1 Respira Therapeutics, Inc., San Mateo, California.
2 Merck Research Laboratories, Merck & Co., Rahway, New Jersey.
J Aerosol Med Pulm Drug Deliv. 2019 Apr;32(2):55-69. doi: 10.1089/jamp.2018.1497. Epub 2018 Dec 6.
This review discusses how advances in formulation and device design can be utilized to dramatically improve lung targeting and dose consistency relative to current marketed dry powder inhalers (DPIs). Central to the review is the development of engineered particles that effectively bypass deposition in the upper respiratory tract (URT). This not only reduces the potential for off-target effects but it also reduces variability in dose delivery to the lungs resulting from anatomical differences in the soft tissue in the mouth and throat. Low-density porous particles are able to largely bypass URT deposition due to the fact that both the primary particles and their agglomerates are respirable. The low-density particles also exhibit dose delivery to the lungs that is largely independent of inspiratory flow rate across a range of flow rates that most subjects achieve with portable DPIs. Coupling this with delivery devices that are breath actuated, simple to operate (open-inhale-close), and have adherence-tracking capability enables drug delivery that is largely independent of how a subject inhales, with a user experience that is close to that of an "idealhaler."
这篇综述讨论了如何通过制剂和装置设计的进步，与当前市售干粉吸入器（DPI）相比，显著提高肺部靶向和剂量一致性。综述的核心是开发工程化颗粒，这些颗粒可有效地绕过在上呼吸道（URT）的沉积。这不仅降低了脱靶效应的可能性，而且还降低了由于口腔和喉咙软组织的解剖差异导致的肺部剂量传递的可变性。由于初级颗粒及其团聚体都具有可呼吸性，低密度多孔颗粒能够在很大程度上绕过 URT 沉积。低密度颗粒还表现出与吸气流量无关的肺部剂量传递，该吸气流量跨越大多数患者使用便携式 DPI 达到的一系列流量。将其与呼吸驱动的、操作简单（打开-吸入-关闭）的输送装置相结合，并具有顺应性跟踪能力，可实现药物输送，其在很大程度上独立于患者如何吸入，并且用户体验接近“理想吸入器”。
