DEVELOPMENT AND OPTIMIZATION OF GUAR GUM-BASED RIFAXIMIN MICROSPHERES FOR COLON-TARGETED DRUG DELIVERY USING 32 FACTORIAL DESIGN

Abstract

Objectives: The present study aimed to develop and optimize guar gum-based rifaximin microspheres for colon-targeted drug delivery using a 32 factorial design to achieve controlled drug release and improve localized delivery to the colon. Methods: Rifaximin-loaded microspheres were prepared by the emulsion solvent evaporation method using guar gum, hydroxypropyl methylcellulose, and ethyl cellulose. A 32 factorial design was employed to investigate the effects of polymer concentration and stirring speed on particle size, entrapment efficiency (EE), and drug release. Preformulation studies, including Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD), were performed to evaluate drug purity and compatibility with excipients. The prepared microspheres were characterized for particle size, EE, micromeritic properties, surface morphology (scanning electron microscopy [SEM]), and in vitro drug release. Results: The optimized formulation (RFX-MS8) exhibited a particle size of 237 nm, EE of 93.93%, cumulative drug release of 94.15%, and a production yield of 86.3%. FTIR, DSC, and XRD analyses confirmed drug–excipient compatibility and preservation of rifaximin crystallinity. SEM demonstrated uniformly spherical, compact microspheres with improved morphology. The optimized formulation also exhibited excellent flow properties, with a Hausner’s ratio of 1.17, Carr’s index of 13.23%, and an angle of repose of 24.11°. Quadratic models were statistically significant (R2=0.9656–0.9956; p<0.05), confirming the significant influence of formulation variables on microsphere characteristics. Conclusion: The optimized guar gum-based rifaximin microspheres demonstrated excellent physicochemical characteristics, high drug entrapment, controlled colon-targeted drug release, and robust statistical optimization, indicating their potential as an effective colon-specific delivery system. Further in vivo pharmacokinetic and therapeutic investigations are warranted to establish their clinical utility for the treatment of colonic disorders.