Permeability of ionized salicylate derivatives through guinea pig dorsal skin

pH-dependency of skin permeability to salicylic acid was examined in excised guinea pig dorsal skin. Permeation followed the pH-partition theory at acidic pH. However, above pH 5.0 the observed permeability coefficients were larger than the estimated values obtained from the ratio of the undissociated forms. These findings are quite different from those obtained using the same drug and a silicone rubber membrane, in which permeability coefficients were consistent with the pH-partition theory. The findings suggested that permeation of salicylate as anions occurred at a neutral skin pH. The permeability coefficient of the ionized form was estimated to be about 1.6% of the nonionized form. We also examined the skin permeability of salicylate and its five 5-substituents and two 3-substituents at pH 7.4. We investigated the relationship between their permeability coefficients and the physico-chemical properties of the substituents. Multi regression analysis on the permeability coefficients showed a parabolic relationship between the values of the hydrophobic parameter (pi) and the logarithms of the permeability coefficients. These findings suggested that the ionic permeation pathway of salicylate derivatives is controlled by hydrophobic as well as hydrophilic properties.