Effect of vapour pressure on the deposition pattern from solution phase metered dose inhalers

Harnor, K.J.; Perkins, Alan C.; Wastie, M. L.; Wilson, Clive G.; Sims, E; Feely, Liam C.; Farr, Stephen J.

doi:10.1016/0378-5173(93)90397-x

Cited by 26 publications

(6 citation statements)

References 9 publications

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“…This results in part from the formulation of drug in an ethanolic solution, which evaporates rapidly, leaving many fine droplets in the spray, such that over 10% of the metered dose was contained in droplets small enough to enter the lungs but to be exhaled subsequently. Whole lung deposition values as high as the mean value of 39.7% in this study have also been reported previously for MDI formulations containing a propellant soluble radiolabel, 15,16 which would also comprise rapidly evaporating droplets. When an aqueous solution of fenoterol was delivered by the multidose nebulizer, lung deposition of >30% of the dose was recorded.…”

Section: Discussionsupporting

confidence: 73%

Efficient Delivery to the Lungs of Flunisolide Aerosol From a New Portable Hand-Held Multidose Nebulizer

Newman¹,

Steed²,

Reader

et al. 1996

Journal of Pharmaceutical Sciences

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In order to provide asthmatic patients with an inhaler that does not use chlorofluorocarbon propellants, a novel multidose hand-held nebulizer (RESPIMAT, Boehringer Ingelheim Ltd.) has been developed. This device delivers 200 x 15 microL metered doses of drug solution, but does not use propellants of any kind. In this study of 10 healthy volunteers, the deposition pattern in the lungs and oropharynx of an ethanolic solution of flunisolide delivered via a prototype III multidose nebulizer has been determined by gamma scintigraphy. A comparison was made with the same dose (250 micrograms) of flunisolide delivered by a pressurized metered dose inhaler (MDI) and MDI plus Inhacort spacer. Mean (SD) whole lung deposition from the multidose nebulizer (39.7 (9.9) % of the metered dose) was significantly higher than that from either MDI (15.3 (5.1) %, P < 0.01) or MDI plus spacer (28.0 (7.0) %, P = 0.01). A mean 10.4% of the dose was recovered from an exhaled air filter for the multidose nebulizer, but less than 2% of the dose for MDI or MDI plus spacer. Oropharyngeal deposition was significantly reduced for the multidose nebulizer (39.9 (9.4) %) compared to MDI (66.9 (7.1) %), but was reduced further for the MDI plus spacer (27.3 (11.3) %). The multidose nebulizer delivers an unusually high percentage of an aerosol dose to the lungs, and it "targets" flunisolide to the lungs more effectively than the MDI. The multidose nebulizer could constitute a viable alternative to MDIs in asthma maintenance therapy.

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Section: Discussionsupporting

confidence: 73%

Efficient Delivery to the Lungs of Flunisolide Aerosol From a New Portable Hand-Held Multidose Nebulizer

Newman¹,

Steed²,

Reader

et al. 1996

Journal of Pharmaceutical Sciences

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show abstract

“…Figures 4 and 5 show that the inverse relationship between velocity and droplet size, which is present in the measured data, is adequately captured by model predictions. This confirms the previous findings of Baeckstroem and Nilsson (1988) and Harnor et al (1993) for CFC formulations, as well as those of Clark (1991) and Wigley et al (2002) for HFA formulation. It should be noted that the LISA model predicts a "characteristic droplet size."…”

Section: Velocity and Droplet Sizesupporting

confidence: 92%

A model of transient internal flow and atomization of propellant/ethanol mixtures in pressurized metered dose inhalers (pMDI)

Gavtash

Versteeg

Hargrave

et al. 2018

Aerosol Science and Technology

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This article reports the extension to binary propellant/excipient mixtures of the multiphase model of transient internal flow and atomization in pressurized metered dose inhalers (pMDIs) of Gavtash and colleagues for propellant-only flows. The work considers different accounts of the effect of less volatile ethanol on the saturated vapor pressure (SVP), viscosity and surface tension of HFA-based pMDI formulations. Representation of the SVP of HFA/ethanol mixtures by Raoult's law is compared with the empirical model developed by Gavtash and colleagues as well as different theoretical mixing rules for surface tension and viscosity. For initial ethanol contents ranging from 0 to 20% by mass, the temperature, pressure and spray velocity were predicted to be almost independent of ethanol concentration when using the empirical SVP model of Gavtash and colleagues. The predicted aerosol droplet size increases with increasing concentration of ethanol. These model predictions compare favorably with phase Doppler anemometry (PDA) measurements of pMDI sprays. Exploration of model predictions with different mixing rules suggest that variations of the dynamic viscosity could result in 0.7 mm droplet size change, and different surface tension models yield around 1.5 mm droplet size change. The findings of this work challenge the view that the increase of droplet size is caused by the low volatility of excipients such as ethanol. Instead, attention is focused on composition-dependent viscosity and surface tension as potential controlling parameters with significant effect on the droplet size of HFA/ethanol sprays.

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“…Additional experiments conducted with heating the solution formulation Qvar 50 (at 40° and 55°C) showed a temperature‐dependent reduction in Dv 50. This observation can be expected because heating the formulation will increase the vapor pressure (as described in Table 7 for our experimental pMDIs),25 which increases the rate of atomization of the emitted droplets from the pMDI with a greater initial forward velocity 2,26. This results in a finer aerosol and contributes to the lower particle size of the emitted aerosol 27,28.…”

Section: Discussionmentioning

confidence: 79%

Evaluation of the Malvern Spraytec® with inhalation cell for the measurement of particle size distribution from metered dose inhalers

Haynes

Shaik

Krarup³

et al. 2004

Journal of Pharmaceutical Sciences

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Effect of vapour pressure on the deposition pattern from solution phase metered dose inhalers

Cited by 26 publications

References 9 publications

Efficient Delivery to the Lungs of Flunisolide Aerosol From a New Portable Hand-Held Multidose Nebulizer

Efficient Delivery to the Lungs of Flunisolide Aerosol From a New Portable Hand-Held Multidose Nebulizer

A model of transient internal flow and atomization of propellant/ethanol mixtures in pressurized metered dose inhalers (pMDI)

Evaluation of the Malvern Spraytec® with inhalation cell for the measurement of particle size distribution from metered dose inhalers

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