To evaluate the treatment of the skin by abrasion with the Spontex® Brillant sponge as an alternative model of a damaged skin barrier, the percutaneous absorption and skin permeation of three model substances (caffeine, sorbic acid and testosterone) were studied using tape-stripped and abraded skin in comparison to untreated skin. Sorbic acid was used instead of the OECD proposed benzoic acid [26]. Preliminary permeation studies (n=3, data not shown) with benzoic OTX015 in vitro acid were not pursued due to high variation in drug recovery (41–84%), which did not meet the requirements of corresponding

guidelines [26, 35]. The results of the penetration and permeation study are summarized in Table 1. Caffeine is a relatively small (MW = 194.19 g/mol), highly hydrophilic molecule (log P=−0.13), and its penetration into skin should be restricted mainly by the stratum corneum. The mean cumulative amount of caffeine that permeated the porcine ear skin over 25 h as well as the apparent permeability (Papp) after 25 h for the different treated skin samples are shown in Fig. 3. With intact stratum

corneum (untreated skin), caffeine permeation through porcine skin was lowest, followed by the tape-stripped skin and then abraded skin. The higher permeability of caffeine with abraded skin compared to the tape-stripped skin can be associated to the skin preparation. Using the tape-stripping method, the layers of the stratum corneum buy Cilengitide are gradually removed from the skin surface resulting in reduction of stratum corneum thickness. The mechanical abrasion with an aluminum-coated sponge also leads to a reduction in the thickness of the stratum corneum thickness and a partially roughened surface of the skin, possibly resulting in a less compact stratum corneum like in certain skin diseases. The flux and Papp values of caffeine penetration across untreated skin are consistent with the published values of 0.31×10−6 cm/s [36] and 0.46–6.82 µg/cm2/h [37]. In accordance with the permeation results, the lag time for caffeine was the shortest with the abraded skin and the tape-stripped skin and was almost twice as long for the untreated skin. The lag time depends on

the lipophilicity and the molecular weight of the substance and the thickness of the skin. Tape stripping LY294002 as well as the abrasion of the skin using the Spontex® Brillant decreased the thickness of the skin, more precisely the stratum corneum, and thus the main penetration barrier for caffeine, resulting in an increased flux and a decreased lag time. Sorbic acid is frequently used as a preservative in cosmetics, pharmaceuticals and food. The common concentration in cosmetics (0.1%) was applied in this experiment. Compared to caffeine, sorbic acid is more lipophilic (log P=1.268; MW =112.13 g/mol). Sorbic acid permeation was lowest with intact stratum corneum (untreated skin) followed by the tape-stripped skin and the abraded skin (Fig. 4).