Optimization of Beta Sitosterol Phytosome Formulation using BoxBehnken Design for Enhanced Bioavailability

Beta-sitosterol, a plant-derived phytosterol, holds promise as an anti-obesity medication. However, its limitedbioavailability and low aqueous solubility hinder its therapeutic application. This research aimed to utilize phytosometechnology, 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. Entrapmentefficiency (EE%), particle size, zeta potential, and polydispersity index (PDI) were the four dependent responses, and theeffects 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 uniformitywith an entrapment efficiency of 86.41%, particle size of 163.53nm, zeta potential of -30.06mV, and Poly dispersity indexof 0.2148. When compared to the pure drug, in vitro drug release experiments showed a noticeable, improved andprolonged release profile of beta-sitosterol from the phytosomal formulation. The ideal formulation parameters, determinedat 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 werevalidated by overlay plot analysis. These results demonstrate the potential of this phytosomal strategy to enhance theadministration of poorly soluble phytoconstituents, including beta-sitosterol, for anti-obesity treatment and validate theeffective use of BBD in modifying phytosomal formulations.