Modulation of aerosol clouds produced by pressurised inhalation aerosols

Brambilla, G.; Ganderton, D.; Garzia, Raffaella; Lewis, David; Meakin, B. J.; Ventura, Paolo

doi:10.1016/s0378-5173(99)00137-4

Cited by 77 publications

(37 citation statements)

References 4 publications

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“…In general, the ex-valve dose for all the formulations were within 15% of the nominal dose, with USP induction port having the highest amount of particle deposition. This is in good agreement with previously published data for similar formulations (Brambilla et al 1999).…”

Section: Andersen Cascade Impactor Measurementssupporting

confidence: 83%

The Formation of Aerosol Particles from Solution-Based Pressurized Metered Dose Inhalers and Implications of Incomplete Droplet Drying: Theoretical and Experimental Comparison

Zhu

Traini

et al. 2015

Aerosol Science and Technology

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The aerosol particle size distributions of solution-based pressurized metered dose inhalers containing 15%w/w ethanol and different quantities of nonvolatile component (NVC) (drug and glycerol) were evaluated at 25 C and 55 C, using a custombuilt heating rig that preheated air prior to aerosolization. Particle size distributions were assessed using an Andersen cascade impactor and massÀweighted cumulative aerodynamic diameter distributions were compared to a theoretical model that predicts the final size distribution, based on initial droplet size, vapor pressure of the formulation containing HFA 134a and percent NVC. In general, the mass median aerodynamic diameter was proportional to NVC 1/3 , with experimental particle size distributions following theoretical values. However, when comparing theoretical vs. experimental data over the range of mass-weighted cumulative aerodynamic diameter distributions between 10 and 90%, the 55 C experimental measurements more closely fitted the theoretical equation when compared to 25 C. This was attributed to incomplete drying of some of the larger initial droplets prior to impaction. Additionally, postinduction port measurements of volumetric size distribution using laser diffraction, showed a reduction in median particle diameter at 55 C, compared to 25 C and a change from bimodal to monomodal distribution, indicating complex drying kinetics under ambient conditions.

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Section: Andersen Cascade Impactor Measurementssupporting

confidence: 83%

The Formation of Aerosol Particles from Solution-Based Pressurized Metered Dose Inhalers and Implications of Incomplete Droplet Drying: Theoretical and Experimental Comparison

Zhu

Traini

et al. 2015

Aerosol Science and Technology

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“…Another important feature of Figures 4a and b is the prediction of smaller droplet size for HFA134a propellant system compared with HFA227 propellant system, by both atomization model variants. This trend was previously observed in several studies such as Brambilla et al (1999), Stein and Myrdal (2004), and Myrdal et al (2004), who measured the residual droplet size issued from a pMDI. The trend is attributable to higher saturated vapor pressure of HFA134a compared with HFA227, providing greater energy source for flow acceleration.…”

Section: Resultssupporting

confidence: 55%

“…This was previously suggested by Smyth (2003) and would imply that control of particle size may be possible by careful adjustment of the viscosity of the formulation. It is interesting to note that Brambilla et al (1999) have successfully managed to achieve such a result by adding specific amounts of ethanol to pharmaceutical propellants. Ethanol is an excipient, which is thought to reduce the vapor pressure, but will also modify the surface tension and viscosity of the formulation.…”

Section: Resultsmentioning

confidence: 99%

“…However, impactors characterize the final particle size distribution, whereas the aerosol source produced by a pMDI will contain significant quantities of propellant liquid. More recent studies (Brambilla et al 1999;Stein and Myrdal 2004;Ivey et al 2014) have developed empirical correlations for the initial spray droplet size, i.e., the spray source produced at the actuator orifice. The models predict the initial droplet size at the spray orifice exit from the residual droplet size measured by cascade impactors assuming that (i) evaporation is the only mechanism responsible for reduction of the droplet size after emission from the pMDI and (ii) all volatile formulation components are fully evaporated at point of impaction.…”

Section: Introductionmentioning

confidence: 99%

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Transient aerodynamic atomization model to predict aerosol droplet size of pressurized metered dose inhalers (pMDI)

Gavtash

Versteeg

Hargrave

et al. 2017

Aerosol Science and Technology

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Pressurized metered dose inhalers (pMDI) produce large numbers of droplets with smaller sizes than 5 mm to treat asthma and other pulmonary diseases. The mechanism responsible for droplet generation from bulk propellant liquid is poorly understood, mainly because the small length scales and short time scales make it difficult to characterize transient spray formation events. This article describes the development and findings of a numerical atomization model to predict droplet size of pharmaceutical propellants from first principles. In this model, the velocity difference between propellant vapor and liquid phase inside spray orifice leads to formation of wave-like instabilities on the liquid surface. Two variants of the aerodynamic atomization model are presented based on assumed liquid precursor geometry: (1) cylindrical jet-shaped liquid ligaments surrounded by vapor annulus; (2) annular liquid film with vapor flow in the core. The growth of instabilities on the liquid precursor surfaces and the size of the subsequently formed droplets are predicted by numerical solutions of dispersion equations. The droplet size predictions were compared with phase doppler anemometry (PDA) data and the predictions were in good agreement with the number mean diameter D 10 , which is representative of the respirable droplets. The temporal behavior of droplet size production was captured consistently well during the period of the first 95% of the propellant mass emission. The outcome of our modeling activities also suggests that, in addition to saturated vapor pressure of the propellant, its viscosity and surface tension are also key properties that govern pMDI droplet size. EDITORWarren Finlay

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“…However, one other parameter that should be considered is the diameter of the commercial pMDI actuator nozzles. Generally, this ranges from 0.14 to 0.6 mm ( 27 ) and the flash boiling atomisation is a rapid process. Therefore, it is unknown whether there are opportunities for these hypothesised hydrophobic/hydrophilic interactions between liquid formulation and the actuator surface to cause changes in plume geometry during such limited length and short transit times.…”

Section: Fig 10mentioning

confidence: 99%

High-Speed Laser Image Analysis of Plume Angles for Pressurised Metered Dose Inhalers: The Effect of Nozzle Geometry

et al. 2016

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Modulation of aerosol clouds produced by pressurised inhalation aerosols

Cited by 77 publications

References 4 publications

The Formation of Aerosol Particles from Solution-Based Pressurized Metered Dose Inhalers and Implications of Incomplete Droplet Drying: Theoretical and Experimental Comparison

The Formation of Aerosol Particles from Solution-Based Pressurized Metered Dose Inhalers and Implications of Incomplete Droplet Drying: Theoretical and Experimental Comparison

Transient aerodynamic atomization model to predict aerosol droplet size of pressurized metered dose inhalers (pMDI)

High-Speed Laser Image Analysis of Plume Angles for Pressurised Metered Dose Inhalers: The Effect of Nozzle Geometry

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