可吸入伊维菌素粉末作为COVID-19潜在治疗药物的制备和表征

IF 2 4区 医学 Q3 RESPIRATORY SYSTEM
Ahmed H Albariqi, Wei-Ren Ke, Dipesh Khanal, Stefanie Kalfas, Patricia Tang, Warwick J Britton, John Drago, Hak-Kim Chan
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引用次数: 2

摘要

背景:伊维菌素在体外对SARS-CoV-2显示出抗病毒活性后,作为一种潜在的COVID-19治疗药物受到了全世界的关注。然而,与口服给药相关的药代动力学限制被认为是其生物利用度和功效的限制因素。这些限制可以通过定向输送到肺部来克服。在本研究中,制备了伊维菌素和乳糖晶体的可吸入干粉,并对其进行了表征,用于治疗COVID-19。方法:伊维菌素与乳糖一水结晶共喷雾干燥,在43%和58%相对湿度下贮存一周。使用中高阻渗透器连接下一代冲击器,以60 L/min的流速检测存储粉末的体外分散性能。采用激光衍射、扫描电镜、拉曼光谱、x射线粉末衍射、热重分析、差示扫描量热法和动态蒸汽吸附等方法,对伊维菌素原料和喷雾干燥样品的粒径分布、形貌、结晶度和吸湿特性进行了评价。结果:新鲜喷雾干燥制剂(T0)和条件样品均能达到预期的治疗剂量,细颗粒剂量为300 μg, FPFrecovered率为70%,fpfemfi率为83%。此外,两种配方的体积中值直径均为4.3 μm,跨度均为1.9 μm。喷雾干燥的配方是稳定的,即使经过调理和暴露于不同的RH点,因为伊维菌素仍然是无定形的,主要是结晶乳糖。结论:制备了一种可吸入性稳定的伊维菌素乳糖晶体干粉。这种粉末吸入剂伊维菌素候选疗法似乎能够提供安全有效的剂量来治疗SARS-COV-2感染。这种疗法的进一步发展是必要的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Preparation and Characterization of Inhalable Ivermectin Powders as a Potential COVID-19 Therapy.

Background: Ivermectin has received worldwide attention as a potential COVID-19 treatment after showing antiviral activity against SARS-CoV-2 in vitro. However, the pharmacokinetic limitations associated with oral administration have been postulated as limiting factors to its bioavailability and efficacy. These limitations can be overcome by targeted delivery to the lungs. In this study, inhalable dry powders of ivermectin and lactose crystals were prepared and characterized for the potential treatment of COVID-19. Methods: Ivermectin was co-spray dried with lactose monohydrate crystals and conditioned by storage at two different relative humidity points (43% and 58% RH) for a week. The in vitro dispersion performance of the stored powders was examined using a medium-high resistance Osmohaler connecting to a next-generation impactor at 60 L/min flow rate. The solid-state characteristics including particle size distribution and morphology, crystallinity, and moisture sorption profiles of raw and spray-dried ivermectin samples were assessed by laser diffraction, scanning electron microscopy, Raman spectroscopy, X-ray powder diffraction, thermogravimetric analysis, differential scanning calorimetry, and dynamic vapor sorption. Results: All the freshly spray-dried formulation (T0) and the conditioned samples could achieve the anticipated therapeutic dose with fine particle dose of 300 μg, FPFrecovered of 70%, and FPFemitted of 83%. In addition, the formulations showed a similar volume median diameter of 4.3 μm and span of 1.9. The spray-dried formulations were stable even after conditioning and exposing to different RH points as ivermectin remained amorphous with predominantly crystalline lactose. Conclusion: An inhalable and stable dry powder of ivermectin and lactose crystals was successfully formulated. This powder inhaler ivermectin candidate therapy appears to be able to deliver doses that could be safe and effective to treat the SARS-COV-2 infection. Further development of this therapy is warranted.

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来源期刊
CiteScore
6.70
自引率
2.90%
发文量
34
审稿时长
>12 weeks
期刊介绍: Journal of Aerosol Medicine and Pulmonary Drug Delivery is the only peer-reviewed journal delivering innovative, authoritative coverage of the health effects of inhaled aerosols and delivery of drugs through the pulmonary system. The Journal is a forum for leading experts, addressing novel topics such as aerosolized chemotherapy, aerosolized vaccines, methods to determine toxicities, and delivery of aerosolized drugs in the intubated patient. Journal of Aerosol Medicine and Pulmonary Drug Delivery coverage includes: Pulmonary drug delivery Airway reactivity and asthma treatment Inhalation of particles and gases in the respiratory tract Toxic effects of inhaled agents Aerosols as tools for studying basic physiologic phenomena.
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