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Insights into Spray Development from Metered-Dose Inhalers Through Quantitative X-ray Radiography

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Abstract

Purpose

Typical methods to study pMDI sprays employ particle sizing or visible light diagnostics, which suffer in regions of high spray density. X-ray techniques can be applied to pharmaceutical sprays to obtain information unattainable by conventional particle sizing and light-based techniques.

Methods

We present a technique for obtaining quantitative measurements of spray density in pMDI sprays. A monochromatic focused X-ray beam was used to perform quantitative radiography measurements in the near-nozzle region and plume of HFA-propelled sprays.

Results

Measurements were obtained with a temporal resolution of 0.184 ms and spatial resolution of 5 μm. Steady flow conditions were reached after around 30 ms for the formulations examined with the spray device used. Spray evolution was affected by the inclusion of ethanol in the formulation and unaffected by the inclusion of 0.1% drug by weight. Estimation of the nozzle exit density showed that vapour is likely to dominate the flow leaving the inhaler nozzle during steady flow.

Conclusions

Quantitative measurements in pMDI sprays allow the determination of nozzle exit conditions that are difficult to obtain experimentally by other means. Measurements of these nozzle exit conditions can improve understanding of the atomization mechanisms responsible for pMDI spray droplet and particle formation.

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Abbreviations

EMI:

Electronic metering inhaler

EtOH:

Ethanol

HFA:

Hydrofluoroalkane

IPBr:

Ipratropium bromide

PDA:

Phase doppler anemometry

pMDI:

Pressurised metered-dose inhaler

SLPM:

Standard litres per minute

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors gratefully acknowledge the support given to the project by the Australian Research Council. The authors wish to thank Dr. Chris Powell and Dr. Andrew Swantek, Energy Systems Division, Argonne National Laboratory. This research was performed at the 7-BM beamline of the Advanced Photon Source at Argonne National Laboratory. Use of the APS is supported by the U.S. Department of Energy (DOE) under Contract No. DE-AC02-06CH11357. The submitted manuscript has been created by UChicago Argonne, LLC, Operator of Argonne National Laboratory (“Argonne”). Argonne, a U.S. Department of Energy Office of Science laboratory, is operated under Contract No. DEAC02-06CH11357. The U.S. Government retains for itself, and others acting on its behalf, a paid-up nonexclusive, irrevocable worldwide license in said article to reproduce, prepare derivative works, distribute copies to the public, and perform publicly and display publicly, by or on behalf of the Government.

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Authors and Affiliations

  1. Laboratory for Turbulence Research in Aerospace and Combustion, Department of Mechanical and Aerospace Engineering, Monash University, Melbourne, Australia

    Nicholas Mason-Smith, Julio Soria, Daniel Edgington-Mitchell & Damon Honnery

  2. Energy Systems Division, Argonne National Laboratory, Lemont, Illinois, USA

    Daniel J. Duke

  3. X-ray Science Division, Argonne National Laboratory, Lemont, Illinois, USA

    Alan L. Kastengren

  4. Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Australia

    Peter J. Stewart

  5. Respiratory Technology, Woolcock Institute of Medical Research and the Discipline of Pharmacology, Sydney Medical School, Sydney, Australia

    Daniela Traini, Paul M. Young & Yang Chen

  6. Chiesi Ltd, Chippenham, UK

    David A. Lewis

  7. Department of Aeronautical Engineering, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia

    Julio Soria

Authors
  1. Nicholas Mason-Smith
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  2. Daniel J. Duke
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  3. Alan L. Kastengren
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  4. Peter J. Stewart
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  5. Daniela Traini
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  6. Paul M. Young
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  7. Yang Chen
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  8. David A. Lewis
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  9. Julio Soria
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  10. Daniel Edgington-Mitchell
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  11. Damon Honnery
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Correspondence to Nicholas Mason-Smith.

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Mason-Smith, N., Duke, D.J., Kastengren, A.L. et al. Insights into Spray Development from Metered-Dose Inhalers Through Quantitative X-ray Radiography. Pharm Res 33, 1249–1258 (2016). https://doi.org/10.1007/s11095-016-1869-5

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  • DOI: https://doi.org/10.1007/s11095-016-1869-5

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