Percutaneous penetration enhancers: local versus transdermal activity

Abstract

The stratum corneum, poses a formidable challenge to formulators of drug delivery systems. Several approaches have been utilized to facilitate entry of drugs into the lower skin layers. Traditionally, permeation enhancers were designed to deliver high drug concentrations across the skin into the systemic circulation. The use of many of these agents resulted in unpleasant or toxic side effects. However, in recent years there has been a search for compounds that exhibit low toxicity, and maintain their enhancing activity. More recently, there has been interest in agents that may be used in topical formulations to prevent the passage of active ingredients or excipients into the lower skin layers. These so-called skin retardants have potential uses in many over-the-counter (OTC) skin formulations, such as sunscreens and pesticides, where the site of action is restricted to the skin surface or upper skin layers. Research in the area of permeation enhancement or retardation is yielding valuable insights into the structure–activity relationships of enhancers as well as retardants.