A comparative in vitro 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 (Kp), lag time (T1, 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 Kp 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 (Kp; 4.9 x 10(-3) cm.h-1) value than the other dihydropyridines. Nifedipine showed the shortest mean T1 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 less than 0.01). Nicardipine would be the most suitable candidate for formulation in a TTS design.
Diez
I
I
Department of Pharmacy, University of Barcelona, Spain.
Colom
H
H
Moreno
J
J
Obach
R
R
Peraire
C
C
Domenech
J
J
D000279:Administration, Cutaneous; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D012869:Skin Absorption / Q000502:physiology*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
D002121:Calcium Channel Blockers