Capryol-ethyl oleate self-microemulsifying system for improved intestinal absorption and hypoglycemic activity of empagliflozin
Abstract
Empagliflozin (EMPA) is a poorly permeable oral hypoglycemic agent. It is potential substrate for P-glycoprotein (P-gp). This work assessed the impact of anatomical sites on EMPA intestinal absorption and assessed self-microemulsifying drug delivery systems (SMEDDS) as a novel strategy for augmented intestinal permeability and oral hypoglycemia of EMPA. A pseudo-ternary phase diagram was used to select a nano-formulation encompassing 60% tween 60: 30% transcutol: 5% capryol: 5% ethyl oleate. This was characterized for droplet size which was 31.2 nm, PDI was 0.292, and zeta potential which was -1.2 mV. EMPA absorption was assessed using in situ intestinal absorption, and the system was evaluated in vivo using diabetic rats. In situ intestinal absorption studies from aqueous solutions demonstrated poor permeability of EMPA from all tested segments relating to the regional distribution of P-gp efflux transporters. Perfusion of EMPA as microemulsion resulting from reconstitution of SMEDDS enhanced ileal and colonic absorption by 1.9 and 1.85-fold, respectively. Furthermore, in vivo studies demonstrated significant augmentation in oral hypoglycemic activity of EMPA, revealed as 1.45-fold elevation in area under blood glucose reduction curve after administration of SMEDDS compared to EMPA aqueous dispersion. SMEDDS formulation successfully improved intestinal absorption, hypoglycemic efficacy and hence oral bioavailability of EMPA.
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