Pasteka Richard, Schöllbauer Lara Alina, Santos da Costa Joao Pedro, Kolar Radim, Forjan Mathias
Department Life Science Engineering, University of Applied Sciences Technikum Wien, Höchstaedtplatz 6, 1200 Vienna, Austria.
Department of Biomedical Engineering, Brno University of Technology, Technicka 3058, 616 00 Brno, Czech Republic.
Pharmaceutics. 2022 Feb 24;14(3):500. doi: 10.3390/pharmaceutics14030500.
Dry powder inhalers are used by a large number of patients worldwide to treat respiratory diseases. The objective of this work is to experimentally investigate changes in aerosol particle diameter and particle number concentration of pharmaceutical aerosols generated by four dry powder inhalers under realistic inhalation and exhalation conditions. To simulate patients undergoing inhalation therapy, the active respiratory system model (xPULM™) was used. A mechanical upper airway model was developed, manufactured, and introduced as a part of the xPULM™ to represent the human upper respiratory tract with high fidelity. Integration of optical aerosol spectrometry technique into the setup allowed for evaluation of pharmaceutical aerosols. The results show that there is a significant difference (p < 0.05) in mean particle diameter between inhaled and exhaled particles with the majority of the particles depositing in the lung, while particles with the size of (>0.5 μm) are least influenced by deposition mechanisms. The fraction of exhaled particles ranges from 2.13% (HandiHaler®) over 2.94% (BreezHaler®), and 6.22% (Turbohaler®) to 10.24% (Ellipta®). These values are comparable to previously published studies. Furthermore, the mechanical upper airway model increases the resistance of the overall system and acts as a filter for larger particles (>3 μm). In conclusion, the xPULM™ active respiratory system model is a viable option for studying interactions of pharmaceutical aerosols and the respiratory tract regarding applicable deposition mechanisms. The model strives to support the reduction of animal experimentation in aerosol research and provides an alternative to experiments with human subjects.
全球大量患者使用干粉吸入器来治疗呼吸道疾病。这项工作的目的是通过实验研究在实际吸入和呼出条件下，四种干粉吸入器产生的药物气雾剂的气溶胶粒径和气溶胶颗粒数浓度的变化。为了模拟接受吸入治疗的患者，使用了主动呼吸系统模型（xPULM™）。开发、制造了一个机械上呼吸道模型，并将其作为xPULM™的一部分引入，以高保真地代表人类上呼吸道。将光学气溶胶光谱技术集成到该装置中，可以评估药物气雾剂。结果表明，吸入颗粒和呼出颗粒的平均粒径存在显著差异（p < 0.05），大多数颗粒沉积在肺部，而粒径大于0.5μm的颗粒受沉积机制的影响最小。呼出颗粒的比例范围从2.13%（HandiHaler®）、2.94%（BreezHaler®）、6.22%（Turbohaler®）到10.24%（Ellipta®）。这些值与先前发表的研究结果相当。此外，机械上呼吸道模型增加了整个系统的阻力，并对粒径大于3μm的较大颗粒起到过滤作用。总之，xPULM™主动呼吸系统模型是研究药物气雾剂与呼吸道在适用沉积机制方面相互作用的一个可行选择。该模型致力于支持减少气雾剂研究中的动物实验，并为人体实验提供了一种替代方案。
