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Article

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

1
School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK
2
School of Chemistry, University of Bristol, Bristol BS8 1TS, UK
3
Chiesi Farmaceutici S.p.A, Chippenham SN14 0AB, UK
*
Author to whom correspondence should be addressed.
Current address: Oz-UK Limited, Chippenham SN14 6RZ, UK.
Academic Editors: Fabio Sonvico and Francesca Buttini
Pharmaceutics 2021, 13(7), 941; https://doi.org/10.3390/pharmaceutics13070941
Received: 14 April 2021 / Revised: 5 June 2021 / Accepted: 6 June 2021 / Published: 24 June 2021
(This article belongs to the Special Issue Advanced Characterization of Inhalation Medicinal Products)
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. View Full-Text
Keywords: metered dose inhaler; spray plume aging; water condensation; aerosol hygroscopic growth; deposition modelling metered dose inhaler; spray plume aging; water condensation; aerosol hygroscopic growth; deposition modelling
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MDPI and ACS Style

Legh-Land, V.; Haddrell, A.E.; Lewis, D.; Murnane, D.; Reid, J.P. Water Uptake by Evaporating pMDI Aerosol Prior to Inhalation Affects Both Regional and Total Deposition in the Respiratory System. Pharmaceutics 2021, 13, 941. https://doi.org/10.3390/pharmaceutics13070941

AMA Style

Legh-Land V, Haddrell AE, Lewis D, Murnane D, Reid JP. Water Uptake by Evaporating pMDI Aerosol Prior to Inhalation Affects Both Regional and Total Deposition in the Respiratory System. Pharmaceutics. 2021; 13(7):941. https://doi.org/10.3390/pharmaceutics13070941

Chicago/Turabian Style

Legh-Land, Victoria, Allen E. Haddrell, David Lewis, Darragh Murnane, and Jonathan P. Reid 2021. "Water Uptake by Evaporating pMDI Aerosol Prior to Inhalation Affects Both Regional and Total Deposition in the Respiratory System" Pharmaceutics 13, no. 7: 941. https://doi.org/10.3390/pharmaceutics13070941

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