Formulation of canagliflozin hemihydrate-loaded bilosomes for the treatment of Type-2 diabetes mellitus: In vitro, in vivoand in silicomolecular docking studies

Diabetes mellitus (type-2) is a metabolic disease characterized by increased blood glucose levels from the average level due to insulin resistance or a lack of insulin production. Canagliflozin hemihydrate (CGZ) is one of the drugs of choice in the treatment of the same. However, CGZ belongs to BCS class IV making it difficult to formulate into suitable dosage form. In the present work, CGZ loaded bilosomes (CGZ-BIL) were prepared by a solvent evaporation method to overcome the drawbacks of CGZ. Box-Behnken design was used for batch optimization considering particle size and percent entrapment efficiency (%EE) as dependent variables. The optimized formulation was screened for in-vitrodrug release study, in vivopharmacokinetic evaluation and in-silicomolecular docking to screen hypoglycemic potential of bile salt sodium deoxycholate (SDC) which is one of the formulation components. The optimized CGZ-BIL showed vesicle size of 177.40 ± 2.5 nm with %EE of 92.60 ± 3.5% w/w. The TEM images revealed spherical vesicles. The in vitrodrug release study showed significant increase in CGZ release (82.19 ± 3.85%w/w) from CGZ-BIL compared to aqueous dispersion of CGZ (A-CGZ, 39.01 ± 3.2 %w/w). Further CGZ-BIL showed approximately 1.5 folds increase in Cmaxwhen compared to A-CGZ dispersion. The pharmacokinetic study suggested 1.6 folds increase in relative bioavailability of CGZ when formulated as BIL. In-silicomolecular docking proved hypoglycemic potential of SDC suggesting possibility of synergistic hypoglycemic activity upon use of CGZ-BIL. Thus the prepared CGZ-BIL could be better treatment alternative for Diabetes mellitus with improved therapeutic efficacy.