Formulation, Optimization, and In-vitro Characterization of Chitosan Microparticles Loaded with Benzoyl Peroxide for Topical Delivery

Abstract

Benzoyl peroxide (BPO) is one of the most effective topical agents for the treatment of acne vulgaris; however, its clinical application is often limited by poor skin retention, rapid drug release, and local irritation. The present study aimed to formulate and optimize benzoyl peroxide-loaded chitosan microparticles for controlled topical drug delivery using the ionotropic gelation technique and a Quality by Design (QbD) approach. A three-factor, three-level Box–Behnken design was employed to optimize critical formulation variables, including chitosan concentration, sodium tripolyphosphate (TPP) concentration, and stirring speed. The prepared microparticles were evaluated for particle size, polydispersity index, zeta potential, drug loading, entrapment efficiency, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), in-vitro drug release, release kinetics, and stability. The optimized formulation exhibited a particle size of 109.8 nm, polydispersity index of 0.243, zeta potential of +32.6 mV, drug loading of 12.1%, and entrapment efficiency of 83.9%. SEM analysis confirmed the formation of nearly spherical microparticles, while FTIR and DSC studies demonstrated successful drug encapsulation without significant drug–polymer incompatibility. The optimized formulation showed sustained drug release of 89.6% over 24 hours and remained stable under accelerated storage conditions. These findings indicate that chitosan-based microparticles prepared by ionotropic gelation provide an efficient controlled-release topical delivery system for benzoyl peroxide and represent a promising approach for improving the efficacy and safety of acne vulgaris therapy.