Optimization of Beta Sitosterol Phytosome Formulation using Box Behnken Design for Enhanced Bioavailability

Abstract

Beta-sitosterol, a plant-derived phytosterol, holds promise as an anti-obesity medication. However, its limited bioavailability and low aqueous solubility hinder its therapeutic application. This research aimed to utilize phytosome technology, developed and optimized using Box-Behnken Design (BBD), to enhance the bioavailability of beta-sitosterol. L-α-phosphatidylcholine was used as the lipid carrier in the thin-film hydration process to create phytosomes. Entrapment efficiency (EE%), particle size, zeta potential, and polydispersity index (PDI) were the four dependent responses, and the effects of three independent variables, such as molar ratio, reaction time, and temperature, were systematically assessed. The improved formulation demonstrated robust drug encapsulation, nanoscale size, good colloidal stability, and uniformity with an entrapment efficiency of 86.41%, particle size of 163.53nm, zeta potential of -30.06mV, and Poly dispersity index of 0.2148. When compared to the pure drug, in vitro drug release experiments showed a noticeable, improved and prolonged release profile of beta-sitosterol from the phytosomal formulation. The ideal formulation parameters, determined at a molar ratio of 2:1, a time taken for the reaction of 74.79 minutes at an operating temperature of 38.260C and they were validated by overlay plot analysis. These results demonstrate the potential of this phytosomal strategy to enhance the administration of poorly soluble phytoconstituents, including beta-sitosterol, for anti-obesity treatment and validate the effective use of BBD in modifying phytosomal formulations.