A comparative study on stevioside-and rubusoside-assisted micellar solubilization of clofazimine for physicochemical and in vitro release properties

Abstract

This study compares the micellization and encapsulation abilities of stevioside (STE) and rubusoside (RUB) for enhancing the solubility, stability, and bioavailability of clofazimine (CFZ), a poorly water-soluble antibiotic. CFZ-loaded micelles were prepared and characterized by FT-IR, XRD, DSC, SEM, and NMR. RUB showed a lower critical micelle concentration and significantly improved CFZ solubility (up to 2.06 mg/mL) compared to STE. CFZ-RUB complexes offered greater protection against UV and oxidative degradation. In vitro release tests indicated sustained and enhanced CFZ release in simulated gastrointestinal fluids. CFZ-RUB also showed higher permeability across Caco-2 cell monolayers (62.5 %) and reduced cytotoxicity versus free CFZ. These results suggest that RUB's amphiphilic structure facilitates stable micelle formation and efficient drug loading. Overall, RUB presents a promising natural solubilizer and oral delivery vehicle for lipophilic bioactives in food and pharmaceutical applications, providing new insights into the structure-function roles of steviol glycosides.