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Branched-chain alkanols as skin permeation enhancers: quantitative structure-activity relationships.

One long-standing approach for improving transdermal drug delivery is using penetration enhancers which reversibly decrease the skin barrier resistance. Though the skin permeation enhancement effect of chemical penetration enhancers has been studied extensively, their quantitative structure-activity relationships have not been adequately investigated. In this paper, we established the correlation equations between enhancement potencies and the physico-chemical parameters relevant to lipophilicity and position of hydroxyl group for 16 alkanols using the stepwise multiple linear regression analysis. These equations reveal that the enhancement potencies of alkanols are excellently correlated with their lipophilicity and position of the hydroxyl group. The enhancement potency of an alkanol will increase when it has greater lipophilicity but will decrease as the hydroxyl group moves from the end of the alkyl chain towards the center.