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

Nicholas Mason-Smith, Daniel J. Duke, Alan L. Kastengren, Daniela Traini, Paul M. Young, Yang Chen, David A. Lewis, Daniel Edgington-Mitchell, Damon Honnery

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13 Citations (Scopus)


Purpose: 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.

Methods: 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.

 Results: 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%.

 Conclusion: 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.

Original languageEnglish
Pages (from-to)718-729
Number of pages12
JournalPharmaceutical Research
Issue number4
Publication statusPublished - 1 Apr 2017


  • S phase contrast imaging
  • . pressurised metered-dose inhaler
  • radiography
  • synchrotron radiation

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