Introduction: Skin has been used as an administration route for local or systemic action since ancient times. The efficacy and toxicity of any product applied to the skin is determined by the chemical composition and physicochemical properties of the active(s) and excipients, which in turn govern their percutaneous absorption and effects.
Areas covered: This review addresses market trends, skin physiology, solute permeability, formulation properties and effects that are most relevant to a drug discovery scientist designing potentially active solutes for topical application. It also summarizes in silico model strategies, strengths, and limitations associated with the drug delivery design of topical products, with relevant examples.
Expert opinion: From a drug discovery perspective, many factors can determine the percutaneous absorption of an active solute. Current in silico models are limited by their dependence on data generated from the permeation of solutes across normal human skin from aqueous solutions. In practice, the choice of formulation, the pertinent skin physiology, and the solute properties, including its clearance, potency, and enhancement, also define dermal delivery. Consequently, there is an emerging trend of using in silico methods to inform effective drug design and development that are based on a combination of QSAR/QSPR with physiologically based pharmacokinetic and pharmacodynamic (PBPKPD) models.
Keywords: in silico modeling; Clearance; PBPKPD; QSAR/QSPR; exposure; percutaneous absorption; physicochemical properties; potency; skin irritancy; toxicity.