Experimental and Numerical Investigation of Multiphase (Solid-Liquid-Gas) Flow: Application to Respiratory Drug Delivery

多相（固-液-气）流的实验和数值研究：在呼吸药物输送中的应用

• 批准号: RGPIN-2022-05055
• 负责人: Pakzad, Leila
• 金额: $ 2.04万
• 依托单位: Lakehead University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=747174
• 关键词: Experimental; Numerical; Investigation; Multiphase; Solid

Effective treatment of respiratory diseases depends on the properties of the aerosol/particles/droplets produced by the inhaler and the drug deposition efficiency in the lungs, which requires understanding drug particle aerodynamic behavior. Despite advances in inhaler device technology, drug deposition efficiency is 10-50%. My research in multiphase (solid-liquid-gas) flow focuses on interactions between solid particles, liquid droplets, and gas bubbles in drug inhalation systems. The short-term objectives are to: (1) understand the mechanisms of multiphase flow during drug aerosol delivery by pressurized meter-dose, dry powder, and soft mist inhalers; and (2) develop computational fluid dynamics (CFD) models to simulate inhaler-mouth-throat pathways. The long-term objective is to link drug deposition to inhaler design and operation and ultimately to drug deposition efficiency. Short-term objective 1 will be achieved using the Next Generation ImpactorTM (NGITM) system in my multiphase flow laboratory at LU. The NGI comprises various inhaler devices, a mouth-throat induction port, and a cascade impactor. An inhaler device is connected to the induction port, which actuates a given dose. After each test, the mass of the drug deposited in each stage of the NGI is quantified. A smart online particle analysis technology ("SOPAT") probe will be used to investigate the effect of design parameters on inhaler device performance. It measures the drug aerosol delivery and flow pattern inside the mouth-throat airway and allows us to identify and eliminate conditions leading to aerosol, particle, and droplet flow pathologies. For short-term objective 2, CFD and discrete element modeling will simulate drug aerosol, particle, and droplet flow and interactions in the mouth-throat airway. NGI and SOPAT probe data will be used to refine and validate the models. The statistical experimental design with response surface methodology will be applied to predict the lung deposition efficiency for a given parameter (e.g., flow rate) to determine the optimum parameter value to maximize drug deposition efficiency. The program will use experimental, numerical, and theoretical methods to address fundamental challenges related to inhaler device design. It will assess the performance of inhalers, provide guidance to upgrade current designs, and facilitate design of new devices. This will lower costs through more efficient use of drugs, enhance drug delivery monitoring and control, and increase throughput for existing inhalation systems. Improved inhaler devices will contribute to the Canadian pharmaceutical industry. Research outcomes will enhance human health and quality of life by treating pulmonary disease and mitigating the effects of air pollution, which is expected to increase with global climate change. The program will train HQP in multiphase flow, drug delivery systems, and advanced computational techniques, which will support future economic development in Canada.

呼吸疾病的有效治疗取决于吸入器产生的气溶胶/颗粒/液滴的特性以及肺中的药物沉积效率，这需要了解药物颗粒的空气动力学行为。尽管吸入器设备技术取得了进步，但药物沉积效率为10-50％。我在多相（固液气体）流动中的研究集中在药物吸入系统中固体颗粒，液滴和气泡之间的相互作用。短期目标是：（1）通过加压的仪表剂量，干粉和软雾吸入剂在药物气溶胶输送过程中多相流的机理； （2）开发计算流体动力学（CFD）模型，以模拟吸入器口throat途径。长期目标是将药物沉积与吸入器设计和操作联系起来，并最终与药物沉积效率联系起来。使用下一代ImpactM（NGITM）系统，将在LU的多相实验室中实现短期目标1。 NGI包括各种吸入器设备，一个口troat感应端口和级联撞击器。吸入器设备连接到感应端口，该端口可操纵给定的剂量。每次测试后，定量沉积在NGI每个阶段的药物的质量。智能在线粒子分析技术（“ SOPAT”）探针将用于研究设计参数对吸入器设备性能的影响。它测量了在喉咙throat气道内的药物气溶胶递送和流动模式，使我们能够识别和消除导致气溶胶，颗粒和液滴流动病变的条件。对于短期目标2，CFD和离散元素建模将模拟嘴 - throat气道中的药物气溶胶，颗粒和液滴流以及相互作用。 NGI和SOPAT探针数据将用于完善和验证模型。具有响应表面方法的统计实验设计将应用于预测给定参数（例如流速）的肺沉积效率，以确定最佳参数值，以最大程度地提高药物沉积效率。该计划将使用实验，数值和理论方法来解决与吸入器设备设计相关的基本挑战。它将评估吸入器的性能，为升级当前设计提供指导，并促进新设备的设计。这将通过更有效地使用药物，增强药物输送监测和控制并增加现有吸入系统的吞吐量来降低成本。改进的吸入设备将为加拿大制药行业做出贡献。研究成果将通过治疗肺部疾病并减轻空气污染的影响来增强人类健康和生活质量，预计随着全球气候变化的增加。该计划将在多相流，药物输送系统和先进的计算技术中培训HQP，这将支持加拿大未来的经济发展。