Preclinical Development – Biomolecular
2019 PharmSci 360
Establishing the equivalence of topical products is challenging due to formulation complexity and variability in skin physiology. Traditional pharmacokinetic studies are hampered by low systemic concentrations, which do not necessarily reflect the concentration at the site of action. This has led to a search for alternative methods for demonstrating equivalence.
Mechanistic dermal absorption modelling predicts the kinetics of a compound as it is released from a formulation, and moves through layers of the skin. Coupled with full-body PBPK modelling, prediction of tissue-distribution following application of topical products is made; including expected variability due to physiology. Measured formulation parameters such as pH and particle size are included explicitly. Models are refined and verified on measured systemic and local concentration.
The Simcyp dermal absorption model (developed with support from an FDA grant) established a link between local and systemic concentration following topical application. This supported FDA approval of a complex generic topical.