ABSTRACT
In the last decade, a number of investigations describing the percutaneous permeation of different stereoforms of chiral compounds have been reported. The rational development of products for transdermal drug delivery requires a thorough understanding of both the biological composition of the skin barrier and the physicochemical properties of drug molecules. For chiral drugs with the biological activity associated with one enantiomer, enantioselective permeation would affect the pharmaco-dynamic profile of the racemate. In such cases, development of a trans-dermal delivery system based on a single enantiomer, rather than racemate, could reduce the optimal therapeutic dose required to achieve the desired pharmacological effect, which in turn can minimize or eliminate the adverse effects associated with chiral drugs. This chapter provides an overview of research carried out on the skin permeation of enantiomers as well as racemates of chiral molecules, particularly focusing on the stereoselective skin binding, metabolism, and pharmacodynamic effects in the skin. Further, a mathematical model to predict and correlate the flux characteristics of enantiomer(s) and racemate of chiral drugs is described. Finally, the use of eutectics/chiral terpenes to enhance the percutaneous permeation of selected chiral drugs is also discussed. An outline of the skin structure and its barrier function precedes the discussion on enantioselective skin permeation of chiral drugs in the presence and absence of chiral terpene enhancers.
