title: Insights into Spray Development from Metered-Dose Inhalers Through Quantitative X-ray Radiography.
abstract: OBJECTIVE
  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.
authors.affiliation: Laboratory for Turbulence Research in Aerospace and Combustion, Department of Mechanical and Aerospace Engineering, Monash University, Melbourne, Australia. nick.masonsmith@gmail.com.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Mason-Smith
authors.affiliation: Energy Systems Division, Argonne National Laboratory, Lemont, Illinois, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Duke
authors.affiliation: X-ray Science Division, Argonne National Laboratory, Lemont, Illinois, USA.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Kastengren
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Stewart
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research and the Discipline of Pharmacology, Sydney Medical School, Sydney, Australia.
authors.forename: Daniela
authors.initials: D
authors.lastname: Traini
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research and the Discipline of Pharmacology, Sydney Medical School, Sydney, Australia.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Young
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research and the Discipline of Pharmacology, Sydney Medical School, Sydney, Australia.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Chiesi Ltd, Chippenham, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Lewis
authors.affiliation: Laboratory for Turbulence Research in Aerospace and Combustion, Department of Mechanical and Aerospace Engineering, Monash University, Melbourne, Australia.|Department of Aeronautical Engineering, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Julio
authors.initials: J
authors.lastname: Soria
authors.affiliation: Laboratory for Turbulence Research in Aerospace and Combustion, Department of Mechanical and Aerospace Engineering, Monash University, Melbourne, Australia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Edgington-Mitchell
authors.affiliation: Laboratory for Turbulence Research in Aerospace and Combustion, Department of Mechanical and Aerospace Engineering, Monash University, Melbourne, Australia.
authors.forename: Damon
authors.initials: D
authors.lastname: Honnery
mesh_terms: D000335:Aerosol Propellants / Q000737:chemistry*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004867:Equipment Design; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D009241:Ipratropium / Q000008:administration & dosage*; D036501:Metered Dose Inhalers; D014835:Volatilization; D014965:X-Rays
chemical_list: D000335:Aerosol Propellants; D001993:Bronchodilator Agents; D006845:Hydrocarbons, Fluorinated; D009241:Ipratropium
keywords: X-ray; pressurised metered dose inhaler; radiography; synchrotron radiation