Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
The Department of Pharmaceutics, Faculty of Pharmacy, Jazan University, Jazan, Saudi Arabia.
J Aerosol Med Pulm Drug Deliv. 2021 Feb;34(1):20-31. doi: 10.1089/jamp.2020.1648. Epub 2020 Nov 10.
Hydroxychloroquine (HCQ) is one of the repurposed drugs proposed for the treatment of coronavirus disease 2019 (COVID-19). However, all the published clinical trials involve oral administration of the drug, although the disease is primarily a respiratory one. Direct inhaled delivery could reduce the side effects associated with oral use and ensure a high concentration of the drug in the lungs. In this study, inhalable HCQ powders were prepared and characterized for potential COVID-19 therapy. Hydroxychloroquine sulfate (HCQ-sul) was jet milled (JM) followed by conditioning by storage at different relative humidities (43%, 53%, 58%, and 75% RHs) for 7 days. The solid-state properties, including particle morphology and size distribution, crystallinity, and vapor moisture profiles of HCQ-sul samples, were characterized by scanning electron microscopy, laser diffraction, X-ray powder diffraction, differential scanning calorimetry, thermogravimetric analysis, and dynamic water vapor sorption. The aerosol performance of the HCQ-sul powders was assessed using a medium-high resistance Osmohaler coupling to a next-generation impactor (NGI) at a flow rate of 60 L/min. The jet-milled powder showed a volume median diameter of 1.7 μm (span 1.5) and retained the same crystalline form as the raw HCQ-sul. A small amount of amorphous materials was present in the jet-milled HCQ-sul, which was convertible to the stable, crystalline state after conditioning at 53%, 58%, and 75% RH. The recovered fine particle fraction (FPF) and the emitted fine particle fraction (FPF) of the HCQ-sul sample immediately after jet milling and the samples after conditioning at 43%, 53%, and 58% RH were similar at ∼43% and 61%, respectively. In contrast, the sample having conditioned at 75%RH showed lower corresponding values at 33% and 26% respectively, due to the formation of solid bridges caused by excessive moisture. Inhalable crystalline powders of HCQ-sul were successfully prepared, which can be used for clinical testing as a potential inhaled COVID-19 treatment.
羟氯喹 (HCQ) 是一种被提议用于治疗 2019 年冠状病毒病 (COVID-19) 的重新利用药物。然而，所有已发表的临床试验都涉及药物的口服给药，尽管该疾病主要是一种呼吸道疾病。直接吸入给药可以减少与口服使用相关的副作用，并确保药物在肺部的高浓度。在这项研究中，制备了可吸入的 HCQ 粉末并对其进行了表征，以用于潜在的 COVID-19 治疗。硫酸羟氯喹 (HCQ-sul) 进行了喷射磨 (JM) 处理，然后在不同相对湿度 (43%、53%、58% 和 75%RHs) 下储存 7 天以进行条件处理。HCQ-sul 样品的固态特性，包括颗粒形态和粒度分布、结晶度以及蒸汽湿度分布，通过扫描电子显微镜、激光衍射、X 射线粉末衍射、差示扫描量热法、热重分析和动态水蒸气吸附进行了表征。使用中高阻力 Osmohaler 与下一代撞击器 (NGI) 耦合，在 60 L/min 的流速下评估 HCQ-sul 粉末的气溶胶性能。喷射磨碎的粉末显示出 1.7 μm 的体积中位径（跨度 1.5），并保留了与原始 HCQ-sul 相同的结晶形式。喷射磨碎的 HCQ-sul 中存在少量无定形材料，在 53%、58% 和 75%RH 条件处理后可转化为稳定的结晶态。HCQ-sul 样品在喷射磨碎后立即以及在 43%、53%和 58%RH 条件处理后，回收的细颗粒分数 (FPF) 和发射的细颗粒分数 (FPF) 相似，分别约为 43%和 61%。相比之下，在 75%RH 条件处理的样品由于过多的水分形成了固体桥，其相应值分别为 33%和 26%。成功制备了可吸入的 HCQ-sul 结晶粉末，可作为潜在的吸入 COVID-19 治疗方法用于临床测试。
