Design and Evaluation of Transdermal Drug Delivery System of Nebivolol Hydrochloride

Abstract

Nebivolol hydrochloride is a selective β1-receptor antagonist with antihypertensive properties having plasma half life of 10 h and 12 % oral bioavailability. In the present work transdermal matrix patches of Nebivolol hydrochloride were prepared to improve its therapeutic efficacy and to avoid its extensive hepatic first pass metabolism of the drug. Nine formulations using 32 full factorial design (composed of Hydroxypropyl methyl cellulose K15M and Eudragit RL100 at a ratios of 1: 1) containing 15% w/w triethyl citrate as plasticizer were prepared. HPMC K15M and Eudragit RL100 were taken as independent variables. Folding endurance, % moisture content, tensile strength, in vitro drug release and flux were taken as dependent variables. Compatibility between drug and polymer was accessed by Fourier transform infrared spectroscopy (FTIR). The prepared TDDSs were evaluated for physicochemical parameters and in vitro skin permeation. F7 formulation exhibit maximum drug release of 99.53% for 24 h due to its higher amount of hydrophobic polymer concentration. Formulation F5 was optimized on the basis of results of dependent variables. The short term accelerated stability study was carried out for the optimized formulation and results revealed that all dependent variables and other parameters were within acceptable limits. Skin irritation study on albino rats have not shown any sign of erythema or edema. Result of high f2 value showed similarity between in vitro drug release profile of reference and test formulation of before and after stability period. Thus, the prepared matrix transdermal film may prove to be a potential candidate to provide sustained drug release for 24 h.