Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, 401 West Main Street, P.O. Box 843015, Richmond, VA, 23284-3015, USA.
Department of Pharmaceutics, Virginia Commonwealth University, 410 North 12th Street, P.O. Box 980533, Richmond, VA, 23298-0533, USA.
Pharm Res. 2021 Sep;38(9):1615-1632. doi: 10.1007/s11095-021-03094-w. Epub 2021 Aug 30.
In order to improve the delivery of dry powder aerosol formulations to the lungs of infants, this study implemented an infant air-jet platform and explored the effects of different air sources, flow rates, and pulmonary mechanics on aerosolization performance and aerosol delivery through a preterm nose-throat (NT) in vitro model.
The infant air-jet platform was actuated with a positive-pressure air source that delivered the aerosol and provided a full inhalation breath. Three different air sources were developed to provide highly controllable positive-pressure air actuations (using actuation volumes of ~10 mL for the preterm model). While providing different flow waveform shapes, the three air sources were calibrated to produce the same flow rate magnitude (Q90: 90th percentile of flow rate). Multiple air-jet DPI designs were coupled with the air sources and evaluated with a model spray-dried excipient enhanced growth formulation.
Compared to other designs, the D1-Single air-jet DPI provided improved performance with low variability across all three air sources. With the tested D1-Single air-jet and Timer air source, reducing the flow rate from 4 to 1.7 L/min marginally decreased the aerosol size and significantly increased the lung delivery efficiency above 50% of the loaded dose. These results were not impacted by the presence of downstream pulmonary mechanics (resistance and compliance model).
The selected design was capable of providing an estimated >50% lung delivery efficiency of a model spray-dried formulation and was not influenced by the air source, thereby enabling greater flexibility for platform deployment in different environments.
为了提高干粉气溶胶制剂递送至婴儿肺部的效果，本研究构建了婴儿空气喷射平台，并通过早产口鼻（NT）体外模型探索了不同气源、气流速率和肺部力学对雾化性能和气溶胶传递的影响。
婴儿空气喷射平台采用正压气源驱动，输送气溶胶并提供全吸入呼吸。开发了三种不同的气源以提供高度可控的正压空气驱动（为早产模型提供约 10 mL 的驱动体积）。这三种气源在提供不同的气流波形形状的同时，被校准为产生相同的流量大小（Q90：流量的第 90 百分位数）。多个空气喷射 DPI 设计与气源耦合，并使用模型喷雾干燥赋形剂增强生长制剂进行评估。
与其他设计相比，D1-Single 空气喷射 DPI 在所有三种气源下均表现出更好的性能，且变异性较低。使用测试的 D1-Single 空气喷射和 Timer 气源，将气流速率从 4 L/min 降低至 1.7 L/min 略微减小了气溶胶粒径，显著提高了肺输送效率，使其超过了加载剂量的 50%。这些结果不受下游肺部力学（阻力和顺应性模型）的影响。
所选设计能够提供模型喷雾干燥制剂的估计超过 50%的肺输送效率，且不受气源的影响，从而为平台在不同环境中的部署提供了更大的灵活性。
