Variation Assessment for in Vitro Permeabilities through Yucatan Micropig Skin

Hiroyuki Takeuchi, Shuichi Terasaka, Takanobu Sakurai, Atsushi Furuya, Hidetoshi Urano, Kenji Sugibayashi
2011 Biological and Pharmaceutical Bulletin  
Animal skins are frequently used as an alternative to human skin in percutaneous absorption studies, because human skin is not always available and the use of human tissues and organs creates ethical problems. In addition, a large variation has been found among human skin specimens as a result of differences in gender, age, race and anatomical donor site. [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] Numerous animal models, including primate, porcine, mouse, rat, guinea pig and snake, have been
more » ... zed for skin permeability studies. 1, 3, 4, [11] [12] [13] Animal skins with a small variation in skin permeability may be much better than human skin for determining or estimating the skin permeability of drugs and for developing transdermal formulations. 1, 14, 15) In our earlier study, 16) we investigated the in vitro permeation studies of the three model drugs, nicorandil (NR), isosorbide dinitrate (ISDN) and flurbiprofen (FP), through human abdominal skin (human skin) and Sprague-Dawley rat dorsal skin (SD rat skin) were performed using Franz-type diffusion cells. The three model drugs were selected because of their different log K ow (logarithm of octanol/water partition coefficient at 37°C) (Table 1) . NR, ISDN and FP were used as hydrophilic, lipophilic and highly lipophilic drugs, respectively. The permeation rates of the three model drugs were determined, and their variations were evaluated. The inter-individual variations in human skin permeability for each model drug were larger than the intra-individual variations in human skin permeability. Although the interindividual variations in SD rat skin permeability for each model drug were much lower than those in human skin permeability, and the permeation rates of those drugs through the SD rat skin were approximately twice that through human skin. 16) The markedly smaller variation in the perme-ability through SD rat skin compared with that through human skin indicated that the in vitro permeation studies using SD rat skin would be particularly useful for evaluating differences in the skin permeability of the three model drugs as well as for predicting human skin permeability. Recently, pig skin has been frequently used for skin permeation studies. 1,17-22) It has been reported that the histological characteristics and permeability properties of pig skin closely resemble those of human skin. 6, 7, [23] [24] [25] [26] [27] [28] In addition, the Yucatan micropig (YMP) has been utilized for numerous research applications and has been suggested as an animal April 2011 555 Regular Article The purpose of this study was to evaluate the variations in the in vitro Yucatan micropig (YMP) skin permeabilities of drugs and to clarify whether YMP skin can be used to predict human skin permeability. In vitro permeation studies of the three model drugs, nicorandil, isosorbide dinitrate and flurbiprofen, through YMP skin were performed using Franz-type diffusion cells. The permeation rates of the three model drugs were determined, and their variations were evaluated. The inter-individual variations in YMP skin permeability for the three model drugs were smaller than that in human skin permeability, and the permeation rates of the three model drugs through the YMP skin were approximately half that through human skin. In addition, the intraindividual variations in YMP skin permeability for nicorandil and flurbiprofen were much smaller than the inter-individual variations in YMP skin. The inter-and intra-regional variations in YMP skin permeability were very small. The markedly smaller variation in the permeability through YMP skin as compared with that through human skin indicated that in vitro permeation studies using YMP skin would be particularly useful for evaluating differences in the skin permeability of the three model drugs as well as for predicting human skin permeability. Each value represents the meanϮS.D. (nϭ3 for YMP skin). Full-thickness of each YMP skin was measured in the center of each YMP skin sheet of three YMP skin sets.
doi:10.1248/bpb.34.555 pmid:21467645 fatcat:khfrd2hkvbft3esezsxza7phhu