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

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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.

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Acknowledgements

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

Funding

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.

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Authors and Affiliations

  1. Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, 401 West Main Street, P. O. Box 843015, Richmond, Virginia, 23284, USA

    Worth Longest & Dale Farkas

  2. Department of Pharmaceutics, Virginia Commonwealth University, 410 North 12th Street, P.O. Box 980533, Richmond, Virginia, 23284, USA

    Worth Longest

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  1. Worth Longest
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  2. Dale Farkas
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Correspondence to Worth Longest.

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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.

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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)

High resolution image (TIF 278 kb)

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)

High resolution image (TIF 232 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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Longest, W., Farkas, D. Development of a New Inhaler for High-Efficiency Dispersion of Spray-Dried Powders Using Computational Fluid Dynamics (CFD) Modeling. AAPS J 21, 25 (2019). https://doi.org/10.1208/s12248-018-0281-y

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