Advanced Drug Delivery Group, School of Pharmacy, The University of Sydney Faculty of Medicine and Health, Sydney, NSW, 2006, Australia.
Department of Pharmacy, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen, Denmark.
BMC Pulm Med. 2019 Feb 15;19(1):42. doi: 10.1186/s12890-019-0807-9.
Aerosol delivery through a nasal high flow (NHF) system is attractive for clinicians as it allows for simultaneous administration of oxygen and inhalable drugs. However, delivering a fine particle fraction (FPF, particle wt. fraction < 5.0 μm) of drugs into the lungs has been very challenging, with highest value of only 8%. Here, we aim to develop an efficient nose-to-lung delivery system capable of delivering improved quantities (FPF > 16%) of dry powder aerosols to the lungs via an NHF system.
We evaluated the FPF of spray-dried mannitol with leucine with a next generation impactor connected to a nasopharyngeal outlet of an adult nasal airway replica. In addition, we investigated the influence of different dispersion (20-30 L/min) and inspiratory (20-40 L/min) flow rates, on FPF.
We found an FPF of 32% with dispersion flow rate at 25 L/min and inspiratory flow rate at 40 L/min. The lowest FPF (21%) obtained was at the dispersion flow rate at 30 L/min and inspiratory flow rate at 30 L/min. A higher inspiratory flow rate was generally associated with a higher FPF. The nasal cannula accounted for most loss of aerosols.
In conclusion, delivering a third of inhalable powder to the lungs is possible in vitro through an NHF system using a low dispersion airflow and a highly dispersible powder. Our results may lay the foundation for clinical evaluation of powder aerosol delivery to the lungs during NHF therapy in humans.
通过鼻高流量 (NHF) 系统输送气雾剂对于临床医生来说很有吸引力,因为它可以同时输送氧气和可吸入药物。然而,将药物的细颗粒分数 (FPF,重量分数 < 5.0 μm 的颗粒) 输送到肺部一直是极具挑战性的,最高值仅为 8%。在这里,我们旨在开发一种有效的鼻内-肺部输送系统,该系统能够通过 NHF 系统向肺部输送改进数量的(FPF > 16%)干粉气雾剂。
我们使用下一代撞击器评估了与亮氨酸喷雾干燥的甘露醇的 FPF,该撞击器连接到成人鼻气道模型的鼻咽出口。此外,我们研究了不同分散(20-30 L/min)和吸气(20-40 L/min)流速对 FPF 的影响。
我们发现,在分散流速为 25 L/min 和吸气流速为 40 L/min 时,FPF 为 32%。在分散流速为 30 L/min 和吸气流速为 30 L/min 时,获得的最低 FPF(21%)。较高的吸气流速通常与较高的 FPF 相关。鼻插管导致大部分气雾剂损失。
总之,通过 NHF 系统使用低分散气流和高分散性粉末,有可能在体外将三分之一的可吸入粉末输送到肺部。我们的结果可能为在人类 NHF 治疗期间对肺部粉末气雾剂输送进行临床评估奠定基础。