Nicholas Mason-Smith1, Daniel J Duke2, Alan L Kastengren3, Daniela Traini4, Paul M Young4, Yang Chen4, David A Lewis5, Daniel Edgington-Mitchell6, Damon Honnery6. 1. Laboratory for Turbulence Research in Aerospace and Combustion, Department of Mechanical and Aerospace Engineering, Monash University, Clayton, Australia. Nicholas.Mason-Smith@Monash.edu. 2. Energy Systems Division, Argonne National Laboratory, Lemont, Illinois, USA. 3. X-ray Science Division, Argonne National Laboratory, Lemont, Illinois, USA. 4. Respiratory Technology, Woolcock Institute of Medical Research and the Discipline of Pharmacology, Sydney Medical School, Sydney, Australia. 5. Chiesi Ltd, Chippenham, UK. 6. Laboratory for Turbulence Research in Aerospace and Combustion, Department of Mechanical and Aerospace Engineering, Monash University, Clayton, Australia.
Abstract
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.
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.
Authors: Daniel J Duke; Alan L Kastengren; Nicholas Mason-Smith; Yang Chen; Paul M Young; Daniela Traini; David Lewis; Daniel Edgington-Mitchell; Damon Honnery Journal: Pharm Res Date: 2015-11-12 Impact factor: 4.200
Authors: Nicholas Mason-Smith; Daniel J Duke; Alan L Kastengren; Peter J Stewart; Daniela Traini; Paul M Young; Yang Chen; David A Lewis; Julio Soria; Daniel Edgington-Mitchell; Damon Honnery Journal: Pharm Res Date: 2016-02-17 Impact factor: 4.200
Authors: Yang Chen; Paul M Young; Seamus Murphy; David F Fletcher; Edward Long; David Lewis; Tanya Church; Daniela Traini Journal: AAPS PharmSciTech Date: 2016-06-17 Impact factor: 3.246
Authors: Alan Kastengren; Christopher F Powell; Dohn Arms; Eric M Dufresne; Harold Gibson; Jin Wang Journal: J Synchrotron Radiat Date: 2012-05-11 Impact factor: 2.616
Authors: Victoria Legh-Land; Allen E Haddrell; David Lewis; Darragh Murnane; Jonathan P Reid Journal: Pharmaceutics Date: 2021-06-24 Impact factor: 6.321