Controlled Release Floating Matrix Tablets for Clopidogrel Bisulfate Based on Gas Generating System: Development, Optimization and In-Vitro Evaluation

摘要

ABSTRACT The objective of the present work was to formulate and characterize a Gastro retentive drug delivery system (GRDDS) for Clopidogrel Bisulphate to improve bioavailability and to minimize the side effects such as gastric bleeding and drug resistance development. Clopidogrel floating tablets were prepared by direct compression technique by using HPMC K-100M(Hydroxy Propyl Methyl Cellulose), PEO(polyethylene oxide POLYOX WSR 303) and Carbopol 971P as release retarding agents in different concentrations. Sodium bicarbonate and microcrystalline cellulose (MCC) were used as gas generating agent and diluents respectively. Studies were carried out on floating behavior and influence of polymer type on drug release rate. All the formulations were subjected to various quality control and in-vitro dissolution studies. All the formulations followed first order kinetics, Higuchi drug release kinetics with diffusion as the dominant mechanism of drug release. As per Korsmeyer-Peppas equation, the release exponent “n” ranged 0.381-0.561 indicating that drug release from all the formulations was by non-Fickian diffusion mechanism. The release rate of Clopidogrel was found to be affected by the type and concentration of the polymer used in the formulation. As the concentration of the polymer was increased, the drug release was found to be retarded. Based on the results, Clopidogrel floating matrix tablets prepared by employing HPMCK100M at concentration 35% w/w (F9) was the best formulation with desired in-vitro floating time and dissolution. The FT-IR and DSC studies revealed that there was no interaction between drug and excipients. Keywords: Clopidogrel bisulfate, Gas generating system, floating matrix tablets, in-vitro buoyancy.