CFD Guided Optimization of Nose-to-Lung Aerosol Delivery in Adults: Effects of Inhalation Waveforms and Synchronized Aerosol Delivery.

The objective of this study was to optimize nose-to-lung aerosol delivery in an adult upper airway model using computational fluid dynamics (CFD) simulations in order to guide subsequent human subject aerosol delivery experiments. A CFD model was developed that included a new high-flow nasal cannula (HFNC) and pharmaceutical aerosol delivery unit, nasal cannula interface, and adult upper airway geometry. Aerosol deposition predictions in the system were validated with existing and new experimental results. The validated CFD model was then used to explore aerosol delivery parameters related to synchronizing aerosol generation with inhalation and inhalation flow rate. The low volume of the new HFNC unit minimized aerosol transit time (0.2 s) and aerosol bolus spread (0.1 s) enabling effective synchronization of aerosol generation with inhalation. For aerosol delivery correctly synchronized with inhalation, a small particle excipient-enhanced growth delivery strategy reduced nasal cannula and nasal depositional losses each by an order of magnitude and enabled ~80% of the nebulized dose to reach the lungs. Surprisingly, nasal deposition was not sensitive to inhalation flow rate due to use of a nasal cannula interface with co-flow inhaled air and the small initial particle size. The combination of correct aerosol synchronization and small particle size enabled high efficiency nose-to-lung aerosol delivery in adults, which was not sensitive to inhalation flow rate.