Ex vivo permeability study and in vitro solubility characterization of oral Canagliflozin self-nanomicellizing solid dispersion using Soluplus as a nanocarrier

Abstract

Background and objective: Self-nanomicellizing solid dispersion is a new formulation that combines solid dispersion and nanomicelle strategies; the strategy involves utilizing a suitable carrier that self-assembles into nanomicelles when interacting with gastrointestinal fluids. Canagliflozin, a sodium-glucose cotransporter-2 inhibitor for treating type 2 diabetes, has been linked to poor absorption due to its insolubility in aqueous media. The study aimed to create self-nanomicellizing solid dispersion systems for canagliflozin to overcome its pharmaceutical limitations and improve oral bioavailability. Materials and Methods: Soluplus was chosen as a nanocarrier for improving canagliflozin solubility after screening several polymers by phase solubility study. The solvent evaporation method was selected. The Optimized formula was characterized through ex-vivo and in-vitro studies. Results: The CFZ-SNMSD formula, with a particle size of 60.7nm and polydispersity index of 0.06, has a stable distribution upon dilution to 20-fold with water. The apparent solubility of canagliflozin in the optimized CFZ-SNMSD formula was enhanced by 904.4 folds due to amorphization and nanomicellization, as demonstrated by transmission electron microscopy. CFZ-SNMSD formula showed a significant enhancement in dissolution rate compared to the physical mixture and pure drugs. The dissolution efficiency parameter confirms these findings (DE30, CFZ-SNMSD = 77.2% compared to  DE30, pure drug = 18.28%). Studies show that canagliflozin's permeability increases exponentially over time due to soluplus's dispersibility, solubilization, and glycoprotein inhibitory effect, enhancing bioavailability and overcoming GIT membrane barriers. Conclusions: The study indicates that canagliflozin self-nanomicellizing solid dispersion systems are promising methods for improving the oral bioavailability of the medication.