title: Temporally and Spatially Resolved x-ray Fluorescence Measurements of in-situ Drug Concentration in Metered-Dose Inhaler Sprays.
abstract: OBJECTIVE
  Drug concentration measurements in MDI sprays are typically performed using particle filtration or laser scattering. These techniques are ineffective in proximity to the nozzle, making it difficult to determine how factors such as nozzle design will affect the precipitation of co-solvent droplets in solution-based MDIs, and the final particle distribution.
  
  
  METHODS
  In optical measurements, scattering from the constituents is difficult to separate. We present a novel technique to directly measure drug distribution. A focused x-ray beam was used to stimulate x-ray fluorescence from the bromine in a solution containing 85% HFA, 15% ethanol co-solvent, and 1 [Formula: see text] / [Formula: see text] IPBr.
  
  
  RESULTS
  Instantaneous concentration measurements were obtained with 1 ms temporal resolution and 5 [Formula: see text] spatial resolution, providing information in a region that is inaccessible to many other diagnostics. The drug remains homogeneously mixed over time, but was found to be higher at the centerline than at the periphery. This may have implications for oropharyngeal deposition in vivo.
  
  
  CONCLUSIONS
  Measurements in the dynamic, turbulent region of MDIs allow us to understand the physical links between formulation, inspiration, and geometry on final particle size and distribution. This will ultimately lead to a better understanding of how MDI design can be improved to enhance respirable fraction.
authors.affiliation: Energy Systems Division, Argonne National Laboratory, Lemont, Illinois, USA. dduke@anl.gov.
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: Laboratory for Turbulence Research in Aerospace & Combustion, Department of Mechanical & Aerospace Engineering, Monash University, Melbourne, Victoria, Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Mason-Smith
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Young
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Daniela
authors.initials: D
authors.lastname: Traini
authors.affiliation: Chiesi Limited, Chippenham, UK.
authors.forename: David
authors.initials: D
authors.lastname: Lewis
authors.affiliation: Laboratory for Turbulence Research in Aerospace & Combustion, Department of Mechanical & Aerospace Engineering, Monash University, Melbourne, Victoria, Australia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Edgington-Mitchell
authors.affiliation: Laboratory for Turbulence Research in Aerospace & Combustion, Department of Mechanical & Aerospace Engineering, Monash University, Melbourne, Victoria, Australia.
authors.forename: Damon
authors.initials: D
authors.lastname: Honnery
mesh_terms: D000335:Aerosol Propellants / Q000737:chemistry; D001966:Bromine / Q000737:chemistry; D004867:Equipment Design; D000431:Ethanol / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry; D036501:Metered Dose Inhalers; D004364:Pharmaceutical Preparations / Q000032:analysis*; D012997:Solvents / Q000737:chemistry; D013052:Spectrometry, X-Ray Emission / Q000379:methods*; D005466:Fluorocarbons
chemical_list: D000335:Aerosol Propellants; D001966:Bromine; D000431:Ethanol; D006845:Hydrocarbons, Fluorinated; D004364:Pharmaceutical Preparations; D012997:Solvents; C094049:apaflurane; D005466:Fluorocarbons
keywords: fluorescence; pressurized metered dose inhaler; synchrotron radiation; x-ray