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

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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.