YAKUGAKU ZASSHI 2002-09-01

[Enhancing effects of ion-pair complexes on skin permeation of cromolyn in vitro].

Yasuhiro Okamoto, Magobei Yamamoto, Hatsumi Aki

Index: Yakugaku Zasshi 122(9) , 673-9, (2002)

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Abstract

Lipophilic ion-pair complexes of 3-dl-alpha-tocopherylcarbonyl-1-n-alkyl-pyridinium-cromolyn (TAP-CG) were designed to enhance the percutaneous absorption of cromolyn (CG), and the effect of n-alkyl chainlength of the ion-pair complexes on the CG permeation through hairless mouse skin was evaluated in vitro. The permeation rates of CG were examined in isopropyl myristate (IPM) suspension using static Keshany-Chien type diffusion cells at 32 degrees C. The permeation parameters, steady-state flux, diffusion coefficient, partition coefficient between skin and IPM, and permeability coefficient were determined. Steady-state fluxes of CG increased linearly with the increasing n-alkyl chain-length of TAP-CG, and 3-dl-alpha-tocopherylcarbonyl-1-n-hexyl-pyridinium-cromolyn (THP-CG) produced the highest CG flux (0.62 +/- 0.11 nmol.cm-2.h-1), which was 14-fold greater than that of CG.Na in IPM suspension and more than 480-fold greater than that of CG.Na in aqueous solution due to increasing lipophilicity. In the case of TAP-CG with longer n-alkyl chainlength than THP-CG, however, the steady-state fluxes of CG decreased due to the high molecular weight and/or the high lipophilicity of the ion-pair complexes. It is suggested that lipophilic ion-pair complexes, especially THP-CG, are effective in absorption of cromoglicate through the skin. The results would be useful for studies on the role of each counterion in the lipophilic ion-pair complexes.