A Comparative In Vitro Study of Transdermal Absorption of a Series of Calcium Channel Antagonists

doi:10.1002/jps.2600801006

Journal of Pharmaceutical Sciences

Volume 80, Issue 10, October 1991, Pages 931-934

https://doi.org/10.1002/jps.2600801006 Get rights and content

Abstract

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 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 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 < 0.01). Nicardipine would be the most suitable candidate for formulation in a TTS design.

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For practical purposes, the logarithm of the partition coefficient has been widely used for predicting some physicochemical properties such as membrane transport and water solubility. By comparison, log P (1.34) was slightly lower than the specified scope, that is, 2–3, which was considered to be optimal for a drug to permeate through the skin.33, 34 The possible reason was that SMH in molecule form had considerably higher water solubility (10.5 ± 1.8 mg/mL, Tab. 1),
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Research ArticlesA Comparative In Vitro Study of Transdermal Absorption of a Series of Calcium Channel Antagonists

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Research Articles
A Comparative In Vitro Study of Transdermal Absorption of a Series of Calcium Channel Antagonists