Application of Box–Behnken design for preparation of glibenclamide loaded lipid based nanoparticles: Optimization, in vitro skin permeation, drug release and in vivo pharmacokinetic study

Abstract

The objective of the present study was to develop nanostructured lipid carrier (NLC) for enhanced transdermal delivery of glibenclamide. The NLC of glibenclamide was prepared by employing Box–Behnken design. Optimization of glibenclamide loaded NLC was based on evaluation of particle size, entrapment efficiency and drug loading. NLC was further evaluated for in vitro permeation study, in vitro release kinetics, and in vivo pharmacokinetic study. The particle size, polydispersity index, zeta potential, entrapment efficiency, and drug loading of the optimized glibenclamide loaded NLC was found to be 120.687±2.13nm, 0.217±0.041, −31.0±2.13mV, 80.75±2.69% and 12.70±2.38%, respectively. The gel of optimized NLC formulation depicted higher transdermal flux (42.07±5.63μg/cm2/h), when compared with conventional gel (13.31±3.40μg/cm2/h) (p<0.001). Confocal laser microscopy of rat skin treated with sodium fluorescein labeled NLC showed a significantly (p<0.001) deeper penetration (187.34μm) as compared with the conventional gel (19.25μm). Furthermore, in vivo pharmacokinetic study of optimized formulation showed a significant increase in the bioavailability (1.36 times) compared with oral formulation of glibenclamide by virtue of better permeation through rat skin. It concluded that Capryol™ 90 based glibenclamide loaded NLC was successfully optimized using Box–Behnken design and merits further investigations.