QUALITY BY DESIGN APPROACH FOR DEVELOPMENT AND OPTIMIZATION OF CHITOSAN-BASED FLOATING MICROSPHERES FOR TOPOTECAN HCl

Abstract

Objective: To develop floating microspheres for the topotecan in order to prevent its onversion into inactive carboxylate form in intestinal pH conditions so as to improve its bioavailability. Methods: Chitosan-based porous floating microspheres containing sodium bicarbonate by coacervation technique were developed. Quality by design approach using Box-Behnken Design was adopted to assess the influences of selected formulation variables and their importance on the quality of the finished product. Results: The selected model was analyzed and optimized. The microspheres floated immediately without any lag time upon addition into water and remained floatable for more than 24 h-1. The optimized formulation was found to have the particle size of 379.2 µm, entrapment efficiency of 76.3% and the drug release rate constant of 0.29 h i.e., the release was extended up to 16 h-1. Conclusion: The results affirmed that controlled-release porous microspheres of Topotecan with inherent floating without lag were successfully developed.