Skin penetration enhancers.

The skin has evolved to prevent excessive water loss from the internal organs and to limit the ability of xenobiotics and hazardous substances to enter the body. Notwithstanding this barrier function, a number of strategies have been developed by scientists to deliver drugs to and through the skin. The aim of this review is to consider the various types of chemical penetration enhancers (CPEs) which have been investigated in the scientific literature. Potential pathways for CPEs to exert their action are examined with reference to the physical chemistry of passive skin transport. The emphasis is on those studies which have focussed on human and porcine skin because of the limitations associated with skin permeation data collated from other species. Where known, the mechanisms of action of these compounds are also discussed. Examples of enhancers used in commercial topical and transdermal formulations are provided. It is proposed that overall the effects of CPEs on the skin barrier may best be explained by a Diffusion-Partition-Solubility theory. Finally, some of the limitations of studies in the literature are considered and the importance of monitoring the fate of the penetration enhancer as well as the active is highlighted.