Development of a New Inhaler for High-Efficiency Dispersion of Spray-Dried Powders Using Computational Fluid Dynamics (CFD) Modeling.

Abstract

Computational fluid dynamics (CFD) modeling offers a powerful tool for the development of drug delivery devices using a first principles approach but has been underutilized in the development of pharmaceutical inhalers. The objective of this study was to develop quantitative correlations for predicting the aerosolization behavior of a newly proposed dry powder inhaler (DPI). The dose aerosolization and containment (DAC) unit DPI utilizes inlet and outlet air orifices designed to maximize the dispersion of spray-dried powders, typically with low air volumes (~ 10mL) and relatively low airflow rates (~ 3L/min). Five DAC unit geometries with varying orifice outlet sizes, configurations, and protrusion distances were considered. Aerosolization experiments were performed using cascade impaction to determine mean device emitted dose (ED) and mass median aerodynamic diameter (MMAD). Concurrent CFD simulations were conducted to predict both flow field-based and particle-based dispersion parameters that captured different measures of turbulence. Strong quantitative correlations were established between multiple measures of turbulence and the experimentally observed aerosolization metrics of ED and MMAD. As expected, increasing turbulence produced increased ED with best case values reaching 85% of loaded dose. Surprisingly, decreasing turbulence produced an advantageous decrease in MMAD with values as low as approximately 1.6μm, which is in contrast with previous studies. In conclusion, CFD provided valuable insights into the performance of the DAC unit DPI as a new device including a two-stage aerosolization process offering multiple avenues for future enhancements.