Comparison of protocols measuring diffusion and partition coefficients in the stratum corneum

Abstract

Partition (K) and diffusion (D) coefficients are important to measure for the modelling of skin penetration of chemicals through the stratum corneum (SC). We compared the feasibility of three protocols for the testing of 50 chemicals in our main studies, using three cosmetics‐relevant model chemicals with a wide range of logP values. Protocol 1: SC concentration‐depth profile using tape‐stripping (measures KSC/v and DSC/HSC 2, where HSC is the SC thickness); Protocol 2A: incubation of isolated SC with chemical (direct measurement of KSC/v only) and Protocol 2B: diffusion through isolated SC mounted on a Franz cell (measures KSC/v and DSC/HSC 2, and is based on Fick's laws). KSC/v values for caffeine and resorcinol using Protocol 1 and 2B were within 30% of each other, values using Protocol 2A were ~two‐fold higher, and all values were within 10‐fold of each other. Only indirect determination of KSC/v by Protocol 2B was different from the direct measurement of KSC/v by Protocol 2A and Protocol 1 for 7‐EC. The variability of KSC/v for all three chemicals using Protocol 2B was higher compared to Protocol 1 and 2A. DSC/HSC 2 values for the three chemicals were of the same order of magnitude using all three protocols. Additionally, using Protocol 1, there was very little difference between parameters measured in pig and human SC. In conclusion, KSC/v, and DSC values were comparable using different methods. Pig skin might be a good surrogate for human skin for the three chemicals tested. Copyright © 2017 The Authors Journal of Applied Toxicology published by John Wiley & Sons Ltd.

Measurement of the penetration of 56 cosmetic relevant chemicals into and through human skin using a standardized protocol

“…For example, IQ is less lipophilic (logP is 1.47), only slowly reacts with peptides in the DPRA (11% depletion of cysteine after 24 hours) and has a lag time of 1.5 hours but was present in high amounts in both the total SC tape strips and epidermis (16% and 8% of the applied dose in the total SC tape strips and epidermis, respectively). Further investigations into reservoir effects are needed, e.g., correlating with partition coefficients, which provides information on the interaction of chemicals with the skin layers (Rothe et al, ).…”

“…The Cosmetics Europe ADME Task Force has several projects aimed at measuring relevant parameters to help predict local and systemic bioavailability of topically exposed compounds. Endpoint measurements include solubility in different solvents (Grégoire et al, ); partition and diffusion coefficients (Rothe et al, ), metabolism (Genies et al, ) and skin penetration (Gerstel et al, ; Jacques‐Jamin et al, ). The development of predictive in silico skin penetration models for the safety assessment of dermally applied cosmetics is needed to enable moving away from a 50% dermal bioavailability assumption (SCCS, ) to a more realistic one assessing the actual fraction of a systemically absorbed compound.…”

Solubility of Foreign Molecules in Stratum Corneum Brick and Mortar Structure

“…One common approach to measure the solubility of chemicals in SC is to study their partitioning between SC and an excess aqueous solution or a formulation. − A fundamental complication with these methods is that besides the uptake of various chemicals from the formulation into SC, there will also be extraction of molecules from the SC into the external solution (Figure Ai). The extracted chemicals can be small polar molecules as part of the natural moisturizing factor (NMF) if the SC is placed in contact with an excess aqueous solution, or hydrophobic compounds like fatty acids if the SC is instead exposed to a more hydrophobic formulation/solvent .…”

Characterization of optical clearing mechanisms in muscle during treatment with glycerol and gadobutrol solutions

“…The evaluation of such diffusion properties, namely the diffusion time ( τ ) and the diffusion coefficient ( D ), can be made using different techniques, as previously reported [1]. Two examples of techniques that have been used to evaluate the D values of OCAs in tissues are the one that use the Franz diffusion cell setup [10, 11] and the one based on the time dependence of the optical coherence tomography (OCT) signal [12, 13]. Considering the technique that uses the Franz diffusion cell setup, which can only be used with ex vivo tissue samples, the vertical crossing of the tissue sample by the OCA is induced by gravity.…”

“…Considering the technique that uses the Franz diffusion cell setup, which can only be used with ex vivo tissue samples, the vertical crossing of the tissue sample by the OCA is induced by gravity. By measuring the OCA concentration on the recipient below the tissue sample as a function of time, Fick's law of diffusion can be applied to determine the diffusion properties of the OCA in the tissue [1, 10, 11]. Considering the technique based on the evaluation of the time dependence of the OCT signal, a decrease of the in‐depth slope of the signal will be observed during the OCA diffusion in the tissue sample caused by the reduction of light scattering [12, 13].…”