Cutaneous biodistribution of topically applied active ingredients: Evaluation of intra- and inter-laboratory reproducibility.

A robust method to quantify the spatial distribution of active ingredients and their concentrations as a function of depth within the epidermis and dermis would be advantageous for both cosmetic and pharmaceutical products. Here, a cassette-based in vitro permeation test (IVPT) was performed (at a given site) under finite dose conditions with five physicochemically distinct substances (with a > 350,000-fold difference in lipophilicity) using human abdominal skin - both permeation and total deposition were determined. A total of eighteen skin discs (area = 2 cm2, 6 female donors, 3 samples per donor) were used for the IVPT. They were subsequently divided into three groups and distributed to L'Oréal Operator 1 (L1, n = 6), L'Oréal Operator 2 (L2, n = 6), and University of Geneva (UG, n = 6). The cutaneous biodistribution method was then used to determine the spatial distribution of the five substances at a high resolution from the stratum corneum down to the upper dermis. Twenty skin lamellae with a thickness of 20 μm were obtained from each disc and the amount of each substance in each lamella was quantified. A novel statistical analysis was employed to investigate the variability/reproducibility of the data generated intra-laboratory (L1 vs. L2) and inter-laboratory (L1 vs. UG and L2 vs. UG). The results demonstrated the absence of significant difference in the permeation, total deposition, and cutaneous biodistribution data obtained following the identical protocols at both the intra- and inter-laboratory level and confirmed the robustness of the cutaneous biodistribution method in understanding the disposition of topically applied substances in the skin.