Skin barrier function is principally determined by the stratum corneum (SC), which provides an extremely efficient means to retard water loss from the ‘inside–out’ and to the penetration of xenobiotics from the ‘outside–in’. It appears that most compounds are constrained to transport via the tortuous lipid‐filled intercellular domain of the SC, substantially lowering the permeability of the membrane. Molecular penetration of the skin barrier depends upon the drug's lipophilicity, its size and its solubility properties. Various topical drug formulations have been developed to treat dermatological disease. However, typically, only a few per cent of the applied drug dose actually becomes available at the site of action. Consequently, drug treatment of skin disease is associated with large variability and the demonstration of safety and efficacy currently requires clinical trials with very large patient numbers.

Keywords skin barrier function, mechanism of skin penetration, topical drug formulations, dermato‐pharmacokinetics