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Aerodynamic Factors Responsible for the Deaggregation of Carrier-Free Drug Powders to Form Micrometer and Submicrometer Aerosols

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Abstract

Purpose

To employ in vitro experiments combined with computational fluid dynamics (CFD) analysis to determine which aerodynamic factors were most responsible for deaggregating carrier-free powders to form micrometer and submicrometer aerosols from a capsule-based platform.

Methods

Eight airflow passages were evaluated for deaggregation of the aerosol including a standard constricted tube, impaction surface, 2D mesh, inward radial jets, and newly proposed 3D grids and rod arrays. CFD simulations were implemented to evaluate existing and new aerodynamic factors for deaggregation and in vitro experiments were used to evaluate performance of each inhaler.

Results

For the carrier-free formulation considered, turbulence was determined to be the primary deaggregation mechanism. A strong quantitative correlation was established between the mass median diameter (MMD) and newly proposed non-dimensional specific dissipation (NDSD) factor, which accounts for turbulent energy, inverse of the turbulent length scale, and exposure time. A 3D rod array design with unidirectional elements maximized NDSD and produced the best deaggregation with MMD<1 μm.

Conclusions

The new NDSD parameter can be used to develop highly effective dry powder inhalers like the 3D rod array that can efficiently produce submicrometer aerosols for next-generation respiratory drug delivery applications.

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Abbreviations

2D:

two-dimensional

3D:

three-dimensional

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

HPMC:

hydroxypropyl methylcellulose

LES:

large eddy simulation

LPM:

liters per minute

LRN:

low Reynolds number

MMAD:

mass median aerodynamic diameters

MMD:

mass median diameter

MN:

mannitol

MP:

mouthpiece

MT:

mouth-throat

NDSD:

non-dimensional specific dissipation

NGI:

Next Generation Impactor

PDA:

photo diode array

R2 :

coefficient of determination

RH:

relative humidity

SD:

standard deviation

TB:

tracheobronchial

UV:

ultraviolet

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Acknowledgments and Disclosures

This study was supported by Award Number R21 HL104319 and R01 HL107333 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health.

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Authors and Affiliations

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

    P. Worth Longest & Landon Holbrook

  2. Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia, USA

    P. Worth Longest, Yoen-Ju Son & Michael Hindle

  3. Virginia Commonwealth University, 401 West Main Street, P.O. Box 843015, Richmond, Virginia, 23284-3015, USA

    P. Worth Longest

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  1. P. Worth Longest
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Correspondence to P. Worth Longest.

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Longest, P.W., Son, YJ., Holbrook, L. et al. Aerodynamic Factors Responsible for the Deaggregation of Carrier-Free Drug Powders to Form Micrometer and Submicrometer Aerosols. Pharm Res 30, 1608–1627 (2013). https://doi.org/10.1007/s11095-013-1001-z

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