Improved dissolution and pharmacokinetics of insufficiently water-soluble canagliflozin in solid dispersions with gelucire 50/13 as a drug carrier

Abstract

Abstract The European Union has licensed canagliflozin as a monotherapy for type II diabetes to improve glycemic control. Canagliflozin is crystalline and soluble in organic solvents but not water. The absolute bioavailability of canagliflozin was below 65% due to its low water solubility. This study sought to improve canagliflozin solubility and pharmacokinetics. Solid dispersions were made with Gelucire 50/13. DSC, PXRD, and SEM confirmed canagliflozin's crystal structure. The solid dispersions were made via fusing and solvent evaporation. Finding out how effectively solvents combine with pharmaceutical dispersions. Scanning electron microscopy, powder X-ray diffraction, and differential thermal analysis showed drug amorphization in solid dispersions. The solvent evaporation and fusion methods boosted canagliflozin's water solubility by 11–23 and 12–25, respectively. Higher gelucire concentrations improve pharmacokinetics. Over 4 hours (tmax), AUC values increased from 23440 µgh/mL with pure CGF to 52217 with GDF 1:7. Gelucire 50/13 improves biological membrane penetration, making it a good choice for solid dispersion drug delivery systems. This biomaterial carrier may improve the bioavailability of canagliflozin, a poorly soluble molecule in water. The fusion technique disperses a drug and carrier so the drug binds molecularly.