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The AAPS Journal

, 21:25 | Cite as

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

  • Worth LongestEmail author
  • Dale Farkas
Research Article
  • 10 Downloads

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 (~ 10 mL) and relatively low airflow rates (~ 3 L/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 1.6 μm, 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.

KEY WORDS

aerosol delivery to children aerosolization with low air volumes dry powder inhalers pharmaceutical aerosols quantitative analysis and design spray-dried powders 

Notes

Acknowledgements

Dr. Michael Hindle is gratefully acknowledged for reviewing the manuscript and making helpful suggestions.

Funding Information

Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Number R01HD087339 and by the National Heart, Lung and Blood Institute of the National Institutes of Health under Award Number R01HL139673. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Compliance with Ethical Standards

Conflict of Interest

Virginia Commonwealth University is currently pursuing patent protection of devices and methods described in this study, which if licensed and commercialized, may provide a future financial interest to the authors.

Supplementary material

12248_2018_281_Fig9_ESM.png (4.3 mb)
Figure S1

Contours of turbulent kinetic energy (k) on two axial planes for designs (a) Case 1, (b) Case 2, (c) Case 3, (d) Case 4, and (e) Case 5. Different patterns and magnitudes are observed with Case 2 experiencing the highest levels of overall k and Cases 1, 4 and 5 having lowest k in the region of the initial powder bed. (PNG 4436 kb)

12248_2018_281_MOESM1_ESM.tif (279 kb)
High resolution image (TIF 278 kb)
12248_2018_281_Fig10_ESM.png (3.7 mb)
Figure S2

Contours of specific dissipation rate (ω) on two axial planes for designs (a) Case 1, (b) Case 2, (c) Case 3, (d) Case 4, and (e) Case 5. Profiles appear similar among the designs with values increasing significantly at the wall, where differences among the geometries are expected to be greater. (PNG 3819 kb)

12248_2018_281_MOESM2_ESM.tif (232 kb)
High resolution image (TIF 232 kb)
12248_2018_281_MOESM3_ESM.jpg (350 kb)
Figure S3 Contours of total wall shear stress (WSS) on surfaces of the DAC unit inner walls for designs (a) Case 1, (b) Case 2, (c) Case 3, (d) Case 4, and (e) Case 5. Values differ among cases and are highly non-uniform for each case. (JPG 350 kb)

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  1. 1.Department of Mechanical and Nuclear EngineeringVirginia Commonwealth UniversityRichmondUSA
  2. 2.Department of PharmaceuticsVirginia Commonwealth UniversityRichmondUSA

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