluziak, Maciej

2004-01-01

81

Comparative bioavailability of alpha-methyldopa normal and film tablet formulations after single oral administration in healthy volunteers.  

PubMed

In a single dose, randomized, cross-over study, with one week of wash-out period, the relative bioavailability of Dopegyt tablets containing 250 mg alpha-methyldopa (AMD) and Presinol film tablets with identical active ingredient content was examined in 24 healthy volunteers. Since technologically two completely different preparations (a film-tablet and a non-film-tablet) having significantly different in vitro dissolution were to be compared, both preparations were compared to a third one, AMD solution (Dopegyt solution) with 250 mg/50 ml concentration. Plasma concentrations of the drug were measured for 24 hours post-dose, applying HPLC with fluorometric detection. Pharmacokinetic parameters calculated from individual data (AUC0-infinity, AUC0-t, Cmax, Cmax/AUC0-infinity, t(max)) were evaluated statistically. Wilcoxon's nonparametric test and the four-way variance analysis could not detect any significant difference at the usual a=95% probability level in these pharmacokinetic parameters of the two tablet preparations. For AUC0-infinity at the 90% probability level, the confidence interval was 0.883-1.237 (with an estimated geometric mean of 1.045), for the test/reference ratio of Dopegyt and Presinol tablets, thus the two preparations proved to be bioequivalent. The relative bioavailability of Dopegyt (test preparation) and Presinol (reference preparation) calculated from the AUC0-infinity values was 116.7+/-56.7% that also confirmed bioequivalence. The results of all the applied statistical tests suggest that Dopegyt and Presinol can be considered as bioequivalent preparations. PMID:11554430

Róna, K; Ary, K; Renczes, G; Gachályi, B; Grézal, G Y; Drabant, S; Klebovich, I

2001-01-01

82

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

83

Morphine preexposure facilitates morphine place preference and attenuates morphine taste aversion  

Microsoft Academic Search

Repeated morphine preexposure has been reported to enhance measures of morphine reward (conditioned place preference; CPP) and attenuate measures of morphine aversion (conditioned taste aversion; CTA). These effects are generally independently assessed, limiting the ability to determine if the enhancing and attenuating effects of morphine exposure are mediated by a common factor. To assess any potential relationship between these two

Gregory R. Simpson; Anthony L. Riley

2005-01-01

84

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

85

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

86

Nalmefene: blockade of intravenous morphine challenge effects in opioid abusing humans.  

PubMed

No studies have assessed the dose-effect or duration of opioid blockade in opioid abusers produced by oral nalmefene, a micro-opioid antagonist. The present study examined the profile and time course of oral nalmefene blockade of subjective and physiological effects produced by intravenous morphine. To assess these effects, seven opioid abusers received oral nalmefene (0, 50 and 100 mg) followed by intravenous morphine (0, 10 and 20 mg) challenges every 24 h for 96 h using a Latin square randomized cross-over design. The duration of blockade varied by measure and dose. Both 50 and 100 mg nalmefene blocked morphine's effects up to 48 h. PMID:10821987

Jones, H E; Johnson, R E; Fudala, P J; Henningfield, J E; Heishman, S J

2000-07-01

87

Preoperative Dextromethorphan Reduces Intraoperative but Not Postoperative Morphine Requirements After Laparotomy  

Microsoft Academic Search

N-methyl-D-aspartate (NMDA) antagonists combined with opioids are thought to be effective in the control of pain states. We evaluated morphine use and analgesia in 37 patients postlaparotomy. Patients received 60 mg of oral dextromethorphan or placebo the night before and again 1 h before surgery. Morphine was titrated intraoperatively to maintain blood pressure and heart rate within 20% of baseline

Robert F. Grace; Ian Power; Hamed Umedaly; Alexandra Zammit; Michael Mersiades; Michael J. Cousins; Laurence E. Mather

1998-01-01

88

Comparison of morphine and morphine with ketamine for postoperative analgesia  

Microsoft Academic Search

Purpose  The purpose of this study was to compare morphine with ketamine to morphine alone in a doubleblind investigation of postsurgical\\u000a pain control.\\u000a \\u000a \\u000a \\u000a Methods  Fortytwo ASA 1 and 2 patients undergoing elective microdiscectomy were administered either 1 mg · ml? 1 of morphine (n = 20) or 1 mg · ml? 1 of both morphine and ketamine (n = 22) via iv

Keith B. Javery; Todd W. Ussery; Herbert G. Steger; George W. Colclough

1996-01-01

89

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

PubMed

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

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

2002-08-01

90

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

PubMed Central

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

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

2014-01-01

91

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

PubMed

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

Wang, Wen-Ping; Liu, Na; Kang, Qian; Du, Pei-Pei; Lan, Yi; Zhao, Bo-Chen; Chen, Yan-Yan; Zhang, Qing; Li, Hui; Zhang, Ye-Wen; Wu, Qing

2014-11-01

92

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

93

Morphine6Glucuronide: Morphine??s Successor for Postoperative Pain Relief?  

Microsoft Academic Search

In searching for an analgesic with fewer side effects than morphine, examination of morphine's active metabolite, morphine-6-glucuronide (M6G), sug- gests that M6G is possibly such a drug. In contrast to morphine, M6G is not metabolized but excreted via the kidneys and exhibits enterohepatic cycling, as it is a substrate for multidrug resistance transporter pro- teins in the liver and intestines.

Eveline L. A. van Dorp; Raymonda Romberg; Elise Sarton; James G. Bovill; Albert Dahan

2006-01-01

94

Sex-specific differences in levels of morphine, morphine-3-glucuronide, and morphine antinociception in rats  

Microsoft Academic Search

A number of studies reported striking differences in antinociceptive responses to morphine as a function of sex. Although sex differences in the sensitivity to morphine are widely characterized in rodents, the underlying causes are not identified. Gonadal steroids are believed to contribute to sex differences in response to opioid-induced antinociception. In rats, morphine is metabolized by glucuronidation to morphine-3-glucuronide (M3G).

Lanning Baker; Anna Ratka

2002-01-01

95

Morphine Tolerance as Habituation  

Microsoft Academic Search

We propose that the development of drug tolerance is congruent with the behavioral characteristics of habituation. Specifically, we show that morphine tolerance development conforms to Wagner's priming model of habituation. Tolerance develops through both associational and nonassociational routes; We attribute associational tolerance development to retrieval-generated priming of memory, whereas nonassociational tolerance we attribute to self-generating priming. This model accounts for

Timothy B. Baker; Stephen T. Tiffany

1985-01-01

96

Identification of Site of Morphine Action in Pregnant Wistar Rat Placenta Tissue: A C14-Morphine Study  

PubMed Central

Objective: In previous studies it has been emphasized that the site of morphine action may be either in the embryo or the placenta. In the present study, we attempt to identify the site of morphine action on the fetal section of Wistar rat placenta by using C14-morphine. Materials and Methods: In this study (experimental), female Wistar rats (weights: 170-200 g) were mated with male rats and their coupling times recorded. Experimental groups received daily doses of 0.05 mg/ml of C14-morphine in their drinking water. On the 9th and14th embryonic days, the pregnant rats were anesthetized and the placenta and uterus surgically removed. Placentas were fixed in 10% formalin for two weeks, then processed, sectioned in 5 µm and 25 µm thicknesses, and fixed on glass slides for further evaluation. The 25 µm sections were delivered to black and white film for three days. Films were processed and evaluated with a digital inverse microscope for possible radiological impression. The 5 µm sections were processed for hematoxylin and eosin (H&E) staining, and evaluated by light microscope and MOTIC software. Results: Our results indicated that the site of action of C14-morphine was possibly located on the blood plexus of the fetal portion of the placenta. In addition, oral morphine consumption was shown to inhibit fetal and maternal placental development in the experimental groups. Conclusion: We conclude that morphine’s effectiveness on the reduction of embryo growth and development may be via its effects on the blood plexus of the fetal section of the placenta. PMID:23508019

Kazemi, Masoomeh; Sahraei, Hedayat; Dehghani, Leila

2012-01-01

97

[Consumption of morphine preparations in Toyama Medical and Pharmaceutical University Hospital].  

PubMed

Morphine is the dominant medication to control cancer pain. Morphine consumption has been increasing each year in many countries including Japan based on the understanding of the WHO report on the treatment of cancer pain. To evaluate the recent and current state of palliative medication for cancer patients in Toyama Medical and Pharmaceutical University (TMPU) Hospital, the amount of and trend in the use of morphine preparations from 1992 to 2001 were investigated. The amount used increased every year to 3.9-fold of that in 1992 at the end of this survey. In particular, the consumption of morphine sulfate sustained-release tablets and morphine hydrochloride injection increased markedly, because both total dose in individual patients and the number of patients treated with high-dose morphine increased. The distribution of the maximum daily dose in TMPU Hospital was similar to that in a specialist hospital in oncology. In conclusion, morphine consumption will increase to achieve better palliative care and to improve quality of life in cancer patients, and therefore appropriate use and regulation of narcotic preparations are necessary. PMID:14768350

Yamanouchi, Tsuneaki; Nagata, Yoshie; Kawashiri, Noriyuki; Mimura, Yasuhiko; Kawakami, Junichi; Adachi, Isao

2004-01-01

98

Can extremely low or high morphine formation from codeine be predicted prior to therapy initiation?  

PubMed

Activation of codeine by O-demethylation into morphine is a prerequisite for its analgesic effects and severe toxicity. Identifying patients in whom morphine is formed either at extremely low or at extremely high amounts may improve efficacy and safety of codeine therapy. To assess how well this identification is possible, we compared the performance of current CYP2D6 phenotype association systems (traditional genotype-based classification, a recently proposed CYP2D6 activity score, and the plasma dextromethorphan metabolic ratio) in 57 healthy Caucasians after oral administration of 30 mg dextromethorphan hydrobromide or 50 mg codeine. Most subjects (87.5%) at the lower 15% of morphine formation from codeine and thus likely to not to respond to codeine therapy were correctly identified by CYP2D6 genotype- or phenotype-based systems. In contrast, in subjects at the upper 15% of morphine formation being at risk for opioid toxicity, CYP2D6 genotyping predicted only the 50% who carried gene duplication, whereas dextromethorphan-based phenotyping identified 67.5% of the subjects with high morphine formation. However, satisfactory prediction (87.5%) of high morphine formation was only achieved when combining genotyping with phenotyping. In conclusion, insufficient morphine formation from codeine and thus likely failure of analgesia can currently be well predicted. However, to make codeine therapy safe, extremely high morphine formation has to be predicted as well, which has to be obtained at the effort of combining genotyping with phenotyping. PMID:19395173

Lötsch, Jörn; Rohrbacher, Maren; Schmidt, Helmut; Doehring, Alexandra; Brockmöller, Jürgen; Geisslinger, Gerd

2009-07-01

99

[Opium (heroin * morphine)].  

PubMed

The number of people dependent on opiate drugs, including heroin, is still high, and these abused drugs are major social issues, both in the social science and medically. The mechanisms of physical dependence and withdrawal symptoms in laboratory animals are becoming clear; however, no useful method to detoxify abusers with opioid dependence in clinical situation has been established, and alternative therapy with methadone, used in Europe and America, cannot be used in Japan. Here, I will outline the global trend of opium abuse, including heroin and morphine, and summarize the problems of heroin abuse. PMID:20715484

Hiramatsu, Masayuki

2010-08-01

100

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

PubMed Central

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

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

2014-01-01

101

Delayed postoperative gastric emptying following intrathecal morphine and intrathecal bupivacaine  

Microsoft Academic Search

Purpose  A decrease in the rate of gastric emptying can delay resumption of enterai feeding, alter bioavailability of orally administered\\u000a drugs, and result in larger residual gastric volumes, increasing the risk of nausea and vomiting. We compared the effects\\u000a of 1) intrathecal bupivacaine (17.5 mg) and 2) the combination of intrathecal morphine (0.6 mg) and intrathecal bupivacaine\\u000a (17.5 mg) on the

Avine M. Lydon; Thomas Cooke; Finbarr Duggan DSC; George D. Shorten

1999-01-01

102

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

103

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

104

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

105

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

106

21 CFR 520.62 - Aminopentamide hydrogen sulphate tablets.  

Code of Federal Regulations, 2011 CFR

...nausea, acute abdominal visceral spasm, pylorospasm, or hypertrophic gastritis. Note: Not for use in animals with glaucoma because of the occurrence of mydriasis. (2) Dosage is administered by oral tablet every 8 to 12 hours, as follows:...

2011-04-01

107

21 CFR 520.903e - Febantel tablets.  

Code of Federal Regulations, 2013 CFR

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

2013-04-01

108

21 CFR 520.903e - Febantel tablets.  

Code of Federal Regulations, 2012 CFR

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

2012-04-01

109

21 CFR 520.2604 - Trimeprazine tartrate and prednisolone tablets.  

Code of Federal Regulations, 2011 CFR

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

2011-04-01

110

21 CFR 520.2604 - Trimeprazine tartrate and prednisolone tablets.  

Code of Federal Regulations, 2013 CFR

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

2013-04-01

111

21 CFR 520.62 - Aminopentamide hydrogen sulphate tablets.  

Code of Federal Regulations, 2010 CFR

...nausea, acute abdominal visceral spasm, pylorospasm, or hypertrophic gastritis. Note: Not for use in animals with glaucoma because of the occurrence of mydriasis. (2) Dosage is administered by oral tablet every 8 to 12 hours, as follows:...

2010-04-01

112

Morphine Induces Splenocyte Trafficking into the CNS  

PubMed Central

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

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

2013-01-01

113

Morphine induces albuminuria by compromising podocyte integrity.  

PubMed

Morphine has been reported to accelerate the progression of chronic kidney disease. However, whether morphine affects slit diaphragm (SD), the major constituent of glomerular filtration barrier, is still unclear. In the present study, we examined the effect of morphine on glomerular filtration barrier in general and podocyte integrity in particular. Mice were administered either normal saline or morphine for 72 h, then urine samples were collected and kidneys were subsequently isolated for immunohistochemical studies and Western blot. For in vitro studies, human podocytes were treated with morphine and then probed for the molecular markers of slit diaphragm. Morphine-receiving mice displayed a significant increase in albuminuria and showed effacement of podocyte foot processes. In both in vivo and in vitro studies, the expression of synaptopodin, a molecular marker for podocyte integrity, and the slit diaphragm constituting molecules (SDCM), such as nephrin, podocin, and CD2-associated protein (CD2AP), were decreased in morphine-treated podocytes. In vitro studies indicated that morphine modulated podocyte expression of SDCM through opiate mu (MOR) and kappa (KOR) receptors. Since morphine also enhanced podocyte oxidative stress, the latter seems to contribute to decreased SDCM expression. In addition, AKT, p38, and JNK pathways were involved in morphine-induced down regulation of SDCM in human podocytes. These findings demonstrate that morphine has the potential to alter the glomerular filtration barrier by compromising the integrity of podocytes. PMID:23555556

Lan, Xiqian; Rai, Partab; Chandel, Nirupama; Cheng, Kang; Lederman, Rivka; Saleem, Moin A; Mathieson, Peter W; Husain, Mohammad; Crosson, John T; Gupta, Kalpna; Malhotra, Ashwani; Singhal, Pravin C

2013-01-01

114

Can coadministration of oxycodone and morphine produce analgesic synergy in humans? An experimental cold pain study  

PubMed Central

Aims The coadministration of subantinociceptive doses of oxycodone with morphine has recently been shown to result in a synergistic antinociceptive effect in rats. The present study was aimed to investigate the possibility that coadministration of morphine and oxycodone can produce a similar synergistic effect in humans exposed to an experimental model of cold pressor test (CPT). Methods The enriched enrolment design was used to exclude ‘stoic’ and ‘placebo responders’ in a single-blind fashion. ‘Nonstoic’, placebo ‘nonresponder’ female volunteers (n = 30) were randomly assigned to receive 0.5 mg kg?1 oral morphine sulphate, 0.5 mg kg?1 oral oxycodone hydrochloride, and the combination of 0.25 mg kg?1 morphine sulphate with 0.25 mg kg?1 oxycodone hydrochloride, 1 week apart from each other, in a double-blind crossover design. Latency to pain onset (threshold), pain intensity (VAS), and pain tolerance (time until removal of the hand from the water) were measured six times over a 3-h period, subsequent to the administration of each medication, and were used to assess their antinociceptive effect. Results The combination produced a significantly higher effect on latency to pain onset than that of morphine alone [difference in mean postbaseline value 2.2; 95% confidence interval (CI) 0.48, 3.9; P = 0.01] but the effect was nonsignificantly smaller that that of oxycodone alone. Similarly, the effect of the combination on pain tolerance was significantly larger than that of morphine alone (combination difference 8.4; 95% CI 2.5, 14.3; P = 0.007), whereas oxycodone alone caused a nonsignificantly larger effect than that of the combination treatment. Comparisons of pain magnitude failed to show any significant differences between the three treatments. Conclusions These results indicate that at the doses tested, morphine and oxycodone do not produce synergistic antinociceptive effects in healthy humans exposed to the CPT. PMID:15327582

Grach, Michael; Massalha, Wattan; Pud, Dorit; Adler, Rivka; Eisenberg, Elon

2004-01-01

115

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

116

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

PubMed

Breakthrough pain, a transitory severe pain with the background of otherwise controlled persistent pain has a prevalence between 52% and 67% in outpatients with cancer. Medications for such sudden-onset pain require non-invasive delivery of a potent and short-acting opioid for rapid pain relief. Although oral transmucosal delivery of fentanyl citrate (OTFC) has been shown to provide better pain relief than a typical oral opioid administration such as morphine sulfate immediate release (MSIR) in the management of breakthrough pain in patients with cancer-related pain, newer delivery systems offer a potential for further enhancement of pain relief. The fentanyl effervescent buccal tablet (FBT) formulation employs a novel drug delivery system that relies on an effervescence reaction to improve buccal fentanyl absorption. Using the effervescence reaction results in the production and dissipation of carbon dioxide with a dynamic shift in pH as the tablet dissolves. The induced low pH favors dissolution of fentanyl citrate in saliva (higher water solubility). The subsequent increase in pH thereafter favors the buccal absorption of non-ionized fentanyl across the buccal mucosa. Such a pH "pumping" mechanism increases the permeation of fentanyl into and through the buccal to the vascular system from where the agent is transported to the specific opioid receptor sites in the CNS. Compared with OTFC, data in healthy volunteers show that the effervescence reaction employed in FBT increases the total amount and the speed of absorption of fentanyl being absorbed. Compared with OTFC there is an increase in peak fentanyl blood concentrations, and an enhancement of the amount of buccal delivery of fentanyl. Such favorable data are underlined by the results of clinical studies where the FBT technology was studied in patients with breakthrough pain in chronic malignant pathologies. PMID:21197291

Freye, Enno

2008-01-01

117

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

Microsoft Academic Search

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

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

2005-01-01

118

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

Microsoft Academic Search

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

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

2011-01-01

119

Prior Morphine Exposure Enhances Ibogaine Antagonism of Morphine-induced Dopamine Release in Rats  

Microsoft Academic Search

The present study examines the effect of prior morphine exposure on ibogaine antagonism of morphine-induced dopamine release. Female Sprague-Dawley rats were pretreated once a day for 2 days with morphine (20 mg\\/kg, i.p.) or saline and given a low dose of ibogaine (10 mg\\/kg, i.p.) or saline 5 hr after the last morphine or saline injection. Nineteen hours later, rats

SANDRA M PEARL; ISABELLE M MAISONNEUVE; STANLEY D GLICK

1996-01-01

120

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. PMID:12736382

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

121

Pharmacokinetics and relative bioavailability of ofloxacin tablets in 12 healthy volunteers.  

PubMed

Single oral dose of tablet A (Daiichi Pharmaceutical Co Ltd, Japan) and B (Jining Pharmaceutical Factory, Shandong, China) of 300 mg ofloxacin (Ofl) were given to 12 Chinese healthy male volunteers in an open, randomized crossover study. Drug concentrations in serum and urine were assayed by HPLC and partial least squares spectrophotometric method, respectively. The serum concentration-time course after medication conformed to a 2-compartment open model with a first order absorption. Pharmacokinetic parameters after tablet B did not differ significantly from the corresponding values after tablet A. The bioavailability of tablet B was comparable to that of tablet A. PMID:1598824

Diao, Y; Li, L; Zhou, G H; Cheng, Y

1992-03-01

122

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

PubMed

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 C(max) (96.14-114.53%) and AUC(0-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.). PMID:22896827

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

2012-06-01

123

Place Aversion by Morphine in Offspring Born of Female Morphine Administered Wistar Rats  

PubMed Central

This research was designed to study sexual differences in place conditioning induced by morphine in offspring born of female Wistar rats mated with drug-naïve males. Mothers were exposed to morphine during the 14th-16th days of gestational. Control dams were simply saline-injected. Female and male virgin offspring born of morphine-treated or saline-treated mothers were separately housed until become fully matured. A 3-day schedule of an unbiased conditioning procedure was used to the induce conditioning to morphine (2.5-7.5 mg/Kg, SC) in the offspring. According to the results, female offspring born of saline-administered mothers were morphine place-conditioned at lower doses of opioid (2.5 mg/Kg) in comparison to the males. An increase in locomotor activity in the females at 7.5 mg/Kg of opioid was also revealed. In contrast, administration of morphine (2.5-7.5 mg/Kg, SC), induced a significant aversion in either sexes of offspring born of morphine-exposed mothers. Moreover, female offspring of this category acquired more pronounced aversion at higher doses of morphine than males. In addition, a significant morphine-dose effect (7.5 mg/Kg, SC) on locomotor activity of these females’ offspring was observed. This study may highlight sex differences in conditioning effects induced by morphine between offspring derived of morphine-treated mothers and those of saline-treated. PMID:24250391

Karami, Manizheh; Zarrindast, Mohammad Reza

2011-01-01

124

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

PubMed Central

Objective: Antinociceptive effect of morphine in offspring born of mothers that received saline or morphine during the gestation period was investigated. Materials and Methods: Wistar rats (200-250 g) received saline, morphine 0.5 mg/kg or 5 mg/kg during gestation days 14-16. All pups after weaning were isolated treatment/sex dependently and were allowed to fully mature. The antinociceptive effect of morphine was assessed in formalin test. Morphine (0.5-7.5 mg/kg) or saline (1 ml/kg) was injected intraperitoneally 10 min before formalin (50 ?l of 2.5% solution in right hind-paw). Results: Male offspring born of saline-treated mothers were less morphine-sensitive than females. On the contrary, male offspring exposed prenatally to morphine (5 mg/kg) were more sensitive to morphine-induced antinociceptive response in formalin test. However, no difference in antinociceptive effect was observed amongst offspring of either sex born of mothers treated with morphine 0.5 mg/kg, identifying a lower dose effect of the opioid. Conclusion: The exposure to morphine during the developmental period may result in altered development of tolerance to morphine and thus involved in drug abuse. PMID:23833363

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

2013-01-01

125

Contribution of morphine and morphine-6-glucuronide to respiratory depression in a child.  

PubMed

A morphine plasma concentration/respiratory rate relationship has been described for both adults and children although that of its metabolite, morphine-6-glucuronide, remains uncertain. We describe this relationship in a child with end-stage renal failure who received repeat morphine administration over two days. An EMAX model for additive morphine and morphine-6-glucuronide respiratory effects described respiratory rate better than models describing either alone. Failure to clear morphine-6-glucuronide renally led to respiratory depression episodes occurring later than those predicted by modelling morphine levels only. These findings support the use of alternative analgesics (e.g. fentanyl) that are cleared by non-renal pathways and have no active metabolites in patients with end-stage renal disease. PMID:22934872

Hannam, J A; Anderson, B J

2012-09-01

126

Carbamazepine potentiates morphine analgesia on postoperative pain in morphine-dependent rats.  

PubMed

Postoperative pain and its control remain one of the most important issues in the field of surgery and health care systems. Morphine is a potent and effective analgesic, but substance abuse patients can manifest cross-tolerance to it, making it difficult to satisfy their analgesic/anesthetic requirements. As carbamazepine has shown antinociceptive properties in a variety of experimental and clinical settings, in the present study, we evaluated its potential antiallodynic effects on postoperative pain in naïve and morphine-dependent rats. Male rats were assigned to morphine-dependent and naïve groups and received intraperitoneally drug vehicles as control group, 3mg/kg morphine, 5, 10 or 15 mg/kg carbamazepine or 5mg/kg carbamazepine plus 3mg/kg morphine as a combination therapy 2 and 24h after surgery. Morphine-dependency was induced with multiple doses of morphine administered i.p. and plantar incision was made on the hind paw to simulate the postoperative pain. Paw withdrawal threshold (PWT) was obtained by von Frey filaments every 30 min after drug injection for up to 180 min. Morphine at 3mg/kg exerted antiallodynic effects in naïve rats and a decreased antinociception was observed in morphine-dependent rats. In contrast, 5mg/kg carbamazepine did not significantly alter PWT in naives but it was effective in dependent rats. 10 and 15 mg/kg carbamazepine attenuated allodynia following surgery in both groups. Co-administration of 5mg/kg carbamazepine with 3mg/kg morphine produced higher analgesia in morphine-dependent incised rats and prolonged antinociception as compared to morphine alone (P<0.05). Thus carbamazepine may potentiate the analgesic effect of chronically administered morphine on postoperative pain model in morphine-dependent rats. PMID:22061686

Naseri, Kobra; Sabetkasaei, Masoumeh; Moini Zanjani, Taraneh; Saghaei, Elham

2012-01-15

127

Synthetic substances with morphine-like effect  

PubMed Central

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

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

1955-01-01

128

Morphine modulates proliferation of kidney fibroblasts.  

PubMed

Renal interstitial scarring is an important component of heroin-associated nephropathy. Kidney fibroblasts have been demonstrated to play a role in the development of renal scarring in a variety of renal diseases. We studied the effect of morphine, an active metabolite of heroin, on the proliferation of kidney fibroblasts. Morphine at a concentration of 10(-12) M enhanced (P < 0.001) the proliferation of kidney fibroblasts (control, 67.5 +/- 2.0 vs. morphine, 112.2 +/- 10.1 x 10(4) cells/well). [3H]thymidine incorporation studies further confirmed these results. Morphine at concentrations of 10(-12) M to 10(-10) M also modulated mRNA expression of early growth related genes (c-fos, c-jun and c-myc). Morphine at concentrations of 10(-8) to 10(-4) M promoted apoptosis of kidney fibroblasts and also enhanced the synthesis of p53 by kidney fibroblasts. We speculate that morphine-induced kidney fibroblast proliferation may be mediated through the activation of early growth related genes, whereas morphine induced kidney fibroblast apoptosis may be mediated through the generation of p53. The present in vitro study provides a hypothetical basis for the role of morphine in the development of renal interstitial scarring in patients with heroin-associated nephropathy. PMID:9461094

Singhal, P C; Sharma, P; Sanwal, V; Prasad, A; Kapasi, A; Ranjan, R; Franki, N; Reddy, K; Gibbons, N

1998-02-01

129

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

130

Proglumide potentiates morphine analgesia for acute postsurgical pain  

Microsoft Academic Search

Proglumide, an antagonist of cholecystokinin, has been shown to potentiate morphine analgesia in animal and human experimental pain models. This study was undertaken to determine whether proglumide enhances morphine analgesia for patients experiencing postoperative pain. At onset of pain after the removal of impacted third molars, patients (n = 60) received intravenously either 4 mg morphine, 8 mg morphine, or

Gilles J Lavigne; Kenneth M Hargreaves; Elizabeth A Schmidt; Raymond A Dionne; Raymond A Dionne DDS

1989-01-01

131

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

PubMed

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

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

1994-02-01

132

Clinical study on the bioequivalence of two tablet formulations of flurbiprofen  

Microsoft Academic Search

Summary  Flurbiprofen (CAS 5104-49-4) is a member of phenylaikanoic acid derivative group of nonsteroid anti-inflammatory drugs. It\\u000a exhibits anti-inflammatory, analgesic and antipyretic activities. Two different tablets containing flurbiprofen (FLU) were\\u000a investipted in 24 healthy volunteers to prove the bioequivalence between both treatments after single oral dose administrations.\\u000a Fluroben® 100 mg tablet and 100 mg tablet of the originator product were used

Latif Ozbay; Durisehvar Ozer Unal; Iclal Cakici; Ay?en Fenercioglu; Dilek Erol

2009-01-01

133

Sensitization to morphine withdrawal in guinea-pigs  

Microsoft Academic Search

The aim of this study was to determine whether sensitization occurred to morphine withdrawal. Guinea-pigs were treated twice daily with increasing doses of morphine (10–100 mg\\/kg s.c.) for 3 days followed by injection of morphine 100 mg\\/kg on the fourth day. Sixty min after the last morphine injection, animals were withdrawn from morphine with naltrexone, 15 mg\\/kg s.c., and locomotor

Akiko Mizutani; Jenny Arvidsson; Loris A. Chahl

2005-01-01

134

Prior morphine exposure enhances ibogaine antagonism of morphine-induced locomotor stimulation  

Microsoft Academic Search

Ibogaine is currently being investigated for its potential use as an anti-addictive agent. In the present study we sought to determine whether prior morphine exposure influences the ability of ibogaine to inhibit morphine-induced locomotor stimulation. Female Sprague-Dawley rats were pretreated once a day for 1–4 days with morphine (5, 10, 20 or 30 mg\\/kg, IP) or saline and then received

S. M. Pearl; S. D. Glick; D. W. Johnson

1995-01-01

135

Tablet Splitting: A Risky Practice  

MedlinePLUS

... practice of splitting tablets, the Food and Drug Administration (FDA), the American Medical Association, and other medical organizations advise against it unless it's specified in the drug's labeling. Tablet splitting often involves buying higher strength tablets and then breaking the tablets in ...

136

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

Microsoft Academic Search

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

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

2006-01-01

137

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

138

Clearance of continuous intravenous morphine for severe cancer pain.  

PubMed

Four cancer patients with intractable pain received continuous morphine infusions in doses of 15-275 mg/h for a time period ranging from 4 to 27 days. Serum morphine concentrations were determined periodically following adjustments in infusion rates. As doses were changed and continued at static hourly rates, serum morphine concentrations were relatively constant 20 hours and beyond the time of the respective change, thus suggesting morphine elimination half-lives of less than or equal to 4 hours. High doses did not influence the time required to achieve steady-state concentrations. Steady serum morphine concentrations corresponded with hourly morphine doses in a parallel manner. High interpatient variabilities in clearances and steady-state serum morphine concentrations were noted. These data suggest that at morphine infusions up to 275 mg/h elimination pathways permit handling of increasing concentrations of morphine without nonlinear blood level increases. Also, marked interpatient and intrapatient variations in patient dose requirements were noted. PMID:3428164

Citron, M L; Reynolds, J R; Lin, W N; Frade, P D; Schemansky, M; Cohen, M H; Krasnow, S H; Johnston-Anderson, A; Seltzer, V L

1987-12-01

139

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

Microsoft Academic Search

Objective This study was undertaken to evaluate the adequacy of a hospital formulated oral morphine preparation for management of neonatal\\u000a abstinence syndrome (NAS) and to compare clinical features in infants exposed to methadone or buprenorphine in utero. Method Between October 1998 and October 2004 all infants born to mothers treated with buprenorphine or methadone during pregnancy\\u000a were enrolled into this prospective

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

2008-01-01

140

In vivo drug release from hydrophilic dextran tablets capable of forming polyion complex.  

PubMed

The aim of this comparative study was to investigate the in vivo drug release property of hydrophilic dextran tablets with or without swelling in the upper gastrointestinal tract (GIT) in humans. Two kinds of theophylline (TH) tablets were prepared by direct compression from a mixture of carboxymethyldextran and [2-(diethylamino)ethyl]dextran as a matrix capable of forming polyion complex (PIC-tablet), and a mixture of low and medium molecular weight hydroxypropylcellulose as a representative hydrophilic matrix (HPC-tablet). In these tablets, in vitro drug release behaviors and saliva TH level profiles after oral administration to humans were similar to each other, indicating equivalent AUC value. The tablets were then coated with Eudragit S100, enteric-coating polymer, by a dipping method in order to reveal drug release without full swelling in the upper GIT. Although the two enteric-coated tablets showed a similar in vitro release pattern, saliva level profiles were quite different as reflected in AUC values of 16.4 and 4.68 microg h/ml for enteric-coated PIC- and enteric-coated HPC-tablet, respectively. These results demonstrated that HPC-tablet could not release sufficiently without swelling in the upper GIT. In contrast, enteric-coated PIC-tablet showed an equivalent AUC value to PIC-tablet, indicating that TH was released well even in the lower GIT. PMID:16824636

Miyazaki, Yasunori; Tanaka, Yoichi; Yakou, Shigeru; Takayama, Kozo

2006-08-10

141

Fast disintegrating tablets: Opportunity in drug delivery system  

PubMed Central

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

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

2011-01-01

142

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

PubMed

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

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

2014-08-01

143

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

PubMed Central

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

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

2013-01-01

144

Neuropharmacology. Author manuscript Effects of chronic morphine and morphine withdrawal on gene expression  

E-print Network

Neuropharmacology. Author manuscript Page /1 12 Effects of chronic morphine and morphine withdrawal Analysis of Variance ; Animals ; Behavior, Animal ; drug effects ; Gene Expression Profiling ; Gene nervous system and induce long-term behavioral and cellular alterations. A current challenge in opiate

Paris-Sud XI, Université de

145

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

PubMed

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

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

2014-01-01

146

Ultra-low doses of naltrexone or etorphine increase morphine's antinociceptive potency and attenuate tolerance/dependence in mice.  

PubMed

In previous studies we showed that low (pM) concentrations of naloxone (NLX), naltrexone (NTX) or etorphine selectively antagonize excitatory, but not inhibitory, opioid receptor-mediated functions in nociceptive types of sensory neurons in culture. Cotreatment of these neurons with pM NTX or etorphine not only results in marked enhancement of the inhibitory potency of acutely applied nM morphine [or other bimodally-acting (inhibitory/excitatory) opioid agonists], but also prevents development of cellular manifestations of tolerance and dependence during chronic exposure to microM morphine. These in vitro studies were confirmed in vivo by demonstrating that acute cotreatment of mice with morphine plus a remarkably low dose of NTX (ca. 10 ng/kg) does, in fact, enhance the antinociceptive potency of morphine, as measured by hot-water tail-flick assays. Furthermore, chronic cotreatment of mice with morphine plus low doses of NTX markedly attenuates development of naloxone-precipitated withdrawal-jumping in physical dependence assays. The present study provides systematic dose-response analyses indicating that NTX elicited optimal enhancement of morphine's antinociceptive potency in mice when co-administered (i.p.) at about 100 ng/kg together with morphine (3 mg/kg). Doses of NTX as low as 1 ng/kg or as high as 1 microg/kg were still effective, but to a lesser degree. Oral administration of NTX in the drinking water of mice was equally effective as i.p. injections in enhancing the antinociceptive potency of acute morphine injections and even more effective in attenuating development of tolerance and NLX-precipitated withdrawal-jumping during chronic cotreatment. Cotreatment with a subanalgesic dose of etorphine (10 ng/kg) was equally effective as NTX in enhancing morphine's antinociceptive potency and attenuating withdrawal-jumping after chronic exposure. These studies provide a rationale for the clinical use of ultra-low-dose NTX or etorphine so as to increase the antinociceptive potency while attenuating the tolerance/dependence liability of morphine or other conventional bimodally-acting opioid analgesics. PMID:9200746

Shen, K F; Crain, S M

1997-05-23

147

21 CFR 862.3640 - Morphine test system.  

Code of Federal Regulations, 2013 CFR

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

2013-04-01

148

21 CFR 862.3640 - Morphine test system.  

Code of Federal Regulations, 2011 CFR

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

2011-04-01

149

21 CFR 862.3640 - Morphine test system.  

Code of Federal Regulations, 2010 CFR

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

2010-04-01

150

21 CFR 520.2150b - Stanozolol chewable tablets.  

Code of Federal Regulations, 2012 CFR

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

2012-04-01

151

21 CFR 520.2150b - Stanozolol chewable tablets.  

Code of Federal Regulations, 2010 CFR

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

2010-04-01

152

21 CFR 520.2150b - Stanozolol chewable tablets.  

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

2014-04-01

153

21 CFR 520.2150b - Stanozolol chewable tablets.  

Code of Federal Regulations, 2013 CFR

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

2013-04-01

154

21 CFR 520.2150b - Stanozolol chewable tablets.  

Code of Federal Regulations, 2011 CFR

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

2011-04-01

155

Microstructural investigation of tablet compaction and tablet pharmacological properties  

E-print Network

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

Mao, Kangyi

2010-01-01

156

The effect of morphine in rat small mesenteric arteries  

Microsoft Academic Search

We investigated the effect of morphine in phenylephrine (PE)- or KCl-precontracted rat small mesenteric arteries. Morphine (10?6–10?4 M) administration caused concentration-dependent relaxation responses in small mesenteric arteries precontracted by PE or KCl. Removal of endothelium did not significantly alter the relaxation responses to morphine. The relaxant responses to morphine were partially inhibited by pre-treatment of tissues with naloxone (NAL, 10?5

Sadi S. Ozdem; Ozlem Batu; Fatma Tayfun; Ozlem Yalcin; Herbert J. Meiselman; Oguz K. Baskurt

2005-01-01

157

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

PubMed

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

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

2012-05-01

158

The Addition of Epinephrine Enhances Postoperative Analgesia by Intrathecal Morphine  

Microsoft Academic Search

To investigate whether the addition of epinephrine would enhance postoperative pain relief by intrathecal morphine, we studied 36 patients scheduled to have spinal anesthesia for gynecologic surgery. Patients were randomly allocated to one of three groups: the first received epinephrine 0.12 mg, morphine 0.2 mg, and hyperbaric tetracaine 12 mg intrathecally (EMT group, n = 11); the second received morphine

Toru Goyagi; Toshiaki Nishikawa

1995-01-01

159

Heightened aggressive behavior during morphine withdrawal: effects of d -amphetamine  

Microsoft Academic Search

The morphine withdrawal syndrome is composed of profound short- and long-term changes in autonomic, somato-motor and affective functions. In mice, morphine withdrawal produces heightened aggressive behavior and alterations in motor behavior; however, it is unclear whether these changes in behavior occur in unison and are dependent on a common mechanism or occur independently. In order to characterize the morphine withdrawal

J. W. Tidey; K. A. Miczek

1992-01-01

160

Chimeric DNA Vaccine Reverses Morphine-Induced Immunosuppression and Tumorigenesis  

Microsoft Academic Search

Although long-term use of morphine has been shown to promote tumor growth, the question whether tumorigenesis occurs as a result of an immunosuppressive effect remains to be investigated. In mice rendered tolerant to morphine, the efficacy and mechanism of a vaccination to rescue morphine-induced immunosuppression and prevent tumor growth was assessed both in vitro and in vivo. Herein, we found

Wen-Fang Cheng; Li-Kuei Chen; Chi-An Chen; Ming-Cheng Chang; Po-Ni Hsiao; Yi-Ning Su; Chien-Nan Lee; Huei-Jiuan Jeng; Chang-Yao Hsieh; Wei-Zen Sun

2006-01-01

161

Oral calcitonin  

PubMed Central

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

Hamdy, Ronald C; Daley, Dane N

2012-01-01

162

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

163

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

PubMed

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

Skaftason, Jóhannes F; Jóhannesson, Thorkell

2013-04-01

164

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

165

Synthetic substances with morphine-like effect  

PubMed Central

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

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

1957-01-01

166

A randomised trial of glucose tablets to aid smoking cessation  

Microsoft Academic Search

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

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

2010-01-01

167

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

PubMed Central

Background. A comprehensive care package for patients undergoing hepatectomy was developed with the aim of minimal physiological disturbance in the peri-operative period. Peri-operative analgesia with few gastrointestinal effects and reduced requirement for intravenous (IV) fluid therapy was central to this plan. Methods. Data on 100 consecutive patients managed with continuous epidural infusion (n = 50; bupivicaine 0.125% and fentanyl 2??g/mL at 0.1?mL/kg/hr) or intrathecal morphine (n = 50; 300??g in combination with oral gabapentin 1200?mg preoperatively and 400?mg bd postoperatively) was compared. Results. The epidural and intrathecal morphine groups were equivalent in terms of patient demographics, procedures and complications. Patients receiving intrathecal morphine received less intra-operative IV fluids (median 1500?mL versus 2200?mL, P = .06), less postoperative IV fluids (median 1200?mL versus 4300?mL, P = .03) than patients receiving epidural infusion. Patients managed with intrathecal morphine established a normal dietary intake sooner (16 hours versus 20 hours, P = .05) and had shorter hospital stays than those managed with epidural infusions (4.7 ± 0.9 days versus 6.8 ± 1.2 days, P = .02). Conclusions. Single dose intrathecal morphine is a safe and effective means of providing peri-operative analgesia. Patients managed with intrathecal morphine have reduced peri-operative physiological disturbance and return home within a few days of hepatic resection. PMID:20029637

Koea, Jonathan B.; Young, Yatin; Gunn, Kerry

2009-01-01

168

Ellagic acid enhances morphine analgesia and attenuates the development of morphine tolerance and dependence in mice.  

PubMed

According to our previous study, ellagic acid has both dose-related central and peripheral antinociceptive effect through the opioidergic and l-arginine-NO-cGMP-ATP sensitive K(+) channel pathways. In the present study, the systemic antinociceptive effects of ellagic acid in animal models of pain, and functional interactions between ellagic acid and morphine in terms of analgesia, tolerance and dependence were investigated. Ellagic acid (1-30mg/kg; i.p.) showed significant and dose-dependent antinociceptive effects in the acetic acid-induced writhing test. Intraperitoneal ellagic acid acutely interacted with morphine analgesia in a synergistic manner in this assay. Ellagic acid (1-10mg/kg; i.p.) also exerted analgesic activity in the hot-plate test. Pre-treatment with naloxone (1mg/kg; i.p.) significantly reversed ellagic acid, morphine as well as ellagic acid-morphine combination-induced antinociceptin in these two tests. More importantly, when co-administered with morphine, ellagic acid (1-10mg/kg) effectively blocked the development of tolerance to morphine analgesia in the hot-plate test. Likewise, ellagic acid dose-dependently prevented naloxone-precipitated withdrawal signs including jumping and weight loss. Ellagic acid treatment (1-30mg/kg; i.p.) had no significant effect on the locomotion activity of animals using open-field task. Therefore, these results showed that ellagic acid has notable systemic antinociceptive activity for both tonic and phasic pain models. Altogether, ellagic acid might be used in pain relief alone or in combination with opioid drugs because of enhancing morphine analgesia and preventing morphine-induced tolerance to analgesia and dependence. PMID:25179576

Mansouri, Mohammad Taghi; Naghizadeh, Bahareh; Ghorbanzadeh, Behnam

2014-10-15

169

Surgical pain attenuates acute morphine tolerance in rats.  

PubMed

Nociceptive stimuli, such as formalin-induced pain and adjuvant-induced arthritis, attenuate tolerance to morphine antinociception. In this study, we have explored the effect of upper and lower abdominal surgical pain on the prevention of acute tolerance to morphine antinociception in Sprague-Dawley rats. Group I received lower abdominal surgery (LAS) and i.v. morphine infusion; group II received LAS and i.v. saline infusion; group III received upper abdominal surgery (UAS) and i.v. morphine infusion; group IV received UAS and i.v. saline infusion; group V received i.v. morphine infusion; and group VI received i.v. saline infusion. The antinociceptive effects of morphine were measured by an infrared thermal tail flick test. We also measured plasma concentrations of morphine in rats receiving morphine infusions with or without surgical treatment. We found that acute tolerance to morphine antinociception developed after 2 h following i.v. infusion of morphine alone. However, both UAS and LAS significantly slowed the rate of development of acute tolerance to morphine. The area under the time-response curves (AUC) of groups I and III were mean 34,556 (SD 5607) and 32,548 (9783), respectively, which were significantly different from that of group V (18,759 (8225)) (P < 0.01). Also, there were no significant differences between groups I and III. There were no significant differences between groups for plasma morphine concentrations during the 8-h study (e.g. groups I, III and V: 179.9 (22.6), 182.7 (14.4) and 170.9 (15.8) ng ml-1 at 8 h, respectively) and we suggest that the appearance of acute morphine tolerance after morphine infusion is not pharmacokinetic in nature. PMID:10325847

Ho, S T; Wang, J J; Liaw, W J; Lee, H K; Lee, S C

1999-01-01

170

Intrathecal Lamotrigine Attenuates Antinociceptive Morphine Tolerance and Suppresses Spinal Glial Cell Activation in Morphine-Tolerant Rats  

PubMed Central

Glial cells play a critical role in morphine tolerance, resulting from repeated administration of morphine. Both the development and the expression of tolerance are suppressed by the analgesic lamotrigine. This study investigated the relationship between the ability of lamotrigine to maintain the antinociceptive effect of morphine during tolerance development and glial cell activation in the spinal cord. In a rat model, morphine (15 µg) was intrathecally injected once daily for 7 days to induce morphine tolerance. Lamotrigine (200 µg) was co-administered with morphine either for 7 days or the first or last 3 days of this 7 day period. Thermal nociception was measured. OX-42 and GFAP immunoreactivity, indicating spinal microglial and astrocytic activation were evaluated on day 8. Tolerance developed after 7 days of intrathecal morphine administration; however, this was completely blocked and reversed by co-administration of lamotrigine. When lamotrigine was coinjected with morphine on days 5-7, the morphine effect was partially restored. Glial cell activation increased with the development of morphine tolerance but was clearly inhibited in the presence of lamotrigine. These results suggest that, in association with the suppression of spinal glial cell activity, intrathecally coadministered lamotrigine attenuates antinociceptive tolerance to morphine. PMID:23399922

Jun, In-Gu; Kim, Sung-Hoon; Yoon, Yang-In

2013-01-01

171

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

172

Intrathecal morphine as sole analgesic during labour  

Microsoft Academic Search

In 12 consecutive unselected patients admitted to a consultant maternity unit one single injection of subarachnoid morphine sulphate 1.5 mg abolished pain during the first stage of labour. Pain in the second stage was abolished in four patients and lessened in three. During the early puerperium, pain at the site of the episitotomy was much reduced. Side effects included itching

P V Scott; F E Bowen; P Cartwright; B C Rao; D Deeley; H G Wotherspoon; I M Sumrein

1980-01-01

173

77 FR 15960 - Oral Dosage Form New Animal Drugs; Pergolide  

Federal Register 2010, 2011, 2012, 2013

...prescription use of pergolide mesylate tablets in horses for the control of clinical signs associated...for the veterinary prescription use in horses of PRASCEND (pergolide mesylate) Tablets...this chapter. (c) Conditions of use in horses--(1) Amount. Administer orally...

2012-03-19

174

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

PubMed

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

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

2008-08-25

175

Formulation and evaluation of sublingual tablets containing Sumatriptan succinate  

PubMed Central

Objective: Sumatriptan succinate is a selective 5-hydroxytryptamine-1 receptor agonist effective in the acute treatment of migraine headaches, having low bioavailability of about 15% orally due to first-pass metabolism. The purpose of this research was to mask the intensely bitter taste of Sumatriptan succinate and to formulate fast-acting, taste-masked sublingual tablet formulation. Materials and Methods: Taste masking was performed by solid dispersion method with mannitol and ion exchange with Kyron T 114 because it releases the drug in salivary pH. The resultant batches were evaluated for in-vivo taste masking as well compatability study (Fourier transform infrared (FTIR) and differential scanning calorimetry (DSC)). For a better feel in the mouth, menthol and sweetener Na saccharine were added to the tablet formulation. The tablets were prepared by direct compression and evaluated for weight variation, thickness, friability, drug content, hardness, disintegration time, wetting time, in vitro drug release, and in vitro permeation study. Results and Discussion: Optimized batches disintegrated in vitro within 28-34 s. Maximum drug release could be achieved with in 10 min for the solid dispersion batches and 14-15 min for the ion-exchange batches with Kyron T 114. The optimized tablet formulation showed better taste and the formulated sublingual tablets may act as a potential alternate for the Sumatriptan succinate oral tablet. Conclusion: Sumatriptan succinate can be successfully taste-masked by both the solid dispersion method using mannitol by the melting method and Ion exchange resin with Kyron T114. It was also concluded that prepared formulation improve bioavailability by prevention of first pass metabolism. PMID:23373008

Prajapati, Shailesh T; Patel, Parth B; Patel, Chhagan N

2012-01-01

176

[Sanhuang tablets research].  

PubMed

Sanhuang tablets is one of common traditional Chinese patent preparation, it has effects of clear fever, detoxifcation, dispel inflammation, purgation. It was contained in the ministerial standards of Ministry of Health in 1997, and was contained in Chinese pharmacopoeia version 1 of 2000 and 2005. Its improvement of dosage form, preparation technique, quality analysis, pharmacology and clinical usage were reviewed in this paper. PMID:17993010

Liu, Cui-zhe; Chen, Da-wei

2007-09-01

177

Formulation and evaluation of effervescent floating tablets of tizanidine hydrochloride.  

PubMed

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

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

2011-06-01

178

In vitro--in vivo evaluation of tableted caseinchitosan microspheres containing diltiazem hydrochloride.  

PubMed

Casein-chitosan microspheres containing diltiazem hydrochloride (DTZ.HCL) were prepared using aqueous coacervation technique. The formed microspheres were not suitable for tableting by direct compression due to their poor binding properties. The effect of hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC), carbopol 940 and egg albumin as dry binders at different concentrations on the properties of the tablets was studied. Each blend of microspheres with dry binder and 2% w/w magnesium stearate as glidant was hand-filled into the die cavity of a single punch tablet machine to ensure constant amount of drug (90 mg) in each tablet. The compression force was adjusted to produce tablets with hardness value about 7.73 +/- 0.79 Kp. The prepared tablets showed good appearance and low friability. The tested binders HPMC (10 and 30% w/w) and EC (20 and 30% w/w) gave fast tablet disintegration with high initial drug release (burst effect) while, carbopol 940 (5 and 10% w/w) and egg albumin (30% w/w) gave non-disintegrating tablets with low initial drug release. Tableted microspheres prepared with 30% egg albumin showed drug release profile similar to one of the commercial tablets (Dilzem retard, 90 mg) and was chosen for in-vivo study. Tableted microspheres and commercial tablets were administered orally in different occasions to six beagle dogs and diltiazem was assayed in dog plasma. The pharmacokinetic parameters including maximum drug concentration (Cmax) and time to reach that maximum (Tmax) were 106.24 +/- 17.96 ng.ml-1 and 5.8 +/- 2.04 hours, respectively, for the commercial sustained release DTZ tablets while, those were 107.9 +/- 12.89 ng.ml-1 and 3.6 +/- 1.36 hours, respectively for tableted microspheres. The elimination half-lives were nearly the same for the commercial and the formulated tablets (8.22 +/- 4.19 and 7.95 +/- 4.28 hours, respectively). No statistical differences (P > 0.05) were found between the two treatments for area under the plasma concentration curve (AUC0 infinity), mean residence time (MRT) and rate of drug absorption (Cmax/AUC0 infinity) indicating comparable extent and rate of drug absorption for both formulations. It was concluded that the formulated tableted microspheres provide an acceptable delivery for DTZ over an extended period of time. PMID:12680034

al-Suwayeh, Saleh A; el-Helw, Abdel-Rehim M; al-Mesned, Abdullah F; Bayomi, Mohsen A; el-Gorashi, Abobakr S

2003-01-01

179

Ketorolac potentiates morphine in postoperative patient-controlled analgesia  

Microsoft Academic Search

The authors conducted a prospective randomised double-blind comparison of patient-controlled analgesia (PCA), with a combination of morphine and ketorolac versus morphine alone and ketorolac alone in the management of postoperative pain after orthopaedic surgery. Forty-two patients were randomly assigned to three groups. Group 1 was given 1 mg\\/ml morphine, group 2 was given 3 mg\\/ml ketorolac and group 3 half-doses

Pascale Picard; Jean E Bazin; Nathalie Conio; Franck Ruiz; Pierre Schoeffler

1997-01-01

180

Morphine and other opiates from beef brain and adrenal.  

PubMed Central

We describe nonpeptide opioids found in extracts of beef hypothalamus and adrenal, which are recognized by antisera raised against morphine. Four have been purified to homogeneity. One is morphine. The structures of the other three have not been determined yet. None of them are derived from morphine or normorphine after extraction from the tissues. It is not known whether the opiates described here are of endogenous or exogenous origin. PMID:3860854

Goldstein, A; Barrett, R W; James, I F; Lowney, L I; Weitz, C J; Knipmeyer, L L; Rapoport, H

1985-01-01

181

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

PubMed

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

Leppert, Wojciech; Majkowicz, Mikolaj; Forycka, Maria

2013-12-01

182

Chimeric DNA vaccine reverses morphine-induced immunosuppression and tumorigenesis.  

PubMed

Although long-term use of morphine has been shown to promote tumor growth, the question whether tumorigenesis occurs as a result of an immunosuppressive effect remains to be investigated. In mice rendered tolerant to morphine, the efficacy and mechanism of a vaccination to rescue morphine-induced immunosuppression and prevent tumor growth was assessed both in vitro and in vivo. Herein, we found that morphine-injected mice exhibited higher tumor growth rates and lower percentages of CD8+ T lymphocytes. The mechanism of morphine suppression of immunity might be through the suppression of E7-specific CD8+ T lymphocyte proliferation and the promotion of apoptosis of these cells by the Bcl-2 and Bax pathways. The suppressive effect of E7-specific CD8+ T lymphocytes by morphine could be reversed by naloxone. We have previously shown that calreticulin linked with E7 (CRT/E7) could enhance the CD8+ T cell response and the anti-tumor effects (W. F. Cheng et al. (2001) J. Clin. Invest. 108, 669-678). CRT/E7 DNA vaccine could overcome the immunosuppressive effect of morphine and suppress tumor growth. Our findings reveal that long-term morphine treatment dose-dependently promotes tumor growth and a DNA vaccine may serve as a useful approach to treat the profound immunosuppressive function and prevent tumorigenesis after long-term morphine treatment. PMID:16140583

Cheng, Wen-Fang; Chen, Li-Kuei; Chen, Chi-An; Chang, Ming-Cheng; Hsiao, Po-Ni; Su, Yi-Ning; Lee, Chien-Nan; Jeng, Huei-Jiuan; Hsieh, Chang-Yao; Sun, Wei-Zen

2006-01-01

183

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. PMID:24961764

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

2014-01-01

184

Catecholamines bind to enkephalins, morphiceptin, and morphine.  

PubMed

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

Root-Bernstein, R S

1987-04-01

185

Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose.  

PubMed

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

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

1995-06-01

186

Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose.  

PubMed Central

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

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

1995-01-01

187

An osmotic bioequivalent nifedipine tablet  

Microsoft Academic Search

A new osmotic nifedipine tablet with a controlled release profile of 24 hours, was developed. It is composed of a core containing nifedipine, a polymeric membrane and a laser drilled orifice to allow the release of the drug. The aim of the study was to assess the bioequivalency between the osmotic nifedipine tablet and the innovator Procardia® XL (nifedipine extended

E. C. Feleder; M. Befumo; M. A. Ricci; M. A. Coppari; J. Faour

2004-01-01

188

Morphine, but not trauma, sensitizes to systemic Acinetobacter baumannii infection.  

PubMed

Acinetobacter baumannii is an important nosocomial pathogen in civilian intensive care units. Recently the incidence has increased in wounded military personnel. Morphine is documented in numerous animal studies to be immunosuppressive and to sensitize to infection. The hypotheses were tested that morphine, administered for analgesia in the battlefield, predisposes to Acinetobacter infection, and that the opioid may have an additive or synergistic effect with trauma. To test these hypotheses, an intraperitoneal infection model was established in mice using several Acinetobacter strains. Morphine administered for 48 h by implantation of a slow-release morphine pellet increased mortality compared to animals receiving a placebo pellet, an effect that was blocked by the mu-opioid receptor antagonist, naltrexone. Acinetobacter burdens in the blood, spleens, livers, and lungs of morphine-treated mice, were significantly higher than those in placebo-treated animals, confirming that mortality was due to potentiated growth of the bacteria. There were also elevated levels of pro-inflammatory cytokines in morphine-treated versus placebo-treated mice. Morphine caused a reduction in the total number of cells in the peritoneal cavity, a decrease in the percentage and total numbers of neutrophils, and a decrease in the total number of macrophages. Morphine treatment also suppressed levels of the neutrophil-inducing molecules, IL-17A and KC/CXCL1. However, IL-17A(-/-) mice given morphine were not sensitized to Acintobacter infection to a greater degree than similarly treated wild-type mice. Trauma alone did not sensitize to Acinetobacter infection, and there was no additive effect between morphine and trauma. These results support the hypothesis that morphine potentiates Acinetobacter infection. PMID:21826405

Breslow, Jessica M; Monroy, M Alexandra; Daly, John M; Meissler, Joseph J; Gaughan, John; Adler, Martin W; Eisenstein, Toby K

2011-12-01

189

A study on maize proteins as a potential new tablet excipient.  

PubMed

This investigation has examined the use of zein proteins from maize as the major component in oral controlled-release tablets, such formulations often being required to improve patient compliance. Tablets containing ground zein proteins, calcium hydrogen orthophosphate, polyvinyl pyrrolidone, theophylline and magnesium stearate were produced by wet granulation and compression on a single station tablet press and were compared to directly compressed tablets based on zein proteins, calcium hydrogen orthophosphate and theophylline. Non invasive techniques such as Fourier Transform infrared spectroscopy and Fourier Transform Raman spectroscopy were employed to investigate any changes in the secondary structure of zein proteins during tablet production. Random coils, alpha helices and beta sheets predominated and their relative content remained unaffected during grinding, wet granulation and compression, indicating that formulations based on zeins will be robust, i.e. insensitive to minor changes in the production conditions. Drug release from the tablets was studied using a standard pharmacopoeial dissolution test. Dissolution profiles in water, 0.1M HCl (pH=1) and phosphate buffer (pH=6.8) show that only a limited amount of theophylline was released after 4.5h, suggesting that zein proteins could act as a potential vehicle for oral controlled drug release. Analysis of the theophylline release profiles using the Peppas and Sahlin model reveals that diffusion and polymer relaxation occurred in acidic (pH=1) and buffered (pH=6.8) conditions for wet granulated tablets, whereas diffusion was predominant in directly compressed tablets. In conclusion, the present study has shown that zeins can be successfully used as a pharmaceutical excipient, and in particular as a matrix in monolithic controlled release tablets. PMID:18294824

Georget, Dominique M R; Barker, Susan A; Belton, Peter S

2008-06-01

190

Continuous co-administration of dextromethorphan or MK-801 with morphine: attenuation of morphine dependence and naloxone-reversible attenuation of morphine tolerance.  

PubMed

N-Methyl-D-aspartate (NMDA) receptor antagonists have been repeatedly shown to attenuate the development of opiate tolerance and dependence in rodents. In the present experiments, continuous subcutaneous infusion of either MK-801 (0.01 mg/kg/h but not 0.005 mg/kg/h) or DM (0.133, 0.67 and 1.33 mg/kg/h) reliably prolonged the antinociceptive effect of continuous subcutaneous infusion of morphine sulfate (2.0 mg/kg/h), indicating attenuation of the development of morphine tolerance. Furthermore, this prolonged antinociception was completely reversible by naloxone (10 mg/kg, i.p.). Doses of MK-801 and DM that were equipotent in attenuating morphine tolerance (0.01 mg/kg/h and 1.33 mg/kg/h, respectively) revealed different profiles of effects, however, on locomotor activity and naloxone-precipitated abstinence/withdrawal symptoms. With regard to locomotor activity, rats having received continuous (48 h) subcutaneous infusion of morphine sulfate and MK-801, but not rats having received morphine sulfate and DM, displayed a reliable and striking increase in locomotor activity as compared with rats having received morphine alone. With regard to naloxone-precipitated withdrawal symptoms, continuous (48 h) subcutaneous co-infusion of either MK-801 (0.01 mg/kg/h) or DM (1.33 mg/kg/h) with morphine attenuated naloxone-precipitated hyperalgesia as compared with rats infused with morphine alone. MK-801 (0.01 mg/kg/h) was more effective than DM (0.133, 0.67, or 1.33 mg/kg/h), however, in reducing other naloxone-precipitated withdrawal symptoms (teeth chattering, jumping and wet dog shakes). The effects of MK-801 on all withdrawal symptoms were confounded, however, by the appearance of flaccidity following naloxone administration to rats having received MK-801 and morphine. These results extend previous observations by showing that the prolonged antinociception observed following co-administration of morphine and an NMDA antagonist is completely naloxone-reversible, supporting the notion that this antinociception reflects prolongation of an opioid receptor-mediated effect. The different profiles of side effects associated with MK-801 and DM, however, suggest that (1) attenuation of naloxone-precipitated withdrawal symptoms by MK-801 may be an artifact of toxicity, and (2) DM may prove clinically useful for the prevention of morphine tolerance, given its lack of observable side effects when administered concurrently with morphine to rodents. PMID:8895234

Manning, B H; Mao, J; Frenk, H; Price, D D; Mayer, D J

1996-09-01

191

Potentiation action of ibogaine (bogadin TM) on morphine analgesia  

Microsoft Academic Search

Zusammenfassung Ibogain-hydrochlorid zeigte an der Maus einen ausgesprochen potenzierenden Effekt auf die analgetische Wirkung von Morphin und morphinähnlichen Analgetika und erhöhte, bei derselben Tierart, auch die Toxizität von Morphin. Die analgetische Wirkung von Aminopyrin hingegen wurde selbst durch hohe Dosen von Ibogain nicht beeinflusst.

J. A. Schneider; Marie McArthur

1956-01-01

192

Tests for addiction (chronic intoxication) of morphine type  

PubMed Central

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

Halbach, H.; Eddy, Nathan B.

1963-01-01

193

Cytoskeletal Genes Regulation by Chronic Morphine Treatment in Rat Striatum  

Microsoft Academic Search

It has been previously suggested that morphine can regulate the expression and function of some proteins of the cytoskeleton. In the present study, we used real-time quantitative polymerase chain reaction to examine the effects of chronic morphine administration, in rat striatum, on 14 proteins involved in microtubule polymerization and stabilization, intracellular trafficking, and serving as markers of neuronal growth and

Cynthia Marie-Claire; Cindie Courtin; Bernard P Roques; Florence Noble

2004-01-01

194

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

195

Pioglitazone prevents morphine antinociception tolerance and withdrawal symptoms in rats.  

PubMed

Long-term exposure to opiates induces tolerance to the analgesic effect and dependence. The purpose of the present study is to investigate the effects of pioglitazone, a peroxisome proliferator-activated receptors gamma (PPAR-?) agonist, on the morphine-induced tolerance and dependence. Groups of rats received morphine in combination with a vehicle or pioglitazone (5, 10, 20, and 40 mg/kg) daily. Thirty minutes before pioglitazone (40 mg/kg), GW-9662, a selective PPAR-? antagonist, (2 mg/kg) was administrated in order to evaluate the possible role of the PPAR-?. Nociception was assessed by a tail flick apparatus, and the percentage of the maximal possible effect was calculated as well. For 9 days, rats received additive doses of morphine to induce dependence. Naloxone was administrated 2 h after the morphine last dose, and withdrawal symptoms were recorded for 45 min. Morphine administration to rats over a duration of 17 days resulted in the development of tolerance, whereas pioglitazone (40 mg/kg) delayed the day of the established tolerance for 15 days. Administration of pioglitazone also prevented morphine-induced 50 % effective dose (ED50) shift to the right in the dose-response curve and increased the global analgesic effect of morphine. In addition, pioglitazone decreased the total withdrawal score significantly, whereas GW-9662 significantly reversed the pioglitazone effects on the morphine tolerance and dependence. The prevention of the morphine-induced glia activation and the proinflammatory responses were the possible mechanisms for pioglitazone effect on delaying the morphine tolerance and attenuating the dependence. PMID:24899385

Ghavimi, Hamed; Hassanzadeh, Kambiz; Maleki-Dizaji, Nasrin; Azarfardian, Alireza; Ghasami, Saeed; Zolali, Elmira; Charkhpour, Mohammad

2014-09-01

196

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

Microsoft Academic Search

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

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

2007-01-01

197

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. PMID:22877734

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

2012-01-01

198

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.

199

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

200

Microporous bilayer osmotic tablet for colon-specific delivery.  

PubMed

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 pectin could form in situ delivery pores for drug release. The effect of formulation variables like inclusion of osmogen, amount of HPMC and NaCMC in core, amount of pore former in semipermeable membrane was studied. Scanning electron microscopic photographs showed formation of in situ delivery pores after predetermined time of coming in contact with dissolution medium. The number of pores was dependent on the amount of the pore former in the semipermeable membrane. In vitro dissolution results indicated that system showed acid-resistant, timed release and was able to deliver drug at an approximate zero order up to 24h. The developed tablets could be effectively used for colon-specific drug delivery to treat IBS. PMID:21255646

Chaudhary, Anil; Tiwari, Neha; Jain, Vikas; Singh, Ranjit

2011-05-01

201

Formulation, Characterization and Physicochemical Evaluation of Ranitidine Effervescent Tablets  

PubMed Central

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

Aslani, Abolfazl; Jahangiri, Hajar

2013-01-01

202

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

E-print Network

Tablet PC and Computing Curriculum Initiative 2006 Evaluation of Tablet PC Supported Pedagogy http holders react to the technology? Does the student submissions pedagogy increase engagement? Which types

Anderson, Richard

203

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

204

Changes in morphine reward in a model of neuropathic pain.  

PubMed

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

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

2013-06-01

205

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

PubMed

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

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

2014-09-01

206

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 ...

207

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

208

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

209

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

210

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

PubMed

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

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

2013-03-01

211

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. PMID:24574593

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

2014-01-01

212

In vitro Release Kinetics Study of Ranolazine from Swellable Hydrophilic Matrix Tablets  

Microsoft Academic Search

The objective of this study was to design oral sustained release matrix tablets of Ranolazine using hydroxypropyl methylcellulose (HPMC) as the retardant polymer and to study the effect of formulation factors such as polymer proportion and polymer viscosity on the release of drug. In vitro release studies were performed using USP type II apparatus (paddle method) in 900 mL of

Mohammad Nezab Uddin; Ishtiaq Ahmed; Monzurul Amin Roni; Muhammad Rashedul Islam; Mohammad Habibur Rahman; Reza-ul Jalil

2010-01-01

213

Morphine induces splenocyte apoptosis and enhanced mRNA expression of cathepsin-B.  

PubMed

Morphine has been demonstrated to modulate immune function. We studied whether morphine modulates apoptosis of splenocytes. Splenocytes were isolated from control and morphine treated rats. Splenocytes isolated from morphine treated rats showed increased percentage (P < 0.001) of apoptosis when compared to splenocytes isolated from untreated rats (control, 4.7 +/- 1.0% apoptotic splenocytes/field vs. morphine, 47.8 +/- 3.4% apoptotic splenocytes/field). These results were further confirmed by gel electrophoresis as well as by end-labeling DNA of splenocytes isolated from control and morphine treated rats. Splenocytes from morphine treated rats showed a classical ladder pattern with integer multiples of 180 base pairs. Splenocytes from morphine treated rats also showed increased mRNA expression of cathepsin-B, a gene associated with active cell death. These results suggest that morphine may also be modulating immune function by enhancing apoptosis of splenocytes. PMID:9429908

Singhal, P C; Reddy, K; Franki, N; Sanwal, V; Gibbons, N

1997-12-01

214

Characterization of Morphine Self-Administration Following Spinal Cord Injury  

E-print Network

opioid analgesics, including morphine, for the treatment of pain in both the acute and chronic phases of SCI. Yet, despite the prevalence of opioid use, no studies have examined the addictive potential of opioids, or their secondary effects, following...

Woller, Sarah Ann

2013-07-16

215

For a Child's Fracture, Use Ibuprofen, Not Morphine  

MedlinePLUS

... please enable JavaScript. For a Child's Fracture, Use Ibuprofen, Not Morphine: Study Fewer side effects reported with ... 2014 (HealthDay News) -- For children with broken bones, ibuprofen is a better choice for pain relief than ...

216

21 CFR 520.1510 - Nitenpyram tablets.  

Code of Federal Regulations, 2010 CFR

...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ...Conditions of use —(1) Dogs —(i) Amount —(A) One 11.4-mg tablet for dogs weighing less than 25 pounds...or one 57-mg tablet for dogs weighing more than 25...

2010-04-01

217

21 CFR 520.312 - Carnidazole tablets.  

Code of Federal Regulations, 2013 CFR

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

2013-04-01

218

21 CFR 520.312 - Carnidazole tablets.  

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

2014-04-01

219

21 CFR 520.312 - Carnidazole tablets.  

Code of Federal Regulations, 2012 CFR

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

2012-04-01

220

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

221

A comparative assay of nefopam, morphine and d -amphetamine  

Microsoft Academic Search

Nefopam is a non-opioid analgesic reported to have some stimulant properties. The subjective, behavioral and physiological effects of nefopam, morphine and d-amphetamine were compared in seven non-dependent substance abusers to assess the abuse potential of nefopam. Morphine and d-amphetamine had significant effects on a number of measures generally consistent with the effects of drugs of the opioid and psychomotor stimulant

D. R. Jasinski; K. L. Preston

1987-01-01

222

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

223

Mitragynine Attenuates Withdrawal Syndrome in Morphine-Withdrawn Zebrafish  

PubMed Central

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

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

2011-01-01

224

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

PubMed

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

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

2014-01-01

225

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

226

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

227

Touch Screen Tablets and Emergent Literacy  

ERIC Educational Resources Information Center

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

Neumann, Michelle M.; Neumann, David L.

2014-01-01

228

Naloxone, not proglumide or MK-801, alters effects of morphine preexposure on morphine-induced taste aversions  

Microsoft Academic Search

Both cholecystokinin (CCK) antagonists and N-methyl-d-aspartate (NMDA) antagonists block or reduce the development of morphine tolerance in several analgesic assays. The present experiments were performed to assess the ability of the CCK antagonist proglumide and the NMDA antagonist MK-801 to affect tolerance to the aversive properties of morphine as indexed by conditioned taste aversion (CTA) learning. Specifically, male Sprague–Dawley rats

Meredith A. Fox; Glenn W. Stevenson; Kenner C. Rice; Anthony L. Riley

2006-01-01

229

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. PMID:23071937

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

2011-01-01

230

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

PubMed

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

Niwa, Masahiro; Hiraishi, Yasuhiro

2014-01-30

231

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

232

Morphine, haloperidol and hyoscine N-butyl bromide combined in s.c. infusion solutions: compatibility and stability. Evaluation in terminal oncology patients.  

PubMed

The administration of drugs by subcutaneous infusion is routinely practiced in palliative medicine for the management of patients who are no longer able to take oral medication. It is common for two or more drugs to be combined in subcutaneous solutions. The combination of an opioid with other drugs (haloperiol lactate and hyoscine N-butyl bromide) can be very valuable. Unfortunately, the compatibility and stability of morphine hydrochloride, haloperidol lactate and hyoscine N-butyl bromide combined in the same solution has not yet been determined. Therefore, this study examined the stability of ternary solutions containing morphine HCl, haloperidol lactate and hyoscine N-butyl bromide at different dose ranges. Twelve different solutions were assessed for 15 days after preparation in polypropylene syringes using 0.9% saline as diluent. Triplicate syringes were stored at 25 degrees C. HPLC was the analytical technique used to measure morphine HCl, haloperidol lactate and hyoscine N-butyl bromide. Initial concentration ranges were 1.67-10.0 mg/ml for morphine HCl, 0.417-0.625 mg/ml for haloperidol lactate and, 5.0-6.67 mg/ml for hyoscine N-butyl bromide. All three drugs were very stable (>92.5%) when stored at 25 degrees C. The clinical performance of the admixture was retrospectively assessed in 21 terminal oncology patients. Total symptom control was achieved in 17 out of 21 patients with very good local tolerance. PMID:16297583

Negro, S; Reyes, R; Azuara, M L; Sánchez, Y; Barcia, E

2006-01-13

233

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

PubMed Central

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

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

2014-01-01

234

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

PubMed Central

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

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

2011-01-01

235

Lack of bioequivalence of a generic mefloquine tablet with the standard product  

Microsoft Academic Search

Objective: To assess the bioequivalence between a generic tablet of mefloquine (Mephaquin®?= M1) with the reference tablet (Lariam®?=?M2) in healthy volunteers.\\u000a \\u000a \\u000a \\u000a Methods: This open label, randomized two-way cross-over study was performed in a single centre. Following an overnight fast, eighteen\\u000a healthy volunteers received a single oral dose of 750?mg mefloquine either in the form of three M1 lactabs or three

E. Weidekamm; G. Rüsing; H. Caplain; F. Sörgel; C. Crevoisier

1998-01-01

236

Plastic Changes of Calcitonin Gene-Related Peptide in Morphine Tolerance: Behavioral  

E-print Network

Plastic Changes of Calcitonin Gene-Related Peptide in Morphine Tolerance: Behavioral Biotechnology, Peking University, Beijing, People's Republic of China The present study was undertaken to investigate the plasticity of calcitonin gene-related peptide (CGRP) in antinociception after morphine

Stephens, Matthew

237

Involvement of cannabinoid receptors in peripheral and spinal morphine analgesia.  

PubMed

The interactions between the cannabinoid and opioid systems for pain modulation are reciprocal. However, the role and the importance of the cannabinoid system in the antinociceptive effects of opioids remain uncertain. We studied these interactions with the goal of highlighting the involvement of the cannabinoid system in morphine-induced analgesia. In both phases of the formalin test, intra paw and intrathecal morphine produced similar antinociceptive effects in C57BL/6, cannabinoid type 1 and type 2 receptor wild-type (respectively cnr1WT and cnr2WT) mice. In cnr1 and cnr2 knockout (KO) mice, at the dose used the antinociceptive effect of intra paw morphine in the inflammatory phase of the formalin test was decreased by 87% and 76%, respectively. Similarly, the antinociceptive effect of 0.1?g spinal morphine in the inflammatory phase was abolished in cnr1KO mice and decreased by 90% in cnr2KO mice. Interestingly, the antinociceptive effect of morphine in the acute phase of the formalin test was only reduced in cnr1KO mice. Notably, systemic morphine administration produced similar analgesia in all genotypes, in both the formalin and the hot water immersion tail-flick tests. Because the pattern of expression of the mu opioid receptor (MOP), its binding properties and its G protein coupling remained unchanged across genotypes, it is unlikely that the loss of morphine analgesia in the cnr1KO and cnr2KO mice is the consequence of MOP malfunction or downregulation due to the absence of its heterodimerization with either the CB1 or the CB2 receptors, at least at the level of the spinal cord. PMID:24365460

Desroches, J; Bouchard, J-F; Gendron, L; Beaulieu, P

2014-03-01

238

Real-time tablet formation monitoring with ultrasound measurements in eccentric single station tablet press.  

PubMed

A real-time ultrasound measurement system for tablet compression monitoring is introduced. The measurement system was tested in actual manufacturing environment and found to be capable of measuring the ultrasound response of the tabletting process from bulk to tablet. The tablet sets were compressed and the ultrasound measurements were conducted as implemented in eccentric single station tabletting apparatus in through transmission geometry. The speed of sound and ultrasound spectrum was measured during dynamic compression for microcrystalline cellulose/paracetamol tablets. The ultrasound system introduced in this study was found to be suitable for tabletting process monitoring as the mechanical properties of compressed tablets can be estimated during compression using the ultrasound system. In addition, it was found that the ultrasound was sensitive to the mixing time of magnesium stearate and the concentration of paracetamol. Thus, ultrasound measurements made during the compression can be used to monitor the tablet formation process. PMID:22985771

Leskinen, Jari T T; Simonaho, Simo-Pekka; Hakulinen, Mikko; Ketolainen, Jarkko

2013-02-14

239

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. PMID:21197323

Balch, Robert J; Trescot, Andrea

2010-01-01

240

Preparation and evaluation of sublingual tablets of zolmitriptan  

PubMed Central

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

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

2014-01-01

241

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. PMID:23776728

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

2013-01-01

242

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

243

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

Microsoft Academic Search

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

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

2010-01-01

244

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

Microsoft Academic Search

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

Benjamin McNaull; Tuan Trang; Maaja Sutak; Khem Jhamandas

2007-01-01

245

Dissolution profile of 24 levofloxacin (100 mg) tablets.  

PubMed

Although there are 23 generic levofloxacin (100 mg) tablets (LVFX tablets) and 1 brand name LVFX tablet (supply now discontinued) in Japan, there have been no reports that have evaluated and compared the dissolution profiles of LVFX tablets using the same dissolution method. We studied the dissolution profile of LVFX tablets by the Paddle method, a standard dissolution test method. Among 23 generic LVFX tablets, 2 LVFX tablets had lower dissolution rates and 14 had higher dissolution rates than the brand name LVFX tablet. It is suggested that LVFX tablets have different dissolution profiles, which could cause different pharmacokinetic profiles. PMID:23380968

Maezawa, Kayoko; Yajima, Ryo; Terajima, Tomoko; Kizu, Junko; Hori, Seiji

2013-10-01

246

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

247

Effects of mu, kappa or delta opioids administered by pellet or pump on oral Salmonella infection and gastrointestinal transit.  

PubMed

Our laboratory has shown previously that subcutaneously implanted, slow-release morphine pellets markedly enhanced susceptibility to oral infection with Salmonella typhimurium. Further, morphine, kappa and delta opioid receptor agonists infused via osmotic minipumps were immunosuppressive. The present study compared morphine pellets to morphine pumps and also examined the differential effects of morphine versus U50,488H (kappa agonist), deltorphin II (delta2 agonist), and (D-Pen2, D-Pen5)-enkephalin (DPDPE, delta1 agonist), administered via Alzet minipumps, on oral Salmonella infection and on gastrointestinal transit. The results show that all morphine-pelleted mice (26/26) had a marked increase in Salmonella burden in the Peyer's Patches, mesenteric lymph nodes and spleen. In comparison, only 8/20 mice receiving morphine by minipump at doses ranging from 1 to 25 mg/kg/day had any culturable Salmonella in their organs and the number of bacteria was very low. The level of Salmonella colonization correlated with blood morphine levels and gut transit measured using an intragastric charcoal meal. Morphine pellets inhibited gut transit by 38%, while mice receiving morphine by minipump at doses of 1 to 25 mg/kg/day showed only a dose-dependent 7% to 17% inhibition. Mice receiving various doses of U50,488H or DPDPE had no culturable Salmonella in the three sites. Deltorphin II given by minipump resulted in a moderate level of Salmonella in the spleen. Deltorphin II and U50,488H (0.1 to 10 mg/kg/day) did not suppress gut transit. The present studies indicate that a predominantly mu opioid receptor agonist, morphine, given by slow-release pellet, potentiated Salmonella infection and inhibited gastrointestinal transit. In contrast, morphine in pumps slightly inhibited intestinal transit, but did not sensitize to Salmonella infection. A delta1 opioid receptor agonist did not sensitize to infection, and a delta2 and a kappa opioid receptor agonist had minimal effects on either parameter. PMID:16513108

Feng, Pu; Rahim, Rahil T; Cowan, Alan; Liu-Chen, Lee-Yuan; Peng, Xiaohui; Gaughan, John; Meissler, Joseph J; Adler, Martin W; Eisenstein, Toby K

2006-03-18

248

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

PubMed

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

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

2000-11-01

249

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 ...

250

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. PMID:20815879

2010-01-01

251

Acceptability of different oral formulations in infants and preschool children  

PubMed Central

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

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

2013-01-01

252

Quaternary naltrexone reverses radiogenic and morphine-induced locomotor hyperactivity  

SciTech Connect

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

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

1984-04-01

253

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

254

Ontogenesis of morphine-induced behavior in the cat.  

PubMed

We analyzed the behavioral responses to a single dose of morphine in kittens at postnatal (P) ages 7, 15, 30, 60, 90, and 120 days. Each kitten received 0.5 or 3.0 mg/kg i.p. of morphine sulphate or saline vehicle. An average of 6.5 kittens were studied at each dose and age. An ethogram was constructed, based on morphine effects in adult cats, to score appropriate behaviors from direct observation and video sampling. After injection behaviors were sampled for periods of 2 min every 15-30 min for a total of 4 h. The frequency of each selected behavior was scored at 2 s intervals during each of the 2 min periods and it was expressed as a percent of all time samples scored for the 4 h period. Statistical comparisons were made with control (saline) littermates. At P7-15 the drug's main effect was behavioral depression; i.e., kittens, away from the litter, laid sprawled as if with no muscle tonus; Nursing was suppressed and Vocalization was distressed. Mainly with the higher dose, at P30, morphine-specific behaviors appeared for the first time. With the kitten in a Sitting position, these included stereotypical Head and Paw Movements and body Torsion. At P60 other drug-elicited behaviors emerged, including Spinning, Retching, and Vomiting. By P90-120 the frequency of Head (16.0%) and Paw (16.9%) Movements doubled relative to P30-60. Morphine significantly changed frequencies of newly matured behaviors (in control kittens) including Sniffing and Licking (increased), and Grooming (decreased/blocked). Retching and Vomiting increased to adult levels. Morphine-induced hyperthermia was first detected at P60 and peaked by P90-P120. The early behavioral depression shifted to a pattern of increasing activity starting at P30 and peaking at P90-120, at which time Sleep was absent and Laying was reduced, while Walking and Sitting were increased. We concluded that the maturation of the stereotypical behavioral responses to morphine in cats begins at about P30 and is completed between P90 and 120. Results are discussed in terms of developmental parameters and putative brain sites of morphine's actions. PMID:17196189

Burgess, J Wesley; Villablanca, Jaime R

2007-02-23

255

Automated radiosynthesis of [11C]morphine for clinical investigation  

PubMed Central

To meet a multiple-dose clinical evaluation of the P-gp modulation of [11C]morphine delivery into the human brain, radiosynthesis of [11C]morphine was accomplished on an automated system by N-methylation of normorphine with [11C]CH3I. A methodology employing optimized solid-phase extraction of the HPLC eluent was developed. Radiosynthesis took 45 min with a radiochemical yield ranging from 45 – 50% and specific activity ranging from 20 – 26 Ci/?mol (decay corrected to end-of-bombardment); radiochemical and chemical purities were >95% (n = 28). PMID:21112214

Fan, Jinda; Meissner, Konrad; Gaehle, Gregory G.; Li, Shihong; Kharasch, Evan D.; Mach, Robert H.; Tu, Zhude

2010-01-01

256

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

257

21 CFR 520.88f - Amoxicillin trihydrate tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 false Amoxicillin trihydrate tablets. 520.88f ...ANIMAL DRUGS § 520.88f Amoxicillin trihydrate tablets. (a) Specifications... Each tablet contains amoxicillin trihydrate equivalent to 50,...

2010-04-01

258

Oral Medication  

MedlinePLUS

... Size: A A A Listen En Español Oral Medication The first treatment for type 2 diabetes blood ... new — even over-the-counter items. Explore: Oral Medication How Much Do Oral Medications Cost? Save money ...

259

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. PMID:24904720

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

2014-01-01

260

Human liver morphine UDP-glucuronyl transferase enantioselectivity and inhibition by opioid congeners and oxazepam.  

PubMed

1. Morphine uridine diphosphate glucuronyl transferase (UDP-GT) was studied in human liver microsomes. The (-)- and (+)-morphine enantiomers were used as substrates and inhibitors, such as oxazepam and various opioid congeners were employed to characterize the different glucuronidation pathways. The kinetics of the oxazepam inhibition were studied in the rat liver. 2. The overall glucuronidation of (+)-morphine was higher than that of (-)-morphine. The morphine congeners tested, potently inhibited the formation of (-)-morphine-3-glucuronide ((-)-M3G), except for normorphine and codeine. The formation of (+)-morphine-6-glucuronide [+)-M6G) was potently inhibited by only dextromethorphan and (+)-naloxone. All drugs except normorphine inhibited the formation of (+)-M3G by 18-50%. 3. The metabolism of (-)-morphine to (-)-M3G was more sensitive to oxazepam inhibition than the formation of (+)-M3G from (+)-morphine in the rat liver. 4. The glucuronidation of natural morphine is subject to in vitro interaction with oxazepam and several opiate drugs. Our study supports the theory of more than one type of UDP-GT being involved in morphine glucuronidation. PMID:3140993

Wahlström, A; Pacifici, G M; Lindström, B; Hammar, L; Rane, A

1988-07-01

261

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

PubMed Central

The aim of the present study was to assess the effects of chronic and acute treatment of the essential oil (EO) of Kelussia odoratissima Mozaff. on the development of morphine tolerance and dependence in mice. Mice were rendered tolerant to and dependent on morphine by subcutaneous injection of morphine over a period of 5 days. Tolerance was assessed using the tail-pinch test and withdrawal signs of morphine were precipitated by injecting naloxone 2?h after the final morphine injection. Repeated injection of the EO of K. odoratissima (5 and 10?mg/kg) for 4 days significantly suppressed morphine-withdrawal jumps, a sign of the development of dependence to opiate as assessed by naloxone precipitation withdrawal on day 5 of testing. A single injection (25, 50, 100?mg/kg) of the EO on day 5, 1?h prior to morphine failed to produce any significant change in morphine withdrawal signs. Neither the acute nor the chronic administration of EO of the K. odoratissima did significantly influence the development of tolerance to the analgesic effect of morphine. Alleviation in morphine signs of withdrawal after chronic injection with K. odoratissima is indicative of reversal of neuronal adaptation that takes place during morphine presence in the brain. PMID:22829859

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

2012-01-01

262

In vitro release of valerenic and hydroxyvalerenic acids from valerian tablets.  

PubMed

Although most commercial valerian formulations are coated tablets not any comparison study of their drug release profiles has been published so far. The main objective of this work is to establish a drug release test suitable for studying and comparing different valerian tablets. Thus, hydroxyvalerenic and valerenic acid concentrations were assayed by HPLC using a C18 Kromasil (200 x 4.6 mm, 5 microm) column and a mobile phase containing methanol and an orthophosphoric acid solution 0.5% v/v in water at a ratio of 75:25 at a constant flow rate of 1 ml/min. Saturation solubilities for hydroxyvalerenic and valerenic acid at pH 6.8 were 26 +/- 5.1 and 1 +/- 0.6 microg/ml, respectively. Usually for drugs with such low solubility values, their oral absorption and hence bioavailability are limited by their dissolution characteristics. A dissolution test was conducted according to the general method 2 (paddles) of USP 24 using 500 ml buffer medium (pH 6.8) at 50 rpm. Five different formulations were studied and compared: one uncoated tablet formulation and four marketed coated tablets. The uncoated tablet formulation had the fastest release profile, whereas the coated tablets manifested very different release patterns, depending on the type of formulation. Because of these differences in drug release pattern not every tablet formulation may be appropriate for the same clinical indications. Clinical data are required to confirm the correlation between drug release pattern and the therapeutically value of each formulation. PMID:14531459

Torrado, J J

2003-09-01

263

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

264

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

PubMed Central

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

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

2014-01-01

265

Development and Evaluation of Gastroretentive Floating Tablets of an Antihypertensive Drug Using Hydrogenated Cottonseed Oil  

PubMed Central

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

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

2013-01-01

266

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

267

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

PubMed

The purpose of the present study was to develop and characterize an oral controlled release drug delivery system for concomitant administration of diclofenac sodium (DS) and chondroitin sulfate (CS). A hydrophilic matrix-based tablet using different concentrations of hydroxypropylmethylcellulose (HPMC) was developed using wet granulation technique to contain 100 mg of DS and 400 mg of CS. Formulations prepared were evaluated for the release of DS and CS over a period of 9 hours in pH 6.8 phosphate buffer using United States Pharmacopeia (USP) type II dissolution apparatus. Along with usual physical properties, the dynamics of water uptake and erosion degree of tablet were also investigated. The in vitro drug release study revealed that HPMC K100CR at a concentration of 40% of the dosage form weight was able to control the simultaneous release of both DS and CS for 9 hours. The release of DS matched with the marketed CR tablet of DS with similarity factor (f(2)) above 50. Water uptake and erosion study of tablets indicated that swelling followed by erosion could be the mechanism of drug release. The in vitro release data of CS and DS followed Korsmeyer-Peppas and zero-order kinetics, respectively. In conclusion, the in vitro release profile and the mathematical models indicate that release of CS and DS can be effectively controlled from a single tablet using HPMC matrix system. PMID:18181548

Avachat, Amelia; Kotwal, Vikram

2007-01-01

268

Effect of modified multi-walled carbon nanotubes on release characteristics of indomethacin from symmetric membrane coated tablets  

Microsoft Academic Search

In this study, symmetric membrane coated tablets were prepared to control delivery of drug in oral osmotic pump system. Effects of various preparation parameters such as concentration of the polymer, concentration of the pore former, thickness of membrane and presence of carbon nanotubes as additives on the permeability and the release characteristics of indomethacin drug was evaluated. The main purpose

Sayed Siavash Madaeni; Katayoun Derakhshandeh; Sara Ahmadi; Vahid Vatanpour; Sirus Zinadini

269

Pharmacokinetics and relative bioavailability evaluation of linezolid suspension and tablet formulations.  

PubMed

The oral liquid formulations poses an alternative way in providing medications to pediatric patients, geriatric patients, patients with feeding tubes, and patients who cannot swallow solid dosage forms. This study was conducted to evaluate the pharmacokinetics (PKs) and relative bioavailability of suspension (reference) and tablet (test) formulations of Linezolid (LZD). In vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, 2 Way, Cross-Over Study with a washout period of 1-week. Under fasting conditions, 28 healthy Egyptian male volunteers were randomly allocated to receive a single oral dose of either 30 ml LZD or 1 tablet (600 mg LZD) of marketed suspension and tablet formulations. Plasma samples were obtained over a 48-h interval and analyzed for LZD by reversed phase liquid chromatography with ultraviolet detection. The 90% confidence intervals for the ratio of log transformed values of Cmax, AUC0-t, and AUCt-? of the two treatments were within the acceptable range (0.8-1.25) for bioequivalence. From PK perspectives, in this small study in healthy Egyptian adult male volunteers, a single 600 mg dose of the tablet formulation demonstrated comparable rate and extent of absorption to a single 600 mg dose of the suspension formulation based on the US FDA's regulatory definition. No adverse events occurred or were reported after a single 600 mg LZD and both formulations were well tolerated. PMID:23740384

Helmy, S A

2013-09-01

270

Development and optimization of a novel sustained-release dextran tablet formulation for propranolol hydrochloride.  

PubMed

A novel oral controlled delivery system for propranolol hydrochloride (PPL) was developed and optimized. The in vitro dissolution profiles of sustained-release matrix tablets of racemic PPL were determined and compared with the United States Pharmacopeia (USP) tolerance specifications for Propranolol Hydrochloride Extended-Release Capsules. The influence of matrix forming agents (native dextran, hydroxypropyl methylcellulose (HPMC), cetyl alcohol) and binary mixtures of them on PPL release in vitro was investigated. A central composite design was applied to the optimization of a sustained-release tablet formulation. The sustained-release matrix tablets with good physical, mechanical and technological properties were obtained with a matrix excipient:PPL ratio of 60:40 (w/w), with a dextran:HPMC ratio of 4:1 (w/w) and with a cetyl alcohol amount of 15% (w/w). A comparative kinetic study of the present matrix tablets and commercial SUMIAL RETARD capsules (Spain) was established. The value for the similarity factor (f(2)=69.6) suggested that the dissolution profile of the present two sustained-release oral dosage forms are similar. Higuchi (diffusion) and Hixon-Crowell (erosion) kinetic profiles were achieved and this codependent mechanism of drug release was established. PMID:16584856

Gil, Eddy Castellanos; Colarte, Antonio Iraizoz; Bataille, Bernard; Pedraz, José Luis; Rodríguez, Fernand; Heinämäki, Jyrki

2006-07-01

271

Evaluation of named binders in Rauwolfia vomitoria root tablets.  

PubMed

Some physical properties of Rauwolfia vomitoria root tablets were studied. Tablet characteristics studied were: weight uniformity, tensile strength, friability, disintegration time and content uniformity. Tablet property varied depending on the type and concentration of the binder. The tablets had type and concentration of the binder. The tablets had acceptable hardness and friability profiles. Although tablets containing 150 mg R. vomitoria root had lower tensile strength values. All the tablets passed the B.P. disintegration time test of 15 min. Moreover tablets containing 150 mg R. vomitoria root disintegrated under 1 min. at 4% w/w binder concentration. PMID:10961024

Onunkwo, G C

2000-01-01

272

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

PubMed

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

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

2012-11-01

273

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

274

Use of morphine in cholescintigraphy for obstructive cholecystitis  

SciTech Connect

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

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

1985-05-01

275

Morphine-augmented cholescintigraphy in the diagnosis of acute cholecystitis  

SciTech Connect

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

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

1986-12-01

276

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

277

Spielewoy et al. 1 Increased Rewarding Properties of Morphine  

E-print Network

plays a crucial role in the behavioral responses to drugs of abuse. In particular, increased to increase locomotor activity in DAT-/- mice, while enhancing locomotion in DAT+/- and DAT+/+ animals extracellular DA levels compared to control animals. Morphine also induced a higher rate of c-fos transcription

Paris-Sud XI, Université de

278

Site and mechanism of morphine tolerance in the gastrointestinal tract.  

PubMed

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

Akbarali, H I; Inkisar, A; Dewey, W L

2014-10-01

279

Mighty Morphin Power Ranger Play: Research and Reality.  

ERIC Educational Resources Information Center

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

Crosser, Sandra

1995-01-01

280

The reality of in-line tablet coating.  

PubMed

The possibility of continuous processing in pharmaceutical tablet manufacturing is hampered by the viscoelastic recovery of tablets post-compaction. Compacted tablets are typically aged before coating to allow complete viscoelastic recovery so as to avoid subsequent coating defects. There has been little attempt to overcome tablet recovery in order to enable continuous processing and improve manufacturing efficiency. However, with the introduction of improved or newly developed types of tablet-coating equipment, there is renewed interest in the coating of tablets in-line. In-line tablet coating is defined as the coating of tablets immediately after compaction. It is a one-step highly integrated system that circumvents the delay in processing time typically given to allow viscoelastic recovery of tablets. This review aims to summarize the requirements of an in-line tablet-coating system. The possibility of carrying out in-line tablet coating in the near future will also be discussed. PMID:21649557

Cahyadi, Christine; Chan, Lai Wah; Heng, Paul Wan Sia

2013-02-01

281

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

Microsoft Academic Search

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

Amelia Avachat; Vikram Kotwal

2007-01-01

282

In Vitro Release Kinetics and Bioavailability of Gastroretentive Cinnarizine Hydrochloride Tablet  

Microsoft Academic Search

An oral sustained release dosage form of cinnarizine HCl (CNZ) based on gastric floating matrix tablets was studied. The release\\u000a of CNZ from different floating matrix formulations containing four viscosity grades of hydroxypropyl methylcellulose, sodium\\u000a alginate or polyethylene oxide, and gas-forming agent (sodium bicarbonate or calcium carbonate) was studied in simulated gastric\\u000a fluid (pH 1.2). CNZ release data from the

Ramesh C. Nagarwal; Devendra N. Ridhurkar; J. K. Pandit

2010-01-01

283

Influence of fentanyl and morphine on intestinal circulation  

SciTech Connect

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

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

1985-06-01

284

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. PMID:22536056

Wade, Alan G; Crawford, Gordon M; Young, David

2012-01-01

285

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

286

Inhibiting a spinal dynorphin A component enhances intrathecal morphine antinociception in mice.  

PubMed

Morphine given intracerebroventricularly releases spinal dynorphin A (Dyn) in mice. The present study was undertaken to determine whether morphine given intrathecally (IT) released Dyn. We demonstrated that the antinociceptive action of morphine was enhanced by procedures that are known to attenuate Dyn action. First, coadministration of the opiate antagonists, naloxone (5 fg), norbinaltorphimine (5 fg) or beta-funaltrexamine (0.25 ng) with IT morphine (0.15 microgram, 5 min) increased antinociceptive percentage maximum possible effect (%MPE) from 30% to 65%. Second, dynorphin antiserum (5 micrograms, 1 h, IT), which neutralizes Dyn action, enhanced morphine (0.2 microgram, 5 min, IT) action; MPE of 27% was increased to 60%. Third, production of desensitization to the antagonistic action of Dyn, IT, by pretreatment with morphine [10 mg/kg, 3 h, subcutaneously (SC)], or 2 micrograms, 3 h, IT) or Dyn (1 ng, 1 h, IT) increased the 30% MPE of IT morphine to 60%. Naloxone [1 ng/kg, intraperitoneally (IP)] enhanced IT morphine at a peak time of 20 min. Nalmefene [1 to 100 ng/kg, per os (PO)] enhanced IT morphine action. In conclusion, the present study showed that IT morphine putatively released spinal Dyn. PMID:7902680

Holmes, B B; Fujimoto, J M

1993-12-01

287

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

288

Preparation and in vitro evaluation of guar gum based triple-layer matrix tablet of diclofenac sodium.  

PubMed

The objective of the present study was to design an oral controlled drug delivery system for sparingly soluble diclofenac sodium (DCL) using guar gum as triple-layer matrix tablets. Matrix tablet granules containing 30% (D1), 40% (D2) or 50% (D3) of guar gum were prepared by the conventional wet granulation technique. Matrix tablets of diclofenac sodium were prepared by compressing three layers one by one. Centre layer of sandwich like structure was incorporated with matrix granules containing DCL which was covered on either side by guar gum granule layers containing either 70, 80 or 87% of guar gum as release retardant layers. The tablets were evaluated for hardness, thickness, drug content, and drug release studies. To ascertain the kinetics of drug release, the dissolution profiles were fitted to various mathematical models. The in vitro drug release from proposed system was best explained by the Hopfenberg model indicating that the release of drug from tablets displayed heterogeneous erosion. D3G3, containing 87% of guar gum in guar gum layers and 50% of guar gum in DCL matrix granule layer was found to provide the release rate for prolonged period of time. The results clearly indicate that guar gum could be a potential hydrophilic carrier in the development of oral controlled drug delivery systems. PMID:23181081

Chavda, H V; Patel, M S; Patel, C N

2012-01-01

289

Tablet PCs: A Physical Educator's New Clipboard  

ERIC Educational Resources Information Center

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

Nye, Susan B.

2010-01-01

290

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

291

Risperidone: effects of formulations on oral bioavailability.  

PubMed

The bioavailability of risperidone was evaluated in an open-label, randomized, two-way, crossover study comparing a 1-mg tablet with a 1-mg/ml oral solution. Both formulations were administered as a single 1-mg dose with a 10-day washout period between treatments. Of 26 healthy men who entered the study, 23 completed both treatment periods. Plasma concentrations of risperidone and the active moiety (risperidone plus its active metabolite, 9-hydroxyrisperidone) were determined by radioimmunoassays. For key pharmacokinetic values (Cmax, AUC), the 90% CIs on the relative bioequivalence of risperidone, 9-hydroxyrisperidone, and the active moiety were contained within the equivalence range of 80-120% (80-125% for log-transformed data). The results demonstrate that the 1-mg/ml oral solution and the 1-mg tablet are bioequivalent. PMID:9165565

Gutierrez, R; Lee, P I; Huang, M L; Woestenborghs, R

1997-01-01

292

Interactions of "ultra-low" doses of naltrexone and morphine in mature and young male and female rats.  

PubMed

Sex and age influence morphine analgesia in humans and animals. Mature rats show greater morphine analgesia in males than in females. Ultra-low doses of naltrexone enhance morphine analgesia. In mature rats (18-22 weeks), naltrexone (0.002-2.0 mg/kg)-morphine (2 mg/kg) cotreatment enhanced morphine analgesia in females, an effect inversely related to naltrexone dose. Conversely, in mature male rats, naltrexone tended to decrease morphine analgesia with increasing dose. In young rats (8-10 weeks), morphine analgesia was unrelated to sex and in both sexes the naltrexone-morphine interaction was negligible. These data show that dose, age, and sex alter the naltrexone-morphine interaction in rats. PMID:15204037

Hamann, Scott R; Malik, Hammad; Sloan, Jewell W; Wala, Elzbieta P

2004-01-01

293

Enhanced bioavailability of buspirone hydrochloride via cup and core buccal tablets: formulation and in vitro/in vivo evaluation.  

PubMed

This work aims to prepare sustained release buccal mucoadhesive tablets of buspirone hydrochloride (BH) to improve its systemic bioavailability. The tablets were prepared according to 5×3 factorial design where polymer type was set at five levels (carbopol, hydroxypropyl methylcellulose, sodium alginate, sodium carboxymethyl cellulose and guar gum), and polymer to drug ratio at three levels (1:1, 2:1 and 3:1). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h) and time for release of 50% BH (T(??%)) were chosen as dependent variables. Additional BH cup and core buccal tablets were prepared to optimize BH release profile and make it uni-directional along with the tablets mucoadhesion. Tablets were evaluated in terms of content uniformity, weight variation, thickness, diameter, hardness, friability, swelling index, surface pH, mucoadhesion strength and time and in vitro release. Cup and core formula (CA10) was able to adhere to the buccal mucosa for 8h, showed the highest Q8h (97.91%) and exhibited a zero order drug release profile. Pharmacokinetic study of formula CA10 in human volunteers revealed a 5.6 fold increase in BH bioavailability compared to the oral commercial Buspar® tablets. Conducting level A in vitro/in vivo correlation showed good correlation (r²=0.9805) between fractions dissolved in vitro and fractions absorbed in vivo. PMID:24412520

Kassem, Mohamed A A; Elmeshad, Aliaa N; Fares, Ahmed R

2014-03-10

294

Morphine-6?-glucuronide has a higher efficacy than morphine as a mu-opioid receptor agonist in the rat locus coeruleus  

PubMed Central

The pharmacological properties of the active morphine metabolite, morphine-6?-D-glucuronide (M6G), and the parent compound were compared in rat locus coeruleus neurons by electrophysiological recording in brain slices.M6G and morphine activated potassium currents in voltage clamped neurons, which were blocked by the opioid receptor antagonist naloxone.Both M6G and morphine behaved as partial agonists that produced maximal responses smaller than the system maximum, which was measured using [Met5]-enkephalin. M6G produced a larger maximal response (78%) than morphine (62%), which we estimated was due to a 2–4 fold difference in the relative efficacy of the agonists.3-O-methoxynaltrexone, which has been reported to behave as a selective antagonist of a M6G preferring receptor, was equally effective at blocking currents produced by M6G and the selective mu-opioid receptor agonist DAMGO.M6G currents were occluded by a prior application of morphine, and were reduced when mu-opioid receptors were desensitized by using [Met5]-enkephalin.Morphine-3?-D-glucuronide did not affect action potential firing or membrane currents in locus coeruleus neurons and had no effect on currents produced by M6G.These results show that the relative efficacy of M6G is higher than morphine in locus coeruleus neurons, contrary to what has been shown using mu-opioid receptors expressed in cell clones. PMID:11090116

Osborne, Peregrine B; Chieng, Billy; Christie, MacDonald J

2000-01-01

295

Development of taste masked oral formulation of ornidazole.  

PubMed

Taste masked microspheres of ornidazole were prepared using amino alkyl methacrylate copolymers (Eudragit E-100) by solvent evaporation technique. Taste assessment of these microspheres was done by both spectrophotometric taste evaluation technique and panel testing. Compressed tablets of taste masked ornidazole microspheres which rapidly disintegrated in the oral cavity were prepared using microcrystalline cellulose as directly compressible filler and sodium starch glycolate as a super-disintegrant. These were subsequently evaluated for various pharmacopoeial tests, drug release, and disintegration time in the oral cavity. Sensory taste evaluation was carried by panel testing in 20 healthy human volunteers. Results indicate successful formulation of oral fast disintegrating tablets which disintegrated in the oral cavity in about 30 s and possessed good taste. PMID:20838525

Shishu; Kamalpreet; Kapoor, V R

2010-03-01

296

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. PMID:20838525

Shishu; Kamalpreet; Kapoor, V. R.

2010-01-01

297

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

298

A novel morphine electrochemical biosensor based on intercalative and electrostatic interaction of morphine with double strand DNA immobilized onto a modified Au electrode.  

PubMed

The intercalative and electrostatic interaction of morphine with double-stranded DNA (ds-DNA), which was immobilized onto mercapto-benzaldehyde-modified Au electrode, was employed for designing a sensitive biosensor. The interaction of morphine with the immobilized ds-DNA onto the electrode surface has been studied by differential pulse voltammetry (DPV). Under the optimum conditions, a linear dependence for the morphine concentration in the range of 0.05-500?molL(-1) and its oxidation signal were observed and a detection limit of 0.01?molL(-1) for the morphine was obtained. The reproducibility and applicability of the analysis to real samples were also investigated and results demonstrated that this DNA biosensor could be utilized for the sensitive, rapid, simple, and cost effective determination of morphine in urine and blood plasma samples. PMID:25281127

Talemi, Rasoul Pourtaghavi; Mashhadizadeh, Mohammad Hossein

2015-01-01

299

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

PubMed Central

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

Chen, Yukun; Evola, Marianne

2013-01-01

300

Long-term stability of morphine and bupivacaine mixture for spinal use.  

PubMed

From clinical studies it has been proven that morphine in combination with bupivacaine is applicable in cancer pain. The availability of a ready to use parental dosage form of morphine and bupivacaine is comfortable for health care workers. Stability of a morphine or a bupivacaine preparation or a combination of both in a PVC cassette or polypropylene syringe for spinal use is examined in several studies. Apart from one study no data on long-term stability of morphine-bupivacaine mixture is available. A forced degradation study and a shelf-life study at room temperature (20-25 degrees C) were started on morphine hydrochloride 0.2 mg/ml and bupivacaine hydrochloride 7.5 mg/ml in 50 ml sterilized glass bottles type II. The results of the stability study showed that this mixture was stable up to 18 months at room temperature, whereafter morphine showed a slight degradation (5%) and bupivacaine remained stable. PMID:10427586

Essink-Tjebbes, C M; Burger, D M; Beelen, M; Wuis, E W; Hekster, Y A

1999-06-01

301

[Oral ulcers].  

PubMed

Ulcers commonly occur in the oral cavity, their main symptom being pain. There are different ways to classify oral ulcers. The most widely accepted form divides them into acute ulcers--sudden onset and short lasting--and chronic ulcers--insidious onset and long lasting. Commonest acute oral ulcers include traumatic ulcer, recurrent aphthous stomatitis, viral and bacterial infections and necrotizing sialometaplasia. On the other hand, oral lichen planus, oral cancer, benign mucous membrane pemphigoid, pemphigus and drug-induced ulcers belong to the group of chronic oral ulcers. It is very important to make a proper differential diagnosis in order to establish the appropriate treatment for each pathology. PMID:16277953

Bascones-Martínez, Antonio; Figuero-Ruiz, Elena; Esparza-Gómez, Germán Carlos

2005-10-29

302

A Comparison of Subcutaneous Morphine and Fentanyl in Hospice Cancer Patients  

Microsoft Academic Search

This study compares subcutaneous (sc) morphine and fentanyl with respect to pain control and side effects using a 6-day randomized, double-blind, cross-over design. Results were obtained from 23 patients (12 males and 11 females: mean age of 70.5 years) who could tolerate morphine. Thirteen patients were randomized to receive morphine for the first 3 days followed by fentanyl; 10 received

Roger Hunt; Belinda Fazekas; David Thorne; Mary Brooksbank

1999-01-01

303

Distribution of c-Fos in guinea-pig brain following morphine withdrawal  

Microsoft Academic Search

The distribution of the immediate-early gene and transcription factor protein, c-Fos, was examined in the brains of guinea-pigs following treatment with morphine, naloxone or naltrexone, or the induction of morphine withdrawal by these opioid antagonists. Guinea-pigs were given subcutaneous injections of morphine sulphate or tartrate three times per day in increasing doses for three days (total dose 690 mg\\/kg as

L. A. Chahl; J. Leah; T. Herdegen; L. Trueman; A. M. Lynch-Frame

1996-01-01

304

Activation of stress-related hypothalamic neuropeptide gene expression during morphine withdrawal  

Microsoft Academic Search

Morphine withdrawal results in serious affective and somatic symptoms including activation of the hypothalamo-pituitary- adrenocortical (HPA) axis. To reveal secretory, activational and transcriptional changes in the hypothalamus of morphine- dependent rats during naloxone precipitated opioid withdrawal, we measured corticosterone secretion, c-Fos induction and heteronuclear (hn)RNA levels of corticotropin- releasing hormone (CRH) and arginine vasopressin (AVP) in naõ¨ve and morphine dependent

Cristina Nunez; Anna Földes; M. Luisa Laorden; M. Victoria Milanes; Krisztina J. Kovács

2007-01-01

305

Tissue reaction of morphine applied to the epidural space of dogs  

Microsoft Academic Search

Epidural morphine has found increasing popularity in clinical trials for the relief of chronic and postoperative pain relief.\\u000a This study was conducted to determine if there was any adverse tissue reaction when morphine was applied to the epidural space\\u000a of dogs. Sixteen dogs were given 0.07 mg·kg-1of morphine in a volume of 2 cc of normal saline into the epidural

F. G. King; A. D. Baxter; G. Mathieson

1984-01-01

306

Morphine Suppresses Tumor Angiogenesis through a HIF-1?/p38MAPK Pathway  

PubMed Central

Morphine, a highly potent analgesic agent, is frequently prescribed for moderate to severe cancer pain. In this study, morphine was administered at a clinically relevant analgesic dose to assess tumor cell-induced angiogenesis and subcutaneous tumor growth in nude mice using mouse Lewis lung carcinoma cells (LLCs). Implantation of mice with a continuous slow-release morphine pellet achieved morphine plasma levels within 250–400 ng/ml (measured using a radioimmunoassay, Coat-A-Count Serum Morphine) and was sufficient to significantly reduce tumor cell-induced angiogenesis and tumor growth when compared with placebo treatment. Morphometric analysis for blood vessel formation further confirmed that morphine significantly reduced blood vessel density (P < 0.003), vessel branching (P < 0.05), and vessel length (P < 0.002) when compared with placebo treatment. Morphine’s effect was abolished in mice coadministered the classical opioid receptor antagonist, naltrexone, and in mu-opioid receptor knockout mice, supporting the involvement of the classical opioid receptors in vivo. Morphine’s inhibitory effect is mediated through the suppression of the hypoxia-induced mitochondrial p38 mitogen-activated protein kinase (MAPK) pathway. Our results suggest that in vitro morphine treatment of LLCs inhibits the hypoxia-induced nuclear translocation of hypoxia-inducible transcription factor 1? to reduce vascular endothelial growth factor transcription and secretion, in a manner similar to pharmacological blockade with the p38 MAPK-specific inhibitor, SB203585. These studies indicate that morphine, in addition to its analgesic function, may be exploited for its antiangiogenic potential. PMID:20616349

Koodie, Lisa; Ramakrishnan, Sundaram; Roy, Sabita

2010-01-01

307

Reversal of morphine tolerance and dependence by melatonin: possible role of central and peripheral benzodiazepine receptors  

Microsoft Academic Search

Possible reversal by melatonin of morphine-induced tolerance and dependence was studied in mice. A 10-day repeated injection regimen was followed to induce morphine tolerance and dependence. Co-administration of melatonin (1–10 mg\\/kg, i.p.) with morphine (10 mg\\/kg, s.c.) during the induction phase (day 1 to 9) reversed the development of opioid tolerance and dependence tested on 10th day. On the other

V. Raghavendra; Shrinivas K. Kulkarni

1999-01-01

308

The clinically available NMDA receptor antagonist dextromethorphan attenuates acute morphine withdrawal in the neonatal rat  

Microsoft Academic Search

We investigated the ability of dextromethorphan, a clinically available NMDA receptor antagonist, to attenuate the behaviors and the expression of c-fos mRNA associated with acute morphine withdrawal in the 7-day-old rat. The intensity of the acute morphine withdrawal behaviors and the elevation in c-fos mRNA expression in the brain induced by acute morphine withdrawal were reduced by dextromethorphan. Thus, dextromethorphan

Hongbo Zhu; Shirzad Jenab; Kathy L. Jones; Charles E. Inturrisi

2003-01-01

309

Behavioural effects in rats of morphine and amphetamine and of a combination of the two drugs  

Microsoft Academic Search

Small single doses of morphine (1 mg\\/kg s.c.) and of amphetamine (1 mg\\/kg s. c.) induce excitation in rats. Locomotion and rearing are selectively stimulated by amphetamine, and grooming by morphine. Higher doses of morphine (5 mg\\/kg s. c.) cause sedation or catalepsy (20 mg\\/kg s. c.) but no stereotypies are seen as after amphetamine (10 mg\\/kg s. c.). Repeated

Rasmus Fog

1970-01-01

310

Gabapentin enhances the antinociceptive effects of spinal morphine in the rat tail-flick test  

Microsoft Academic Search

The antinociceptive effects of the combination of spinal morphine and gabapentin were evaluated in the tail-flick test in rats. The intrathecal coadministration of a subantinociceptive dose of morphine at 0.2 ?g and gabapentin at 300 ?g produced significant antinociception. Pretreatment with spinal gabapentin at 300 ?g shifted the dose-response curve of spinal morphine to the left with a decrease in

Megumi Shimoyama; Naohito Shimoyama; Charles E Inturrisi; Kathryn J Elliott

1997-01-01

311

75 FR 39025 - Determination That ACTONEL (Risendronate Sodium) Tablets, 75 Milligrams, and ACTONEL WITH CALCIUM...  

Federal Register 2010, 2011, 2012, 2013

...CALCIUM (Risendronate Sodium and Calcium Carbonate (Copackaged)) Tablets, 35...CALCIUM (risendronate sodium and calcium carbonate (copackaged)) Tablets, 35...CALCIUM (risendronate sodium and calcium carbonate (copackaged)) Tablets,...

2010-07-07

312

Evaluation of epidural morphine and incisional bupivacaine for analgesia following hemilaminectomy in the dog.  

E-print Network

??A blind, placebo â controlled clinical trial was performed to evaluate the postoperative analgesic effect of topically administered, intraoperative, epidural morphine (Duramorphâ¢) and intramuscular infiltration… (more)

Horowitz, Farrah B

2009-01-01

313

Chronic morphine consumption decreases wheel running and wheel running-reinforced behavior in rats.  

PubMed

The purpose of this experiment was to evaluate the effects of morphine self-administration on wheel running and wheel running-reinforced lever pressing in rats. The home cage was equipped with a bottle that contained either water, a saccharin-flavored 0.5-mg/ml morphine solution, or saccharin (0.25%). The bottle was available for either 1 or 3 h. The bottle was then removed, and 20-22 h after removal, the rats were moved to an operant chamber in which lever presses earned 15 s access to a running wheel (according to a variable interval (VI) 40-s schedule). The morphine condition was in effect for 69 days, and consumption gradually increased to a level of 67 mg/kg/day. During the morphine condition, wheel running and lever pressing decreased. Following the removal of morphine, (so that the home-cage bottles provided a 0.25% saccharin solution), the two instrumental behaviors increased to the pre-morphine (water) levels. However, the increases were not immediate, and in the first post-morphine session, lever pressing and wheel turning remained at the depressed morphine level. The post-morphine increase in lever pressing was substantially larger than the increase in wheel running. The results support the hypothesis that chronic opiate consumption reduces the frequency of some nondrug-related behaviors, and that this, in turn, increases preference for the opiate. PMID:11420068

Silva, M T; Heyman, G M

2001-01-01

314

Dual effect of morphine in long-term social memory in rat  

PubMed Central

Background and Purpose Bimodal dose–response relationships have been demonstrated in animals and humans following morphine administration. We examined if systemic administration of morphine, in extremely low (?g) and high (mg, analgesic) doses, changed the learning process. Experimental Approach In the social learning test, an adult rat investigates a juvenile. The juvenile is submitted to a second encounter after a few days and investigation by the adult should be reduced. Morphine was administered before the first encounter between rats, and the critical test was performed 24, 72 or 168 h later, when animals were re-exposed to each other, in the absence of morphine. Key Results Low doses of morphine, comparable with endogenous brain concentrations, enhanced long-term memory recognition; while high doses did the reverse, indicating the adult failed to recognize the juvenile. Recognition of a familiar rat appeared to be mediated within the brain accessory olfactory bulb (AOB) by an opioid system intrinsic to the olfactory system through ?-opioid receptors (MORs). At this supraspinal site, the PLC/PKC signalling pathway was activated by extremely low morphine doses. Conclusions and Implications Morphine treatment administration may either disrupt or facilitate social memory, depending on the dose, extending to memory formation the bimodal effects of morphine previously shown in pain. Social memory formation elicited by extremely low morphine doses, was mediated within the AOB by an opioid system, intrinsic to the olfactory system through MORs. PMID:23171436

Bianchi, Enrica; Menicacci, Cristina; Ghelardini, Carla

2013-01-01

315

Involvement of adrenomedullin in the attenuation of acute morphine-induced analgesia in rats.  

PubMed

Adrenomedullin (AM) is a member of calcitonin gene-related peptide (CGRP) family and a pain-related peptide. We have shown that chronic administration of morphine (20 ?g) upregulates AM activity contributing to morphine tolerance. The present study investigated if AM is involved in acute morphine-induced analgesia. Single intrathecal (i.t.) injection of morphine at a dose of 5 ?g increased the tail-flick latency (TFL). This analgesic effect was potentiated by the co-administration of the AM receptor antagonist AM22-52 (5 and 10 nmol). Exposure of sensory ganglion culture to morphine increased AM content in the ganglia in concentration (0.33-10 ?M)- and time (10-240 min)-dependent manners. However, treatment with morphine (3.3 ?M) for 30-240 min did not alter AM mRNA levels in the cultured ganglia. Furthermore, exposure of ganglion cultures to morphine (3.3 ?M) for 30-240, but not 10 min induced an increase in AM content in the culture medium. These results reveal that a single morphine treatment potentiates post-translational change and the release of AM in sensory ganglia masking morphine-induced analgesia. Thus, targeting AM and its receptors should be considered as a novel approach to improve the analgesic potency of opiates during their acute use. PMID:24468549

Wang, Dongmei; Huo, Yuanhui; Quirion, Rémi; Hong, Yanguo

2014-04-01

316

State dependent control of discrimination by morphine and pentobarbital  

Microsoft Academic Search

Rats were trained in state dependent discrimination to escape shock in a T-maze by turning one way under a drug and the other way under saline without aid of exteroceptive cues. In experiment 1, 9.0 nig\\/kg of morphine, 20 mg\\/kg of pentobarbital and 0.3 cc of saline were used with a balanced order of training which employed 18 training days

Harris E. Hill; B. E. Jones; E. C. Bell

1971-01-01

317

Postoperative Epidural Morphine for Postpartum Tubal Ligation Analgesia  

Microsoft Academic Search

Womenundergoingpostoperativepostpartumtuballiga- tion (PPTL) often experience considerable pain. We hy- pothesized that epidural morphine, as part of a multi- modal analgesic regimen, would decrease postoperative pain and the need for systemic analgesia after PPTL. In a double-blinded study, patients were randomized to re- ceiveepiduralsalineormorphine2mg,3mg,or4mgafter epidural anesthesia for PPTL. Postoperatively, ibuprofen 600 mg was administered every 6 h and patients could requestacetaminophen325mg\\/hydrocodone10mg.The

R-Jay L. Marcus; Cynthia A. Wong; Amy Lehor; Robert J. McCarthy; Edward Yaghmour; Meltem Yilmaz

2005-01-01

318

Budget impact analysis of the fentanyl buccal tablet for treatment of breakthrough cancer pain  

PubMed Central

Background The purpose of this study was to assess the economic impact of the fentanyl buccal tablet for the management of breakthrough cancer pain (BTcP) in Spain. Methods A 4-year budget impact model was developed for the period 2012–2015 for patients with BTcP from the perspective of the Spanish National Health System. BTcP products included in this model were rapid-onset opioids containing fentanyl (buccal, sublingual, or nasal transmucosal). Prevalence data on cancer, BTcP, opioid use, and number of BTcP episodes were obtained from the literature. Input data on health care resources associated with opioid use and opioid-induced side effects were obtained by consulting experts in oncology from different Spanish hospitals. Resources used included drugs, medical and emergency visits, other nonpharmacologic treatments, and treatment of opioid-induced side effects. Unit costs were obtained from the literature, and a 3% discount rate was applied to costs. Based on the unit costs for drugs and health care resources, the annual BTcP treatment costs per patient associated with each fentanyl product were determined to estimate the overall budget impact based on the total treatment population and the percentage of drug utilization associated with each product. One-way sensitivity analyses were conducted to test the robustness of the model. Results Patients treated with oral opioids for BTcP were estimated at 23,291 in 2012, with an increase up to 23,413 in 2015. The average annual budget savings, with an increase of fentanyl buccal tablets, fentanyl sublingual tablets, and intranasal fentanyl spray, and a decrease in oral transmucosal fentanyl citrate, was estimated at €2.6 million, which represents a 0.5% decrease in the total costs of BTcP over the next 4 years. Results of the sensitivity analysis showed that the model was most sensitive to drug cost per day for the fentanyl buccal tablet. A 50% decrease in the daily cost of the fentanyl buccal tablet resulted in the largest overall decrease in budget impact of €5.4 million. Conclusion The increase in use of the fentanyl buccal tablet leads to overall savings in the budget impact for the Spanish National Health System. Although the economic impact of treatment for BTcP was shown to increase over 4 years due to population growth, the average annual cost per patient was reduced by €29 with increased use of the fentanyl buccal tablet. PMID:24368889

Darba, Josep; Kaskens, Lisette; Sanchez-de la Rosa, Rainel

2014-01-01

319

Continuous co-administration of dextromethorphan or MK-801 with morphine: attenuation of morphine dependence and naloxone-reversible attenuation of morphine tolerance  

Microsoft Academic Search

N-Methyl- d-aspartate (NMDA) receptor antagonists have been repeatedly shown to attenuate the development of opiate tolerance and dependence in rodents. In the present experiments, continuous subcutaneous infusion of either MK-801 (0.01 mg\\/kg\\/h but not 0.005 mg\\/kg\\/h) or DM (0.133, 0.67 and 1.33 mg\\/kg\\/h) reliably prolonged the antinociceptive effect of continuous subcutaneous infusion of morphine sulfate (2.0 mg\\/kg\\/h), indicating attenuation of

Barton H. Manning; Jianren Mao; Hanan Frenk; Donald D. Price; David J. Mayer

1996-01-01

320

Degradation of morphine in opium poppy processing waste composting.  

PubMed

To investigate morphine degradation and optimize turning frequency in opium poppy processing waste composting, a pilot scale windrow composting trial was run for 55 days. Four treatments were designed as without turning (A1), every 5 days turning (A2), every 10 days turning (A3) and every 15 days turning (A4). During composting, a range of physicochemical parameters including the residual morphine degradation, temperature, pH, and the contents of total C, total N, total P and total K were investigated. For all treatments, the residual morphine content decreased below the detection limit and reached the safety standards after day 30 of composting, the longest duration of high temperature (?50 °C) was observed in A3, pH increased 16.9-17.54%, total carbon content decreased 15.5-22.5%, C/N ratio reduced from 46 to 26, and the content of total phosphorus and total potassium increased slightly. The final compost obtained by a mixture of all four piles was up to 55.3% of organic matter, 3.3% of total nutrient (N, P2O5 and K2O) and 7.6 of pH. A turning frequency of every ten days for a windrow composting of opium poppy processing waste is recommended to produce homogenous compost. PMID:24613672

Wang, Yin Quan; Zhang, Jin Lin; Schuchardt, Frank; Wang, Yan

2014-09-01

321

Life span extension in Drosophila melanogaster induced by morphine.  

PubMed

The influence of morphine on the life span of Drosophila melanogaster fruit flies has been investigated. Morphine hydrochloride (MH) at concentrations of 0.01, 0.05 and 0.25 mg/ml was added to a medium starting from day 5 or 54 of imaginal life. Supplementation with MH starting from day 5 of imaginal life has resulted in significant increases in the mean life span of males at all concentrations studied. In females, a significant increase in life span compared with control was obtained only for those treated with 0.25 mg/ml MH. In flies with MH feeding from day 54, residual life span was significantly increased in both males and females after treatment with 0.05 mg/ml MH. The present data, together with those of our earlier study in mice (Dubiley et al. Probl Aging Longvity 9:331–332, 2000) suggest that morphine supplementation can result in life extension in both vertebrate and invertebrate animal species. PMID:21061062

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

2011-06-01

322

Does sleep deprivation and morphine influence wound healing?  

PubMed

The contrast between present-day sleep habits and those of the pre-industrial era are quite evident. One study recent has shown that the amount of sleep has decreased 2 h per night over the past 50 years. Such sleep curtailment, ubiquitous in the modern lifestyle, inflicts adverse repercussions upon health and well being. Investigations examining the relationship between stress and the skin have shown that different types of stress affect the healing process. Morphine is an immunosuppressive drug, and when it is used chronically, it can lead to an increased incidence of infections and a delay in the healing process. Therefore, our hypothesis is that the lack of sleep associated with chronic treatment with morphine is detrimental to the healing of the skin in the animal model we have adopted. Thus, it is important that future studies consider the paradigm of sleep curtailment when investigating the mechanisms involved in the process of skin healing in individuals who are dependent on morphine. PMID:21652152

Egydio, F; Tomimori, J; Tufik, S; Andersen, M L

2011-09-01

323

Morphine After Tubal Ligation With Bupivacaine: Dosage Versus Body Weight  

PubMed Central

Background and Objectives: We investigated whether there was a statistically significant difference in patient need for postoperative analgesia based on adjusted body weight between heavier and lighter women who underwent laparoscopic tubal ligation with bupivacaine injection at the skin incision. Methods: We examined 49 records of women who underwent laparoscopic tubal ligation at Oklahoma State University Medical Center between 2000 and 2005 and received an injection of bupivacaine at the surgical site during the procedure. Postsurgical morphine was measured as doses per kilogram of body weight against total body weight and as total milligrams per kilogram of body weight against total body weight. A regression was performed for each measurement. Results: Heavier women required significantly fewer total milligrams of morphine per kilogram of body weight and fewer total doses of morphine per kilogram of body weight than lighter women (2-tailed P = .0035 and P = .0018, respectively). Conclusion: Our data may suggest that lipophilic bupivacaine injected at a surgical site is held in place better and works for a longer period when more fat is present.

Roehl, Bryan C.; Payton, Mark E.; Witter, LouAnn C.

2014-01-01

324

Preparation and In Vitro/In Vivo Characterization of Porous Sublingual Tablets Containing Ternary Kneaded Solid System of Vinpocetine with ?-Cyclodextrin and Hydroxy Acid  

PubMed Central

The demand for sublingual tablets has been growing during the previous decades especially for drugs with extensive hepatic first-pass metabolism. Vinpocetine, a widely used neurotropic agent, has low oral bioavailability due to its poor aqueous solubility and marked first-pass metabolism. Accordingly, the aim of this work was to develop tablets for the sublingual delivery of vinpocetine. Initially, the feasibility of improving vinpocetine’s poor aqueous solubility by preparing kneaded solid systems of the drug with ?-Cyclodextrin and hydroxy acids (citric acid and tartaric acid) was assessed. The solid system with improved solubility and dissolution properties was incorporated into porous tablets that rapidly disintegrate permitting fast release of vinpocetine into the sublingual cavity. The pores were induced into these tablets by directly compressing the tablets’ excipients with a sublimable material, either camphor or menthol, which was eventually sublimated leaving pores. The obtained results demonstrated that the tablets prepared using camphor attained sufficient mechanical strength for practical use together with rapid disintegration and dissolution. In vivo absorption study performed in rabbits indicated that the sublingual administration of the proposed porous tablets containing vinpocetine solid system with ?-Cyclodextrin and tartaric acid could be useful for therapeutic application. PMID:21179352

Aburahma, Mona H.; El-Laithy, Hanan M.; Hamza, Yassin El-Said

2010-01-01

325

CONTROLLED RELEASE MATRIX UNCOATED TABLETS OF ENALAPRIL MALEATE USING HPMC ALONE  

PubMed Central

Hydroxy propyl methyl cellulose (HPMC) is generally combined with hydrophobic polymers in fabricating oral controlled solid dosage forms. This study evaluated the utility of diverse grades of HPMC in developing a controlled release formulation for a hydrophilic drug, enalapril maleate. Controlled release uncoated tablets were prepared by direct compression technique. Two grades of HPMC (K100 and K4M) in different proportions were used to prepare the tablets, and were evaluated for physical properties, drug content, in vitro drug release and drug release kinetics as well. All the formulations demonstrated good physical integrity and the drug content were in the official limits. The formulation with HPMC K100 (25 mg/tablet) and K4M (15 mg/tablet) have been found to release the required amount of drug (2.97 mg/h) through out the study period (14 h). The calculated regression coefficients showed higher r2 value with Higuchi model and zero order kinetics. Given the excellent release profile, the study concluded that HPMC in different grades with low concentration alone can control the enalapril maleate release over a period of time (14 h). PMID:24825968

Nair, Anroop B.; Vyas, Hiral; Kumar, Ashok

2010-01-01

326

Sustained release of highly water-soluble drugs with micelle forming ability from polyionic matrix tablets.  

PubMed

The aim of present study was to evaluate the application of a hydrophilic matrix tablet capable of polyion complex (PIC-tablet) to a controlled-release device for highly water-soluble drugs. The PIC-tablet was prepared from a mixture of dextran sulfate and [2-(diethylamino)ethyl] dextran chloride, and diltiazem hydrochloride was used as a model drug. Release tests revealed that the drug release was sustained even in 50% drug loading and was influenced by ionic strength but not by pH in medium. The drug release mechanism was thus investigated from the viewpoint of drug micelle forming property. The micelle forming ability of diltiazem was examined by the conductivity method, and was found to be influenced by ionic strength but not by pH value in accordance with the release tests. The results suggested that the drug's micelle interacted with the polyionic matrix. Further studies were conducted using metoprolol tartrate and thiamine hydrochloride as cationic drugs and sodium cloxacillin and sodium salicylic acid as anionic ones. The release profiles of the micelle-forming drugs metoprolol tartrate and sodium cloxacillin were also suppressed in spite of different solubility or opposite ionic charge from diltiazem hydrochloride. These findings demonstrated that the PIC-tablet is a promising device for oral controlled release delivery of water-soluble drugs with good micelle-forming ability. PMID:17294812

Tanaka, Y; Miyazaki, Y; Yakou, S; Takayama, K

2007-01-01

327

Formulation and optimization of mucoadhesive bilayer buccal tablets of atenolol using simplex design method  

PubMed Central

Introduction: In the present study, mucoadhesive buccal bilayer tablets of atenolol were fabricated with the objective of avoiding first pass metabolism and to improve its bioavailability with reduction in dosing frequency. Hence, the aim of this work was to design oral controlled release mucoadhesive tablets of atenolol and to optimize the drug release profile and bioadhesion. Materials and Methods: Bilayer buccal tablets of atenolol were prepared by direct compression method using simplex method of optimization to investigate the combined effect of hydroxypropyl methylcellulose 15 cps (X1), Carbopol (X2) and mannitol (X3); the in vitro drug release (Y1) and mucoadhesive strength (Y2) were taken as responses. The designed tablets were evaluated for various physical and biological parameters like drug content uniformity, in vitro drug release, short-term stability, and drug- excipient interactions (FTIR). Results: The formulation C containing hydroxypropyl methylcellulose 15 cps (10% w/w of matrix layer), Carbopol 934p (10% w/w of matrix layer) and mannitol (channeling agent, 40% w/w of matrix layer) was found to be promising. This formulation exhibited an in vitro drug release of 89.43% in 9 h along with satisfactory bioadhesion strength (7.20 g). Short-term stability studies on the promising formulation indicated that there are no significant changes in drug content and in vitro dissolution characteristics (P<0.05). IR spectroscopic studies indicated that there are no drug-excipient interactions. PMID:23071958

Shirsand, SB; Suresh, Sarasija; Keshavshetti, GG; Swamy, PV; Reddy, P Vijay Prakash

2012-01-01

328

Design and development of polyethylene oxide based matrix tablets for verapamil hydrochloride.  

PubMed

In the present investigation an attempt has been made to increase therapeutic efficacy, reduced frequency of administration and improved patient compliance by developing controlled release matrix tablets of verapamil hydrochloride. Verapamil hydrochloride was formulated as oral controlled release matrix tablets by using the polyethylene oxides (Polyox WSR 303). The aim of this study was to investigate the influence of polymer level and type of fillers namely lactose (soluble filler), swellable filler (starch 1500), microcrystalline cellulose and dibasic calcium phosphate (insoluble fillers) on the release rate and mechanism of release for verapamil hydrochloride from matrix tablets prepared by direct compression process. Higher polymeric content in the matrix decreased the release rate of drug. On the other hand, replacement of lactose with anhydrous dibasic calcium phosphate and microcrystalline cellulose has significantly retarded the release rate of verapamil hydrochloride. Biopharmaceutical evaluation of satisfactory formulations were also carried out on New Zealand rabbits and parameters such as maximum plasma concentration, time to reach peak plasma concentration, area under the plasma concentration time curve(0-t) and area under first moment curve(0-t) were determined. In vivo pharmacokinetic study proves that the verapamil hydrochloride from matrix tablets showed prolonged release and were be able to sustain the therapeutic effect up to 24 h. PMID:24019567

Vidyadhara, S; Sasidhar, R L C; Nagaraju, R

2013-03-01

329

Assessment of xanthan gum based sustained release matrix tablets containing highly water-soluble propranolol HCl.  

PubMed

The present study was carried out to develop oral sustained release tablets of propranolol HCl by different ratios of drug : matrix. Tablets were prepared by direct compression technique using xanthan gum and lactose. All the formulations (tablets) were evaluated for thickness, diameter, hardness, friability, weight variation, content of active ingredient, in vitro dissolution using USP dissolution apparatus-II and swelling index. In case of dissolution, an inverse relationship was noted between amount of xanthan gum and release rate of propranolol HCl and the drug release was gradually enhanced as the amount of the lactose increased. The direct release was observed between swelling index and xanthan gum concentration. Significant difference in different media was observed in release profile, indicating that propranolol HCI has better solubility in HCI buffer pH 1.2. Moreover, dissolution data at differing stirring speeds was also analyzed, indicating that the drug release profile was at 50 rpm comparative to 100 rpm. The kinetic treatment showed the best fitted different mathematical models (zero order, first order, Higuchi's, Hixson-Crowell and Korsmeyer Peppas model. Most of the formulations showed linearity in Higuchi's model. The drug release from these tablets was by Fickian diffusion and anomalous (non-Fickian) mechanisms. PMID:23614284

Ali, Atif; Iqbal, Muhammad; Akhtar, Naveed; Khan, Haji Muhamad Shoaib; Ullah, Aftab; Uddin, Minhaj; Khan, Muhammad Tahir

2013-01-01

330

Design and Development of Polyethylene Oxide Based Matrix Tablets for Verapamil Hydrochloride  

PubMed Central

In the present investigation an attempt has been made to increase therapeutic efficacy, reduced frequency of administration and improved patient compliance by developing controlled release matrix tablets of verapamil hydrochloride. Verapamil hydrochloride was formulated as oral controlled release matrix tablets by using the polyethylene oxides (Polyox WSR 303). The aim of this study was to investigate the influence of polymer level and type of fillers namely lactose (soluble filler), swellable filler (starch 1500), microcrystalline cellulose and dibasic calcium phosphate (insoluble fillers) on the release rate and mechanism of release for verapamil hydrochloride from matrix tablets prepared by direct compression process. Higher polymeric content in the matrix decreased the release rate of drug. On the other hand, replacement of lactose with anhydrous dibasic calcium phosphate and microcrystalline cellulose has significantly retarded the release rate of verapamil hydrochloride. Biopharmaceutical evaluation of satisfactory formulations were also carried out on New Zealand rabbits and parameters such as maximum plasma concentration, time to reach peak plasma concentration, area under the plasma concentration time curve(0-t) and area under first moment curve(0-t) were determined. In vivo pharmacokinetic study proves that the verapamil hydrochloride from matrix tablets showed prolonged release and were be able to sustain the therapeutic effect up to 24 h. PMID:24019567

Vidyadhara, S.; Sasidhar, R. L. C.; Nagaraju, R.

2013-01-01

331

Hyperspectral techniques in analysis of oral dosage forms.  

PubMed

Pharmaceutical oral dosage forms are used in this paper to test the sensitivity and spatial resolution of hyperspectral imaging instruments. The first experiment tested the hypothesis that a near-infrared (IR) tunable diode-based remote sensing system is capable of monitoring degradation of hard gelatin capsules at a relatively long distance (0.5 km). Spectra from the capsules were used to differentiate among capsules exposed to an atmosphere containing 150 ppb formaldehyde for 0, 2, 4, and 8 h. Robust median-based principal component regression with Bayesian inference was employed for outlier detection. The second experiment tested the hypothesis that near-IR imaging spectrometry of tablets permits the identification and composition of multiple individual tablets to be determined simultaneously. A near-IR camera was used to collect thousands of spectra simultaneously from a field of blister-packaged tablets. The number of tablets that a typical near-IR camera can currently analyze simultaneously was estimated to be approximately 1300. The bootstrap error-adjusted single-sample technique chemometric-imaging algorithm was used to draw probability-density contour plots that revealed tablet composition. The single-capsule analysis provides an indication of how far apart the sample and instrumentation can be and still maintain adequate signal-to-noise ratio (S/N), while the multiple-tablet imaging experiment gives an indication of how many samples can be analyzed simultaneously while maintaining an adequate S/N and pixel coverage on each sample. PMID:12421122

Hamilton, Sara J; Lowell, Amanda E; Lodder, Robert A

2002-10-01

332

Tablets for Timely Design Documentation  

NSDL National Science Digital Library

One of the biggest challenges we have experienced in supervising digital systems senior design projects is the quality and completeness of the individual lab notebooks. Of the five outcomes we continuously track for this capstone course, the lab notebooks have consistently received the lowest quantitative scores. A significant improvement was achieved three years ago when we transitioned from carbon paper and pen notebooks to on-line (HTML) notebooks. Many teams took advantage of (and put to good use) the ability to post digital pictures of prototyping setups, provide hyperlinks to all their device datasheets, post their latest schematics and software listings for evaluation, and post video clips of their project in action (as verification of their project success criteria). The primary drawback has been the need for students to be in front of a networked computer to make lab notebook entries; consequently, the notebook updates still tended to be done in spurts (typically after the fact) rather than in real time. Project work (and inspiration), in fact, does not always occur in a lab setting, where networked computers are readily available, nor does it occur when all team members are working in the same physical location. Our hypothesis is that equipping each project team with wireless Tablet PCs should not only significantly improve the spontaneity (and regularity) with which the on-line lab notebooks are updated, but also facilitate collaboration among team members working on the design project at different locations. An HP Technology for Teaching Grant has provided a critical mass of Tablet PCs to test this hypothesis. A description of how the equipment provided is being utilized, along with a discussion of the preliminary results obtained, is presented in this paper.

Brown, Cordelia; Johnson, Mark; Meyer, David

2009-08-25

333

Prior exposure to repeated morphine potentiates mechanical allodynia induced by peripheral inflammation and neuropathy  

PubMed Central

Opioids, such as morphine, induce potent analgesia and are the gold standard for the treatment of acute pain. However, opioids also activate glia, inducing pro-inflammatory cytokine and chemokine production, which counter-regulates the analgesic properties of classical opioid receptor activation. It is not known how long these adverse pro-inflammatory effects last or whether prior morphine could sensitize the central nervous system (CNS) such that responses to a subsequent injury/inflammation would be exacerbated. Here, multiple models of inflammation or injury were induced 2 d after morphine (5 mg/kg b.i.d., 5 d, s.c.) to test the generality of morphine sensitization of later pain. Prior repeated morphine potentiated the duration of allodynia from peripheral inflammatory challenges (complete Freund’s adjuvant [CFA] into either hind paw skin or masseter muscle) and from peripheral neuropathy (mild chronic constriction injury [CCI] of the sciatic nerve). Spinal cord and trigeminal nucleus caudalis mRNAs were analyzed to identify whether repeated morphine was sufficient to alter CNS expression of pro-inflammatory response genes, measured 2 d after cessation of treatment. Prior morphine elevated IL-1? mRNA at both sites, MHCII and TLR4 in the trigeminal nucleus caudalis but not spinal cord, but not glial activation markers at either site. Finally, in order to identify whether morphine sensitized proinflammatory cytokine release, spinal cord was isolated 2 d after morphine dosing for 5 day, and slices stimulated ex vivo with lipopolysaccharide. The morphine significantly induced TNF? protein release. Therefore, repeated morphine is able to sensitize subsequent CNS responses to immune challenges. PMID:22902523

Loram, Lisa C.; Grace, Peter M.; Strand, Keith A.; Taylor, Frederick R.; Ellis, Amanda; Berkelhammer, Debra; Bowlin, Melissa; Skarda, Bryce; Maier, Steven F.; Watkins, Linda R.

2012-01-01

334

N-methyl-D-aspartate receptors involved in morphine-induced hyperalgesia in sensitized mice.  

PubMed

The aim of this study was to investigate role of the N-Methyl-D-Aspartate (NMDA) receptors in the decrease of morphine analgesia in mice after nociceptive sensitization. We used a hot plate test to assess effects of morphine on pain behavior in male NMRI mice. All drugs were administered through an intraperitoneal route. Sensitization schedule composed of 3-days pre-treatment of morphine (20mg/kg) followed by 5-days washout. The results showed that morphine (5, 7.5, 10 and 15mg/kg) induced a significant analgesia in normal mice. However, the analgesic effects of morphine significantly decreased at higher dose (15mg/kg) in sensitized mice. Injections of either a competitive NMDA receptor antagonist, D-AP5 (0, 0.25, 0.5 and 1mg/kg) or an NMDA receptor channel blocker (30, 60 and 120mg/kg) alone had no effect on pain behavior. However, injections of D-AP5 (1mg/kg), along with morphine over 3-days of the sensitization schedule, significantly prevented the decrease in the analgesic effect of the opioid at doses of 7.5 and 10mg/kg on the hot plate test. Similarly, injections of MgSO4 (120mg/kg), along with morphine over 3-days of the sensitization schedule, significantly prevented the decrease in analgesic effect of morphine at doses of 10 and 15mg/kg. It can be concluded that NMDA receptors are influenced by morphine during the sensitization schedule, which in turn may affect morphine analgesia after the schedule. This may further support the potential effectiveness of NMDA blockade during repeated use of morphine for control of chronic pain. PMID:24842190

Ahmadi, Shamseddin; Golbaghi, Hajar; Azizbeigi, Ronak; Esmailzadeh, Nabaz

2014-08-15

335

Role of D?/D? dopamin receptors antagonist perphenazine in morphine analgesia and tolerance in rats.  

PubMed

While opioid receptors have been implicated in the development of tolerance, the subsequent mechanisms involved in these phenomena have not been completely understood. The purpose of this study was to investigate effects of D1/D2 dopamine receptors antagonist perphenazine on morphine analgesia and tolerance in rats. Male Wistar albino rats weighing 190-205 g were used in these experiments. To constitute of morphine tolerance, animals received morphine (50 mg/kg) once daily for 3 days. After last dose of morphine was injected on day 4, morphine tolerance was evaluated by the analgesia tests. The analgesic effects of perphenazine (1, 5, and 10 mg/kg ), D1-dopamine receptor antagonist SCH 23390 (1 mg/kg), D2-dopamine receptor antagonist eticlopride (1 mg/kg), and morphine were considered at 30-min intervals (0, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests. Obtained data suggested that D1/D2 dopamine receptors antagonist perphenazine was capable of suppressing opioid tolerance, possibly by the mechanism of inhibiting D2-dopamine receptor. Because the data indicated that D2-dopamine receptor antagonist eticloride, but not D1-dopamine receptor antagonist SCH 23390, significantly decreased morphine tolerance in analgesia tests. In addition, administration of perphenazine with morphine increased morphine analgesia. Results from the present study suggested that dopamine receptors play a significant role in the morphine analgesic tolerance. In particular, D2-dopamine receptor has an important role rather than D1-dopamine receptor in development tolerance to morphine. PMID:23725509

Ozdemir, Ercan; Bagcivan, Ihsan; Gursoy, Sinan

2013-05-01

336

Pharmaceutical tablet compaction : product and process design  

E-print Network

This thesis explores how tablet performance is affected by microstructure, and how microstructure can be controlled by selection of excipients and compaction parameters. A systematic strategy for formulation and process ...

Pore, Mridula

2009-01-01

337

Onsite Wastewater Treatment Systems: Tablet Chlorination  

E-print Network

Wastewater that is sprayed onto lawns must first be disinfected to prevent odors and remove disease-causing organisms. This publication explains how tablet chlorinators disinfect wastewater and gives tips on how to maintain them....

Lesikar, Bruce J.

2008-10-23

338

21 CFR 520.1870 - Praziquantel tablets.  

...tablets to weak or debilitated animals and for assistance in the diagnosis, treatment, and control of parasitism. (B) If labeled...to weak or debilitated animals, and for assistance in the diagnosis, treatment, and control of parasitism. [46 FR...

2014-04-01

339

Pre-exposure effects of morphine, diazepam and ? 9 THC on the formation of conditioned taste aversions  

Microsoft Academic Search

Prior to taste aversion conditioning with morphine, diazepam or ?9-tetrahydrocannabinnol (?9-THC), rats received pre-exposures to the vehicle or one of the three drugs. Morphine pre-exposures blocked the aversion normally induced by morphine, but not by ?9-THC or diazepam. Diazepam pre-exposures attenuated both the morphine- and diazepam-induced taste aversions to a significantly greater degree than the taste aversion induced by ?9-THC.

L. Switzman; B. Fishman; Z. Amit

1981-01-01

340

Development and characterization of buccoadhesive nifedipine tablets  

Microsoft Academic Search

The buccoadhesive controlled-release tablets for delivery of nifedipine were prepared by direct compression of carboxymethyl cellulose (CMC) with carbomer (CP), which showed superior bioadhesion properties compared to polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), hydroxypropylmethyl cellulose (HPMC), and acacia in a modified tensiometry method in vitro. The tablets containing 30mg of nifedipine and various amounts of CMC and CP showed a zero-order

J. Varshosaz; Z. Dehghan

2002-01-01

341

Effect of two hydrophobic polymers on the release of gliclazide from their matrix tablets.  

PubMed

Gliclazide is an oral hypoglycemic agent, indicated in non insulin dependent diabetes mellitus and in patients with diabetic retinopathy. It has good tolerability and is a short acting sulfonyl urea that requires large dose to maintain the blood glucose level. So development of a sustained release formulation of gliclazide (GLZ) is required for better patient compliance. This study was conducted to assess the effects of different drug polymer ratios on the release profile of gliclazide from the matrix. Oral matrix tablets of gliclazide were prepared by hot melt method, using pure and blended mixture of glyceryl monostearate (GMS) and stearic acid (SA) in different ratios. In vitro release pattern was studied for 8 h in phosphate buffer media (pH 7.4). Different kinetic models including zero order, first order, Higuchi and Peppas were applied to evaluate drug release behavior. Drug excipient compatibility was evaluated by scanning with DSC and FTIR. Higuchi model was found the most appropriate model for describing the release profile of GLZ and non-Fickian release was found predominant mechanism of drug release. The release of drug from the matrix was greatly controlled by GMS while SA appeared to facilitate the release of drug from matrix tablets. FTIR results showed no chemical interaction between drug and the polymers, and DSC results indicated amorphous state of GLZ and polymers without significant complex formation. The results indicate that matrix tablets of gliclazide using glyceryl monostearate and stearic acid showed marked sustained release properties. PMID:23923399

Hussain, Talib; Saeed, Tariq; Mumtaz, Ahmad M; Javaid, Zeeshan; Abbas, Khizar; Awais, Azeema; Idrees, Hafiz Arfat

2013-01-01

342

Comparison between celiac plexus block and morphine treatment on quality of life in patients with pancreatic cancer pain  

Microsoft Academic Search

Twenty-one patients with pancreatic cancer pain were studied to evaluate the effectiveness of celiac plexus block (CPB) on pain relief and quality of life (QOL), compared to the traditional NSAID-morphine treatment. The criteria were morphine consumption, visual analogue pain scale (VAS), performance status (PS) determined by medical and nursing staffs, and answers to QOL questionnaires. Morphine consumption, VAS, PS, and

Mikito Kawamata; Kunihiko Ishitani; Kunitsugu Ishikawa; Hiromi Sasaki; Koichi Ota; Keiichi Omote; Akiyoshi Namiki

1996-01-01

343

Morphine induces endocytosis of neuronal ?-opioid receptors through the sustained transfer of G? subunits to RGSZ2 proteins  

Microsoft Academic Search

BACKGROUND: In general, opioids that induce the recycling of ?-opioid receptors (MORs) promote little desensitization, although morphine is one exception to this rule. While morphine fails to provoke significant internalization of MORs in cultured cells, it does stimulate profound desensitization. In contrast, morphine does promote some internalization of MORs in neurons although this does not prevent this opioid from inducing

María Rodríguez-Muñoz; Elena de la Torre-Madrid; Pilar Sánchez-Blázquez; Javier Garzón

2007-01-01

344

Bioavailability and pharmacokinetics of oral ofloxacin formulations in normal subjects.  

PubMed

The relative bioavailability and pharmacokinetics of ofloxacin tablets and a reference oral solution of ofloxacin were compared in 32 normal male subjects using a randomized two-way crossover design. After an overnight fast, subjects were randomized to receive a single 200 mg or 300 mg dose of ofloxacin (tablet or solution) and blood samples were obtained prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours after the dose. After a 5-day wash-out period, subjects were administered the same dose but of the other formulation, and blood samples were collected in an identical manner. Plasma concentrations of ofloxacin were determined by high-pressure liquid chromatography. The results showed that ofloxacin tablets were more slowly absorbed when compared to the solution and mean peak plasma concentrations were obtained in about 1.5 hours for the tablet preparation. Maximum plasma concentrations were higher after administration of the solution (Cmax = 2.24 micrograms/ml, 200 mg; Cmax = 3.25 micrograms/ml, 300 mg) compared to the tablet (Cmax = 1.74 micrograms/ml, 200 mg; 2.61 micrograms/ml, 300 mg). The bioavailability of ofloxacin tablets was greater than 98% compared to the solution. The other pharmacokinetic parameters were similar between the two dosage formulations. Ofloxacin tablets revealed an apparent volume of distribution of 1.5 l/kg, an elimination half-life of 5.6 hours, and a total clearance of 251 ml/min. In addition, a linear increase in plasma concentrations was observed when the dose of ofloxacin was increased. In summary, ofloxacin tablets was found to be reliably bioavailable and bioequivalent to the reference solution. PMID:1764952

Stein, G E; LeBel, M; Flor, S C; Zinny, M

1991-01-01

345

Gossypol as oral contraceptive for male: trial case report.  

PubMed

Gossypol has been used as oral contraceptive for man in People's Republic of China. There are also some reports of studies in which gossypol acetic acid is used in animal experiments. In this study we used tablet preparation of gossypol, which is actually used as oral contraceptive for male in People's Republic of China, on a volunteer. The administration of 20 mg/day gossypol tablets for 19 days resulted in a tendency of decreasing sperm density and total sperm count, but had no effect on serum LH, FSH, PRL or testosterone. Furthermore, the volunteer had no complaints of side effects and his general laboratory findings were normal. Ten days after the termination of gossypol administration, sperm density returned to its preadministrative level. Our study suggests gossypol may be effective as a male oral contraceptive with no acute side effect. PMID:6818716

Hoshiai, H; Uehara, S; Mori, R; Nagaike, F; Tsuiki, A; Suzuki, M

1982-11-01

346

Attenuation of morphine-induced delirium in palliative care by substitution with infusion of oxycodone  

Microsoft Academic Search

We have observed among patients of the Southern Community Hospice Programme that up to 25% experience acute delirium when treated with morphine and improve when the opioid is changed to oxycodone or fentanyl. This study aimed to confirm by a prospective trial that oxycodone produces less delirium than morphine in such patients. Oxycodone was administered by a continuous subcutaneous infusion,

Ian Maddocks; Andrew Somogyi; Fay Abbott; Peter Hayball; Deborah Parker

1996-01-01

347

Inhibition of the Ubiquitin-Proteasome Activity Prevents Glutamate Transporter Degradation and Morphine Tolerance  

PubMed Central

Glutamate transporters play a crucial role in physiological glutamate homeostasis and neurotoxicity. Recently, we have shown that downregulation of glutamate transporters after chronic morphine exposure contributed to the development of morphine tolerance. In the present study, we examined whether regulation of the glutamate transporter expression with the proposed proteasome inhibitor MG-132 would contribute to the development of tolerance to repeated intrathecal (twice daily × 7 days) morphine administration in rats. The results showed that MG-132 (5 nmol) given intrathecally blocked morphine-induced glutamate transporter downregulation and the decrease in glutamate uptake activity within the spinal cord dorsal horn. Co-administration of morphine (15 nmol) with MG-132 (vehicle = 1 < 2.5 < 5 = 10 nmol) also dose-dependently prevented the development of morphine tolerance in rats. These findings suggest that prevention of spinal glutamate transporter downregulation may regulate the glutamatergic function that has been implicated in the development of morphine tolerance. The possible relationship between MG-132-mediated regulation of glutamate transporters, ubiquitin-proteasome system, and the cellular mechanisms of morphine tolerance is discussed in light of these findings. PMID:18986766

Yang, Liling; Wang, Shuxing; Lim, Grewo; Sung, Backil; Zeng, Qing; Mao, Jianren

2012-01-01

348

Inhibition of the ubiquitin-proteasome activity prevents glutamate transporter degradation and morphine tolerance.  

PubMed

Glutamate transporters play a crucial role in physiological glutamate homeostasis and neurotoxicity. Recently, we have shown that downregulation of glutamate transporters after chronic morphine exposure contributed to the development of morphine tolerance. In the present study, we examined whether regulation of the glutamate transporter expression with the proposed proteasome inhibitor MG-132 would contribute to the development of tolerance to repeated intrathecal (twice daily x 7 days) morphine administration in rats. The results showed that MG-132 (5 nmol) given intrathecally blocked morphine-induced glutamate transporter downregulation and the decrease in glutamate uptake activity within the spinal cord dorsal horn. Co-administration of morphine (15 nmol) with MG-132 (vehicle=1<2.5<5=10 nmol) also dose-dependently prevented the development of morphine tolerance in rats. These findings suggest that prevention of spinal glutamate transporter downregulation may regulate the glutamatergic function that has been implicated in the development of morphine tolerance. The possible relationship between MG-132-mediated regulation of glutamate transporters, ubiquitin-proteasome system, and the cellular mechanisms of morphine tolerance is discussed in light of these findings. PMID:18986766

Yang, Liling; Wang, Shuxing; Lim, Grewo; Sung, Backil; Zeng, Qing; Mao, Jianren

2008-12-01

349

Relief of pain by infusion of morphine after operation: does tolerance develop?  

Microsoft Academic Search

To see whether continuous intravenous infusion of opiates provides more effective postoperative relief of pain than conventional intramuscular injection these regimens were compared in a prospective double blind trial. Thirty patients undergoing elective cholecystectomy were allocated randomly to receive an infusion of morphine or an infusion of placebo (control group) for 24 hours. Both groups were allowed supplementary morphine boluses

H Marshall; C Porteous; I McMillan; S G MacPherson; W S Nimmo

1985-01-01

350

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

E-print Network

in these patients is of importance because inadequate analgesia is likely to increase postoperative confusionAge-adapted morphine titration produces equivalent analgesia and adverse effects in younger Summary Background To determine efficacy and safety of postoperative titrated morphine in elderly patients

Paris-Sud XI, Université de

351

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

E-print Network

period. Keywords: POSTOPERATIVE ANALGESIA, intravenous morphine titration, efficient and safe pain relief and management of postoperative pain in these patients is of importance because inadequate analgesia is likely1 Age adapted morphine titration produces equivalent analgesia and side effects in younger

Boyer, Edmond

352

he opium poppy is a source of the phar-maceuticals codeine, morphine and  

E-print Network

T he opium poppy is a source of the phar- maceuticals codeine, morphine and their derived analgesics. Here we describe the initial characterization of the poppy mutant known as top1 (for `thebaine oripavine poppy 1'), which accumulates the morphine and codeine precursors thebaine and oripavine and does

Kharasch, Evan

353

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

SciTech Connect

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

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

1986-03-05

354

Social behavior of juvenile rats after in utero exposure to morphine: dose–time–effect relationship  

Microsoft Academic Search

In the present study, the effects of morphine exposure in utero on social behavior in juvenile male rats was investigated. Pinning, a measure for play behavior, and social grooming of the offspring were measured at postnatal day 21. The subjects were offspring of Wistar rat dams given sc. injections of 1 or 10 mg\\/kg body weight morphine HC1 daily from

Raymond J. M. Niesink; Liesbeth van Buren-van Duinkerken; Jan M. van Ree

1999-01-01

355

Analgesic efficacy of ketorolac and morphine in neonatal rats Anju Guptaa  

E-print Network

; Morphine; Neonatal rats; Formalin 1. Background Ketorolac is one of the most potent nonsteroidal antiin (Uphouse et al., 1993). In rats, its analgesic efficacy is 300±500 times that of aspirin (Rooks et al is as effective as morphine and more potent than aspirin in relieving pain. (Granados-Soto et al., 1993

Barr, Gordon A.

356

Generalization of morphine and lysergic acid diethylamide (LSD) stimulus properties to narcotic analgesics  

Microsoft Academic Search

The present investigation sought to determine whether the stimulus properties of morphine and lysergic acid diethylamide (LSD) would generalize to several narcotic analgesics which vary in their subjective effects. Morphine and saline served as discriminative stimuli for one group of rats in a 2-lever discrimination task. LSD and saline were discriminative stimuli for a second group. Depression of one lever

I. D. Hirschhorn; J. A. Rosecrans

1976-01-01

357

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

ERIC Educational Resources Information Center

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

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

2013-01-01

358

Stress Symptoms Induced by Repeated Morphine Withdrawal in Comparison to Other Chronic Stress Models in Mice  

Microsoft Academic Search

The present study was aimed at evaluating chronic stress models in mice with special attention to morphine treatment. We hypothesized that repeated periods of drug withdrawal induce chronic stress. To verify this hypothesis, mice were made dependent on morphine and then subjected to several types of repeated withdrawal. Body weight reduction, thymus involution, adrenal gland enlargement and activation of the

Dóra Zelena; István Barna; Martin Mlynarik; O. P. Gupta; Daniela Jezova; Gábor B. Makara

2005-01-01

359

Morphine Attenuates Testosterone Response to Central Injection of Kisspeptin in Male Rats  

PubMed Central

Background Kisspeptin and naloxone stimulate the reproductive axis while morphine inhibits its function. We have investigated the effect of central injection of kisspeptin-10 on mean plasma testosterone concentration in morphine or naloxone pretreated rats. Materials and Methods In this experimental study, 60 male Wistar rats that were divid- ed into 12 groups (n=5 per group) received saline, kisspeptin (1 nmol, ICV), naloxone (2 mg/kg, subcutaneously), morphine (5 or 10 mg/kg, sc) or co-administrations of kisspeptin, morphine and naloxone at 09:00 - 09:30. In the co-administrated groups, kisspeptin was injected 15 minutes following morphine or naloxone injections. Blood samples were collected 60 minutes following injections via the tail vein. Plasma testosterone concentration was measured by a rat testosterone ELISA kit. Results Central injection of kisspeptin or subcutaneous injection of naloxone significantly increased the mean plasma testosterone concentration compared to saline while subcutaneous injections of different doses of morphine (5 or 10 mg/kg) significantly decreased testosterone compared to saline. The results revealed that morphine significantly attenuated the testosterone increase after kisspeptin injection compared to kisspeptin while a stimulatory additive effect was observed in the kisspeptin/naloxone group compared to either naloxone or kisspeptin. Conclusion Morphine and kisspeptin systems may interact with each other to control the hypothalamic-pituitary-gonadal (HPG) axis. PMID:25083187

Mahmoudi, Fariba; Khazali, Homayoun; Janahmadi, Mahyar

2014-01-01

360

Amperometric determination of morphine on cobalt hexacyanoferrate modified electrode in rat brain microdialysates  

Microsoft Academic Search

The analysis of morphine in biological fluids is of vital interest in monitoring opiate abuse and in drug abuse research. In this paper, a cobalt hexacyanoferrate (CoHCF) chemically modified electrode (CME) was prepared. The electrochemical behavior of morphine at this modified electrode has been studied by cyclic voltammetry (CV). The results indicated that the modified electrode exhibited efficiently electrocatalytic oxidation

Fang Xu; Mengnan Gao; Lin Wang; Tianshu Zhou; Litong Jin; Jiye Jin

2002-01-01

361

The effect of polyion complex formation on in vitro/in vivo correlation of hydrophilic matrix tablets.  

PubMed

The aim of this study was to investigate the effects of polyion complex formation on in vivo performance of hydrophilic matrix tablets. Three kinds of controlled release theophylline tablets were prepared by direct compression using carboxymethyldextran (CMD), a mixture of CMD and [2-(diethylamino)ethyl]dextran (EA), and a mixture of dextran sulfate (DS) and EA. According to a conventional dissolution test, in vitro drug release profiles of these tablets were similar to each other. In vivo absorption profiles of theophylline after oral administration to beagle dogs, however, were quite different and were not consistent with in vitro release profiles. Thus, we applied a modified in vitro release test considering destructive forces. An excellent in vitro/in vivo correlation was obtained in the cases of CMD/EA- and DS/EA-tablets. The results suggested that the drug was released constantly in the overall gastrointestinal tract, and even in the colon. Then, hydrophilic matrices were characterized by swelling rate, matrix density and strength in a wet state. DS/EA-tablets showed limited swelling, higher density and a larger value of wet strength than the others. These findings indicated that polyion complex formation in gel layer contributes to prevent over-swelling and strengthen the wetted matrices. PMID:12932710

Miyazaki, Yasunori; Yakou, Shigeru; Nagai, Tsuneji; Takayama, Kozo

2003-09-01

362

Preparation and evaluation of once-daily sustained-release coated tablets of tolterodine-L-tartrate.  

PubMed

In this study, once-daily, sustained-release matrix tablets of tolterodine l-tartrate (TOL) for treatment of overactive bladder (OAB) were prepared by direct compression using various amounts of hydrophilic polymers such as HPMC 2910 and HPMC 2208 along with other tablet excipients; the tablets were then coated. In vitro dissolution studies were carried out under different pH conditions. The dissolution data were fitted into zero-order, first-order, Higuchi and Korsemeyer-Peppas models to identify the pharmacokinetics and mechanism of drug release. Among the four formulations (F1-F4), the dissolution profiles of formulation F2 were most similar to the marketed product with similarity and difference factors of 70.25 and 1.59 respectively. Furthermore, pharmacokinetic studies were carried out in healthy human volunteers after oral administration of the prepared TOL sustained-release matrix-coated tablet and the marketed product. The results revealed that the pharmacokinetic parameters of AUC, Cmax, Tmax, t1/2, Kel, and MRT of TOL for the developed formulation (F2) were not significantly different from that for the marketed product, suggesting that they were bioequivalent. Therefore, the developed sustained-release tablet formulation of TOL could be an alternative dosage form to the SR capsule for treatment of OAB. PMID:24184032

Pradhan, Roshan; Kim, Yong-Il; Chang, Sun Woo; Kim, Jong Oh

2014-01-01

363

Considerations in the development of an in vitro dissolution condition for lacidipine tablets: in vivo pharmacokinetic evaluation.  

PubMed

In this study, a new discriminative dissolution condition for lacidipine tablets was developed by the established in vitro-in vivo relationship. Series of dissolution media of phosphate buffer solution (PBS) covering the pH range of 1-7.2 and pH 6.8 PBS containing different concentrations of sodium dodecyl sulfate (SDS), were prepared and used to investigate the dissolution behavior of lacidipine tablets. There was an obvious difference in the dissolution profiles of the both brands in pH 6.8 PBS medium containing 0.1% SDS. The pharmacokinetic study of the two lacidipine tablets was carried out in the healthy beagle dogs at a single dose of 4 mg. Statistical comparison of the AUC(????), C(max), and T(max) showed a significant difference in the two brand tablets, coinciding with the dissolution performance with pH 6.8 PBS containing 0.1% SDS. The superiority of the proposed system, pH 6.8 PBS containing 0.1% SDS, could serve as a dissolution medium for lacidipine tablets, and more important it could discriminate the in vivo pharmacokinetic behavior for different brands of products. In summary, in vivo pharmacokinetic evaluation is essential to develop an appropriate in vitro dissolution condition for oral solid dosage forms of poorly soluble drugs. PMID:22188158

Sun, Mingyu; Sun, Jin; He, Shuangfeng; Wang, Yongjun; Sun, Yinghua; Liu, Xiaohong; He, Zhonggui

2012-09-01

364

Paradoxical effects of the opioid antagonist naltrexone on morphine analgesia, tolerance, and reward in rats.  

PubMed

Opioid agonists such as morphine have been found to exert excitatory and inhibitory receptor-mediated effects at low and high doses, respectively. Ultra-low doses of opioid antagonists (naloxone and naltrexone), which selectively inhibit the excitatory effects, have been reported to augment systemic morphine analgesia and inhibit the development of tolerance/physical dependence. This study investigated the site of action of the paradoxical effects of naltrexone and the generality of this effect. The potential of ultra-low doses of naltrexone to influence morphine-induced analgesia was investigated in tests of nociception. Administration of intrathecal (0.05 and 0.1 ng) or systemic (10 ng/kg i.p.) naltrexone augmented the antinociception produced by an acute submaximal dose of intrathecal (5 microg) or systemic (7.5 mg/kg i.p.) morphine in the tail-flick test. Chronic intrathecal (0.005 and 0.05 ng) or systemic (10 ng/kg) naltrexone combined with morphine (15 microg i.t.; 15 mg/kg i.p.) over a 7-day period inhibited the decline in morphine antinociception and prevented the loss of morphine potency. In animals rendered tolerant to intrathecal (15 microg) or systemic (15 mg/kg) morphine, administration of naltrexone (0.05 ng i.t.; 10 and 50 ng/kg i.p.) significantly restored the antinociceptive effect and potency of morphine. Thus, in ultra-low doses, naltrexone paradoxically enhances morphine analgesia and inhibits or reverses tolerance through a spinal action. The potential of naltrexone to influence morphine-induced reward was also investigated using a place preference paradigm. Systemic administration of ultra-low doses of naltrexone (16.7, 20.0, and 25.0 ng/kg) with morphine (1.0 mg/kg) extended the duration of the morphine-induced conditioned place preference. These effects of naltrexone on morphine-induced reward may have implications for chronic treatment with agonist-antagonist combinations. PMID:11805221

Powell, Kelly J; Abul-Husn, Noura S; Jhamandas, Asha; Olmstead, Mary C; Beninger, Richard J; Jhamandas, Khem

2002-02-01

365

In vitro and in vivo sustained-release characteristics of theophylline matrix tablets and novel cluster tablets.  

PubMed

We compared the in vitro/in vivo properties of theophylline between two sustained-release preparations, which are administered once a day. Tablet A is a swelling/disintegration-type matrix tablet consisting of hydrophobic wax granules and hydrophilic polymer granules (cluster tablets). Tablet B is a matrix tablet consisting of hydrophilic polymer granules. We conducted a dissolution test with JPXIV in vitro, and compared the results between the two preparations. Neither pH nor agitation intensity influenced these preparations. After they were immersed in oleic acid, there were no marked changes in the dissolution properties in the dissolution test. After administration of Tablets A and B containing theophylline at 200mg to fasted dogs, we compared plasma level profiles of theophylline. The mean plasma level of theophylline gradually increased to a maximum (7.17microg/mL) 4h after administration of Tablet A. After administration of Tablet B, a similar finding was noted, with a maximum of 6.09microg/mL. Tablet B showed a higher coefficient of variation (CV) for the plasma level at each point. Subsequently, we administered two tablets of preparations A and B containing theophylline at 200mg to healthy volunteers who had not been fasted, and compared plasma level concentration of theophylline. The mean plasma level of theophylline gradually increased to a maximum (6.09microg/mL) 12h after administration of Tablet A, but then decreased, with a half-life of 9.10h. After administration of Tablet B, a similar finding was noted, with a maximum of 7.87microg/mL and a half-life of 7.76h. Tablet A showed a significantly higher plasma concentration 1 and 2h after administration; however, there were no significant differences at other points. The C(max) of Tablet B was significantly higher than that of Tablet A. However, there were no significant differences in other pharmacokinetic parameters between the two preparations. The T(max) of Tablet A was 10-12h after administration, relatively constant. However, that of Tablet B was 10-18h after administration. The CV for T(max) was 9.8% for Tablet A and 22.0% for Tablet B. After administration of Tablet B, the plasma level of theophylline varied at each point. Based on these results, inter-subject variations after administration of Tablet A may be less marked than those after administration of Tablet B. It is concluded that, the cluster tablets A developed in this study showed significantly less inter-subject variation of theophylline plasma levels than the conventional matrix tablets B. PMID:17512147

Hayashi, Tetsuo; Kanbe, Hideyoshi; Okada, Minoru; Kawase, Ichiro; Ikeda, Yasuo; Onuki, Yoichi; Kaneko, Tetsuo; Sonobe, Takashi

2007-08-16

366

The selective mGlu2\\/3 receptor antagonist LY341495 exacerbates behavioral signs of morphine withdrawal and morphine-withdrawal-induced activation of locus coeruleus neurons  

Microsoft Academic Search

Previous research has demonstrated that mGlu2\\/3 agonists can decrease many behavioral signs and the activation of locus coeruleus (LC) neurons observed during morphine withdrawal. However, it is not known if mGlu2\\/3 receptors are activated during morphine withdrawal by endogenous glutamate. Therefore, we investigated the effect of a novel metabotropic glutamate 2, 3 (mGlu2\\/3) receptor antagonist (LY341495) on naltrexone-precipitated behavioral signs

Kurt Rasmussen; Mei-Ann Hsu; Jim Vandergriff

2004-01-01

367

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

SciTech Connect

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

Thomassin, J.; Tephly, T.R. (Univ. of Iowa, Iowa City (USA))

1990-09-01

368

The effect of gp120 on morphine's antinociceptive and neurophysiological actions  

PubMed Central

Recently, we have shown that morphine's analgesic activity can be attenuated by chemokines, specifically CCL5 and CXCL12. Because the HIV-1 coat protein, glycoprotein 120 (gp120), binds to the same receptors as do CCL5 and CXCL12, experiments were designed to investigate the effect of gp120 in the brain on antinociception induced by morphine in the cold-water (-3°C) tail-flick (CWT) and hot-plate (+54°C) tests. In addition, mu-opioid-receptor-mediated effects in brain periaqueductal grey (PAG) slices were examined with whole-cell patch-clamp recordings. The results showed that (1) pretreatment with gp120 itself (10, 25, 50, 100 or 133 ng, PAG) had no nociceptive effect in the CWT; (2) pretreatment with gp120 (25 or 100 ng) dose-dependently reduced antinociception induced by subcutaneous (sc) injection of morphine (3 or 6 mg/kg) or PAG injection of morphine (100 ng) in the CWT; (3) a PAG injection of gp120 (133 ng), given 30 min before sc injection of morphine (6 mg/kg), similarly reduced morphine antinociception in the hotplate test; (4) the inhibitory effect of gp120 on morphine-induced antinociception in the CWT was reversed by AMD3100, an antagonist of CXCR4; (5) pretreatment of slices with gp120 (200 pM) prevented morphine (10 ?M)-induced hyperpolarization and reduction of input resistance in PAG neurons. Electrophysiology studies paralleled gp120-induced desensitization of a mu-opioid-receptor-mediated response in PAG neurons at the single-cell level. These studies are the first to demonstrate that the analgesic activity of morphine can be reduced by the presence of gp120 in the PAG and that pretreatment with AMD3100 is able to restore the analgesic effects of morphine. PMID:21569838

Chen, Xiaohong; Kirby, Lynn G.; Palma, Jonathan; Benamar, Khalid; Geller, Ellen B.; Eisenstein, Toby K.; Adler, Martin W.

2014-01-01

369

Ethanol reversal of cellular tolerance to morphine in rat locus coeruleus neurons.  

PubMed

Consumption of ethanol is a considerable risk factor for death in heroin overdose. We sought to determine whether a mildly intoxicating concentration of ethanol could alter morphine tolerance at the cellular level. In rat locus coeruleus (LC) neurons, tolerance to morphine was reversed by acute exposure of the brain slice to ethanol (20 mM). Tolerance to the opioid peptide [d-Ala(2),N-MePhe(4),Gly-ol]-enkephalin was not reversed by ethanol. Previous studies in LC neurons have revealed a role for protein kinase C (PKC)? in ?-opioid receptor (MOPr) desensitization by morphine and in the induction and maintenance of morphine tolerance, but we have been unable to demonstrate that 20 mM ethanol produces significant inhibition of PKC?. The ability of ethanol to reverse cellular tolerance to morphine in LC neurons was absent in the presence of the phosphatase inhibitor okadaic acid, indicating that dephosphorylation is involved. In human embryonic kidney 293 cells expressing the MOPr, ethanol reduced the level of MOPr phosphorylation induced by morphine. Ethanol reversal of tolerance did not appear to result from a direct effect on MOPr since acute exposure to ethanol (20 mM) did not modify the affinity of binding of morphine to the MOPr or the efficacy of morphine for G-protein activation as measured by guanosine 5'-O-(3-[(35)S]thio)triphosphate binding. Similarly, ethanol did not affect MOPr trafficking. We conclude that acute exposure to ethanol enhances the effects of morphine by reversing the processes underlying morphine cellular tolerance. PMID:23716621

Llorente, Javier; Withey, Sarah; Rivero, Guadalupe; Cunningham, Margaret; Cooke, Alex; Saxena, Kunal; McPherson, Jamie; Oldfield, Sue; Dewey, William L; Bailey, Chris P; Kelly, Eamonn; Henderson, Graeme

2013-08-01

370

Ethanol Reversal of Cellular Tolerance to Morphine in Rat Locus Coeruleus Neurons  

PubMed Central

Consumption of ethanol is a considerable risk factor for death in heroin overdose. We sought to determine whether a mildly intoxicating concentration of ethanol could alter morphine tolerance at the cellular level. In rat locus coeruleus (LC) neurons, tolerance to morphine was reversed by acute exposure of the brain slice to ethanol (20 mM). Tolerance to the opioid peptide [d-Ala2,N-MePhe4,Gly-ol]-enkephalin was not reversed by ethanol. Previous studies in LC neurons have revealed a role for protein kinase C (PKC)? in ?-opioid receptor (MOPr) desensitization by morphine and in the induction and maintenance of morphine tolerance, but we have been unable to demonstrate that 20 mM ethanol produces significant inhibition of PKC?. The ability of ethanol to reverse cellular tolerance to morphine in LC neurons was absent in the presence of the phosphatase inhibitor okadaic acid, indicating that dephosphorylation is involved. In human embryonic kidney 293 cells expressing the MOPr, ethanol reduced the level of MOPr phosphorylation induced by morphine. Ethanol reversal of tolerance did not appear to result from a direct effect on MOPr since acute exposure to ethanol (20 mM) did not modify the affinity of binding of morphine to the MOPr or the efficacy of morphine for G-protein activation as measured by guanosine 5?-O-(3-[35S]thio)triphosphate binding. Similarly, ethanol did not affect MOPr trafficking. We conclude that acute exposure to ethanol enhances the effects of morphine by reversing the processes underlying morphine cellular tolerance. PMID:23716621

Llorente, Javier; Withey, Sarah; Rivero, Guadalupe; Cunningham, Margaret; Cooke, Alex; Saxena, Kunal; McPherson, Jamie; Oldfield, Sue; Dewey, William L.; Bailey, Chris P.; Kelly, Eamonn; Henderson, Graeme

2013-01-01

371

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

PubMed

Ultra-low doses of opioid receptor antagonists inhibit development of chronic spinal morphine tolerance. As this phenomenon mechanistically resembles acute tolerance, the present study examined actions of opioid receptor antagonists on acute spinal morphine tolerance. In adult rats, administration of three intrathecal injections of morphine (15 microg) at 90 min intervals produced a significant decline of the antinociceptive effect and loss of agonist potency in both the tail-flick and paw-pressure tests. These reduced responses, indicative of acute tolerance, were blocked by co-injection of morphine (15 microg) with naltrexone (NTX, 0.05 ng), D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTAP, 0.001 ng), naltrindole (0.06 ng), or nor-binaltorphimine (0.1 ng). Repeated injections of CTAP, naltrindole, or nor-binaltorphimine without morphine elicited a delayed weak antinociceptive response which was blocked by a high dose of naltrexone (2 microg). In another set of experiments, administration of low dose spinal (0.05 ng) or systemic (0.01 microg/kg) morphine produced a sustained thermal hyperalgesia. This response was blocked by opioid receptor antagonists at doses inhibiting development of acute morphine tolerance. Lastly, an acute spinal injection of morphine (15 microg) with naltrexone (0.05 ng) produced a sustained analgesic response; this was antagonized by adenosine receptor antagonist, 8-phenyltheophylline (3 microg). The results show that ultra-low doses of opioid receptor antagonists block acute tolerance to morphine. This effect may result from blockade of opioid excitatory effects that produce a latent hyperalgesia that then contributes to induction of tolerance. The sustained antinociception produced by combination of morphine with an opioid receptor antagonist shows dependency on the adenosine receptor activity. PMID:17307158

McNaull, Benjamin; Trang, Tuan; Sutak, Maaja; Jhamandas, Khem

2007-04-10

372

Role of C-fibers in pain and morphine induced analgesia/hyperalgesia in rats  

PubMed Central

Background Usual dosage of morphine (10 mg/kg) induces analgesia and ultra-low dose (ULD) of morphine (1 µg/kg); hyperalgesia, and C-fibers are also bearing µ-opioid receptors; here the importance of C-fibers on pain and morphine induced analgesia/hyperalgesia is questioned and investigated using pain evaluation methods and infant capsaicin treating for C-fibers lesioning. Methods Wistar male rats (200-250 grams) were assigned to three categories i.e. control, sham (receiving neonatal capsaicin vehicle) and c-lesion (receiving neonatal capsaicin), each one with three groups (n=7). They were injected intraperitoneally with single dosage of saline, 10 mg/kg or 1 µg/kg morphine, respectively. Thermal pain threshold was evaluated using the tail flick test before and 30 minutes after the injections. Chemical pain was assessed using the formalin test (FT) 30 minutes after the administrations. Results Results indicated that thermal (P < 0.001) and chemical pains in both neurogenic and inflammatory phases of FT (P < 0.05) were reduced in C-lesion animals. In the C-normal and C-lesion animals, 10 mg/kg morphine exerted analgesia both in thermal (P < 0.001) and two phases of FT (P < 0.01), but it was more potent in C-lesion animals (P < 0.05). Although ULD of morphine in C-normal animals produced hyperalgesic effect in thermal and chemical pains (P < 0.001), in C-lesion animals, it produced analgesia (P < 0.05) at the neurogenic phase of FT. Conclusion Results can raise the C-fibers involvement for a significant portion of nociceptive transmission, because C-lesioning potentiated morphine induced analgesia and eliminated ULD of morphine induced hyperalgesia. Therefore C and A? fibers can be involved in morphine analgesia; while, just C-fibers are possibly responsible for only presynaptically hyperalgesic/excitatory action of ULD in morphine. PMID:24800043

Alizadeh, Zahra; Behnam-Rassouli, Morteza; Hosseini, Shirin

2014-01-01

373

Blood–brain barrier transport of morphine in patients with severe brain trauma  

PubMed Central

Aims In experimental studies, morphine pharmacokinetics is different in the brain compared with other tissues due to the properties of the blood–brain barrier, including action of efflux pumps. It was hypothesized in this clinical study that active efflux of morphine occurs also in human brain, and that brain injury would alter cerebral morphine pharmacokinetics. Methods Patients with traumatic brain injury, equipped with one to three microdialysis catheters in the brain and one in abdominal subcutaneous fat for metabolic monitoring, were studied. The cerebral catheter locations were classified as ‘better’ and ‘worse’ brain tissue, referring to the degree of injury. Morphine (10 mg) was infused intravenously over a 10-min period in seven patients in the intensive care setting. Tissue and plasma morphine concentrations were obtained during the subsequent 3-h period with microdialysis and regular blood sampling. Results The area under the concentration–time curve (AUC) ratio of unbound morphine in brain tissue to plasma was 0.64 (95% confidence interval 0.40, 0.87) in ‘better’ brain tissue (P < 0.05 vs. the subcutaneous fat/plasma ratio), 0.78 (0.49, 1.07) in ‘worse’ brain tissue and 1.00 (0.86, 1.13) in subcutaneous fat. The terminal half-life and Tmax were longer in the brain vs. plasma and fat, respectively. The relative recovery for morphine was higher in ‘better’ than in ‘worse’ brain tissue. The Tmax value tended to be shorter in ‘worse’ brain tissue. Conclusions The unbound AUC ratio below unity in the ‘better’ human brain tissue demonstrates an active efflux of morphine across the blood–brain barrier. The ‘worse’ brain tissue shows a decrease in relative recovery for morphine and in some cases also an increase in permeability for morphine over the blood–brain barrier. PMID:15025740

Ederoth, Per; Tunblad, Karin; Bouw, René; Johan, C; Lundberg, F; Ungerstedt, Urban; Nordström, Carl-Henrik; Hammarlund-Udenaes, Margareta

2004-01-01

374

Development of enteric-coated timed-release matrix tablets for colon targeting.  

PubMed

A new oral drug delivery system for colon targeting has been developed based on enteric-coated matrix tablets which suitably exploits both pH-sensitive and time-dependent functions. Matrix-tablets were prepared by direct compression of mixtures of hydroxyethylcellulose (HEC), a hydrophilic swellable polymer, with the inert insoluble ethylcellulose (EC) or micro-crystalline cellulose (MCC) polymers, in which theophylline, selected as model drug, was dispersed. Eudragit S100, a methacrylic acid copolymer soluble at pH 7, was used as pH-sensitive coating polymer. The influence of varying the cellulose-derivative combinations and their relative ratios as well as the level of the coating polymer was investigated. Surface morphology of the tablets was monitored by SEM analysis before and after the release test. The results of release studies, performed according to the USP basket method using a sequence of dissolution media simulating the gastrointestinal physiological pH variation, indicated that the Eudragit S100 enteric-coated matrix tablets were successful in achieving gastric resistance and timed-release of the drug, assuring an adequate lag time for the intended colonic targeting, followed by a controlled-release phase. The enteric-coating level emerged as the critical factor in determining the duration of the lag-phase, whereas the release rate mainly depended on the matrix composition. Formulations with higher HEC content showed a faster drug release rate than those with greater content in inert polymer and the MCC-HEC combinations were more effective than the corresponding EC-HEC ones. The best results were given by the 27% coated 1:0.3:0.7 (w/w) drug/MCC/HEC tablets, which, after a 260 min lag time, regularly released the drug, achieving about 90% of release after 10 h. PMID:15621686

Alvarez-Fuentes, J; Fernández-Arévalo, M; González-Rodríguez, M L; Cirri, M; Mura, P

2004-01-01

375

Randomized controlled trial of sodium phosphate tablets vs polyethylene glycol solution for colonoscopy bowel cleansing  

PubMed Central

AIM: To compare efficacy, patient compliance, acceptability, satisfaction, safety, and adenoma detection rate of sodium phosphate tablets (NaP, CLICOLONTM) to a standard 4 L polyethylene glycol (PEG) solution for bowel cleansing for adults undergoing colonoscopy. METHODS: In this multicenter, randomized, prospective, investigator-blind study, the relatively young (19-60 years) healthy outpatients without comorbidity were randomly assigned to one of two arms. All colonoscopy were scheduled in the morning. The NaP group was asked to take 4 tablets, 5 times the evening before and 4 tablets, 3 times early on the morning of the colonoscopy. The PEG group was asked to ingest 2 L of solution the evening before and 2 L early in the morning of the procedure. Adequacy of bowel preparation was scored using the Boston bowel preparation scale. RESULTS: No significant differences were observed between the NaP group (n = 158) and PEG group (n = 162) in bowel cleansing quality (adequate preparation 93.0% vs 92.6%, P = 0.877), patient compliance (P = 0.228), overall adverse events (63.3% vs 69.1%, P = 0.269), or adenoma detection rate (34.8% vs 35.2%, P = 0.944). Patient acceptability, satisfaction, and patient rating of taste were higher in the NaP group than in the PEG group (P < 0.001). CONCLUSION: NaP tablets, compared with PEG solution, produced equivalent colon cleansing, did not cause more side effects, and had better patient acceptability and satisfaction in the relatively young (age < 60 years) healthy individuals without comorbidity. An oral tablet formulation could make bowel preparation less burdensome, resulting in greater patient participation in screening programs.

Jung, Yoon Suk; Lee, Chang Kyun; Kim, Hyo Jong; Eun, Chang Soo; Han, Dong Soo; Park, Dong Il

2014-01-01

376

Formulation, development, and performance evaluation of metoclopramide HCl oro-dispersible sustained release tablet.  

PubMed

The present study was undertaken to develop and evaluate an oro-dispersible, sustained release tablet of metoclopramide HCl. The technology was comprised of developing sustained release microparticles, and compression of resultant microspheres into a fast dispersible tablet by direct compression. The microspheres of metoclopramide HCl were prepared by an emulsification-solvent evaporation method using ethylcellulose as the matrix polymer. The prepared microspheres were evaluated for morphology, particle size, entrapment efficiency, and in vitro drug release characteristics. Scanning electron microscopy demonstrated spherical particles with a mean diameter of 81.27 ± 5.87 ?m and the drug encapsulation efficiency was found to be 70.15 ± 3.06%. The process and formulation variables such as rotation speed, polymer concentration, and drug concentration influenced the drug encapsulation efficiency and in vitro drug release. Optimized microspheres were compressed into tablets which were comprised of metoclopramide HCl microspheres, 53% (w/v) of D-mannitol granules, 7% (w/w) of Polyplasdone XL 10, and 0.5% (w/w) of calcium stearate. The tablets demonstrated a hardness of 59 ± 3 N, friability of 0.21% and disintegration time of 27 ± 3 sec. The formulations were subjected to stability studies as per ICH guidelines and were found to be stable after a 6 month study. In vivo experiments conducted in rats demonstrated that a constant level of metoclopramide HCl in plasma could be maintained for up to 20 h at a suitable concentration for antiemetic activity. An appropriate combination of excipients made it possible to obtain orally disintegrating sustained release tablets of metoclopramide HCl using simple and conventional techniques. PMID:22076769

Kasliwal, Nikhil; Negi, Jeetendra Singh; Jugran, Vandana; Jain, Rahul

2011-10-01

377

[Antidiabetic fixed-dose combination tablet for the management of type 2 diabetes].  

PubMed

How to use oral antidiabetic fixed-dose combination tablet for the management of type 2 diabetes (T2DM)? In addition to diet and exercise, the majority of diabetic patients need drug therapy to achieve optimal glycemic control. Monotherapy with oral antidiabetic agent is the firstline pharmacologic treatment option. However, in order to maintain glycemic control, additional oral antidiabetic agents are often added to monotherapies resulting in dual therapy. Dual therapy can be prescribed as separate pills, or as a single pill containing two agents. Randomized controlled trials of patients requiring dual therapy, have shown fixed-dose combination therapies to have superior efficacy when compared to loose-pills combination therapies. T2DM patients treated with fixed-dose combination therapies may have better adherence, improved satisfaction, and lower direct costs, compared to those treated with loose-pill combination therapies. PMID:22413513

Sakane, Naoki

2012-01-01

378

Formulation Development and evaluation of fast disintegrating tablets of Lamotrigine using liqui-solid technique  

PubMed Central

Introduction: Epilepsy is a serious neurological disorder. Lamotrigine is an alternative to lithium for the treatment of epilepsy, and its oral bioavailability is 98%; however, its poor aqueous solubility hinders its oral absorption. Among the techniques available to enhance the solubility, dissolution rate and bio availability of poorly soluble drugs, liqui-solid technique is a novel and promising approach. The objectives of the investigation are to formulate, optimize lamotrigine liqui-solid compacts using 23 factorial experiments, validate experimental designs statistically and to compare with the marketed tablets using similarity and difference factors. Materials and Methods: Based on solubility studies tween 20 as nonvolatile liquid, avicel pH 101 as a carrier and aerosil 200 as a coating material were used. Liquid load factor other flow and compression characteristics were determined for different ratios of carrier and coat materials. Suitable quantities of carrier and coat materials were taken, according to the experimental designs other excipients were added, liqui-solid tablets were prepared by direct compression and evaluated. Drug excipient compatibility was determined using Fourier transform infrared spectroscopy (FTIR) analysis. The hardness, disintegration time and T75% were considered for validation of experimental designs. Results: The physicochemical properties of tablets such as hardness (1.5 ± 0.8–4.95 ± 0.96 kg), in vitro disintegration time (40 ± 20–320 ± 25 s) and Friability (0.39 ± 0.5–1.45 ± 0.2% also <1%) possess all the Indian pharmacopoeal requirements. The T75% was calculated and found to be 6.62–22.8 min. The rate of drug release followed first order kinetics. f1 and f2 values indicated the similarity in dissolution profiles between marketed and the optimized formulation and 63.64% similar with that of the marketed fast disintegrating tablets. FTIR studies revealed the absence of drug excipient incompatibility.

Koteswari, Poluri; Sunium, Suvarnala; Srinivasababu, Puttugunta; Babu, Govada Kishore; Nithya, Pinnamraju Durga

2014-01-01

379

Glial activation and midkine and pleiotrophin transcription in the ventral tegmental area are modulated by morphine administration.  

PubMed

Opiates cause persistent restructuring in the mesolimbic reward system. Although a possible role for midkine and pleiotrophin cytokines in the field of synaptic plasticity has been proposed, it has not been assessed whether morphine administration regulates astrogliosis and midkine and pleiotrophin transcription. We observed that single morphine injection and chronic morphine increased glial fibrillary acidic protein expression in the ventral tegmental area (VTA). Interestingly, single morphine injection and chronic morphine increased VTA midkine and pleiotrophin mRNA expression. Given these results, we hypothesize a role for these cytokines in mediating, at least in part, acute neuroprotective effects and chronic neurotrophic adaptations that contribute to drug dependence. PMID:25108770

García-Pérez, Daniel; Luisa Laorden, M; Núñez, Cristina; Victoria Milanés, M

2014-09-15

380

21 CFR 520.62 - Aminopentamide hydrogen sulphate tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 false Aminopentamide hydrogen sulphate tablets. 520.62 Section...ANIMAL DRUGS § 520.62 Aminopentamide hydrogen sulphate tablets. (a) Chemical name...Dimethylamino)-2,2-diphenylvaleramide hydrogen sulfate. (b) Specifications....

2012-04-01

381

SANCTUARY : asymmetric interfaces for game-based tablet learning  

E-print Network

This thesis describes the production of Sanctuary, a multiplayer learning game to be played on two tablet computers. Sanctuary's principle innovation is the splitting of the user interface onto two tablets, separating ...

Haas, Jason M. (Jason Matthew)

2013-01-01

382

[Pharmacokinetics of deflazacort tablets in healthy Chinese volunteers].  

PubMed

Deflazacort (DFZ, a prodrug) is well absorbed and rapidly metabolized into the active metabolite 21-hydroxydeflazacort (21-OH DFZ) after oral administration. The aim of this study is to evaluate the pharmacokinetic properties of 21-OH DFZ in healthy Chinese volunteers after a single and multiple oral administration of DFZ tablets under fed condition. Twelve volunteers (six males and six females) were administered a single dose of 6 mg or 12 mg or 24 mg of DFZ in three different periods separately, according to the 3 x 3 Latin square design. Between each administration period there was a washout period of one week. The multiple-dose study of 12 mg dose DFZ per day for 7 consecutive days was started after a 1 w washout period when the single-dose study completed. The pharmacokinetic parameters of 21-OH DFZ after the single oral administration of 6 mg, 12 mg and 24 mg DFZ tablets were as follows: (37.7 +/- 11.6), (61.5 +/- 17.7) and (123 +/- 23) ng x mL(-1) for C(max); (1.90 +/- 0.32), (1.96 +/- 0.27) and (2.13 +/- 0.34) h for t1/2; (96.6 +/- 25.9), (190 +/- 44) and (422 +/- 107) ng x h x mL(-1) for AUC(0-14 h), respectively. After the multiple dose administration, the mean plasma concentration at steady-state C(av) was (7.00 +/- 1.66) ng x mL(-1) and the degree of plasma concentration fluctuation DF was 7.7 +/- 1.2. The results showed that the pharmacokinetic characteristics of 21-OH DFZ in healthy Chinese volunteers were linear over the dose range of 6 to 24 mg. No significant gender differences were found in the pharmacokinetics of 21-OH DFZ in healthy Chinese volunteers. After the multiple dose administration of 12 mg DFZ for 7 d, no accumulation of 21-OH DFZ in healthy Chinese volunteers was observed. PMID:25212041

Ding, Wen; Ding, Li; Li, Wen-Bo; Pan, Hong; Lin, Hong-Da

2014-06-01

383

Chronic inflammatory pain prevents tolerance to the antinociceptive effect of morphine microinjected into the ventrolateral periaqueductal gray of the rat  

PubMed Central

The ventrolateral periaqueductal gray (vlPAG) contributes to morphine antinociception and tolerance. Chronic inflammatory pain causes changes within the PAG that are expected to enhance morphine tolerance. This hypothesis was tested by assessing antinociception and tolerance following repeated microinjections of morphine into the vlPAG of rats with chronic inflammatory pain. Microinjection of morphine into the vlPAG reversed the allodynia caused by intraplantar administration of Complete Freund's Adjuvant (CFA), and produced antinociception on the hot plate test. Although there was a gradual decrease in morphine antinociception with repeated testing, there was no evidence of tolerance when morphine and saline treated rats with hind paw inflammation were tested with cumulative doses of morphine. In contrast, repeated morphine injections into the vlPAG caused a rightward shift in the morphine dose-response curve in rats without hind paw inflammation, as would be expected with the development of tolerance. The lack of tolerance in CFA treated rats was evident whether rats were exposed to repeated behavioral testing or not (Experiment 2) and whether they were treated with 4 or 8 prior microinjections of morphine into the vlPAG (Experiment 3). These data demonstrate that chronic inflammatory pain does not disrupt the antinociceptive effect of microinjecting morphine into the vlPAG, but it does disrupt the development of tolerance. PMID:24161274

Mehalick, Melissa L.; Ingram, Susan L.; Aicher, Sue; Morgan, Michael M

2013-01-01

384

Development and characterization of buccoadhesive nifedipine tablets.  

PubMed

The buccoadhesive controlled-release tablets for delivery of nifedipine were prepared by direct compression of carboxymethyl cellulose (CMC) with carbomer (CP), which showed superior bioadhesion properties compared to polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), hydroxypropylmethyl cellulose (HPMC), and acacia in a modified tensiometry method in vitro. The tablets containing 30mg of nifedipine and various amounts of CMC and CP showed a zero-order drug release kinetic. The adhesion force was significantly affected by the mixing ratio of CP:CMC in the tablets. The weakest and highest adhesion force was observed at the mixing ratios of 1:0 and 8:2 of CP:CMC, respectively. The tablets containing 15% CMC and 35% CP adhered for over 8h to the upper gums of six healthy human volunteers. These tablets released about 56% of the loaded drug after 8h in vivo with a rate of 2.17h(-1) and were perfectly tolerated, while they released about 100% of their content after the same time with a rate of 3.49h(-1) in vitro. A good correlation (r(2)=0.989) was observed between drug-released in vitro and in vivo. PMID:12191683

Varshosaz, J; Dehghan, Z

2002-09-01

385

Stability study of losartan/hydrochlorothiazide tablets.  

PubMed

The purpose of stability testing is to investigate how the quality of a drug product changes with time under the influence of environmental factors, to establish a shelf life for the product and to recommend storage conditions. Stability study of losartan/hydrochlorothiazide tablets is presented in this paper. Losartan (angiotensin II receptor antagonist) and hydrochlorothiazide (diuretic) are successfully used in association in the treatment of hypertension. Stability study of losartan/hydrochlorothiazide tablets consisted of three steps: stress test (forced degradation study), preliminary testing (selection of packaging) and formal stability testing. The results of stress test suggested that losartan/hydrochlorothiazide tablets are sensitive to moisture. It was demonstrated that the developed analytical methods are stability indicating. Additional preliminary testing was performed in order to select appropriate packaging for losartan/hydrochlorothiazide tablets. OPA/Al/PVC//Al blisters were found to provide adequate protection for the product. Based on the first 12 months of the formal stability study, a shelf life of 24 months was proposed. Losartan/hydrochlorothiazide tablets in OPA/Al/PVC//Al blisters are demonstrated to be chemically, physically and microbiologically stable. PMID:15707739

Lusina, Maja; Cindri?, Tanja; Tomai?, Jadranka; Peko, Marijana; Pozai?, Lidija; Musulin, Nenad

2005-03-01

386

Molecular dynamic simulations of ocular tablet dissolution.  

PubMed

Small tablets for implantation into the subconjunctival space in the eye are being developed to inhibit scarring after glaucoma filtration surgery (GFS). There is a need to evaluate drug dissolution at the molecular level to determine how the chemical structure of the active may correlate with dissolution in the nonsink conditions of the conjunctival space. We conducted molecular dynamics simulations to study the dissolution process of tablets derived from two drugs that can inhibit fibrosis after GFS, 5-fluorouracil (5-FU) and the matrix metalloprotease inhibitor (MMPi), ilomastat. The dissolution was simulated in the presence of simple point charge (SPC) water molecules, and the liquid turnover of the aqueous humor in the subconjunctival space was simulated by removal of the dissolved drug molecules at regular intervals and replacement by new water molecules. At the end of the simulation, the total molecular solvent accessible surface area of 5-FU tablets increased by 60 times more than that of ilomastat as a result of tablet swelling and release of molecules into solution. The tablet dissolution pattern shown in our molecular dynamic simulations tends to correlate with experimental release profiles. This work indicates that a series of molecular dynamic simulations can be used to predict the influence of the molecular properties of a drug on its dissolution profile and could be useful during preformulation where sufficient amounts of the drug are not always available to perform dissolution studies. PMID:24073784

Ru, Qian; Fadda, Hala M; Li, Chung; Paul, Daniel; Khaw, Peng T; Brocchini, Steve; Zloh, Mire

2013-11-25

387

Deletion of guanine nucleotide binding protein alpha z subunit in mice induces a gene dose dependent tolerance to morphine.  

PubMed

The mechanism underlying the development of tolerance to morphine is still incompletely understood. Morphine binds to opioid receptors, which in turn activates downstream second messenger cascades through heterotrimeric guanine nucleotide binding proteins (G proteins). In this paper, we show that G(z), a member of the inhibitory G protein family, plays an important role in mediating the analgesic and lethality effects of morphine after tolerance development. We blocked signaling through the G(z) second messenger cascade by genetic ablation of the alpha subunit of the G protein in mice. The Galpha(z) knockout mouse develops significantly increased tolerance to morphine, which depends on Galpha(z) gene dosage. Further experiments demonstrate that the enhanced morphine tolerance is not caused by pharmacokinetic and behavioural learning mechanisms. The results suggest that G(z) signaling pathways are involved in transducing the analgesic and lethality effects of morphine following chronic morphine treatment. PMID:15033343

Leck, K J; Bartlett, S E; Smith, M T; Megirian, D; Holgate, J; Powell, K L; Matthaei, K I; Hendry, I A

2004-05-01

388

Subcoating with Kollidon VA 64 as water barrier in a new combined native dextran/HPMC-cetyl alcohol controlled release tablet.  

PubMed

A novel oral controlled delivery system for propranolol hydrochloride (PPL) was developed and optimized using wet granulation process. We are studying the ability of subcoating with Kollidon VA 64 as a barrier to water penetration in matrix cores combined hydrophilic (native dextran-HPMC)/hydrophobic (cetyl alcohol) prior to film coating with Opradry II-YS-30-18056. The copovidone (i.e., Kollidon VA 64) not only increases the mechanical properties of tablets (less friability) but also reduces the amount of absorbed water from the air in tropical stability condition (25 degrees C and 75% relative humidity). The in vitro dissolution profiles of coated sustained-release matrix tablets of racemic PPL were determined and compared with uncoated tablet cores according to the United States Pharmacopeia (USP) Tolerance Specifications for Propranolol Hydrochloride Extended-Release Capsules. A comparative kinetic study of the present matrix tablets (coated and uncoated cores) and commercial SUMIAL RETARD capsules (reference formulation (R) (Spain) was established). The values for the similarity factor (f2=61.756, f2=72.326 and f2=88.509 for initial time, one year and two years, respectively (uncoated cores vs. capsule) and f2=63.904, f2=69.502 and f2=76.348 (coated tablets vs. capsule) for initial time, one year and 2 two years, respectively) suggested that the dissolution profiles of the present three sustained-release oral dosage forms are similar and stable during two years under stability condition. PMID:18053697

Castellanos Gil, Eddy; Iraizoz Colarte, Antonio; Lara Sampedro, José Lizardo; Bataille, Bernard

2008-05-01

389

Understanding Tablet Use: A Multi-Method Exploration Hendrik Muller  

E-print Network

provides an in-depth pic- ture of frequent tablet activities (e.g., checking emails, play- ing games, social networking), locations of use (e.g., couch, bed, table), and contextual factors (e.g., watching TV, they watch videos, and they play games on their tablets. Existing insights into tablet ownership and use

Tomkins, Andrew

390

Persistent Peripheral Inflammation Attenuates Morphine-induced Periaqueductal Gray Glial Cell Activation and Analgesic Tolerance in the Male Rat  

PubMed Central

Morphine is among the most prevalent analgesics prescribed for chronic pain. However, prolonged morphine treatment results in the development of analgesic tolerance. An abundance of evidence has accumulated indicating that CNS glial cell activity facilitates pain transmission and opposes morphine analgesia. While the midbrain ventrolateral periaqueductal gray (vlPAG) is an important neural substrate mediating pain modulation and the development of morphine tolerance, no studies have directly assessed the role of PAG-glia. Here we test the hypothesis that morphine-induced increases in vlPAG glial cell activity contribute to the development of morphine tolerance. As morphine is primarily consumed for the alleviation of severe pain, the influence of persistent inflammatory pain was also assessed. Administration of morphine, in the absence of persistent inflammatory pain, resulted in the rapid development of morphine tolerance and was accompanied by a significant increase in vlPAG glial activation. In contrast, persistent inflammatory hyperalgesia, induced by intraplantar administration of Complete Freund’s Adjuvant (CFA), significantly attenuated the development of morphine tolerance. No significant differences were noted in vlPAG glial cell activation for CFA-treated animals versus controls. These results indicate that vlPAG glia are modulated by a persistent pain state, and implicate vlPAG glial cells as possible regulators of morphine tolerance. Perspective The development of morphine tolerance represents a significant impediment to its use in the management of chronic pain. We report that morphine tolerance is accompanied by increased glial cell activation within the vlPAG, and that the presence of a persistent pain state prevented vlPAG glial activation and attenuated morphine tolerance. PMID:23395474

Eidson, Lori N.; Murphy, Anne Z.

2014-01-01

391

Gene Expression Profile of Calcium/Calmodulin-Dependent Protein Kinase II? in Rat's Hippocampus during Morphine Withdrawal  

PubMed Central

Introduction Calcium/calmodulin-dependent protein kinase II (CaMKII) which is highly expressed in the hippocampus is known to play a pivotal role in reward-related memories and morphine dependence. Methods In the present study, repeated morphine injections once daily for 7 days was done to induce morphine tolerance in male Wistar rats, after which gene expression profile of ?-isoform of CaMKII (CaMKII?) in the hippocampus was evaluated upon discontinuation of morphine injection over 21 days of morphine withdrawal. Control groups received saline for 7 consecutive days. For gene expression study, rats’ brains were removed and the hippocampus was dissected in separate groups on days 1, 3, 7, 14, and 21 since discontinuation of of morphine injection. A semi-quantitative RT-PCR method was used to evaluate the gene expression profile. Results Tolerance to morphine was verified by a significant decrease in morphine analgesia in a hotplate test on day 8 (one day after the final repeated morphine injections). Results showed that gene expression of CaMKII? at mRNA level on day 1, 3, 7, 14 and 21 of morphine withdrawal was significantly altered as compared to the saline control group. Post hoc Tukey's test revealed a significantly enhanced CaMKII? gene expression on day 14. Discussion It can be concluded that CaMKII? gene expression during repeated injections of morphine is increased and this increase continues up to 14 days of withdrawal then settles at a new set point. Therefore, the strong morphine reward-related memory in morphine abstinent animals may, at least partly be attributed to, the up-regulation of CaMKII? in the hippocampus over 14 days of morphine withdrawal.

Ahmadi, Shamseddin; Amiri, Shahin; Rafieenia, Fatemeh; Rostamzadeh, Jalal

2013-01-01

392

Alternative oral exemestane formulation: improved dissolution and permeation.  

PubMed

Exemestane (EXE) is an irreversible aromatase inactivator used for the treatment of advanced postmenopausal breast cancer. EXE is orally active but its bioavailability is about 5% due to its low solubility in water and the extensive first pass effect. It is known that cyclodextrin (CD) complexation enhances solubility and oral bioavailability of poorly soluble drugs. Thus, it was aimed to design and develop cyclodextrin complexes in powder and tablet forms containing EXE to improve aqueous solubility and in vitro permeability. In this study, inclusion complexes of EXE were prepared with three different CD derivatives (methyl-beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin and hydroxypropyl-gamma-cyclodextrin) and by two different preparation methods (kneading and colyophilization) and the complexes were characterized with (1)H NMR, FT-IR, SEM, X-ray and DSC analyses. Both inclusion complexes and tablet formulations prepared using EXE:CD inclusion complexes showed significant improvement in the dissolution profile of this oral antiestrogen drug. Furthermore, Caco-2 cell permeation studies revealed that apparent permeability constant for EXE was increased by 3-fold via cyclodextrin complexation. In conclusion, complexation of EXE with cyclodextrin derivatives, randomly methylated-beta-cyclodextrin in particular, results in a more efficient tablet formulation with improved dissolution and better permeation suggesting an enhancement in oral bioavailability of the drug. PMID:20678561

Yavuz, Burçin; Bilensoy, Erem; Vural, Imran; Sumnu, Murat

2010-10-15

393

Preparation and in vitro/in vivo characterization of porous sublingual tablets containing ternary kneaded solid system of vinpocetine with î-cyclodextrin and hydroxy Acid.  

PubMed

The demand for sublingual tablets has been growing during the previous decades especially for drugs with extensive hepatic first-pass metabolism. Vinpocetine, a widely used neurotropic agent, has low oral bioavailability due to its poor aqueous solubility and marked first-pass metabolism. Accordingly, the aim of this work was to develop tablets for the sublingual delivery of vinpocetine. Initially, the feasibility of improving vinpocetineâs poor aqueous solubility by preparing kneaded solid systems of the drug with Î-Cyclodextrin and hydroxy acids (citric acid and tartaric acid) was assessed. The solid system with improved solubility and dissolution properties was incorporated into porous tablets that rapidly disintegrate permitting fast release of vinpocetine into the sublingual cavity. The pores were induced into these tablets by directly compressing the tabletsâ excipients with a sublimable material, either camphor or menthol, which was eventually sublimated leaving pores. The obtained results demonstrated that the tablets prepared using camphor attained sufficient mechanical strength for practical use together with rapid disintegration and dissolution. In vivo absorption study performed in rabbits indicated that the sublingual administration of the proposed porous tablets containing vinpocetine solid system with Î-Cyclodextrin and tartaric acid could be useful for therapeutic application. PMID:21179352

Aburahma, Mona H; El-Laithy, Hanan M; Hamza, Yassin El-Said

2010-01-01

394

Interactions between morphine, scopolamine and nicotine: schedule-controlled responding in rats  

PubMed Central

Functional interactions between drugs acting on either opioid or cholinergic systems have been demonstrated for both neurochemical and behavioral measures. This study used schedule-controlled responding and isobolographic analyses to examine interactions between the ? opioid receptor agonist morphine and the muscarinic acetylcholine receptor antagonist scopolamine as well as the nicotinic acetylcholine receptor agonist nicotine. In 8 rats responding under a fixed ratio 5 schedule of food presentation, morphine (3.2-10 mg/kg), scopolamine (0.032-1.0 mg/kg), and nicotine (0.1-1 mg/kg) each dose dependently decreased responding. Acute injection of scopolamine shifted the morphine dose-response curved leftward and downward and acute injection of morphine shifted the scopolamine and nicotine dose-response curves leftward and downward. The interaction between morphine and nicotine was additive; however, the interaction between morphine and scopolamine was infra-additive or supra-additive, depending on whether scopolamine or morphine was administered first. These results provide quantitative evidence regarding potentially important interactions between drugs acting on either opioid or cholinergic systems, although these interactions are modest and appear to depend on the specific conditions of drug administration. PMID:20420849

Li, Xinwang; Li, Jun-Xu; France, Charles P.

2010-01-01

395

Morphine biosynthesis in opium poppy involves two cell types: sieve elements and laticifers.  

PubMed

Immunofluorescence labeling and shotgun proteomics were used to establish the cell type-specific localization of morphine biosynthesis in opium poppy (Papaver somniferum). Polyclonal antibodies for each of six enzymes involved in converting (R)-reticuline to morphine detected corresponding antigens in sieve elements of the phloem, as described previously for all upstream enzymes transforming (S)-norcoclaurine to (S)-reticuline. Validated shotgun proteomics performed on whole-stem and latex total protein extracts generated 2031 and 830 distinct protein families, respectively. Proteins corresponding to nine morphine biosynthetic enzymes were represented in the whole stem, whereas only four of the final five pathway enzymes were detected in the latex. Salutaridine synthase was detected in the whole stem, but not in the latex subproteome. The final three enzymes converting thebaine to morphine were among the most abundant active latex proteins despite a limited occurrence in laticifers suggested by immunofluorescence labeling. Multiple charge isoforms of two key O-demethylases in the latex were revealed by two-dimensional immunoblot analysis. Salutaridine biosynthesis appears to occur only in sieve elements, whereas conversion of thebaine to morphine is predominant in adjacent laticifers, which contain morphine-rich latex. Complementary use of immunofluorescence labeling and shotgun proteomics has substantially resolved the cellular localization of morphine biosynthesis in opium poppy. PMID:24104569

Onoyovwe, Akpevwe; Hagel, Jillian M; Chen, Xue; Khan, Morgan F; Schriemer, David C; Facchini, Peter J

2013-10-01

396

Inhibitory effects of berberine against morphine-induced locomotor sensitization and analgesic tolerance in mice.  

PubMed

We previously reported that a methanolic extract of Coptis japonica, which is a well-known traditional oriental medicine, inhibits morphine-induced conditioned place preference (CPP) in mice. Berberine is a major component of Coptis japonica extract, and it has been established that the adverse effects of morphine on the brain involve dopamine (DA) receptors. However, to our knowledge, no study has investigated the inhibitory effects of berberine on morphine-induced locomotor sensitization and analgesic tolerance in mice. Here, we investigated the effects of berberine on morphine-induced locomotor sensitization and on the development of analgesic tolerance. Furthermore, we examined the effects of berberine treatment on N-methyl-D-aspartate (NMDA) receptor channel activity expressed in Xenopus laevis oocytes. Berberine was found to completely block both morphine-induced locomotor sensitization and analgesic tolerance, and reduce D(1) and NMDA receptor bindings in the cortex. Moreover, berberine markedly inhibited NMDA current in Xenopus laevis oocytes expressing NMDA receptor subunits. Our results suggest that the inhibitory effects of berberine on morphine-induced locomotor sensitization and analgesic tolerance are closely related to the modulation of D1 and NMDA receptors, and that berberine should be viewed as a potential novel means of attenuating morphine-induced sensitization and analgesic tolerance. PMID:16934942

Yoo, J-H; Yang, E-M; Cho, J-H; Lee, J-H; Jeong, S M; Nah, S-Y; Kim, H-C; Kim, K-W; Kim, S-H; Lee, S-Y; Jang, C-G

2006-11-01

397

Autophagy in superficial spinal dorsal horn accelerates the cathepsin B-dependent morphine antinociceptive tolerance.  

PubMed

Opioids are the most widely used analgesics in the treatment of severe acute and chronic pain. However, opioids have many adverse side effects, including the development of antinociceptive tolerance after long-term use. The antinociceptive tolerance of opioids has limited their clinical use. A recent study has reported that autophagy is responsible for morphine-induced neuronal injury. However, little is known about the role of autophagy in morphine antinociceptive tolerance. In the present study, chronic morphine administration was found to induce the expression of autophagy-related proteins, including Beclin1 and microtubule-associated protein light chain 3 (LC3)-II, in GABAergic interneurons in the superficial layer (lamina I-II) of the spinal cord. A single intrathecal administration of autophagy inhibitors, 3-methyladenine (3MA) or wortmannin, inhibited the development of antinociceptive tolerance in a dose-dependent manner. Autophagy in the lamina I-II neurons was associated with increased level of cathepsin B (CatB), a lysosomal cysteine protease. The pharmacological blockade or gene deletion of CatB markedly prevented the development of morphine antinociceptive tolerance. Furthermore, the intrathecal administration of 3MA suppressed the upregulation of CatB 5 days after morphine administration. Finally, CatB deficiency inhibited the increased release probability of glutamate in the lamina I neurons after chronic morphine treatment. These observations suggest that the dysfunction of the spinal GABAergic system induced by CatB-dependent excessive autophagy is partly responsible for morphine antinociceptive tolerance following chronic treatment. PMID:24973657

Hayashi, Y; Koga, Y; Zhang, X; Peters, C; Yanagawa, Y; Wu, Z; Yokoyama, T; Nakanishi, H

2014-09-01

398

Morphine has latent deleterious effects on the ventilatory responses to a hypoxic-hypercapnic challenge  

PubMed Central

This study explored the concept that morphine has latent deleterious actions on the ventilatory control systems that respond to a hypoxic-hypercapnic challenge. In this study, we examined the ventilatory responses elicited by hypoxic-hypercapnic challenge in conscious rats at a time when the effects of morphine (10 mg/kg) on arterial blood-gas chemistry and minute ventilation had subsided. Morphine induced pronounced changes in arterial blood-gas chemistry (e.g., an increase in pCO2, decreases in pO2 and sO2) and decreases in minute ventilation. Despite the complete resolution of the morphine-induced changes in arterial blood-gas chemistry and minute ventilation and almost complete resolution of the effects on peak inspiratory flow and peak expiratory flow, subsequent exposure to hypoxic-hypercapnic challenge elicited markedly blunted increases in minute ventilation and in peak inspiratory and expiratory flows. These findings demonstrate that (1) the changes in arterial blood-gas chemistry elicited by morphine parallel changes in minute ventilation rather than PIF and PEF, and (2) morphine has latent untoward effects on the ventilatory responses to hypoxic-hypercapnic challenge. These novel findings raise the possibility that patients deemed to have recovered from the acute ventilatory depressant effects of morphine may still be susceptible to the latent effects of this opioid analgesic. The mechanisms underlying these latent effects remain to be elucidated. PMID:25045592

May, Walter J.; Henderson, Fraser; Gruber, Ryan B.; Discala, Joseph F.; Young, Alex P.; Bates, James N.; Palmer, Lisa A.; Lewis, Stephen J.

2014-01-01

399

Morphine protects against intracellular amyloid toxicity by inducing estradiol release and upregulation of Hsp70.  

PubMed

Certain experimental models support morphine can play a beneficial role against damage in the neuronal system. In this study, we find morphine as well as endomorphin-1 and endomorphin-2 can protect against intracellular amyloid ? (iA?) toxicity in human and rat primary neuronal cultures and in rat brains in vivo. Morphine reverses the electrophysiological changes induced by iA?, including current density, resting membrane potential and capacitance. Also morphine improves the spatial memory performance in rats infected by iA? packaged virus and in APP/PS1 mice in Morris water maze tests. Morphine protection is mediated through inducing estradiol release in hippocampal neurons measured by ELISA and liquid chromatography-mass spectrometry, possibly by increasing P450 cytochrome aromatase activity. Released estradiol induces upregulation of heat shock protein 70 (Hsp70). Hsp70 protects against intracellular amyloid toxicity by rescuing proteasomal activity which is impaired by iA?. This is the first time, to our knowledge, that induction of estradiol release in hippocampal neurons by morphine is reported. Our data may contribute to both Alzheimer's disease therapy and pain clinics where morphine is widely used. PMID:22072674

Cui, Jia; Wang, Yunfeng; Dong, Qiping; Wu, Shimin; Xiao, Xianzhong; Hu, Jianying; Chai, Zhen; Zhang, Yan

2011-11-01

400

Ineffective doses of dexmedetomidine potentiates the antinociception induced by morphine and fentanyl in acute pain model.  

PubMed

The aim of this study was to evaluate the synergistic potentiation effect of ineffective doses of dexmedetomidine on antinociception induced by morphine and fentanyl in acute pain model in rats. Seventy albino Wistar rats were separated into 7 groups. Data for the control and sham groups were recorded. The ineffective dose of dexmedetomidine was investigated and found to be 3 µ g/kg. Each group was administered the following medications: 3 mg/kg morphine (intraperitoneal) to Group 3, 5 µg/kg fentanyl (intraperitoneal) to Group 4, dexmedetomidine 3 µ g/kg (subcutaneously) to Group 5, dexmedetomidine 3 µg/kg (subcutaneous)+3 mg/kg morphine (intraperitoneal) to Group 6 and finally 3 µg/kg dexmedetomidine (subcutaneous)+5 µg/kg fentanyl (intraperitoneal) to Group 7. Just before the application and 15, 30, 60, 90 and 120 min after the administration of medication, two measurements of tail flick (TF) and hot plate (HP) tests were performed. The averages of the measurements were recorded. TF and HP latencies were the main outcomes. The analgesic effect of the combinations with dexmedetomidine+morphine (Group 6) and dexmedetomidine+fentanyl (Group 7), compared to the analgesic effect of morphine alone and fentanyl alone was significantly higher at 15, 30, 60 and 90 minutes after administration. In this study, dexmedetomidine in ineffective doses, when combined with morphine and fentanyl, potentiates the effects of both morphine and fentanyl. PMID:24227942

Unal, Mumin; Gursoy, Sinan; Altun, Ahmet; Duger, Cevdet; Kol, Iclal Ozdemir; Kaygusuz, Kenan; Bagcivan, Ihsan; Mimaroglu, Caner

2013-10-01

401

Morphine to methadone conversion: an interpretation of published data.  

PubMed

For the past 20 years, methadone has been experiencing resurgence in the palliative care community as a second-line opioid for the treatment of cancer pain. The advantages of using methadone for refractory pain in patients with cancer or in those who could not tolerate the side effects of other opioids such as morphine are well cited in recent literature. Advantages of methadone over other opioids include dual elimination without active metabolites, allowing safe use with renal and liver failure, N-methyl-D-aspartate (NMDA) and delta receptor activity in addition to mu receptor agonism, multiple routes of administration, rapid onset of action, long half-life, low cost, and fewer adverse effects. Despite the abundance of recent case reports and literature reviews demonstrating the effective use of methadone in patients with cancer, there is a lack of consensus for an appropriate method for converting morphine (and by extension, other opioids) to methadone. This article will review methadone pharmacology and multiple proposed conversion methods; a case report illustrating a popular method for high-dose conversion is also included. PMID:20555039

Pollock, Ashley B; Tegeler, Monica L; Morgan, Vickie; Baumrucker, Steven J

2011-03-01

402

Discriminative stimulus effects of naltrexone in the morphine-dependent rat.  

PubMed

Rats maintained physically dependent upon morphine by scheduled access to drinking water containing morphine were trained to discriminate between s.c. injections of saline and 0.1 mg/kg of naltrexone in a discrete trial avoidance procedure in which a response on one of two choice levers would prevent or terminate the delivery of mild electric shocks to the floor of the test chember. Stimulus control of behavior by naltrexone in the morphine-dependent rat (defined as the reliable completion of at least 18 trials of a 20-trial session on the appropriate choice lever) had many of the features previously described for the stimulus control of behavior by morphine in the nondependent rat: long-term stability and reproducibility, orderly dose- and time-effect relationships and pharmacologic specificity. Stimulus control by naltrexone was blocked in a dose-related manner by morphine, an effect completely surmounted by a 10-fold increase in the dose of naltrexone suggesting a competitive antagonism. The naltrexone-induced discriminative stimuli appeared to be related to precipitated morphine withdrawal phenomena: following the abrupt withdrawal of morphine the amount and time course of naltrexone-appropriate responding were directly related to the degree of physical dependence; loss of body weight, a reliable index of morphine withdrawal in the rat, paralleled changes in naltrexone-appropriate responding; the maximum level of naltrexone-appropriate responding produced by a total of eight narcotic antagonists with agonist activity of differing prominence was a function of the extent of separation of the agonist and antagonist components of action of the drugs. Control of behavior by stimuli associated with morphine withdrawal may afford a specific animal model for studying factors relevant to the perpetuation of chronic drug use by human addicts. PMID:574545

Gellert, V F; Holtzman, S G

1979-12-01

403

Androgens and opiates: testosterone interaction with morphine self-administration in male rats.  

PubMed

Abuse of anabolic androgenic steroids (AAS) and opioids intersects in athletics. Evidence from humans and animals suggests that AAS may act in the brain through opioidergic mechanisms, and may potentiate effects of opioids. To determine whether AAS enhance motivation for opioid intake, in this study, male rats were treated chronically for 6 weeks with high levels of testosterone (7.5 mg/kg) or vehicle subcutaneously, and they were tested for morphine self-administration under fixed-ratio (FR) and progressive-ratio (PR) schedules. Initially, rats received chronic morphine infusion (16.8-50 mg/kg/day) over 7 days. Subsequently, rats were tested for morphine self-administration (3.2 mg/kg) 6 h/day for 3 days under an FR1 schedule, and for 7 days under a PR 9-4 schedule. Under the FR1 schedule, controls self-administered more morphine (95.9±8.5 mg/kg) than testosterone-treated rats (63.2±7.2 mg/kg; P<0.05). Under the PR schedule, there was no effect of testosterone on morphine intake or operant responding (26.7±5.7 responses vs. 30.9±5.9 responses for vehicle; NS). To determine whether testosterone enhances morphine sedation, additional rats were treated with testosterone or vehicle and evaluated for locomotor behavior and rearing activity over 30 min in response to saline or 10 mg/kg morphine. Morphine inhibited locomotor activity and rearing; testosterone selectively reduced rearing behavior, but did not alter locomotor behavior. These results suggest that testosterone does not increase motivation for morphine. PMID:24488032

Cooper, Sarah E; Wood, Ruth I

2014-05-01

404

Dorsal hippocampal muscarinic and nicotinic receptors are involved in mediating morphine reward.  

PubMed

In the present study, the effects of bilateral injections of cholinergic agents into the hippocampal CA1 region on morphine-induced conditioned place preference (CPP) were investigated in male Wistar rats. Subcutaneous (s.c.) administration of different doses of morphine sulphate (0.5-6 mg/kg) produced a dose-dependent CPP. Using a 3-day schedule of conditioning, it was found that intra-CA1 administration of the anticholinesterase, physostigmine (2, 4 and 8 microg/rat) significantly potentiated the morphine (0.5 mg/kg)-induced CPP. Moreover, intra-CA1 administration of the muscarinic receptor antagonist, atropine (1, 4 and 7 microg/rat) inhibited the morphine (6 mg/kg)-induced CPP dose-dependently. On the other hand, atropine (7 microg/rat, intra-CA1) reversed the physostigmine-induced potentiation of the morphine response. Furthermore, intra-CA1 administration of nicotine (0.5, 0.75 and 1 microg/rat) with an ineffective dose of morphine (0.5 mg/kg) elicited a significant CPP. Bilateral injections of different doses of the nicotinic receptor antagonist, mecamylamine (2, 4 and 8 microg/rat) into the CA1 regions significantly inhibited the morphine (6 mg/kg)-induced CPP. Moreover mecamylamine (8 microg/rat, intra-CA1) decreased the effect of nicotine-induced potentiation of the morphine response. Intra-CA1 injections of physostigmine, atropine, nicotine or mecamylamine alone did not induce a significant place preference or place aversion. It may be concluded that the muscarinic and nicotinic