Design of chemical structure for optimal dermal delivery

The process of dermal absorption can be most conveniently divided into four independent steps, each of which is subject to its own structure-deliverability relationship. These are: (1) the process of release of the active agent molecules from the neat state to the dermal; (2) the process of permeation through the barrier layer; (3) the process of release of the drug from the epidermal barrier phase to the immediate subbarrier layer, (4) the micropharmacokinetics of the drug and its metabolite in the dermal compartment. The rate-controlling process can, in most instances, be identified with one of the first three processes. These in turn are largely subject to the physical chemical, thermodynamic characteristics of the transported species. Although the first process has been essentially ignored by earlier workers, it is in most instances of major concern in designing percutaneously available drug species.