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

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

doi:10.1007/s11095-017-2098-2

Cited by 14 publications

(3 citation statements)

References 35 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%

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%

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

Talaat

2022

Pharmaceuticals

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“…In this mechanism, the propellant rapidly expands and undergoes flash evaporation, resulting in the formulation forming a two-phase flow [ 2 , 11 ]. During the swift, subsequent expulsion from the actuator, the remaining liquefied component is dispersed into droplets through shear forces [ 10 , 12 ], and the initial droplets undergo further processes of evaporation (also known as droplet ‘ageing’). The resultant size of this initial droplet distribution has long been shown to be dependent on the formulation characteristics (such as viscosity, surface tension and non-volatile solute concentration) and device design [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Water Uptake by Evaporating pMDI Aerosol Prior to Inhalation Affects Both Regional and Total Deposition in the Respiratory System

et al. 2021

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As pulmonary drug deposition is a function of aerosol particle size distribution, it is critical that the dynamics of particle formation and maturation in pMDI sprays in the interim between generation and inhalation are fully understood. This paper presents an approach to measure the evaporative and condensational fluxes of volatile components and water from and to solution pMDI droplets following generation using a novel technique referred to as the Single Particle Electrodynamic Lung (SPEL). In doing so, evaporating aerosol droplets are shown capable of acting as condensation nuclei for water. Indeed, we show that the rapid vaporisation of volatile components from a volatile droplet is directly correlated to the volume of water taken up by condensation. Furthermore, a significant volume of water is shown to condense on droplets of a model pMDI formulation (hydrofluoroalkane (HFA), ethanol and glycerol) during evaporative droplet ageing, displaying a dramatic shift from a core composition of a volatile species to that of predominantly water (non-volatile glycerol remained in this case). This yields a droplet with a water activity of 0.98 at the instance of inhalation. The implications of these results on regional and total pulmonary drug deposition are explored using the International Commission of Radiological Protection (ICRP) deposition model, with an integrated semi-analytical treatment of hygroscopic growth. Through this, droplets with water activity of 0.98 upon inhalation are shown to produce markedly different dose deposition profiles to those with lower water activities at the point of inspiration.

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“…The propensity of a flow to cavitate, but not the form the cavitation takes, is generally assessed by its cavitation number, which can be determined directly from the vapour phase properties of the liquid and its operating pressure [28]. To obtain the phase state, distribution techniques such as phase contrast imaging and X-ray radiography can be used [7,33]. Phase contrast imaging provides internal and external visualization of vapour and liquid distributions, whereas X-ray radiography provides quantification of the mass distribution from which phase state can be determined, although this approach is limited to the nozzle's external flow.…”

Section: Introductionmentioning

confidence: 99%

Spray flow structure from twin-hole diesel injector nozzles

Nguyen

Duke

Kastengren

et al. 2017

Experimental Thermal and Fluid Science

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a b s t r a c tTwo techniques were used to study non-evaporating diesel sprays from common rail injectors which were equipped with twin-hole and single-hole nozzles for comparison. To characterise the sprays, high speed optical imaging and X-ray radiography were used. The former was performed at the Laboratory for Turbulence Research in Aerospace and Combustion (LTRAC) at Monash University, while the latter was performed at the 7-BM beamline of the Advanced Photon Source (APS) at Argonne National Laboratory. The optical imaging made use of high temporal, high spatial resolution spray recordings on a digital camera from which peripheral parameters in the initial injection phase were investigated based on edge detection. The X-ray radiography was used to explore quantitative mass distributions, which were measured on a point-wise basis at roughly similar sampling rate. Three twin-hole nozzles of different subtended angles and a single-hole nozzle were investigated at injection pressure of 1000 bar in environments of 20 bar back pressure. Evidence of strong cavitation was found for all nozzles examined with their C D ranging from 0.62 to 0.69. Penetration of the twin-hole nozzles was found to lag the single-hole nozzle, before the sprays merged. Switching in hole dominance was observed from one twin-hole nozzle, and this was accompanied by greater instability in mass flow during the transient opening phase of the injectors.

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

Cited by 14 publications

References 35 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

Water Uptake by Evaporating pMDI Aerosol Prior to Inhalation Affects Both Regional and Total Deposition in the Respiratory System

Spray flow structure from twin-hole diesel injector nozzles

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