Enhanced Skin Permeation of Cationic Drug Ketotifen through Excised Guinea Pig Dorsal Skin by Surfactants with Different Electric Charges

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Using excised guinea pig dorsal skin, we examined the effects of three surfactants, anionic sodium dodecylsulfate (SDS), cationic n-dodecyltrimethylammonium bromide and non-ionic n-dodecyl-β-D-maltoside, all of which commonly have an n-dodecyl group, on in vitro skin permeation of the cationic drug ketotifen. All these three surfactants increased the skin permeation of ketotifen. Among the surfactants tested, anionic SDS had the largest enhancement effects, and significantly increased the permeation at concentrations over 1mM. The enhancement effect of the same anionic surfactant on the permeation of anionic salicylate was smaller and similar to that of cationic n-dodecyltrimethylammonium. The enhancement effects of SDS on ketotifen permeation were more marked than those of the cationic surfactant but differed from previous findings of their effects on other drugs permeation. Analysis of the retention of ketotifen in the skin suggested that SDS-induced increase in the transfer of hydrophilic ketotifen to the skin is the main reason for the marked increase in skin permeation.
2003-10-01