Influence of Formulation on Aerosol Particle Size

Polli, Gerald P.; Grim, Wayne M.; Bacher, Frederick A.; Yunker, Martin H.

doi:10.1002/jps.2600580422

Cited by 69 publications

(15 citation statements)

References 3 publications

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“…Increased vapor pressure has been correlated with decreases in particle-size output from MDIs. 7,10 Higher vapor pressure results in greater mechanical disruption of the propellant during actuation, and greater evaporation rate of the propellant droplets. 14 The MDIs produced plumes similar to those produced by commercial MDI products (Figure 1).…”

Section: Effect Of Propellant Composition On the Mmad Gsd And Fpf Omentioning

confidence: 99%

Aerosol generation by metered-dose inhalers containing dimethyl ether/propane inverse microemulsions

Sommerville

Hickey

2003

AAPS PharmSciTech

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Water soluble compounds were incorporated into metered-dose inhalers (MDIs) by using water-in-propellant lecithin microemulsions, in which dimethyl ether (DME) and propane acted as both continuous phase and propellant. Lecithin, water, and water soluble compounds were added to glass MDI containers, valves were crimped on, and propellants were added using a pressure burette. Aerosols were produced using commercially available actuators, and inertial impaction was used to determine the mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), and fine particle fraction (FPF) of the resulting aerosols. The DME/propane/lecithin microemulsion MDIs generated aerosols with particle size distributions suitable for pulmonary delivery (eg, MMAD 3.1 µm, FPF 59% for DME with lecithin content 3%, water content 2.5% [wt/wt]). Increasing water concentration (up to 8% wt/wt) was correlated with a reduction in FPF. Freezing and rewarming had no adverse effect on MMAD, GSD, or FPF. Storage of microemulsion samples for up to 3 weeks did not adversely affect the MMAD, GSD, or FPF. This approach may enable the pulmonary delivery of water soluble therapeutic agents via MDIs.

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Section: Effect Of Propellant Composition On the Mmad Gsd And Fpf Omentioning

confidence: 99%

Aerosol generation by metered-dose inhalers containing dimethyl ether/propane inverse microemulsions

Sommerville

Hickey

2003

AAPS PharmSciTech

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“…34 Although the size of aerosol particles with mesh nebulizers varies, 44,45 a significant proportion are Ͻ 3.3 m. 45,46 The vapor pressure of the propellant mixture, ambient temperature, design of the valve stem and actuator orifice, and drug concentration affect aerosol particle size produced from the pMDI. 47,48 For example, high vapor pressure of propellants generates finer aerosol particles, whereas a higher drug concentration increases the size of aerosol particles produced from the pMDI.…”

Section: Effect Of Particle Sizementioning

confidence: 99%

Aerosol Therapy in Pulmonary Critical Care

Ari

2015

Respir Care

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SummaryAerosolized medications are routinely used for the treatment of critically ill patients. This paper reviews aerosol delivery devices with a focus on issues related to their performance in pulmonary critical care. Factors affecting aerosol drug delivery to mechanically ventilated adults and spontaneously breathing patients with artificial airways are reviewed. Device selection, optimum device technique, and unmet medical needs of aerosol medicine in pulmonary critical care are also discussed.

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“…The mechanism responsible for droplet generation from bulk formulation is known to be transient, turbulent, and highly complex (Finlay 2001). Early experimental work by Polli et al (1969) identified key factors affecting the particle size of pMDI aerosols: propellant vapor pressure and spray orifice size, as well as drug particle size, drug concentration, and presence of surfactant in the suspension formulation. Fletcher (1975) studied steady flows of flashing mixtures of CFC propellants 11, 12, and 114 through a twin-orifice system.…”

Section: Introductionmentioning

confidence: 99%

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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Influence of Formulation on Aerosol Particle Size

Cited by 69 publications

References 3 publications

Aerosol generation by metered-dose inhalers containing dimethyl ether/propane inverse microemulsions

Aerosol generation by metered-dose inhalers containing dimethyl ether/propane inverse microemulsions

Aerosol Therapy in Pulmonary Critical Care

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

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