Comparative in vivo evaluation of simvastatin after oral and transdermal administration in rabbits

Abstract

Membrane-moderated transdermal systems of Simvastatin liposomes 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. The pharmacodynamic and pharmacokinetic performance of Simvastatin following transdermal administration was compared with that of oral administration. This study was carried out in a randomized crossover design in male New Zealand albino rabbits. The estimation of Simvastatinin 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 relative bioavailability of Simvastatin was increased about nine fold after transdermal administration as compared to oral delivery. This may be due to the avoidance of first pass effect of Simvastatin. The concentration of Simvastatin in plasma was found to be stabilized and maintained in a narrow range over the study period up to 24 hrs for transdermal formulation where as the concentration was decreased rapidly up on oral administration. 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.