Inhalation

INH1021

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In this article, the fundamental thermophysical properties that control the complex internal flow and aerosol formation process in a pMDI will be examined, from the perspective of their measurement, representation and prediction. Activity coefficient models that enable simultaneous description and prediction of important formulation thermophysical properties will also be presented. The performance of these models is demonstrated using existing data for HFA134a/ethanol mixtures, to show their potential application alongside experimental property data collection involving future propellants. Inhalation OctOber 2021 21 Context e hydrofluoroalkanes (HFAs) currently used as propellants in pressurized metered dose inhal- ers (pMDIs) are expected to be phased-out of use. is is due to the Kigali amendment to the Mon- treal Protocol [1], which targets scheduled reduction of certain fluorinated gases due their high global warming potential (GWP) and impact on climate change. Although in the pharmaceutical industry, the contribution of HFA gases to overall greenhouse gas emissions is small, for pMDI producers, there is a need to avoid increased costs as the supply of specific HFAs becomes reduced and interest grows in decreasing greenhouse gas emissions and their impact on climate change. Potential replacement propellants include HFA152a and the hydrofluoroolefin HFO1234ze (which has a carbon/carbon double bond). HFA152a is cur- rently being evaluated with respect to a variety of criteria, including patient safety and manufacturing process safety [2]. Its performance as a pMDI aero- sol propellant is being predicted by companies and researchers [3, 4]. is is a large undertaking for the industry as a whole. e fundamental thermophysical and aero- sol formation properties of pMDI formulations will change when HFA134a and HFA227ea are phased- out. However, if a new propellant is introduced for a current product, it is desirable to achieve very similar aerodynamic particle size distribution (APSD) and fine particle fraction (FPF), as well as to provide a very similar and satisfactory experience for patients. Simultaneously, there has been an increase in the use of computational fluid dynamics (CFD) and other predictive modeling tools [5]. For the pharmaceutical industry, crucially, this includes a greater awareness, understanding and availability of specialist CFD that can predict multi-phase flow, with detailed turbulence modeling (for example, Large-Eddy Sim- ulation), cavitation [5] and non-equilibrium phase change [6]. ere is also, of course, ever increasing simulation power and access to high performance computing (HPC) that can offer more numerous, faster and more detailed simulations. In this article, the fundamental thermophysical properties that control the complex internal flow and aerosol formation process in a pMDI will be exam- ined, from the perspective of their measurement, representation, and prediction. Accurate knowledge and understanding of these properties, potentially in comparison with predictive simulation tools, will contribute to the effective development of next- generation pMDI formulation. Activity coefficient models that enable simultaneous description and prediction of important formulation thermophysical properties will also be presented. e performance of these models is demonstrated using existing data for HFA134a/ethanol mixtures, to show their potential application alongside experimental property data collection involving future propellants. Joseph Camm, PhD University of Liverpool As pMDIs with low global warming potential are introduced and the need for accurate thermophysical property prediction grows, models that use activity coefficient are promising. Propellant and formulation properties for next-generation pMDIs: Measurement, representation and prediction

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