Insights into Spray Development from Metered-Dose Inhalers Through Quantitative X-ray Radiography

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

doi:10.1007/s11095-016-1869-5

Cited by 10 publications

(13 citation statements)

References 28 publications

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“…Visualization of MDI actuation and aerosol formation has been attempted by using high-speed camera, laser diffraction, Schlieren optical imaging, and phase-contrast X-ray imaging [31][32][33][34][35][36][37]. With a laser and high-speed camera, Smyth et al observed asymmetrical and ellipsoid spray cross-sections in the vertical direction [38].…”

Section: Introductionmentioning

confidence: 99%

“…With a laser and high-speed camera, Smyth et al observed asymmetrical and ellipsoid spray cross-sections in the vertical direction [38]. Mason-Smith et al recorded the spray plume development in the near-nozzle region at 5 µm spatial and 0.184 ms temporal resolution, using X-ray radiography; they observed that the spray flow reached steady conditions around 30 ms after the actuation of HFA MDIs [34]. It is noted, however, that the MDI spray was discharged into a free space in most previous visualization studies, which could be different from the spray plume when released into a confined space.…”

Section: Introductionmentioning

confidence: 99%

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Effect of MDI Actuation Timing on Inhalation Dosimetry in a Human Respiratory Tract Model

Talaat

2022

Pharmaceuticals

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Accurate knowledge of the delivery of locally acting drug products, such as metered-dose inhaler (MDI) formulations, to large and small airways is essential to develop reliable in vitro/in vivo correlations (IVIVCs). However, challenges exist in modeling MDI delivery, due to the highly transient multiscale spray formation, the large variability in actuation–inhalation coordination, and the complex lung networks. The objective of this study was to develop/validate a computational MDI-releasing-delivery model and to evaluate the device actuation effects on the dose distribution with the newly developed model. An integrated MDI–mouth–lung (G9) geometry was developed. An albuterol MDI with the chlorofluorocarbon propellant was simulated with polydisperse aerosol size distribution measured by laser light scatter and aerosol discharge velocity derived from measurements taken while using a phase Doppler anemometry. The highly transient, multiscale airflow and droplet dynamics were simulated by using large eddy simulation (LES) and Lagrangian tracking with sufficiently fine computation mesh. A high-speed camera imaging of the MDI plume formation was conducted and compared with LES predictions. The aerosol discharge velocity at the MDI orifice was reversely determined to be 40 m/s based on the phase Doppler anemometry (PDA) measurements at two different locations from the mouthpiece. The LES-predicted instantaneous vortex structures and corresponding spray clouds resembled each other. There are three phases of the MDI plume evolution (discharging, dispersion, and dispensing), each with distinct features regardless of the actuation time. Good agreement was achieved between the predicted and measured doses in both the device, mouth–throat, and lung. Concerning the device–patient coordination, delayed MDI actuation increased drug deposition in the mouth and reduced drug delivery to the lung. Firing MDI before inhalation was found to increase drug loss in the device; however, it also reduced mouth–throat loss and increased lung doses in both the central and peripheral regions.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of MDI Actuation Timing on Inhalation Dosimetry in a Human Respiratory Tract Model

Talaat

2022

Pharmaceuticals

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“…All these measurements are also limited to observations downstream of the nozzle orifice. Imaging of transparent models (Versteeg et al, 2006) and X-ray imaging (Mason-Smith et al, 2017) reveal the morphology of the flow inside the expansion chamber, but not the drug distribution. Photon emission tomography techniques (Fleming et al, 2011) provide a useful means of characterising the fate of the drug in-vivo, but do not presently have the high spatial or temporal resolution required to observe the spray when it first exits the nozzle.…”

Section: Introductionmentioning

confidence: 99%

“…This technique exploits the bromine atom in Ipratropium bromide (IPBr) as a molecular tracer, allowing the drug mass distribution to be measured independently of the propellant and co-solvent. Mason-Smith et al (2016) have also shown that X-ray radiography at lower photon energies can be used to measure the total line-of-sight average density of a PMDI spray with high resolution using synchrotron X-rays. To understand how drug mass fraction in the droplets varies throughout the spray, both the total spray mass and the drug mass distributions must be measured simultaneously.…”

Section: Introductionmentioning

confidence: 99%

Drug distribution transients in solution and suspension-based pressurised metered dose inhaler sprays

Duke

Scott

Kusangaya

et al. 2019

International Journal of Pharmaceutics

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“…In addition to diesel sprays, other spray configurations have been investigated using the APS facilities, including shear coaxial jet injectors (Lightfoot et al, 2015;Schumaker et al, 2013), liquid-centered swirl coaxial injectors (Eberhart et al, 2014), impinging jet injectors (Halls et al, 2014a), coaxial airblast atomizers (Bothell et al, 2018), jets in cross flow (Lin et al, 2016), cryogenic rocket injectors (Radke et al, 2017), metered-dose inhalers (Mason-Smith et al, 2016), and cavitating nozzles (Duke et al, 2013).…”

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confidence: 99%

X-Ray Imaging Techniques to Quantify Spray Characteristics in the Near Field

Heindel

2018

Atomiz Spr

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Liquid sprays play a key role in many engineering processes, including, but not limited to, food processing, coating and painting, 3D printing, fire suppression, agricultural production, and combustion systems. Spray characteristics can easily be assessed in the mid-and far-field regions, well after liquid sheet breakup and droplet formation, using various optical and/or laser diagnostic techniques. The conditions in the near-field region influence mid-and far-field characteristics; however, near-field measurements are extremely challenging because the spray in this region is typically optically dense where optical and laser diagnostics are generally ineffective. This paper provides an overview of the various X-ray imaging techniques that can be used to characterize the near-field region of a spray. X-rays produced with tube sources as well as synchrotron sources will be discussed. Using tube-source X-rays, 2D radiographic videos are possible showing qualitative spray information. The 2D radiographs can also provide quantitative measurements of the optical depth (OD) in the near-field region. Tube sources can also provide X-ray computed tomography imaging that can produce time-average 3D density (mass distribution) maps of the spray. X-rays from synchrotron radiation provide a high-flux X-ray beam that can be used to provide high spatial and temporal resolution of the spray equivalent path length (EPL) as well as other characteristics, but it is more challenging to implement than using a common tube source. Various examples of these X-ray imaging techniques will be discussed.

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Insights into Spray Development from Metered-Dose Inhalers Through Quantitative X-ray Radiography

Cited by 10 publications

References 28 publications

Effect of MDI Actuation Timing on Inhalation Dosimetry in a Human Respiratory Tract Model

Effect of MDI Actuation Timing on Inhalation Dosimetry in a Human Respiratory Tract Model

Drug distribution transients in solution and suspension-based pressurised metered dose inhaler sprays

X-Ray Imaging Techniques to Quantify Spray Characteristics in the Near Field

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