A COMPARATIVE INVITRO STUDY OF TRANSDERMAL ABSORPTION OF A SERIES OF CALCIUM-CHANNEL ANTAGONISTS

The in vitro transdermal absorption of five calcium channel antagonists (nifedipine, nitrendipine, nicardipine, felodipine, and nimodipine) was studied using the skin of hairless rats as a membrane. The aim of this study was to determine the penetration parameters [permeability constant (K(p)), lag time (T(i), and flux (J)] as measures of the intrinsic transdermal permeabilities of these drugs, in order to predict the potential capacity of these drugs to be formulated in a therapeutical transdermal system (TTS). Reliable prediction of K(p) values, using K(w) (extrapolated capacity factor in 100% water) and P (n-octanol-water partition coefficient) values as independent variables in the parabolic, bilinear, and hyperbolic functions, were assayed. Nicardipine showed a higher mean transdermal penetration (K(p); 4.9 x 10(-3) cm.h-1) value than the other dihydropyridines. Nifedipine showed the shortest mean T(i) value (5.1 h). The permeability rate constants of the calcium channel antagonists assayed can be predicted from their n-octanol-water partition coefficients, using the parabolic function (r = 0.984, p < 0.01). Nicardipine would be the most suitable candidate for formulation in a TTS design.