DEVELOPMENT OF BIORELEVANT AND DISCRIMINATING METHOD FOR DISSOLUTION OF EFAVIRENZ AND ITS FORMULATIONS

Abstract

Dissolution process is considered as an important in vitro tool for evaluating the bioequivalence of products. Such a method, if properly mimic the in vivo conditions, it would surrogate the in vivo studies. Bioequivalence problems arise in class-II and class-IV categories of Biopharmaceutical Classification of Drugs (BCS). Efavirenz (BCS Class II drug) is used in active anti retroviral therapy. Saturation solubility of efavirenz bulk drug was evaluated in various surfactant media, pH solutions and bio-relevant media. We optimized the dissolution conditions for efavirenz with 900 ml of simulated gastric fluid with 0.25% w/v sodium lauryl sulphate (SGF-0.25% w/v SLS) as discriminating and bio-relevant dissolution medium at 50 rpm for 45 min (5 min time interval) with USP apparatus II. The optimized media contained a less amount of SLS (0.25% w/v) in SGF compared with 1% and 2% SLS concentration stated in the official monographs (IP, BP, USP) and FDA guidelines mimic the GI tract environment. We studied the dissolution profiles of efavirenz bulk drug and its formulations in various concentrations of SLS alone (0.25% - 2.0% w/v) and with simulated gastric fluid with SLS. In vitro dissolution profiles of efavirenz and its formulations in optimized dissolution media (0.25% w/v SLS with SGF) folIowed zero order kinetics with diffusion mechanism drug release.