Avaliação farmacocinética in vivo da dispersão sólida autonanomicelizante de canagliflozina como formas de dosagem de cápsulas orais

Background: Self-nanomicellizing solid dispersion (SNMSD) is a method that integrates the advantages of solid dispersion with nanomicelles, enhancing the oral bioavailability of poorly water-soluble pharmaceuticals. This solid drug delivery system, when it comes into contact with GIT fluids, it forms nanomicelles. Canagliflozin (CFZ), a sodium-glucose co-transporter inhibitor, has become popular for managing type 2 diabetes. CFZ faces biopharmaceutical challenges such as poor water solubility, poor permeation, and susceptibility to P-glycoprotein mediated efflux, posing challenges for its pharmaceutical development. This study aims to compare the in-vivo pharmacokinetic parameters of CFZ in rats when prepared as SNMSD versus CFZ-suspension. Methods: The SNMSD formula was prepared using a solvent evaporation method using soluplus as a nanocarrier in a drug-to-carrier ratio of 1:4. The in-vivo studies were conducted on twelve male Wister rats with an average weight of 230±9.3 g. The rats were divided into two groups. In Group 1, the rats were orally administered pure CFZ in 0.1% w/v carboxymethylcellulose 2mg/mL suspension. In Group 2, the rats were administered the identical dosage of the CFZ-SNMSD formula dissolved in water given orally. Results: The pharmacokinetics parameters in rats were obtained from plasma concentration/time data of the prepared CFZ-SNMSD formula, and these parameters were significantly higher (p < 0.05) when compared with CFZ-suspension. Cmax for the CFZ-SNMSD formula was 4109 ng/ml, and Tmax was 2 hours compared to the CFZ-suspension Cmax value of 1401 ng/mL and 4 hours. The relative bioavailability of canagliflozin for oral SNMSD capsule to oral suspension was equal to 204.7%. This is due to soluplus® dispersibility, solubilization, and p-glycoprotein inhibitory effect, overcoming GIT membrane barriers. Conclusions: The utilization of SNMSD demonstrated great promise as an oral delivery system to enhance the oral bioavailability of canagliflozin