Characterization of A Dual-Drug Liposomal Nanoformulation of Metformin Hydrochloride and Canagliflozin Hemihydrate for Sustained Oral Delivery.

Abstract

Objective: The purpose of this study was to design and optimize a dual-drug-loaded liposomal nanoformulation containing metformin hydrochloride and canagliflozin hemihydrate for sustained oral delivery utilizing a Quality-by-Design (QbD) approach. A Box-Behnken design was used to develop a robust formulation with ideal physicochemical properties.

Methods: Liposomes were created using the thin-film hydration technique using soya lecithin and cholesterol.The effects of lipid content, hydration duration, and sonication time on particle size, zeta potential, and entrapment efficiency were improved using a Box-Behnken design with three factors and three levels. The optimized formulation was thoroughly tested for physicochemical properties, shape, solid-state features, in vitro drug release, release kinetics, and enhanced stability.

Results: The Optimized liposomal nanoformulation had a particle size of 151.2 ± 2.5 nm, polydispersity index of 0.168 ± 0.012, zeta potential of -34.8 ± 1.4 mV, and entrapment efficiencies of 98.4 ± 0.5% and 84.0 ± 0.6% for metformin hydrochloride and canagliflozin hemihydrate, respectively. FTIR verified the absence of substantial drug-excipient interactions, whereas DSC and XRD showed reduced drug crystallinity after encapsulation. SEM examination revealed uniformly distributed spherical vesicles with a smooth shape.The formulation demonstrated a biphasic release profile with sustained drug release over 24 hours, producing cumulative releases of 97.3 ± 1.5% for metformin hydrochloride and 94.1 ± 1.4% for canagliflozin hemihydrate. Drug release followed the Korsmeyer-Peppas model, showing that anomalous diffusion was the primary release mechanism. Enhanced stability experiments revealed excellent physicochemical stability over three months.

Conclusion: The QbD-driven optimization resulted in a stable dual-drug-loaded liposomal nanoformulation with high encapsulation efficiency, regulated drug release, and enhanced stability. These findings emphasize the potential of this nanocarrier as an oral combination delivery method for the treatment of type 2 diabetes mellitus, necessitating additional in vivo pharmacokinetic and pharmacodynamic studies.