Therefore, it is essential to consider skin condition in the early stage of dermal drug formulation development because of possible modified drug transport into and across the skin . To determine the drug levels within the stratum corneum, tape stripping is a well-established method [29,30]. Furthermore, this method is used to obtain an impaired skin barrier [31,32]. Producing the required degree of skin impairment (TEWL: 30±2 g m−2 h−1) needs up to 60 pieces of tape, making the validated tape-stripping method by Simonsen and Fullerton  expensive and less attractive for a high
sample throughput. An appropriate and validated alternative method for in vivo and ex vivo testing of drug transport across the impaired skin barrier
is necessary. Skin integrity can be influenced in vivo and in vitro by various methods including chemical (by solvents Icotinib manufacturer or surfactants) or mechanical damage, UV radiation Nintedanib research buy or clinical diseases; for detailed information, see Gattu and Maibach  and . TEWL measurement is a well-established method for the determination of skin integrity, and the fraction of stratum corneum removed is related to an increase in TEWL [10, 20, 33]. Here, various abrasive materials, for example sandpaper and different sponge surfaces, were tested for reproducibility and effectiveness of the gradual removal of the stratum corneum as well as the increase of the TEWL value (data not shown). The Spontex® Brillant best met these demands ( Fig. 1). The decrease of skin integrity was followed by TEWL measurement. After about ten repetitions, a TEWL value of 30±2 g m−2 h−1 was attained, and a plateau was reached after approximately 30 repetitions, suggesting that the complete stratum corneum was removed. The number of repetitions depends on the user and the skin sample, therefore the degree of skin damage always has to be controlled, for example by TEWL measurement. In literature, the degree of skin GBA3 damage often is not reported or even measured, thus the comparison of penetration data without information of the degree of skin
damage is difficult. Histological inspection of the porcine skin (Fig. 2) confirms the results of the TEWL measurements. After repeated treatment of the skin surface with the aluminum-coated sponge, the stratum corneum was clearly reduced after 10 repetitions ( Fig. 2, center) and finally completely removed after more than 40 repetitions ( Fig. 2, right). Thus, the damaged skin model for skin permeation studies are characterized by a visible reduction of the stratum corneum with a TEWL value of 30±2 g m−2 h−1. The skin consists of two permeation compartments, the lipophilic stratum corneum, with a water content of approximately 15%, and the more hydrophilic viable epidermis and dermis, with a water content of approximately 70% .