Faculty of Pharmacy, Laboratory of Pharmaceutical, Chemical and Pharmacological Drug Development LR12ES09, University of Monastir, Monastir, Tunisia.
Laboratory for Advanced Materials, National School of Engineering, University of Sfax, Sfax, Tunisia.
Pharm Dev Technol. 2020 Jul;25(6):694-703. doi: 10.1080/10837450.2020.1731532. Epub 2020 Feb 21.
The aim of this study was to develop self- nanoemulsifying drug delivery system (SNEDDS) to improve the transcorneal permeability of voriconazole. A 'mixture design around a reference mixture' approach was applied. This latter included four components, namely, isopropyl myristate, PEG 400, Tween 80 and Span 80 as oil, co-solvent, surfactant and co-surfactant, respectively. Droplet size was selected as response. The effect of mixture components on droplet size was analyzed by means of response trace method. Optimal formulation was subjected to stability studies and characterized for droplet size, polydispersity index (PDI), pH, osmolarity, viscosity and percentage of transmittance. transcorneal permeation of the optimal and the marketed formulations was carried out on excised bovine cornea using Franz cell diffusion apparatus. Optimal voriconazole loaded-SNEDDS showed moderate emulsification efficiency and was characterized by a droplet size of 21.447 ± 0.081 nm, a PDI of 0.156 ± 0.004, a pH of 7.205 ± 0.006, an osmolarity of 310 mosmol/Kg and a viscosity of 8.818 ± 0.076 cP. Moreover, it presented an excellent stability and exhibited a significant improvement ( < 0.05) in apparent permeability coefficient (1.982 ± 0.187 × 10cm/s) when compared to commercialized formulation (1.165 ± 0.106 × 10cm/s). These results suggest that SNEDDS is a promising carrier for voriconazole ocular delivery.
本研究旨在开发自微乳药物传递系统（SNEDDS）以提高伏立康唑的经角膜通透性。采用“参考混合物周围的混合物设计”方法。后者包括四种成分，分别为肉豆蔻异丙酯、PEG400、吐温 80 和司盘 80，分别为油、共溶剂、表面活性剂和助表面活性剂。选择液滴尺寸作为响应。通过响应轨迹法分析混合物成分对液滴尺寸的影响。对优化配方进行稳定性研究，并对粒径、多分散指数（PDI）、pH 值、渗透压、粘度和透光率百分比进行表征。使用 Franz 细胞扩散装置在离体牛角膜上进行最佳和市售制剂的经角膜渗透实验。最佳伏立康唑负载 SNEDDS 表现出中等的乳化效率，其特征为液滴尺寸为 21.447±0.081nm、PDI 为 0.156±0.004、pH 值为 7.205±0.006、渗透压为 310mosmol/Kg 和粘度为 8.818±0.076cP。此外，它表现出优异的稳定性，并在表观渗透系数（1.982±0.187×10cm/s）方面表现出显著改善（<0.05），与商业化制剂（1.165±0.106×10cm/s）相比。这些结果表明，SNEDDS 是伏立康唑眼部给药的有前途的载体。
