Topical drug delivery: History, percutaneous absorption, and product development.

Topical products, widely used to manage skin conditions, have evolved from simple potions to sophisticated delivery systems. Their development has been facilitated by advances in percutaneous absorption and product design based on an increasingly mechanistic understanding of drug-product-skin interactions, associated experiments, and a quality-by-design framework. Topical drug delivery involves drug transport from a product on the skin to a local target site and then clearance by diffusion, metabolism, and the dermal circulation to the rest of the body and deeper tissues. Insights have been provided by Quantitative Structure Permeability Relationships (QSPR), molecular dynamics simulations, and dermal Physiologically Based PharmacoKinetics (PBPK). Currently, generic product equivalents of reference-listed products dominate the topical delivery market. There is an increasing regulatory interest in understanding topical product delivery behavior under 'in use' conditions and predicting in vivo response for population variations in skin barrier function and response using in silico and in vitro findings.