Comparison of effects of different ointment bases on the penetration of ketoprofen through heat-separated human epidermis and artificial lipid barriers.

In vitro tests were performed to understand the effects of topical vehicles on the permeability of ketoprofen through artificial lipid barriers and heat-separated human epidermis consisting of stratum corneum and viable epidermis. Ketoprofen was selected as the model penetrant. Human epidermis and artificial membranes made from several mixtures of free fatty acids, cholesterol, cholesteryl ester, ceramides, and triglycerides were used as permeation matrices in untreated conditions and after pretreatment with petrolatum, wool alcohols ointment, or triglycerides. Apparent permeability and diffusion coefficients as well as the solubility of the drug in the artificial lipid matrices were ascertained. The solubilities of drugs and vehicle components that depend on the composition of the lipid matrix predominantly control the permeability of the barrier. Ceramides and cholesterol reduce the permeability and solubility, whereas triglycerides have the opposite effect. The vehicle effects in artificial membranes correspond to those in epidermis observed with samples pretreated with the aforementioned bases. The logarithms of the permeabilities of untreated and pretreated lipid mixtures 3, 4, and 5 are very well correlated with those of the permeabilities of heat-separated epidermis (r > = 0.9868). The artificial mixture containing all five lipids mentioned gives the best approximation to human epidermis. This result indicates comparable vehicle effects although the composition of the artificial mixture was adapted only in a simplified manner to the horny layer lipid phase. This lipid matrix or similar mixtures, therefore, are convenient tools for investigation into the effects of dermatological vehicles. Copyright 2003 Wiley-Liss, Inc. and the American Pharmacists Association