Effects of Removal of Stratum Corneum, Delipidization and Addition of Enhancers, Ethanol and l-Menthol, on Skin Permeation of Benzoic Acid and Its 4-n-Alkyl Substituents in Excised Guinea Pig Dorsal Skin

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Skin penetration of benzoic acid and its 4-alkyl substituents (methyl, ethyl, n-propyl and n-buthyl) through excised guinea pig dorsal skin was examined, and effects of removal of stratum corneum, delipidization and addition of the penetration enhancers, ethanol and l-menthol plus ethanol, were observed. Permeability coefficients, which increased with the increase in their alkyl chain lengths, depended on the ratio of undissociated form of the derivatives. Removal of stratum corneum by tape stripping and delipidization by a chloroform-methanol mixture, whose effects on the permeation were similar, increased the permeability coefficients of the derivatives, especially those of relatively hydrophilic derivatives. Addition of 1% l-menthol plus 15% ethanol increased the permeability coefficient of benzoic acid, but decreased those of ethyl-, n-propyl- and n-butyl-substituents, and differences in the permeability coefficients among these acides almost disappeared. A similar though weaker tendency was observed for the effects of 15% ethanol itself. Analysis of transfer free energy of the methylene group from vehicle to skin revealed taht tape stripping and delipidization induced the reduction of lipophilic barrier property, although it still remained after these treatments. The analysis also showed that the addition of the enhancers made the skin relatively more hydrophilic compared to the vehicle, which induced an increase in permeability coefficient of benzoic acid and decreases in those of its lipophilic substituents.
公益社団法人日本薬学会の論文
1999-01-15

Effects of Removal of Stratum Corneum, Delipidization and Addition of Enhancers, Ethanol and l-Menthol, on Skin Permeation of Benzoic Acid and Its 4-n-Alkyl Substituents in Excised Guinea Pig Dorsal Skin

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