Iino Hayato, Fujii Makiko, Fujino Manami, Kohara Shizuka, Hashizaki Kaname, Kira Hitomi, Koizumi Naoya, Watanabe Yoshiteru, Utoguchi Naoki
Department of Pharmaceutics and Biopharmaceutics, Showa Pharmaceutical University.
Biol Pharm Bull. 2017;40(2):220-226. doi: 10.1248/bpb.b16-00817.
Skin penetration amounts of a highly lipophilic drug, ufenamate, prepared in four oily vehicles, including white petrolatum (WP), liquid paraffin (LP), isopropyl myristate (IPM), and isocetyl stearate (ICS), were compared. Ufenamate was mixed in each vehicle at 5% and applied at a rate of 2 mg/cm to intact, stripped, and delipidized Yucatan micropig skin. The amounts of ufenamate and IPM in the stratum corneum (SC), epidermis, and dermis were determined. The skin penetration amounts of ufenamate from liquid oils were significantly higher than those from WP; the amounts of ufenamate were in the order WP<LP≤ICS<IPM, which was the same as that of the vehicle viscosities. The IPM skin penetration amount was approximately 20 times that of ufenamate. The skin penetration amounts of ufenamate from the liquid vehicles decreased after application to delipidized skin and were not significantly different among the four vehicles. The skin penetration amounts of the vehicle oils were significant and might disrupt intercellular lipid structures, especially in the strips 1-6 of the SC. In the deeper SC, there was no effect of the vehicle or skin condition. Thus, ufenamate mixed in liquid vehicles was found to be an effective dosage form.
比较了在四种油性载体（包括白凡士林（WP）、液体石蜡（LP）、肉豆蔻酸异丙酯（IPM）和异鲸蜡硬脂酸酯（ICS））中制备的高亲脂性药物联苯乙酸酯的皮肤渗透量。将联苯乙酸酯以5%的比例混入每种载体中，并以2mg/cm的速率施用于完整、去角质和脱脂的尤卡坦微型猪皮肤。测定了角质层（SC）、表皮和真皮中联苯乙酸酯和IPM的含量。联苯乙酸酯从液体油中的皮肤渗透量显著高于从WP中的渗透量；联苯乙酸酯的含量顺序为WP＜LP≤ICS＜IPM，这与载体粘度顺序相同。IPM的皮肤渗透量约为联苯乙酸酯的20倍。联苯乙酸酯从液体载体中的皮肤渗透量在施用于脱脂皮肤后降低，且在四种载体之间无显著差异。载体油的皮肤渗透量显著，可能会破坏细胞间脂质结构，尤其是在SC的第1-6条带中。在更深层的SC中，载体或皮肤状况没有影响。因此，发现混入液体载体中的联苯乙酸酯是一种有效的剂型。
