Comparative In vivo Evaluation of Propranolol hydrochloride following Oral and Transdermal administration in Rabbits

Membrane-moderated transdermal systems of Propranolol hydrochloride were prepared by incorporating the drug reservoir within a shallow compartment moulded from a drug-impermeable backing membrane and 2% w/v cellulose acetate rate-controlling membrane casted with ethyl acetate-methanol (8:2) employing dibutyl phthalate (40% w/w of dry polymer) as plasticizer. The pharmacodynamic and pharmacokinetic performance of Propranolol hydrochloride following transdermal administration was compared with that of oral administration. This study was carried out in a randomized cross-over design in male New Zealand albino rabbits. The estimation of Propranolol hydrochloride in plasma was carried out by LC-MS/MS method. The parameters such as maximum plasma concentration (C_max), time for peak plasma concentration (t_max), mean residence time (MRT) and area under curve (AUC_0-∞) were significantly (P< 0.001) differed following transdermal administration compared to oral administration. The terminal elimination half life of transdermally delivered of Propranolol hydrochloride was found to similar that of oral administration. The relative bioavailability of Propranolol hydrochloride was increased about six fold after transdermal administration as compared to oral delivery. This may be due to the avoidance of first pass effect of Propranolol hydrochloride. In agreement with pharmacokinetic data, maximum β -blockade was obtained at 1 h after oral administration and decreased by 80% after 6 h. In the case of transdermal administration, a steady state β-blockade.was observed after 12.0 h and was prolonged over a period of 24 h. It was concluded that the relative rate of extensive first pass metabolism was significantly reduced in transdermal administration, resulted in increased relative bioavailability and reduced frequency of administration.