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Advancement of a Positive-Pressure Dry Powder Inhaler for Children: Use of a Vertical Aerosolization Chamber and Three-Dimensional Rod Array Interface

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Abstract

Purpose

Available dry powder inhalers (DPIs) have very poor lung delivery efficiencies in children. The objective of this study was to advance and experimentally test a positive-pressure air-jet DPI for children based on the use of a vertical aerosolization chamber and new patient interfaces that contain a three-dimensional (3D) rod array structure.

Methods

Aerosolization performance of different air-jet DPI designs was first evaluated based on a 10 mg powder fill mass of a spray-dried excipient enhanced growth (EEG) formulation. Devices were actuated with positive pressure using flow rate (10–20 L/min) and inhaled volume (750 ml) conditions consistent with a 5-year-old child. Devices with best performance were connected to different mouthpiece designs to determine the effect on aerosolization and tested for aerosol penetration through a realistic pediatric in vitro mouth-throat model.

Results

Use of the new vertical aerosolization chamber resulted in high quality aerosol formation. Inclusion of a 3D rod array structure in the mouthpiece further reduced aerosol size by approximately 20% compared to conditions without a rod array, and effectively dissipated the turbulent jet leaving the device. Best case device and mouthpiece combinations produced < 2% mouth-throat depositional loss and > 70% lung delivery efficiency based on loaded dose.

Conclusions

In conclusion, use of a 3D rod array in the MP of a positive-pressure air-jet DPI was found to reduce aerosol size by 20%, not significantly increase MP depositional loss, reduce mouth-throat deposition by 6.4-fold and enable lung delivery efficiency as high as 73.4% of loaded dose based on pediatric test conditions.

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Abbreviations

3D:

Three dimensional

AAV:

Actuation air volume

AS:

Albuterol sulfate

CFD:

Computational fluid dynamics

DPI:

Dry powder inhaler

ED:

Emitted dose

EEG:

Excipient enhanced growth

FPF:

Fine particle fraction

HPLC:

High performance liquid chromatography

LPM:

Liters per minute

MMAD:

Mass median aerodynamic diameter

MP:

Mouthpiece

MT:

Mouth-throat

NGI:

Next Generation Impactor

SD:

Standard deviation

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Authors and Affiliations

  1. Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia, USA

    Dale Farkas, Karl Bass & P. Worth Longest

  2. Department of Pharmaceutics, Virginia Commonwealth University, 410 North 12th Street, P.O. Box 980533, Richmond, 23298-0533, Virginia, USA

    Serena Bonasera, Michael Hindle & P. Worth Longest

Authors
  1. Dale Farkas
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  2. Serena Bonasera
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  3. Karl Bass
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  4. Michael Hindle
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  5. P. Worth Longest
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Correspondence to P. Worth Longest.

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Farkas, D., Bonasera, S., Bass, K. et al. Advancement of a Positive-Pressure Dry Powder Inhaler for Children: Use of a Vertical Aerosolization Chamber and Three-Dimensional Rod Array Interface. Pharm Res 37, 177 (2020). https://doi.org/10.1007/s11095-020-02889-7

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