In vitro and in vivo evaluation of an oral sustained-release floating dosage form of amoxycillin trihydrate
ABSTRACT Various hydrophilic polymers were investigated for the preparation of amoxycillin trihydrate sustained-release (SR) tablets. The most suitable system contained a 1:2 ratio of hydroxypropylcellulose (HPC) to drug, which compressed easily and was not affected by alteration in normal compaction pressure. Intrinsic dissolution studies at pH 2 showed that reduction in drug loading decreased drug release, which being linear with time was characteristic of an eroding matrix with a hydrated layer. Examination of compacts over a wider range of pH showed the slowest rate of drug release at pH 6, corresponding to minimum solubility of the drug. Further formulation to enhance gastric retention time (GRT), by incorporation of a gas-generating system, yielded either bilayer tablets which prematurely failed or large single-layer tablets which remained buoyant for 6 h and had satisfactory in vitro SR. However, when the latter tablets were compared against conventional capsules in fasted humans at 500 mg equivalent dose of amoxycillin, their relative bioavailability was reduced to 80.5% and other pharmacokinetic parameters indicated lack of improved efficacy.
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ABSTRACT: The current studies entail successful formulation of optimized gastroretentive tablets of lamivudine using the floating-bioadhesive potential of carbomers and cellulosic polymers, and their subsequent in-vitro and in-vivo evaluation in animals and humans. Effervescent floating-bioadhesive hydrophilic matrices were prepared and evaluated for in-vitro drug release, floatation and ex-vivo bioadhesive strength. The optimal composition of polymer blends was systematically chosen using central composite design and overlay plots. Pharmacokinetic studies were carried out in rabbits, and various levels of in-vitro/in-vivo correlation (IVIVC) were established. In-vivo gamma scintigraphic studies were performed in human volunteers using (99m) Tc to evaluate formulation retention in the gastric milieu. The optimized formulation exhibited excellent bioadhesive and floatational characteristics besides possessing adequate drug-release control and pharmacokinetic extension of plasma levels. The successful establishment of various levels of IVIVC substantiated the judicious choice of in-vitro dissolution media for simulating the in-vivo conditions. In-vivo gamma scintigraphic studies ratified the gastroretentive characteristics of the optimized formulation with a retention time of 5 h or more. Besides unravelling the polymer synergism, the study helped in developing an optimal once-a-day gastroretentive drug delivery system with improved bioavailability potential exhibiting excellent swelling, floating and bioadhesive characteristics.The Journal of pharmacy and pharmacology. 05/2012; 64(5):654-69.
Article: Floating microspheres: a review[Show abstract] [Hide abstract]
ABSTRACT: Gastric emptying is a complex process, one that is highly variable and that makes in vivo performance of drug delivery systems uncertain. A controlled drug delivery system with prolonged residence time in the stomach can be of great practical importance for drugs with an absorption window in the upper small intestine. The main limitations are attributed to the inter- and intra-subject variability of gastro-intestinal (GI) transit time and to the non-uniformity of drug absorption throughout the alimentary canal. Floating or hydrodynamically controlled drug delivery systems are useful in such applications. Various gastroretentive dosage forms are available, including tablets, capsules, pills, laminated films, floating microspheres, granules and powders. Floating microspheres have been gaining attention due to the uniform distribution of these multiple-unit dosage forms in the stomach, which results in more reproducible drug absorption and reduced risk of local irritation. Such systems have more advantages over the single-unit dosage forms. The present review briefly addresses the physiology of the gastric emptying process with respect to floating drug delivery systems. The purpose of this review is to bring together the recent literature with respect to the method of preparation, and various parameters affecting the performance and characterization of floating microspheres.Brazilian Journal of Pharmaceutical Science 03/2012; 48(1):17-30. · 0.37 Impact Factor
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ABSTRACT: Objectives: The study was aimed to improve bioavailability of baclofen by developing gastroretentive floating drug delivery system (GFDDS). Methods: Preliminary optimization was done to select various release retardants to obtain minimum floating lag time, maximum floating duration and sustained release. Optimization by 3(2) factorial design was done using Polyox WSR 303 (X(1)) and HPMC K(4)M (X(2)) as independent variables and cumulative percentage drug released at 6 h (Q6h) as dependent variable. Results: Optimized formulation showed floating lag time of 4-5 s, floated for more than 12 h and released the drug in sustained manner. In vitro release followed zero ordered kinetics and when fitted to Korsemeyer Peppas model, indicated drug release by combination of diffusion as well as chain relaxation. In vivo floatability study confirmed floatation for more than 6 h. In vivo pharmacokinetic studies in rabbits showed C(max) of 189.96 ± 13.04 ng/mL and T(max) of 4 ± 0.35 h for GFDDS. The difference for AUC((0-T)) and AUC((0-∞)) between the test and reference formulation was statistically significant (p > 0.05). AUC((0-T)) and AUC((0-∞)) for GFDDS was 2.34 and 2.43 times greater than the marketed formulation respectively. Conclusion: GFDDS provided prolonged gastric residence and showed significant increase in bi oavailability of baclofen.Drug Development and Industrial Pharmacy 08/2012; · 1.54 Impact Factor