6 (left). The total recovery after 25 h meet the requirement of the

skin absorption guidelines with 85–100% [35], respectively 100±10% recovery [26]. The total drug uptake was increased using both impaired skin barrier models compared to the untreated skin (Fig. 6, right). The skin permeation of a highly hydrophilic substance, such as caffeine, is primarily restricted by the stratum corneum; thus, increased caffeine uptake by the impaired learn more skin barrier was considerably higher than for sorbic acid and testosterone. This result is consistent with published data [18] and [41]. The sorbic acid uptake was increased by up to 4-fold while testosterone showed only a 2-fold higher skin uptake with impaired skin barrier. Unlike with caffeine and sorbic acid, testosterone shows nearly equal amount of the drug in the acceptor medium and the skin after 25 h. Magnusson and co-workers [39] studied the skin tissue to buffer distribution of steroids of varied lipophilicity. Compared to hydrocortisone (log P=1.43), testosterone showed a clear higher affinity to the different skin Selleckchem MAPK Inhibitor Library layers (viable epidermis>stratum corneum>dermis). Although skin conditions were provided throughout the whole experiment, it cannot be excluded that the acceptor medium restricted the partitioning of testosterone

from the skin to the acceptor medium. Furthermore, the lower percentage of testosterone uptake can be attributed to the lower concentration gradient and the dermis, which may act as a permeation barrier for the lipophilic testosterone. The more lipophilic retinol (log P=6.84) was also found at a low percentage in the receptor medium [42]. Different skin abrasion methods described in the literature resulted in different degrees Vasopressin Receptor of skin barrier damage. It has been shown that the in vivo penetration of salicylic acid depends on the degree of skin barrier damage, defined by TEWL measurement, resulting in a 2.2-fold enhancement after acetone treatment (TEWL 9.1  g m−2 h−1) and up to a 157-fold enhancement after tape-stripping (TEWL 30.6  g m−2 h−1) [43]. Scratching the skin surface

with the tip of a needle (1–4 abrasion lines) caused a lower enhancement than tape-stripping [18], though the use of a rotation brush leads to the opposite effect [41]. It should be noted that the different tape-stripping protocols used can lead to different skin impairments, and thus, comparison of different methods is difficult without standardization. Therefore, the control of the skin damage process by TEWL measurement is essential to track the degree of skin impairment and produce reliable results. Drug uptake from abraded skin was significantly higher compared to intact skin for caffeine, sorbic acid and testosterone; this was also true for sorbic acid and testosterone when comparing tape-stripped skin with intact skin.