Terpenes and improvement of transdermal drug delivery

Abstract

The human skin itself hinders the widespread use of transdermal drug delivery (TDD) for administration of medications. Despite the different strategies devised and employed to reversibly overcome the skin barrier, this noninvasive delivery mode is restricted to potent, low molar mass therapeutic agents. As most drugs would not be able to penetrate the skin in a sufficient quantity to reach the desired therapeutic level, chemical penetration enhancers (CPE) are commonly used to breach the skin barrier and increase drug permeation. Over the years, extensive screening and testing have identified different classes of chemicals as potential adjuvants. Among these, terpenes, which are constituents of plant essential oils, have been widely investigated as skin penetration enhancers for both hydrophilic and hydrophobic drugs. Their enhancing effects on human skin and interactions with skin lipids have been extensively studied. The mechanisms of action of terpenes on excised human skin as determined by several analytical techniques were found to be the extraction and phase separation of stratum corneum intercellular lipids. The enhancing efficacies of terpenes with various physicochemical properties for lipophilic and hydrophilic drugs could be compared and ranked, while their enhancing effects on the skin were found to be reversible and the in vitro permeability of skin recovered once they were removed from the excised skin. Terpenes have been incorporated as adjuvants in the form of penetration enhancers or sorption promoters for improved drug delivery from various dosage forms including solutions, gels, and transdermal therapeutic systems.