Modulation of drug penetration in the skin

Drugs administered topically on skin should act either dermally or transdermally. They have to cross the stratum corneum (SC) which is responsible for the barrier function of the skin. Most of the drugs are not able to penetrate the SC. For this kind of drugs it is necessary to search for penetration enhancers to increase drug absorption. Sometimes systemic side effects caused by drugs applied topically have to be reduced or prevented. In these cases, so called retarders or reducers are applied as penetration modulators. Penetration into and through the SC may be influenced by physical means (hydration, iontophoresis, phonophoresis, temperature) or chemical substances. Alcohols, sulphoxides, fatty acids, esters, Azone, pyrrolidones, urea and polyoles are applied as penetration enhancers. The objectives for the use of a penetration modulator are to change the solubility and diffusivity of the drug in the SC reversibly. It is necessary to distinguish between modulators which influence the lipid pathway and those which are able to modify diffusion via the polar pathway.