Farmacia y Tecnologia Farmaceutica, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramon y Cajal, 28040 Madrid, Spain.
Int J Pharm. 2012 Nov 1;437(1-2):80-2. doi: 10.1016/j.ijpharm.2012.07.065. Epub 2012 Aug 4.
Amphotericin B (AmB) is a wide spectrum antifungal with low incidence of clinical resistance. However, there are no licensed topical formulations with AmB in most developed countries. Extemporaneous preparations of AmB are frequently prepared from available marketed parenteral formulations. Herein, a solution of AmB with γ-cyclodextrin is described as suitable for topical administration as eye drops. This novel formulation is characterised by its ability to solubilise AmB and to maintain its antifungal activity, physicochemical stability and sterility over 30 days. Antifungal activity against Candida albicans was significantly higher (35%) for the new formulation than that obtained with Fungizone(®) based extemporaneous prepared suspension. Optimal 0.1% AmB-10% cyclodextrin formulation remained sterile and with an acceptable osmolarity, pH and particle size for ophthalmic use over 4 weeks. Complexation with γ-cyclodextrins improved AmB chemical stability compared to the reference eye drops suspension based on Fungizone(®). These results illustrate the feasibility of an ophthalmic AmB formulation easy enough to be licensed or prepared in community and hospital pharmacies.
两性霉素 B（AmB）是一种广谱抗真菌药物，临床耐药性发生率低。然而，在大多数发达国家，没有获得许可的 AmB 局部制剂。AmB 的临时制剂通常是由市售的注射用制剂制备的。本文介绍了一种含有γ-环糊精的 AmB 溶液，适合作为滴眼剂局部给药。这种新型制剂的特点是能够溶解 AmB，并保持其抗真菌活性、物理化学稳定性和 30 天的无菌性。与基于 Fungizone®的临时制备混悬剂相比，新制剂对白色念珠菌的抗真菌活性显著提高（35%）。最优的 0.1%AmB-10%环糊精制剂在 4 周内保持无菌，并具有可接受的渗透压、pH 值和用于眼科的粒径。与基于 Fungizone®的参考滴眼剂混悬剂相比，与γ-环糊精络合可提高 AmB 的化学稳定性。这些结果表明，两性霉素 B 眼部制剂具有足够的可行性，易于在社区和医院药房获得许可或制备。
