Quality by Design (QbD) Assisted Formulation and Development of Microsphere Containing Beta-Sitosterol by Design of Expert (DoE) Approach

The present study focuses on the Quality by Design (QbD)–assisted formulation and optimization of beta-sitosterol-loaded microspheres using a Design of Experiments (DoE) approach. Beta-sitosterol, a bioactive phytosterol with proven therapeutic potential, suffers from poor aqueous solubility and limited bioavailability. To overcome these limitations, microspheres were developed using the emulsion solvent evaporation technique with Eudragit RS100 as the polymer. A Box-Behnken design was employed to systematically evaluate the effect of critical formulation variables, namely polymer concentration, surfactant concentration, and stirring time, on particle size and entrapment efficiency. The optimized microsphere formulation exhibited nanosized particles with high drug entrapment efficiency and controlled drug release behavior. Preformulation, physicochemical characterization, in vitro release, antimicrobial activity, and stability studies confirmed the suitability and stability of the developed system. Overall, the QbD–DoE approach proved effective in developing a robust and reproducible beta-sitosterol microsphere formulation with improved delivery characteristics and potential therapeutic applicability.