Skin permeability: dermatologic aspects of transdermal drug delivery

Long considered an impermeable barrier, the skin is now perceived as a potential portal of entry for drugs. This new awareness, coupled with the availability of potent pharmacologic agents that can exert their effects at very low tissue concentrations, has led to the development of new drug delivery systems. Delivery of drugs through the skin utilizes the unique properties of the stratum corneum, which slows down the entry of drug to the circulation, thereby making possible the attainment of blood levels without sharp peaks and valleys. The skin not only acts to govern drug release from an external reservoir but may itself act as a reservoir for the slow, steady release of drug. Application of drug to the skin avoids the metabolic inactivation that may occur in the liver as the result of first-pass metabolism of oral drug formulations. Nitroglycerin ointment has demonstrated the feasibility of drug administration through the skin. One of the first transdermal modalities, the ointment vehicle, has now been replaced by sophisticated devices that allow far greater control of dosage. Rapid advances can be expected in view of the convenience and steady-state kinetics of transdermal systems.