ABSTRACT:
Membrane-moderated transdermal systems of Diltiazem 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 Diltiazem 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 Diltiazem hydrochloride in plasma was carried out by LC-MS/MS method. The parameters such as maximum plasma concentration (Cmax), time for peak plasma concentration (tmax), mean residence time (MRT) and area under curve (AUC0 - 8) were significantly (P< 0.001) differed following transdermal administration compared to oral administration. The terminal elimination half life of transdermally delivered of Diltiazem hydrochloride was found to similar that of oral administration. The relative bioavailability of Diltiazem hydrochloride was increased about seven fold after transdermal administration as compared to oral delivery. This may be due to the avoidance of first pass effect of Diltiazem hydrochloride. The low antiarrhythmic activity after oral administration is in good agreement with pharmacokinetic data which indicates that the plasma concentration of Diltiazem hydrochloride declined rapidly and hence shorter duration of antiarrhythmic action. 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.