Development and Evaluation of Controlled Release Formulation of Zidovudine Based on Microporous Osmotic Tablet Technology Using Fructose as Osmogen

Abstract

The present work was aimed to develop and evaluate controlled porosity osmotic pump (CPOP) tablets of an anti HIV drug zidovudine to provide a uniform concentration of drug at absorption site. The formulations were prepared by wet granulation method using drug, various excipients, controlled release polymer hydroxylpropylmethyl cellulose(HPMCE5M LV) and osmogen (Fructose).The CPOP tablets consist of an osmotic core coated with a micro porous membrane made up of cellulose acetate(CA) which is incorporated with sorbitol as porogen. Prior to compression the prepared granules were evaluated for pre compression parameters such as angle of repose, bulk density, tapped density, Carr’s index and Hausner’s ratio. After compression the prepared granules were evaluated for thickness, coat thickness, hardness, weight variation, friability, drug content, diameter, in vitro drug release study and scanning electron microscopy (SEM) study. The release kinetics for different formulations were analyzed using zero order model equation, first order model equation, Higuchi model equation, Korsmeyer Peppas model equation and Hixson-Crowell equation. The optimized formulation of drug release was independent of pH, agitation intensity, but dependent on the osmotic pressure of the release media. Based on the in vitro dissolution profile optimized formulation ZF4 exhibited Fickian transport mechanism with a drug release of 97.83% in 16 hrs. FTIR and DSC study revealed that there was no interaction between drug and excipients. Formulations subjected to stability testing (at 40±2oC/75±5% RH) as per ICH guidelines for three months indicated stability with no significant changes in thickness, hardness, weight variation, friability drug content and dissolution profiles.