Impact of solvent dry down, vehicle pH and slowly reversible keratin binding on skin penetration of cosmetic relevant compounds: I. Liquids

Abstract

To measure progress and evaluate performance of the newest UB/UC/P&G skin penetration model we simulated an 18-compound subset of finite dose in vitro human skin permeation data taken from a solvent-deposition study of cosmetic-relevant compounds (Hewitt et al., J. Appl. Toxicol. 2019, 1-13). The recent model extension involved slowly reversible binding of solutes to stratum corneum keratins. The selected subset was compounds that are liquid at skin temperature. This set was chosen to distinguish between slow binding and slow dissolution effects that impact solid phase compounds. To adequately simulate the physical experiments there was a need to adjust the evaporation mass transfer coefficient to better represent the diffusion cell system employed in the study. After this adjustment the model successfully predicted both dermal delivery and skin surface distribution of 12 of the 18 compounds. Exceptions involved compounds that were cysteine-reactive, highly water-soluble or highly ionized in the dose solution. Slow binding to keratin, as presently parameterized, was shown to significantly modify the stratum corneum kinetics and diffusion lag times, but not the ultimate disposition, of the more lipophilic compounds in the dataset. Recommendations for further improvement of both modeling methods and experimental design are offered.

Keywords: Absorption; Biophysical models; Dermal delivery; Disposition; Percutaneous; Skin; Transdermal.