Pharmaceutics and Food Technology Department, School of Pharmacy, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.
School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.
Int J Pharm. 2023 Mar 25;635:122788. doi: 10.1016/j.ijpharm.2023.122788. Epub 2023 Mar 1.
The incidence of fungal pulmonary infections is known to be on the increase, and yet there is an alarming gap in terms of marketed antifungal therapies that are available for pulmonary administration. Amphotericin B (AmB) is a highly efficient broad-spectrum antifungal only marketed as an intravenous formulation. Based on the lack of effective antifungal and antiparasitic pulmonary treatments, the aim of this study was to develop a carbohydrate-based AmB dry powder inhaler (DPI) formulation, prepared by spray drying. Amorphous AmB microparticles were developed by combining 39.7 % AmB with 39.7 % γ-cyclodextrin, 8.1 % mannose and 12.5 % leucine. An increase in the mannose concentration from 8.1 to 29.8 %, led to partial drug crystallisation. Both formulations showed good in vitro lung deposition characteristics (80 % FPF < 5 µm and MMAD < 3 µm) at different air flow rates (60 and 30 L/min) when used with a DPI, but also during nebulisation upon reconstitution in water.
真菌性肺部感染的发病率呈上升趋势，但可供肺部给药的市售抗真菌治疗药物却存在惊人的缺口。两性霉素 B（AmB）是一种高效广谱抗真菌药物，仅作为静脉制剂上市。鉴于缺乏有效的抗真菌和抗寄生虫肺部治疗方法，本研究旨在开发一种基于碳水化合物的 AmB 干粉吸入剂（DPI）制剂，通过喷雾干燥制备。通过将 39.7%的 AmB 与 39.7%的γ-环糊精、8.1%的甘露糖和 12.5%的亮氨酸结合，开发出无定形的 AmB 微颗粒。当甘露糖浓度从 8.1%增加到 29.8%时，药物会部分结晶。两种制剂在不同气流速率（60 和 30 L/min）下使用 DPI 时，均显示出良好的体外肺部沉积特性（80%FPF<5 µm，MMAD<3 µm），但在水中重新配制后进行雾化时也是如此。
