Preparation and Evaluation of Sustained Release AZT-Loaded Microspheres: Optimization of the Release Characteristics Using Response Surface Methodology

Abstract

The purpose of the study was to prepare and optimize a sustained release formulation of zidovudine (AZT). Ethylcellulose microspheres containing AZT were prepared using an emulsification/solvent evaporation technique. The critical formulation variables were emulsifier concentration, drug to polymer ratio, and ethyl acetate concentration in the internal phase of the emulsion. The time to release 85% of the contents of the microspheres (t85) was used as a measure for the release time. A second-year polynomial equation was fitted to the release data to systemically investigate the effect of the formulation variables on the release rate. This equation was then used to predict t85 in the optimum region. The t85 was found to be dependent on the three formulation variables, with strong interactions observed between these variables. The microspheres were characterized in terms of their particle size and surface morphology. The study indicated no overall correlation between the mean diameter of the microspheres and the t85.