Effect of penetration enhancers on the permeation of mannitol, hydrocortisone and progesterone through human skin

Mannitol, hydrocortisone and progesterone were selected as model penetrants to assess the mode of action of eight potential penetration enhancers in human skin. Their partition coefficients, octanol: water and stratum corneum: water were measured and correlated with their postulated routes of penetration through human skin. The results suggest that mannitol penetrated via a polar route, hydrocortisone by a mainly lipid route and progesterone via a lipid pathway but its penetration rate was probably affected by aqueous layers. From permeation studies through cadaver skin in which an in-vivo mimic method was used, it was concluded that the penetration enhancers fell into three main categories: solvents which enhanced permeation of polar and non-polar compounds e.g. 2-pyrrolidone, N-methylpyrrolidone, N-methylformamide and propylene glycol plus Azone; enhancers which preferentially affected the polar route e.g. propylene glycol plus decylmethylsulphoxide, and accelerants which mainly modified the non-polar route e.g. propylene glycol plus oleic acid, propylene glycol alone and, to a limited extent, water.