Yousry Carol, Zikry Pakinam Mohsen, Basalious Emad Basalious, El-Gazayerly Omaima Naem
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini, Cairo 11562, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Egypt.
Adv Pharm Bull. 2020 Jul;10(3):389-398. doi: 10.34172/apb.2020.047. Epub 2020 May 11.
Eye drops' formulations of poorly water-soluble drugs, offer the advantage of crossing the lipophilic cornea, but their limited aqueous solubility may lead to low ocular bioavailability limiting their therapeutic uses. Terconazole (TZ) is an antifungal drug with low aqueous solubility, restricting its application in ocular fungal infection. Thus, the aim of the work in this study is to enhance TZ solubilization, permitting better ocular permeation and higher bioavailability. To achieve this goal, different self-nanoemulsifying systems (SNESs) were prepared using different oils, surfactants and co-surfactants. Ternary phase diagrams were constructed to identify self nano-emulsification regions for each oil system examined; either Labrafil M2125CS or Capryol 90. TZ saturated solubility in the different formulated systems were measured and systems showing highest potential for TZ solubilization were selected. The optimized systems were chosen based on their globule size, polydispersity index, self-emulsification characteristics. Finally, TZ release as well as the irritation effect via Hen's Egg test-chorioallantoic membrane (HET-CAM test) of the optimized system was observed in vitro. The optimized system was formulated using 20% w/w Labrafil M2125 CS, 50% w/w Tween 80 and 30% w/w Transcutol HP. Oil globules showed size range of 15.13 nm and self-emulsification time of 12.80 seconds. The system released 100% of the drug within half an hour compared to 2 hours in case of TZ-suspension. Finally, HET-CAM test showed non-irritating response and normal vascularization of the chorioallantoic membrane. The formulated SNES could be a promising approach to enhance ocular efficacy of TZ.
难溶性药物的滴眼液制剂具有穿透亲脂性角膜的优势，但其有限的水溶性可能导致眼部生物利用度较低，从而限制了它们的治疗用途。特康唑（TZ）是一种水溶性较低的抗真菌药物，限制了其在眼部真菌感染中的应用。因此，本研究工作的目的是提高TZ的溶解度，以实现更好的眼部渗透和更高的生物利用度。为实现这一目标，使用不同的油、表面活性剂和助表面活性剂制备了不同的自纳米乳化系统（SNESs）。构建三元相图以确定所研究的每个油系统（Labrafil M2125CS或Capryol 90）的自纳米乳化区域。测量了TZ在不同配方系统中的饱和溶解度，并选择了对TZ增溶潜力最高的系统。根据其球粒大小、多分散指数、自乳化特性选择优化系统。最后，在体外观察了优化系统的TZ释放以及通过鸡胚绒毛尿囊膜试验（HET-CAM试验）的刺激作用。优化系统由20% w/w Labrafil M2125 CS、50% w/w吐温80和30% w/w二乙二醇单乙基醚组成。油球粒径范围为15.13 nm，自乳化时间为12.80秒。与TZ混悬液2小时的情况相比，该系统在半小时内释放了100%的药物。最后，HET-CAM试验显示无刺激反应，绒毛尿囊膜血管化正常。所制备的SNES可能是提高TZ眼部疗效的一种有前景的方法。
