ABSTRACT
This chapter considers chemical modulation of topical and transdermal permeation. Selection of topical and transdermal formulation solvents clearly affects drug uptake into, and flux through, skin, but solvent supramolecular structuring has been used to promote drug residence in the epidermal tissue. The effectiveness of many topical preparations and products, such as patches and ointments, can be attributed to their occlusive effects which increases stratum corneum hydration to promote drug diffusivity through the membrane. Chemicals with penetration-enhancing activity are already well-accepted in numerous formulations, both for topical and transdermal delivery. Generally, prodrugs for topical application are designed with lipophilic moieties attached to the parent compound, since the increased lipophilicity facilitates partitioning of the permeant into the stratum corneum. Many topical formulations are likely to generate supersaturated states when used clinically; formulations applied to skin are typically rubbed in and chaotic processes occur as initial formulations collapse on use.
