Mehrandish Saba, Mirzaeei Shahla
Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Adv Pharm Bull. 2022 Jan;12(1):93-101. doi: 10.34172/apb.2022.009. Epub 2021 Feb 6.
The objective of this study was to design and develop nanoemulsion formulations of Itraconazole (ITZ), a water-insoluble, potent antifungal drug using the spontaneous emulsification method, to improve the ocular delivery and achieve a sustained release of the drug. The oil was selected on the basis of the ITZ solubility while the surfactant and co-surfactant were selected based on the thermodynamic stability and globule size. Following the selection of components, a pseudo-ternary phase diagram was constructed for the most promising formulation (F11) using benzyl benzoate (BB) as the oil, Eumulgin CO40 as the surfactant, and propylene glycol as the co-surfactant, by the design of experiments (DoE). F7 and F11 formulations were found to have an average globule size of 223.5 ± 10.7 nm and 157.5 ± 14.2 nm, besides thermodynamic stability and suitable physicochemical properties. F11 possessed an almost seven-fold higher cumulative percentage of in vitro released ITZ, in comparison to ITZ aqueous suspension after 24 hours. The release data suggested that the best fitted kinetical model for F11 and F7 was the Higuchi and Korsmeyer-Peppas model. The extended-release of the drug beside an acceptable amount of loaded ITZ suggested that nanoemulsion is suitable for the delivery of the ITZ.
本研究的目的是采用自发乳化法设计并开发伊曲康唑（ITZ）的纳米乳剂配方，伊曲康唑是一种水不溶性强效抗真菌药物，旨在改善眼部给药并实现药物的持续释放。根据ITZ的溶解度选择油相，同时基于热力学稳定性和液滴尺寸选择表面活性剂和助表面活性剂。在选择成分后，通过实验设计（DoE），以苯甲酸苄酯（BB）为油相、聚氧乙烯氢化蓖麻油CO40为表面活性剂、丙二醇为助表面活性剂，构建了最有前景配方（F11）的伪三元相图。除了具有热力学稳定性和合适的理化性质外，F7和F11配方的平均液滴尺寸分别为223.5±10.7nm和157.5±14.2nm。与ITZ水悬浮液相比，24小时后F11的体外累积释放ITZ百分比几乎高出七倍。释放数据表明，F11和F7最符合的动力学模型是Higuchi模型和Korsmeyer-Peppas模型。除了可接受的ITZ负载量外，药物的缓释表明纳米乳剂适用于ITZ的递送。
