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

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)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.Peer reviewe

Inhalation Blend Microstructure:Identifying Metrics to Address Q3 Equivalence using Semi-automated X-Ray Microscopy

Assessing the microstructure of inhalation powder blends is important for assessment of Q3 microstructural equivalence, but it remains a challenge to examine a powder in its pre-actuated state. In this work, we demonstrate a robust, user-independent image analysis workflow for using X-ray Computed Tomography (XCT), allowing the fines-rich phase of different blend formulations to be visualized and quantified. The workflow provides qualitative and quantitative information on formulation microstructure. Qualitatively, differences in XCT-characterized microstructure were consistent with differences in aerosolization behavior of carrier lactose blends with micronized lactose, terbutaline sulfate and fluticasone propionate. Quantitatively, metrics for the local thickness of fines-rich phases were derived that quantify the thicker coating of fluticasone propionate fines around carrier lactose particles in a blend, compared to terbutaline sulfate or micronized lactose, which formed agglomerated regions of fines of lower density and a heterogeneous degree of association with carrier lactose particles. This approach links pre-actuated microstructure of inhalation powder blends with product performance and provides the first steps to the application of XCT to a range of dry powder inhalation products