Dermal Physiologically-Based Pharmacokinetic (PBPK) Models Accounting for the Absorption and Evaporation of Vehicle/Co-Solvent Following the Application of Generic Dermatological Products

The Food and Drug Administration (FDA) is seeking to develop an enhanced mechanistic Physiologically-Based Pharmacokinetic (PBPK) model for generic dermatological drug products. The model should account for the absorption and evaporation of vehicle/co-solvent simultaneously and implement the effect of these two dynamic processes on the permeation of a drug molecule through skin. The developed model will be utilized to inform decisions on generic dermatological product development, to enhance the understanding of the effect of metamorphosis of dermatological drug products on skin absorption, and to predict the local and systemic exposure of a drug molecule following topical application of dermatological drug products. Some key points to consider include: • The model should be able to account for the absorption and evaporation of vehicle/co-solvent simultaneously. • The model should implement the effect of these two dynamic processes on the permeation of a drug molecule through skin. • The developed model will be utilized to inform decisions on generic dermatological product development. • The model should enhance the understanding of the effect of metamorphosis of dermatological drug products on skin absorption. • The model should predict the local and systemic exposure of a drug molecule following topical application of dermatological drug products.