University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
J Ocul Pharmacol Ther. 2012 Oct;28(5):484-96. doi: 10.1089/jop.2011.0176. Epub 2012 Jun 13.
Fluconazole is a bis-triazole antifungal agent with a low molecular weight (306 Da). It is hydrophilic in nature and has low protein binding. It is available as eye drops for the treatment of ocular mycoses, the second most common cause of blindness in developing countries. However, its administration often results in poor patient compliance and limited use due to its short half-life (15-30 min) and a low log P (0.25). Therefore, fluconazole was incorporated into a novel sorbitan (spans) based elastic (spanlastic) vesicular system with intent to achieve a prolonged and better effect. Spanlastics are to niosomes what Transfersomes(®) are to liposomes.
Developed spanlastics consisted of spans and an edge activator prepared by the ether injection method. Developed vesicles were characterized for size, shape, and the number of vesicles/ml by optical microscopy. Entrapment efficiency was determined by the dialysis method, and the ex vivo corneal permeability study was performed using porcine cornea. A 3-tier safety of the novel formulation was established by the Ames test, the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, and in rabbits according to the OECD guidelines 404 and 405.
Spanlastics were smaller in size (3 times) and showed a better permeation in comparison to a corresponding niosomal formulation. The system showed an increase (3-fold) in the apparent permeability coefficient compared to the marketed formulation Zocon(®) (0.3% w/v solution of fluconazole) due to its elastic nature. The developed system was found to be stable for 2 months under refrigerated conditions and under extreme storage conditions. Safety was established in terms of genotoxicity (Ames test), cytotoxicity (MTT assay; mouse peritoneal macrophages), acute dermal/eye irritation/corrosion, and chronic eye irritation/corrosion tests (OECD guidelines).
The developed system is novel and provides an effective and safe formulation of fluconazole.
氟康唑是一种低分子量（306Da）的双三唑类抗真菌药物。它具有亲水性，与蛋白质结合率低。它可作为滴眼剂用于治疗眼部真菌感染，这是发展中国家第二大致盲原因。然而，由于其半衰期（15-30 分钟）短和低对数 P（0.25），其给药常常导致患者顺应性差和使用受限。因此，氟康唑被纳入一种新型山梨醇（吐温）基弹性（spanlastic）囊泡系统中，旨在实现延长和更好的效果。Spanlastics 是 niosomes 的同类物，类似于 Transfersomes（®）是 liposomes 的同类物。
通过乙醚注入法制备由吐温和边缘活性剂组成的开发型 spanlastics。通过光学显微镜对囊泡的大小、形状和囊泡/ml 数进行表征。通过透析法测定包封效率，通过猪角膜进行体外角膜渗透研究。通过 Ames 试验、3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定和 OECD 指南 404 和 405 中的兔实验，建立了新型制剂的 3 级安全性。
spanlastics 的尺寸更小（3 倍），与相应的 niosomal 制剂相比，渗透性能更好。由于其弹性，该系统的表观渗透系数增加了（3 倍），与市售制剂 Zocon（®）（氟康唑 0.3%w/v 溶液）相比。在冷藏条件下和极端储存条件下，该系统在 2 个月内保持稳定。在遗传毒性（Ames 试验）、细胞毒性（MTT 测定；小鼠腹腔巨噬细胞）、急性皮肤/眼睛刺激性/腐蚀性和慢性眼睛刺激性/腐蚀性试验（OECD 指南）方面确立了安全性。
该系统是新颖的，提供了一种有效的、安全的氟康唑制剂。
