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

Toria J Legh-Land, Allen E Haddrell, David Lewis, Darragh Murnane, Jonathan P Reid*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

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
Original languageEnglish
Article number941
Number of pages22
Journalpharmaceutics
Volume13
Issue number7
DOIs
Publication statusPublished - 24 Jun 2021

Bibliographical note

Funding Information:
Funding: This research was funded by the EPSRC Centre for Doctoral Training in Aerosol Science (EP/S023593/1) (V.L.-L., D.M. and J.P.R.) the EPSRC research grant EP/N025075/1 INFORM2020 “Molecules to manufacture: Processing and Formulation Engineering of Inhalable Nanoaggregates and Micro-particles” (D.M.). The research was also funded by Chiesi Farmaceutici SpA (A.E.H., J.P.R).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • metered dose inhaler
  • spray plume aging
  • water condensation
  • aerosol hygroscopic growth
  • deposition modelling

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