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CFD Guided Optimization of Nose-to-Lung Aerosol Delivery in Adults: Effects of Inhalation Waveforms and Synchronized Aerosol Delivery

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Abstract

Purpose

The objective of this study was to optimize nose-to-lung aerosol delivery in an adult upper airway model using computational fluid dynamics (CFD) simulations in order to guide subsequent human subject aerosol delivery experiments.

Methods

A CFD model was developed that included a new high-flow nasal cannula (HFNC) and pharmaceutical aerosol delivery unit, nasal cannula interface, and adult upper airway geometry. Aerosol deposition predictions in the system were validated with existing and new experimental results. The validated CFD model was then used to explore aerosol delivery parameters related to synchronizing aerosol generation with inhalation and inhalation flow rate.

Results

The low volume of the new HFNC unit minimized aerosol transit time (0.2 s) and aerosol bolus spread (0.1 s) enabling effective synchronization of aerosol generation with inhalation. For aerosol delivery correctly synchronized with inhalation, a small particle excipient-enhanced growth delivery strategy reduced nasal cannula and nasal depositional losses each by an order of magnitude and enabled ~80% of the nebulized dose to reach the lungs. Surprisingly, nasal deposition was not sensitive to inhalation flow rate due to use of a nasal cannula interface with co-flow inhaled air and the small initial particle size.

Conclusions

The combination of correct aerosol synchronization and small particle size enabled high efficiency nose-to-lung aerosol delivery in adults, which was not sensitive to inhalation flow rate.

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Abbreviations

ACI:

Andersen Cascade Impactor

AS:

Albuterol sulfate

CFD:

Computational Fluid Dynamics

DE:

Deposition efficiency

DF:

Deposition fraction

EEG:

Excipient enhanced growth

FE:

Fraction exhaled

FR:

Fraction remaining

GCI:

Grid convergence index

HFNC:

High flow nasal cannula

HPLC:

High performance liquid chromatography

LPM:

Liters per minute

LRN:

Low Reynolds number

MMAD:

Mass median aerodynamic diameter

NaCl:

sodium chloride

NIV:

Non-invasive ventilation

NMT:

Nose-mouth-throat

NW:

Near-wall

PF:

Penetration fraction

RANS:

Reynolds averaged Navier-Stokes

RH:

Relative humidity

TB:

Tracheobronchial

UDF:

User defined function

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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, 23284-3015, USA

    Rabijit Dutta, Benjamin Spence & P. Worth Longest

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

    Xiangyin Wei, Sneha Dhapare, Michael Hindle & P. Worth Longest

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  1. Rabijit Dutta
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  2. Benjamin Spence
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  3. Xiangyin Wei
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  4. Sneha Dhapare
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  6. P. Worth Longest
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Correspondence to P. Worth Longest.

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Dutta, R., Spence, B., Wei, X. et al. CFD Guided Optimization of Nose-to-Lung Aerosol Delivery in Adults: Effects of Inhalation Waveforms and Synchronized Aerosol Delivery. Pharm Res 37, 199 (2020). https://doi.org/10.1007/s11095-020-02923-8

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