Pharmaceutical Research

, Volume 34, Issue 4, pp 718–729 | Cite as

Revealing pMDI Spray Initial Conditions: Flashing, Atomisation and the Effect of Ethanol

  • Nicholas Mason-SmithEmail author
  • Daniel J. Duke
  • Alan L. Kastengren
  • Daniela Traini
  • Paul M. Young
  • Yang Chen
  • David A. Lewis
  • Daniel Edgington-Mitchell
  • Damon Honnery
Research Paper



Sprays from pressurised metered-dose inhalers are produced by a transient discharge of a multiphase mixture. Small length and short time scales have made the investigation of the governing processes difficult. Consequently, a deep understanding of the physical processes that govern atomisation and drug particle formation has been elusive.


X-ray phase contrast imaging and quantitative radiography were used to reveal the internal flow structure and measure the time-variant nozzle exit mass density of 50 µL metered sprays of HFA134a, with and without ethanol cosolvent. Internal flow patterns were imaged at a magnification of 194 pixels/mm and 7759 frames per second with 150 ps temporal resolution. Spray projected mass was measured with temporal resolution of 1 ms and spatial resolution 6 µm × 5 µm.


The flow upstream of the nozzle comprised large volumes of vapour at all times throughout the injection. The inclusion of ethanol prevented bubble coalescence, altering the internal flow structure and discharge. Radiography measurements confirmed that the nozzle exit area is dominantly occupied by vapour, with a peak liquid volume fraction of 13%.


Vapour generation in pMDIs occurs upstream of the sump, and the dominant volume component in the nozzle exit orifice is vapour at all times in the injection. The flow in ethanol-containing pMDIs has a bubbly structure resulting in a comparatively stable discharge, whereas the binary structure of propellant-only flows results in unsteady discharge and the production of unrespirable liquid masses.


phase contrast imaging pressurised metered-dose inhaler radiography synchrotron radiation 



Advanced Photon Source


Full-width at half-maximum




Homogeneous frozen model


Pressurised metered-dose inhaler


Transverse integrated mass



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. Katarzyna Matusik, Energy Systems Division, Argonne National Laboratory, Dr. Jin Wang and Dr. Don Walko, X-Ray Science Division, Argonne National Laboratory, and Mr. James Harkess, Monash University. This research was performed at the 7-ID and 7-BM beamlines 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 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.

Supplementary material


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Nicholas Mason-Smith
    • 1
    Email author
  • Daniel J. Duke
    • 2
  • Alan L. Kastengren
    • 3
  • Daniela Traini
    • 4
  • Paul M. Young
    • 4
  • Yang Chen
    • 4
  • David A. Lewis
    • 5
  • Daniel Edgington-Mitchell
    • 1
  • Damon Honnery
    • 1
  1. 1.Laboratory for Turbulence Research in Aerospace and Combustion, Department of Mechanical and Aerospace EngineeringMonash UniversityClaytonAustralia
  2. 2.Energy Systems DivisionArgonne National LaboratoryLemontUSA
  3. 3.X-ray Science DivisionArgonne National LaboratoryLemontUSA
  4. 4.Respiratory TechnologyWoolcock Institute of Medical Research and the Discipline of Pharmacology, Sydney Medical SchoolSydneyAustralia
  5. 5.Chiesi LtdChippenhamUK

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