Issue link: https://www.e-digitaleditions.com/i/1417310
22 OctOber 2021 Inhalation In particular, the formulation saturated vapor pres- sure (SVP), strongly affected by the addition of ethanol, has great influence in the overall efficiency of atomization and resultant particle or droplet size distribution. It has been observed that the addi- tion of ethanol, which reduces overall formulation SVP, has tended to increase droplet size metrics [3]. However, addition of ethanol has also been noted to stabilize the internal two-phase flow process and result in a lower Sauter Mean Diameter [7]. e properties in Table 1 should be known relatively accurately for a multi-component formulation. is enables comparison of one formulation's specifica- tions against another, either an existing specification with that of a next-generation, or two different versions of the same formulation (e.g., with concen- tration of ethanol varied). ese properties are also entered into empirical equations (e.g., that of Clark [9]), for one-dimensional (1-D) modeling [10] and 3-D CFD modeling. In the latter, multi-component fluid property evaluation is often handled automat- ically by proprietary industrial software, sometimes using mixing rules designed for ideal mixtures [10]. e properties of multi-component liquids are often not well represented by a simple weighted Formulation and aerosol behavior MDI formulations are a multi-component mix- ture, including active ingredients (APIs), propellant, co-solvent, excipients and surfactants. e formu- lations interact with a variety of metal, polymer elastomer materials and coatings used in MDI canis- ter and valve hardware. Additionally, in experimental work, there may be a dummy or placebo API in the mixture, or tracer compounds to facilitate a certain experimental technique. Next-generation formula- tions, for example containing HFA152a, will have as yet unknown final constituents and composition. e aerosol performance (e.g., flow rate, aero- sol temperature and aerodynamic particle size distribution) of these multi-component solution- and suspension-formulations is influenced strongly by the thermophysical properties of the liquid phase. ese properties govern the complex internal flow behavior that is a precursor to atomization and aero- sol formation, understanding of which has recently been improved through optical [7] and X-ray phase contrast imaging [8]. Table 1 lists various physical properties and characteristics relevant to pMDIs and the phenomena that are dependent on or controlled by them. Table 1 Formulation physical properties and characteristics relevant to pMDIs, and the phenomena that are dependent on them Formulation physical property Phenomena dependent on this property Density Atomization Loss of prime Internal two-phase flow Liquid/Surface interaction Saturated vapor pressure (SVP) Atomization Internal two-phase flow Droplet evaporation/Particle drying Surface tension Atomization Loss of prime Liquid/Surface interaction Liquid viscosity Atomization Liquid/Surface interaction Thermal conductivity Temperature reduction Liquid/Surface interaction Specific heat capacity Temperature reduction Mass diffusion coefficients Canister sealing Bubble growth Droplet evaporation/Particle drying Enthalpy of vaporization Temperature reduction Droplet evaporation/Particle drying Contact angle Particle cohesion and adhesion