In vitro and in vivo enhancement of skin permeation with oleic and lauric acids

The effect of two fatty acids (oleic and lauric) on the transport of the cationic drug naphazoline, neutral caffeine, and an anionic model drug salicylate, across excised human skin was studied using Franz diffusion cells. Oleic and lauric acids both increased the in vitro skin permeation of all penetrants. Oil/water partitioning data and rotating diffusion cell measurements, in the presence of the fatty acids, suggested that the enhanced flux of the cationic naphazoline could be accounted for by an increase in lipophilicity through ion pairing with the carboxylate anion of the acid. Caffeine and sodium salicylate were incapable of forming ion pairs consequently, increases in skin permeability are also due to a disruption of the stratum corneum. This conclusion was further supported by (a) increased transepidermal water loss, and (b) increased in-vivo skin permeation of the non ion-pairing methyl nicotinate, at skin sites pretreated with the fatty acids.