Studies on solvent systems for enhanced skin permeation of venlafaxine hydrochloride

Abstract

Venlafaxine hydrochloride (VH) is a serotonin-noradrenaline reuptake inhibitor indicated for treatment of depression disorder. It shows low biological half-life 5±2 h and low oral bioavailability 45±15 % due to extensive hepatic first-pass metabolism. Frequent administration of VH is required to maintain steady state plasma concentration of drug. To overcome hepatic first pass metabolism and to cross blood brain barrier for effectively achieving plasma concentration of VH in brain, we envisaged to develop transdermal drug delivery system containing VH loaded polymeric nanoparticles. Effect of solvent systems (SS), penetration enhancers (PE), and VH nanoparticles (VHNPs) on transdermal diffusion of drug were studied. VHNPs were prepared by double emulsion solvent evaporation method using high speed homogenizer followed by probe sonication. Poly (lactic-co-glycolic acid) and tween 80 were used as polymer and surfactant respectively. Mean particle size, polydispersity index, zeta potential, entrapment efficiency of optimized VHNPs were found to be 175.4 nm, 0.109, (-) 24 mV and 56 %.respectively. Scanning electron microscopy confirmed spherical shape of drug loaded polymeric nanoparticles. SS comprising 50% PG in EtOH shown maximum flux 158.67 ± 2.9 (µg/cm²/h) and lag time was found to be 5.60 ±0.16 h. The PE 5 (%v/v) limonene shown maximum flux 200.47±3.6 (µg/cm²/h) and lag time 3.17±0.11 h. The flux and lag time in case of VHNPs were found to be 192.24±3.20 (µg/cm²/h) and 4.22±0.14 h respectively. Based on flux, clearance and surface area of transdermal patch, a theoretical meaningful plasma level concentration of VH ranging from 12.85 to 128.5 (ng/mL) can be achieved.

Keywords: Depression, Venlafaxine hydrochloride, Poly (lactic-co-glycolic acid), Solvent systems, Penetration enhancers, Nanoparticles (NPs)