Purpose

Available dry powder inhalers (DPIs) have very poor lung delivery efficiencies in children. The objective of this study was to advance and experimentally test a positive-pressure air-jet DPI for children based on the use of a vertical aerosolization chamber and new patient interfaces that contain a three-dimensional (3D) rod array structure.

Methods

Aerosolization performance of different air-jet DPI designs was first evaluated based on a 10 mg powder fill mass of a spray-dried excipient enhanced growth (EEG) formulation. Devices were actuated with positive pressure using flow rate (10–20 L/min) and inhaled volume (750 ml) conditions consistent with a 5-year-old child. Devices with best performance were connected to different mouthpiece designs to determine the effect on aerosolization and tested for aerosol penetration through a realistic pediatric in vitro mouth-throat model.

Results

Use of the new vertical aerosolization chamber resulted in high quality aerosol formation. Inclusion of a 3D rod array structure in the mouthpiece further reduced aerosol size by approximately 20% compared to conditions without a rod array, and effectively dissipated the turbulent jet leaving the device. Best case device and mouthpiece combinations produced < 2% mouth-throat depositional loss and > 70% lung delivery efficiency based on loaded dose.

Conclusions

In conclusion, use of a 3D rod array in the MP of a positive-pressure air-jet DPI was found to reduce aerosol size by 20%, not significantly increase MP depositional loss, reduce mouth-throat deposition by 6.4-fold and enable lung delivery efficiency as high as 73.4% of loaded dose based on pediatric test conditions.

中文翻译：

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儿童正压干粉吸入器的进步：使用垂直雾化室和三维杆阵列接口。

目的

可用的干粉吸入器 (DPI) 对儿童的肺输送效率非常低。本研究的目的是基于使用垂直雾化室和包含三维 (3D) 杆阵列结构的新患者界面，推进和实验测试儿童正压空气喷射 DPI。

方法

首先基于喷雾干燥赋形剂促进生长 (EEG) 制剂的 10 毫克粉末填充质量评估不同喷气 DPI 设计的气雾化性能。使用与 5 岁儿童一致的流速 (10–20 L/min) 和吸入体积 (750 ml) 条件以正压启动设备。将性能最佳的设备连接到不同的咬嘴设计，以确定对雾化的影响，并通过真实的儿科体外口喉模型测试气雾渗透。

结果

使用新的垂直雾化室可形成高质量的气雾剂。与没有杆阵列的情况相比，在咬嘴中加入 3D 杆阵列结构进一步减少了大约 20% 的气溶胶尺寸，并有效地消散了离开设备的湍流射流。最佳情况下的设备和咬嘴组合产生 < 2% 的口喉沉积损失和 > 70% 的肺输送效率（基于加载剂量）。

结论

总之，发现在正压空气喷射 DPI 的 MP 中使用 3D 杆阵列可将气溶胶大小减少 20%，不会显着增加 MP 沉积损失，将口喉沉积减少 6.4 倍并使肺根据儿科测试条件，递送效率高达加载剂量的 73.4%。