Colledge of Pharmacy, Dankook University, Dongnam-gu, Cheonan 330-714, Chungnam, Korea.
Dong-A Pharmaceutical Co. Ltd., Giheung-gu, Yongin 446-905, Gyeonggi, Korea.
Molecules. 2021 Mar 16;26(6):1650. doi: 10.3390/molecules26061650.
The incorporation of permeation enhancers in topical preparations has been recognized as a simple and valuable approach to improve the penetration of antifungal agents into toenails. In this study, to improve the toenail delivery of efinaconazole (EFN), a triazole derivative for onychomycosis treatment, topical solutions containing different penetration enhancers were designed, and the permeation profiles were evaluated using bovine hoof models. In an in vitro permeation study in a Franz diffusion cell, hydroalcoholic solutions (HSs) containing lipophilic enhancers, particularly prepared with propylene glycol dicaprylocaprate (Labrafac PG), had 41% higher penetration than the HS base. Moreover, the combination of hydroxypropyl-β-cyclodextrin with Labrafac PG further facilitated the penetration of EFN across the hoof membrane. In addition, this novel topical solution prepared with both lipophilic and hydrophilic enhancers was physicochemically stable, with no drug degradation under ambient conditions (25 °C, for 10 months). Therefore, this HS system can be a promising tool for enhancing the toenail permeability and therapeutic efficacy of EFN.
将渗透增强剂纳入局部制剂已被认为是一种简单而有价值的方法，可提高抗真菌药物渗透进入趾甲的能力。在这项研究中，为了改善三唑衍生物依氟康唑（EFN）治疗甲真菌病的趾甲给药，设计了含有不同渗透增强剂的局部溶液，并使用牛蹄模型评估了渗透特性。在 Franz 扩散池中的体外渗透研究中，含有亲脂性增强剂的水醇溶液（HSs），特别是用丙二醇二辛酸/癸酸酯（Labrafac PG）制备的 HSs，其渗透量比 HS 基高 41%。此外，羟丙基-β-环糊精与 Labrafac PG 的组合进一步促进了 EFN 穿过蹄膜的渗透。此外，这种新型局部溶液中同时使用了亲脂性和亲水性增强剂，在环境条件（25°C，10 个月）下物理化学性质稳定，无药物降解。因此，这种 HS 系统可能是增强 EFN 趾甲渗透性和治疗效果的有前途的工具。
