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.

呼吸系统疾病的有效治疗取决于吸入器产生的气溶胶/颗粒/液滴的性质和药物在肺部的沉积效率，这需要了解药物颗粒的空气动力学行为。尽管吸入器装置技术取得了进步，但药物沉积效率为10- 50%。我对多相（固-液-气）流的研究重点是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）了解加压定量、干粉和软雾吸入器给药过程中多相流的机制;（2）开发计算流体动力学（CFD）模型，以模拟吸入器-口腔-咽喉通路。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。短期目标1将使用下一代冲击器TM（NGITM）系统在我的多相流实验室在LU实现。NGI包括各种吸入器装置、口-喉诱导端口和级联冲击器。吸入器装置连接到吸入口，吸入器装置致动给定剂量。在每次测试之后，量化在NGI的每个阶段中沉积的药物的质量。将使用智能在线颗粒分析技术（“SOPAT”）探针研究设计参数对吸入器装置性能的影响。它测量药物气雾剂输送和咽喉气道内的流动模式，使我们能够识别和消除导致气雾剂，颗粒和液滴流动病理的条件。对于短期目标2，计算流体动力学和离散元建模将模拟药物气溶胶、颗粒和液滴流动以及口-喉气道中的相互作用。NGI和SOPAT探测数据将用于改进和验证模型。将应用响应面方法的统计实验设计来预测给定参数（例如，流速）来确定最佳参数值以使药物沉积效率最大化。该计划将使用实验，数值和理论方法来解决与吸入器装置设计相关的基本挑战。它将评估吸入器的性能，为升级现有设计提供指导，并促进新装置的设计。这将通过更有效地使用药物来降低成本，增强药物递送监测和控制，并增加现有吸入系统的吞吐量。改进的吸入器装置将有助于加拿大制药业。研究成果将通过治疗肺部疾病和减轻空气污染的影响来改善人类健康和生活质量，预计空气污染将随着全球气候变化而增加。该计划将培训HQP在多相流，药物输送系统和先进的计算技术，这将支持加拿大未来的经济发展。