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Condensational Growth of Combination Drug-Excipient Submicrometer Particles for Targeted High Efficiency Pulmonary Delivery: Comparison of CFD Predictions with Experimental Results

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ABSTRACT

Purpose

The objective of this study was to investigate the hygroscopic growth of combination drug and excipient submicrometer aerosols for respiratory drug delivery using in vitro experiments and a newly developed computational fluid dynamics (CFD) model.

Methods

Submicrometer combination drug and excipient particles were generated experimentally using both the capillary aerosol generator and the Respimat inhaler. Aerosol hygroscopic growth was evaluated in vitro and with CFD in a coiled tube geometry designed to provide residence times and thermodynamic conditions consistent with the airways.

Results

The in vitro results and CFD predictions both indicated that the initially submicrometer particles increased in mean size to a range of 1.6–2.5 μm for the 50:50 combination of a non-hygroscopic drug (budesonide) and different hygroscopic excipients. CFD results matched the in vitro predictions to within 10% and highlighted gradual and steady size increase of the droplets, which will be effective for minimizing extrathoracic deposition and producing deposition deep within the respiratory tract.

Conclusions

Enhanced excipient growth (EEG) appears to provide an effective technique to increase pharmaceutical aerosol size, and the developed CFD model will provide a powerful design tool for optimizing this technique to produce high efficiency pulmonary delivery.

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Abbreviations

ACI:

Andersen cascade impactor

CA:

citric acid

CAG:

capillary aerosol generator

CFD:

computational fluid dynamics

DPI:

dry powder inhaler

ECG:

enhanced condensational growth

EEG:

enhanced excipient growth

GC:

growth coefficient

HFA:

hydrofluoroalkane

HPLC:

high-performance liquid chromatography

LRN:

low Reynolds number

MDI:

metered dose inhaler

MMAD:

mass median aerodynamic diameter

MN:

mannitol

MT:

mouth-throat

NaCl:

sodium chloride

RH:

relative humidity

SD:

standard deviation

TB:

tracheobronchial

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ACKNOWLEDGMENTS

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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  1. Virginia Commonwealth University, Richmond, Virginia, USA

    P. Worth Longest & Michael Hindle

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

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Longest, P.W., Hindle, M. Condensational Growth of Combination Drug-Excipient Submicrometer Particles for Targeted High Efficiency Pulmonary Delivery: Comparison of CFD Predictions with Experimental Results. Pharm Res 29, 707–721 (2012). https://doi.org/10.1007/s11095-011-0596-1

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