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Inhalation OctOber 2021 23 the CFC to HFA transition in the 1990s [11, 12]. HFO1234ze has been also evaluated as a refrigerant for many applications [13]. Available data from existing work typically relates to pure component properties. However, as dis- cussed, the modeler and designer of a pMDI system needs information about temperature- and compo- sition-dependent formulation mixture properties, with propellant plus ethanol being a key mixture. Accurate room temperature HFA134a/ethanol mixture properties have been recently obtained for density, surface tension and liquid viscosity [14, 15], across a wide range of mixtures, from pure ethanol to pure HFA134a. ese studies used mechani- cal methods: the height of capillary rise for surface tension and the falling ball method for liquid viscos- ity. Other methods can be used as well, including, for surface tension, direct force measurements via an immersed rod, ring or plate (e.g., the Wilhelmy plate method); the droplet shape fitting method for suspended or sessile droplets (requiring imaging of the droplet with a camera); or bubble pressure meth- ods. For liquid viscosity, vibrating-wire viscometers or various proprietary rheometry instruments may also be used. However, such data are required across a wide range of temperatures. Temperature-controlled mechanical measurements are possible using existing instru- ments, including those described here. Alternatively, an optical test method can be used, which employs a laser-based technique to probe a small volume of formulation fluid held in an optical test cell under well-controlled conditions. Two techniques that achieve this are surface light scattering (SLS) and dynamic light scattering (DLS). Both techniques are non-invasive and highly precise since they rely on photon correlation spectroscopy and are there- fore relatively insensitive to noise and fluctuations in signal intensity. e SLS technique can be used for simultaneous measurement of surface tension and liquid viscosity, whereas DLS leads to measurements of mixture mass diffusivity and thermal diffusivity if combined with in situ refractive index measurement. Optical and laser-based techniques have advantages in that they are more easily applied at conditions dif- fering from ambient; for example, below 0°C and at several atmospheres of pressure, as needed for pMDI formulation property measurement. Physical properties of pMDI formulations typi- cally are more strongly influenced by temperature and chemical composition than pressure. However, with a purpose-built optical cell for laser-based mea- surement, it would be possible to condition fluid mixtures to different pressures if desired. Specific mixtures that support development of a par- ticular product (e.g., containing active or dummy pharmaceutical ingredients) can rapidly be tested average of the pure component properties. is is particularly true of so-called non-ideal liquids, of which ethanol/HFA mixtures are an example. erefore, obtaining experimental mixture prop- erty data is a must. Furthermore, physical properties are temperature- dependent (and to a lesser extent, pressure- dependent). is is not just important because pMDIs are used in various climates around the world. e pMDI two-phase flow through the metering chamber, into the expansion chamber and then out of the orifice as an aerosol, goes through rapid transient temperature change. Firstly, cooling due to flash evaporation and expansion of the propellant, then heating once most of the propellant has vaporized, leaving behind less volatile or solid components. In addition, the tem- perature at a fixed location will vary throughout the event, as solid walls reach equilibrium temperature and flow transients settle. e liquid-phase composition will also change markedly as the dose process occurs, varying both temporally and spatially. erefore, the liquid prop- erties will vary, impacting the tendency to boil, atomize, form and grow bubbles, etc., as controlled by the properties and processes in Table 1. Physical properties are typically measured at atmospheric pressure (close to 100 kPa) or at for- mulation vapor pressure, whichever is greater. e expansion chamber sump pressure inside the actu- ator reduces during pMDI actuation from a value close to the formulation saturated vapor pressure down towards atmospheric pressure by the end of dosing [3]. e pressure inside the free aerosol is essentially atmospheric. erefore, the formulation mixture takes a tem- perature, pressure and composition trajectory as it is transformed into an aerosol; meaning that prop- erties that control aerosol formation are also varying throughout. e effects of this can be incorpo- rated into CFD and 1-D modeling, which requires knowledge of the temperature-, pressure- and composition- dependence of properties and proper implementation of these in the model. e models that attempt to predict, for example, the growth of instabilities in liquid surface in the actu- ator orifice during the atomization process, require that liquid physical properties be evaluated at the conditions in the orifice. For a solution formulation, this may be a liquid that is rich in ethanol and at a cooler than ambient temperature. e predictions from models are therefore only as reliable as the data that goes into them. Measuring thermophysical properties Some data already exist: HFA152a was evaluated with respect to many physical properties for con- sideration as a propellant and a refrigerant during