Physiologically based pharmacokinetic modelling of in vitro skin permeation of sunscreen actives under various experimental conditions.

In vitro permeation testing (IVPT) is widely used in pharmaceutical and cosmetic formulation design and in safety assessment of topical products. The U.S. FDA recommends IVPT to screen sunscreen formulations prior to conducting a maximum usage trial (MUsT). For potential permeants such as highly lipophilic UV filters, designing IVPT protocols is a time- and resource-intensive trial-and-error process. Frequently used in clinical pharmacokinetics, physiologically based pharmacokinetic (PBPK) models can also emulate IVPT experiments. We present a PBPK modelling framework simulating the in vitro skin absorption of avobenzone, octocrylene, and oxybenzone investigated using different formulations, applied doses, and skin types. Combining bottom-up parameter predictions with optimizations relevant to changing experimental conditions, the models predict observed receptor cumulative and skin retention amounts within 2-fold and recover the variability obtained in experiments featuring suitable donor/replicate numbers and mass balances. The framework presented herein paves the way for greater integration of PBPK modelling into the design and interpretation of IVPT experiments and, ultimately, towards the design of MUsTs.