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In past decades, the understanding of mechanisms for skin penetration has significantly improved.1 Studies have identified the stratum corneum (SC), the outermost layer of the skin, as the main barrier for penetration of pharmaceutical and cosmetic ingredients,2 and due to its unique composition—i.e., about 50% ceramides, 35% free fatty acids and 15% cholesterol—the SC differs from other biological membranes.3 To facilitate the development of transdermal delivery for the compounds of interest, estimations of skin penetration rates and comparisons of dermatological formulations have become crucial to pharmaceutical and cosmetics research.4
Several methods have been developed for the prediction of skin penetration. Although the most useful data is obtained from in vivo studies in humans, such measurements are expensive, labor-intense and slow to perform. This makes their application in lead selection and optimization impractical. In vivo measurements using rodents5 are well-known to overestimate the penetration rate since compounds can permeate down the hair follicle,6 and although pig ear skin is also used for in vitro tests based on its structural equivalence to human skin,7 the most generally accepted in vitro permeation models are based on human skin as the membrane.