EFFECT OF FATTY-ACIDS AND UREA ON THE PENETRATION OF KETOPROFEN THROUGH RAT SKIN

The effects of several fatty acids and urea on the penetration of ketoprofen in propylene glycol and aqueous vehicles through excised rat skins have been studied. The penetration of ketoprofen through the skins increased 8-50-fold maximum compared to the control with the addition of the fatty acids in PG and urea in water. The enhancement of skin permeability of ketoprofen with the fatty acids in propylene glycol was mainly due to the increase in ketoprofen partitioning between the skin and the vehicle. When the concentration of lauric acid in propylene glycol - responsible for maximum permeation of ketoprofen - was varied from 0 to 10% in propylene glycol, ketoprofen permeation reached maximum with 5% lauric acid. The enhancement effect of urea on the penetration of ketoprofen through excised rat skins depended on the vehicles used. Its permeation constant increased significantly when added to ketoprofen-water vehicle. On the other hand, the effect of urea was not pronounced when added to ketoprofen-PG vehicle and ketoprofen-PG:ethanol:water (1:3:6) mixture. Nevertheless, the diffusion of ketoprofen through the skin increased in all three cases. Urea seemed to form large and extensive hydrophilic diffusion channels that do not exist in fresh skin.