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Optimizing Aerosolization Using Computational Fluid Dynamics in a Pediatric Air-Jet Dry Powder Inhaler

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Abstract

The objective of this study was to optimize the performance of a high-efficiency pediatric inhaler, referred to as the pediatric air-jet DPI, using computational fluid dynamics (CFD) simulations with supporting experimental analysis of aerosol formation. The pediatric air-jet DPI forms an internal flow pathway consisting of an inlet jet of high-speed air, capsule chamber containing a powder formulation, and outlet orifice. Instead of simulating full breakup of the powder bed to an aerosol in this complex flow system, which is computationally expensive, flow-field-based dispersion parameters were sought that correlated with experimentally determined aerosolization metrics. For the pediatric air-jet DPI configuration that was considered, mass median aerodynamic diameter (MMAD) directly correlated with input turbulent kinetic energy normalized by actuation pressure and flow kinetic energy. Emitted dose (ED) correlated best with input flow rate multiplied by the ratio of capillary diameters. Based on these dispersion parameters, an automated CFD process was used over multiple iterations of over 100 designs to identify optimal inlet and outlet capillary diameters, which affected system performance in complex and unexpected ways. Experimental verification of the optimized designs indicated an MMAD < 1.6 μm and an ED > 90% of loaded dose. While extrathoracic depositional loss will be determined in future studies, at an operating flow rate of 15 L/min, it is expected that pediatric mouth-throat or even nose-throat aerosol deposition fractions will be below 10% and potentially less than 5% representing a significant improvement in the delivery efficiency of dry powder pharmaceutical aerosols to children.

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Acknowledgements

Spray dried powder from the VCU Department of Pharmaceutics (Hindle Lab) generated by Serena Bonasera and experimental lab access are gratefully acknowledged. The authors also wish to thank Dr. Hindle for helpful insights and guidance in support of this work.

Funding

This study is 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 W Main Street, PO Box 843015, Richmond, Virginia, 23284, USA

    Karl Bass, Dale Farkas & Worth Longest

  2. Department of Pharmaceutics, Virginia Commonwealth University, 401 West Main Street, P.O. Box 843015, Richmond, Virginia, 23284-3015, USA

    Worth Longest

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

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Conflict of Interest

Virginia Commonwealth University is currently pursuing patent protection of excipient enhanced growth aerosol delivery, DPI aerosol generation devices, and patient interfaces, which if licensed, may provide a future financial interest to the authors.

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Bass, K., Farkas, D. & Longest, W. Optimizing Aerosolization Using Computational Fluid Dynamics in a Pediatric Air-Jet Dry Powder Inhaler. AAPS PharmSciTech 20, 329 (2019). https://doi.org/10.1208/s12249-019-1535-4

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