Transdermal Drug Delivery of Labetolol Hydrochloride: System Development, In Vitro; Ex Vivo and In Vivo Characterization

M.      Aqil; Saqib      Zafar; Asgar      Ali; Shoaib      Ahmad

Abstract

OBJECTIVE. The aim of the present work was to develop and evaluate matrix type transdermal drug delivery systems (TDDS) of labetolol hydrochloride (L-HCL) effective for 48 hours. EXPERIMENTAL. The TDDS were prepared by solvent evaporation technique. Six formulations (carrying Eudragit RL100:Eudragit RS 100 in 7.5:4.5, 5.0:5.0, 3.5:8.5 in formulations X-1, X-2, X-3 and Eudragit RL100:PVP K-30 in 9.0:2.0, 5.0:5.0, 4.0:7.0 in formulations Y-1, Y-2, Y-3, respectively) were prepared. All formulations carried 36% w / w of L-HCL, 10-12% w / w of enhancer dimethyl sulfoxide and 2.5-7.5% w / w of plasticizer PEG 400 in methanol-acetone solvent system. The TDDS were evaluated by in vitro drug release, ex vivo skin permeation, stability and in vivo pharmacodynamic studies. RESULTS. The maximum drug release for X-series was 90.26% in 48 hours (X-1) and for Y-series, it was 83.24% (Y-1). Again formulations X-1 (Kp = 0.221x10-2 cm hr-1) and Y-1 (Kp = 0.210x10-2 cm hr-1) exhibited the best skin permeation potential in the respective series. This might be due to higher permeability characteristics of Eudragit RL100. A shelf life of 2.38 years was predicted for the TDDS. Mean systolic BP of the experimental hypertensive rats was significantly reduced (p < 0.01) on TDDS treatment. CONCLUSION. The TDDS holds promise for clinical trials.

Keywords: transdermal, hypertension, drug release, skin permeation, labetolol