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The Use of Condensational Growth Methods for Efficient Drug Delivery to the Lungs during Noninvasive Ventilation High Flow Therapy

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Abstract

Purpose

The objective of this study was to evaluate the delivery of nasally administered aerosols to the lungs during noninvasive ventilation using controlled condensational growth techniques.

Methods

An optimized mixer, combined with a mesh nebulizer, was used to generate submicrometer aerosol particles using drug alone (albuterol sulfate) and with mannitol or sodium chloride added as hygroscopic excipients. The deposition and growth of these particles were evaluated in an adult nose-mouth-throat (NMT) model using in vitro experimental methods and computational fluid dynamics simulations.

Results

Significant improvement in the lung dose (3–4× increase) was observed using excipient enhanced growth (EEG) and enhanced condensational growth (ECG) delivery modes compared to control studies performed with a conventional size aerosol (~5 μm). This was due to reduced device retention and minimal deposition in the NMT airways. Increased condensational growth of the initially submicrometer particles was observed using the ECG mode and in the presence of hygroscopic excipients. CFD predictions for regional drug deposition and aerosol size increase were in good agreement with the observed experimental results.

Conclusions

These controlled condensational growth techniques for the delivery of submicrometer aerosols were found to be highly efficient methods for delivering nasally-administered drugs to the lungs.

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Abbreviations

ACI:

Andersen cascade impactor

AS:

albuterol sulfate

CFD:

computational fluid dynamics

DF:

deposition fraction

ECG:

enhanced condensational growth

EEG:

excipient enhanced growth

GSD:

geometric standard deviation

HFT:

high flow therapy

HPLC:

high performance liquid chromatography

LRN:

low Reynolds number

MMAD:

mass median aerodynamic diameter

MN:

mannitol

NaCl:

sodium chloride

NIV:

noninvasive ventilation

NMT:

nose-mouth-throat model

NPPV:

noninvasive positive pressure ventilation

RH:

relative humidity

SD:

standard deviation

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Acknowledgments and Disclosures

This study was supported by Award 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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Correspondence to Laleh Golshahi.

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Golshahi, L., Tian, G., Azimi, M. et al. The Use of Condensational Growth Methods for Efficient Drug Delivery to the Lungs during Noninvasive Ventilation High Flow Therapy. Pharm Res 30, 2917–2930 (2013). https://doi.org/10.1007/s11095-013-1123-3

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  • DOI: https://doi.org/10.1007/s11095-013-1123-3

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