Development, Characterization and Evaluation of Nebivolol Hydrochloride Transdermal Drug Delivery Systems

摘要

  ABSTRACT Nebivolol Hydrochloride is a third generation beta blocker used for the treatment of hypertention and heart failure. Nebivolol is rapidly absorbed following oral administration, reaching peak plasma concentrations in 0.5 – 4.0 hrs. The present study was designed to develop a suitable matrix type transdermal drug delivery system (TDDS) for Nebivolol Hydrochloride employing various ratios of hydrophilic and hydrophobic polymers by solvent casting technique. The developed patches were then evaluated for physicochemical characterization, ex-vivo permeation and skin irritation studies. The compatibility of drug with other ingredients was checked by FTIR studies. FTIR results revealed that there was no interaction between dug and other excipients. The transdermal patches obtained were transparent, smooth, uniform and flexible. The results of physicochemical properties were within the pharmacopoeial limits. All the formulations were subjected to ex-vivo skin permeation study by means of Franz’s diffusion cell in order to optimize the suitable formulation. Two formulations with the polymeric blend 3:2 (HPMC E50: ERL 100 and HPMC E15: ERL100 respectively) showed an increase in permeation of drug via skin when compared with the formulations having less proportion of hydrophilic polymer (HPMC), however the formulation with HPMC E50 : ERL 100 showed overall improvement in flux and permeation, hence it was optimized as suitable matrix system. The drug release follows zero order kinetics with diffusion mechanism. The average steady state flux obtained with HPMC E50: ERL 100 (3:2) was 43.3 µg/cm2/hr and the same was increased to 59.2 µg/cm2/hr with the incorporation of 5% v/w of DMSO as permeation enhancer. In conclusion, the present data confirm the feasibility of developing Nebivolol Hydrochloride transdermal system. The release rate of drug through patches increased when the concentration of hydrophilic polymer was increased.  Keywords: Nebivolol Hydrochloride, HPMC E 50, HPMC E15, transdermal patches.