Kleinstreuer Clement, Shi Huawei, Zhang Zhe
Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, North Carolina, USA.
J Aerosol Med. 2007 Fall;20(3):294-309. doi: 10.1089/jam.2006.0617.
The popular pressurized metered dose inhaler (pMDI), especially for asthma treatment, has undergone various changes in terms of propellant use and valve design. Most significant are the choice of hydrofluoroalkane-134a (HFA-134a) as a new propellant (rather than chlorofluorocarbon, CFC), a smaller exit nozzle diameter and attachment of a spacer in order to reduce ultimately droplet size and spray inhalation speed, both contributing to higher deposition efficiencies and hence better asthma therapy. Although asthma medicine is rather inexpensive, the specter of systemic side effects triggered by inefficient pMDI performance and the increasing use of such devices as well as new targeted drug-aerosol delivery for various lung and other diseases make detailed performance analyses imperative. For the first time, experimentally validated computational fluid-particle dynamics technique has been applied to simulate airflow, droplet spray transport and aerosol deposition in a pMDI attached to a human upper airway model, considering different device propellants, nozzle diameters, and spacer use. The results indicate that the use of HFA (replacing CFC), smaller valve orifices (0.25 mm instead of 0.5 mm) and spacers (ID = 4.2 cm) leads to best performance mainly because of smaller droplets generated, which penetrate more readily into the bronchial airways. Experimentally validated computer simulations predict that 46.6% of the inhaled droplets may reach the lung for an HFA-pMDI and 23.2% for a CFC-pMDI, both with a nozzle-exit diameter of 0.25 mm. Commonly used inhalers are nondirectional, and at best only regional drug-aerosol deposition can be achieved. However, when inhaling expensive and aggressive medicine, or critical lung areas have to be reached, locally targeted drug-aerosol delivery is imperative. For that reason the underlying principle of a future line of "smart inhalers" is introduced. Specifically, by generating a controlled air-particle stream, most of the inhaled drug aerosols reach predetermined lung sites, which are associated with specific diseases and/or treatments. Using the same human upper airway model, experimentally confirmed computer predictions of controlled particle transport from mouth to generation 3 are provided.
广受欢迎的压力定量吸入器（pMDI），尤其是用于哮喘治疗的，在推进剂使用和阀门设计方面经历了各种变化。最显著的是选择氢氟烷烃-134a（HFA-134a）作为新的推进剂（而非氯氟烃，CFC），减小出口喷嘴直径并连接一个储雾罐，以最终减小液滴尺寸和喷雾吸入速度，这两者都有助于提高沉积效率，从而实现更好的哮喘治疗效果。尽管哮喘药物价格相当低廉，但低效的pMDI性能引发的全身副作用风险以及此类装置使用的增加，再加上针对各种肺部和其他疾病的新型靶向药物气雾剂递送，使得详细的性能分析势在必行。首次将经过实验验证的计算流体-颗粒动力学技术应用于模拟连接到人体上呼吸道模型的pMDI中的气流、液滴喷雾传输和气溶胶沉积，考虑了不同的装置推进剂、喷嘴直径和储雾罐的使用情况。结果表明，使用HFA（取代CFC）、较小的阀门孔口（0.25毫米而非0.5毫米）和储雾罐（内径 = 4.2厘米）可实现最佳性能，主要是因为产生的液滴更小，更容易穿透进入支气管气道。经过实验验证的计算机模拟预测，对于喷嘴出口直径为0.25毫米的HFA-pMDI，46.6%的吸入液滴可能会到达肺部，而CFC-pMDI则为23.2%。常用的吸入器是无方向性的，充其量只能实现区域性药物气雾剂沉积。然而，当吸入昂贵且刺激性强的药物，或者必须到达关键肺部区域时，局部靶向药物气雾剂递送就至关重要。因此，引入了未来“智能吸入器”系列的基本原理。具体而言，通过产生可控的空气-颗粒流，大部分吸入的药物气雾剂可到达与特定疾病和/或治疗相关的预定肺部部位。利用相同的人体上呼吸道模型，提供了从口腔到第3级的可控颗粒传输的实验证实的计算机预测结果。
