Factorial study on influence of gas generating agent and diluent on drug release kinetics of clopidogrel bisulfate floating tablets

Abstract

The purpose of present work was to formulate and characterize a floating drug delivery system for Clopidogrel bisulphate to improve bioavailability and to minimize the side‑effects of the drug such as gastric bleeding and drug resistance development. Clopidogrel floating tablets were prepared by direct compression technique by the use of xanthan gum at different concentrations (20%, 25% and 30% w/w). Sodium bicarbonate (15% w/w) and microcrystalline cellulose (MCC) (30% w/w) were used as gas generating agent and diluent respectively. The effects of sodium bicarbonate and MCC on the drug release kinetics and floating properties were investigated. A 22 factorial design was applied systematically to optimized formulation. The percentage amount of sodium bicarbonate (X1) and percentage amount of MCC (X2) were selected as independent variables. The drug release rate constant (K) and time required for 85% drug dissolution (T85) was selected as dependent variables. Factorial design revealed that the percentage amount of sodium bicarbonate and MCC had insignificant effect on drug release kinetics (K, T85) within the chosen levels and a high level of sodium bicarbonate (X1) and the low level of MCC (X2) favor the preparation of clopidogrel floating tablets. All the Clopidogrel floating 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 0.455‑0.654 indicating that drug release from all the formulations was by non‑fickian diffusion mechanism. Key words: Clopidogrel bisulfate, factorial study, floating tablets, release kinetics, variables