Transdermal drug delivery of labetolol hydrochloride: system development, in vitro; ex vivo and in vivo characterization.
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.


METHODS
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.


CONCLUSIONS
The TDDS holds promise for clinical trials.
Aqil
M
M
Faculty of Pharmacy, Hamdard University, New Delhi 110 062, India. aqilmalik@yahoo.com
Zafar
Saqib
S
Ali
Asgar
A
Ahmad
Shoaib
S
D000279:Administration, Cutaneous; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D004355:Drug Stability; D005260:Female; D007741:Labetalol / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism*; D012995:Solubility
D007741:Labetalol