A comparative in vitro study of transdermal absorption of a series of calcium channel antagonists

J Pharm Sci. 1991 Oct;80(10):931-4. doi: 10.1002/jps.2600801006.

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 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Calcium Channel Blockers / administration & dosage
  • Calcium Channel Blockers / chemistry
  • Calcium Channel Blockers / pharmacokinetics*
  • Chemical Phenomena
  • Chemistry, Physical
  • Chromatography, High Pressure Liquid
  • In Vitro Techniques
  • Male
  • Rats
  • Skin Absorption / physiology*
  • Solubility
  • Spectrophotometry, Ultraviolet

Substances

  • Calcium Channel Blockers