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Development of a New Technique for the Efficient Delivery of Aerosolized Medications to Infants on Mechanical Ventilation

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Abstract

Purpose

To evaluate the efficiency of a new technique for delivering aerosols to intubated infants that employs a new Y-connector, access port administration of a dry powder, and excipient enhanced growth (EEG) formulation particles that change size in the airways.

Methods

A previously developed CFD model combined with algebraic correlations were used to predict delivery system and lung deposition of typical nebulized droplets (MMAD = 4.9 μm) and EEG dry powder aerosols. The delivery system consisted of a Y-connector [commercial (CM); streamlined (SL); or streamlined with access port (SL-port)] attached to a 4-mm diameter endotracheal tube leading to the airways of a 6-month-old infant.

Results

Compared to the CM device and nebulized aerosol, the EEG approach with an initial 0.9 μm aerosol combined with the SL and SL-port geometries reduced device depositional losses by factors of 3-fold and >10-fold, respectively. With EEG powder aerosols, the SL geometry provided the maximum tracheobronchial deposition fraction (55.7%), whereas the SL-port geometry provided the maximum alveolar (67.6%) and total lung (95.7%) deposition fractions, respectively.

Conclusions

Provided the aerosol can be administered in the first portion of the inspiration cycle, the proposed new method can significantly improve the deposition of pharmaceutical aerosols in the lungs of intubated infants.

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Abbreviations

ACI:

Andersen Cascade Impactor

AS:

Albuterol sulfate

B#:

Airway bifurcation number

CDC:

Centers for Disease Control

CFD:

Computational fluid dynamics

CM:

Commercial

DE:

Deposition efficiency

DF:

Deposition fraction

ED:

Emitted dose

EEG:

Excipient enhanced growth

ETT:

Endotracheal tube

FR:

Fraction remaining

GSD:

Geometric standard deviation

ID:

Internal diameter

LL:

Left lower (lung lobe)

LPM:

Liters per minute

LRN:

Low Reynolds number

MDI:

Metered dose inhaler

MMAD:

Mass median aerodynamic diameter

RH:

Relative humidity

SIP:

Stochastic individual path

SL:

Streamlined

TB:

Tracheobronchial

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ACKNOWLEDGMENTS AND DISCLOSURES

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 R21HD073728. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Michael Hindle of the VCU Department of Pharmaceutics is gratefully acknowledged for helpful comments on this study and for reviewing the manuscript. No conflicts of interest exist.

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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

    P. Worth Longest & Geng Tian

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

    P. Worth Longest

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  1. P. Worth Longest
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  2. Geng Tian
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Correspondence to P. Worth Longest.

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Longest, P.W., Tian, G. Development of a New Technique for the Efficient Delivery of Aerosolized Medications to Infants on Mechanical Ventilation. Pharm Res 32, 321–336 (2015). https://doi.org/10.1007/s11095-014-1466-4

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  • DOI: https://doi.org/10.1007/s11095-014-1466-4

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