Abstract

Finasteride, lipophilic 5-α reductase inhibitor was selected as a model drug to evaluate in vivo iontophoretic transdermal delivery of novel lipid-based vesicular carriers (invasomes). The study included three protocols. The protocol I involved formulation of invasomes with terpenes (limonene, carvone and nerolidol) using Taguchi robust design for optimization. Invasomes were characterized for vesicular shape, size, zeta potential, entrapment efficiency and percutaneous permeation. The vesicles were found to be unilamellar, spherical in shape with size ranging from 4.54±0.30µm to 13.00±0.20µm. They possessed negative charge and entrapment efficiency (58.23±0.41% to 84.56±0.25 %). Formulation IF1 containing lipophilic terpene limonene (0.5%) enhanced permeation by 21.17 fold when compared with control (aqueous solution). The optimized invasomal formulation was checked for the enhanced permeation using the iontophoretic technique in second protocol. Two factors three level Taguchi robust design was used for optimizing the current density and pulse-on/off ratio. Formulation INF9 (0.5 mA/cm2, 3:1 pulse on/off ratio) enhanced flux by 25.83 fold when compared with control. In protocol III in vivo studies of optimized iontophoretic invasomal formulation in the form of gel were performed on rabbits and compared with oral suspension. Plasma samples were analyzed by LCMS and pharmacokinetic parameters were calculated. AUC and T1/2 were increased by 3.03 times and 1.34 times respectively showing effective transdermal delivery. Histopathological studies of the optimized formulation (INF9) on rat skin revealed changes in dermis indicating the effect of ethanol and terpenes present in invasomes. These results indicated invasomes as effective vesicular carriers for iontophoretic transdermal delivery of finasteride.

Keywords: Finasteride, invasomes, iontophoresis, taguchi robust design, transdermal delivery.

Graphical Abstract