Bioavailability enhancement of repaglinide from transdermally applied nanostructured lipid carrier gel: Optimization, in vitro and in vivo studies

Abstract

Repaglinide (RG) is an effective anti-diabetic drug (BCS class II) with limited oral bioavailability < 55% due to poor solubility and high first-pass hepatic metabolism. The aim of the paper was to formulate repaglinide loaded nanostructured lipid carrier-gel (RG-NLCs-gel) system to improve the bioavailability by transdermal route. The RG-NLCs was prepared by high speed homogenizer technique and characterized for size, drug entrapment, viscosity, texture analysis, pH, SEM, XRD, transdermal flux and in vivo pharmacokinetic studies. Box- Behnken design was applied to optimize the RG-NLCs-gel for sustained transdermal delivery. The optimized batch was obtained at X1 [Gelucire (solid lipid)] = 180.41 mg, X2 (Tween 80) = 0.75% and X3 (drug) = 13.97 mg to achieve Y1 (particle size) = 165.08 nm, Y2 (entrapment efficacy) = 70.22% and Y3 (transdermal flux) = 16.12 μg/(cm2/h). The optimized RG-NLCs gel showed sustained release up to 24 h. The in vivo pharmacokinetic study showed 2 times improvement in the bioavailability in comparison to marketed oral tablet in rat model. The data suggest the potential of RG-NLCs gel for transdermal drug delivery to manage diabetes mellitus, and the system can be utilized for other BCS class II drugs to substitute oral route for patient compliance.