Submicrometer and nanoparticle aerosols may significantly improve the delivery efficiency, dissolution characteristics, and bioavailability of inhaled pharmaceuticals. The objective of this study was to explore the formation of submicrometer and nanometer aerosols from mesh nebulizers suitable for respiratory drug delivery using experiments and computational fluid dynamics (CFD) modeling. Mesh nebulizers were coupled with add-on devices to promote aerosol drying and the formation of submicrometer particles, as well as to control the inhaled aerosol temperature and relative humidity. Cascade impaction experiments were used to determine the initial mass median aerodynamic diameters of 0.1% albuterol aerosols produced by the AeroNeb commercial (4.69 μm) and lab (3.90 μm) nebulizers and to validate the CFD model in terms of droplet evaporation. Through an appropriate selection of flow rates, nebulizers, and model drug concentrations, submicrometer and nanometer aerosols could be formed with the three devices considered. Based on CFD simulations, a wire heated design was shown to overheat the airstream producing unsafe conditions for inhalation if the aerosol was not uniformly distributed in the tube cross-section or if the nebulizer stopped producing droplets. In comparison, a counter-flow heated design provided sufficient thermal energy to produce submicrometer particles, but also automatically limited the maximum aerosol outlet temperature based on the physics of heat transfer. With the counter-flow design, submicrometer aerosols were produced at flow rates of 5, 15, and 30 LPM, which may be suitable for various forms of oral and nasal aerosol delivery. Thermodynamic conditions of the aerosol stream exiting the counter-flow design were found be in a range of 21-45 °C with relative humidity greater than 40% in some cases, which was considered safe for direct inhalation and advantageous for condensational growth delivery.

中文翻译：

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从传统网状雾化器生产可吸入亚微米气雾剂以改善呼吸药物输送

亚微米和纳米颗粒气雾剂可以显着提高吸入药物的递送效率、溶出特性和生物利用度。本研究的目的是通过实验和计算流体动力学 (CFD) 建模探索适用于呼吸药物输送的网状雾化器形成亚微米和纳米气溶胶。网状雾化器与附加装置相结合，以促进气溶胶干燥和亚微米颗粒的形成，以及控制吸入的气溶胶温度和相对湿度。级联撞击实验用于确定由 AeroNeb 商用 (4.69 μm) 和实验室 (3.90 μm) 雾化器产生的 0.1% 沙丁胺醇气溶胶的初始质量中值空气动力学直径，并在液滴蒸发方面验证 CFD 模型。Through an appropriate selection of flow rates, nebulizers, and model drug concentrations, submicrometer and nanometer aerosols could be formed with the three devices considered. 根据 CFD 模拟，如果气溶胶在管横截面中分布不均匀或雾化器停止产生液滴，则显示线加热设计会使气流过热，从而产生不安全的吸入条件。相比之下，逆流加热设计提供了足够的热能来产生亚微米颗粒，但也会根据传热物理学自动限制最大气溶胶出口温度。通过逆流设计，亚微米气雾剂以 5、15 和 30 LPM 的流速产生，这可能适用于各种形式的口腔和鼻腔气雾剂输送。