Formulation and Statistical Optimization of Controlled Release Matrix Tablet of Zidovudine

Abstract

The purpose of the present study is to develop and optimize controlled release matrix tablets containing zidovudine (AZT) as model drug by optimization technique. A 2³ factorial design was employed in formulating the matrix tablets with taking concentration of hydroxy propyl methyl cellulose (HPMC) K4M (X₁), ethyl cellulose (X₂) and types of filler MCC or DCP (X₃) as independent variables. Three dependent variables were considered: time required for 50 % drug released (t_50%), mean dissolution time (MDT) and release exponent (n). The main effect and interactive terms were quantitatively evaluated using mathematical model. The results indicated that X₂ and X₃ significantly affected the t_50%, mean dissolution time and n value but the concentration of HPMC K4M was not significant in t_50%. Regression analysis and numerical optimization were performed to identify the best formulation. Mathematical analysis of the release kinetics indicated that non-Fickian release was the predominant mechanism of drug release which implied both polymer erosion and relaxation during the entire course time. Scanning electron microscopy was used to visualize the effect of dissolution media on matrix tablet surface. No incompatibility was observed between the drug and excipients used in the optimized formulation of matrix tablets. Results suggest that the developed controlled-release tablets of zidovudine could perform therapeutically better than marketed dosage forms, leading to improve efficacy, controlling the release and better patient compliance.