The Role of Low Global Warming Potential Propellants on Suspension Metered Dose Inhaler Sprays

The reformulation of suspension-based pressurized metered dose inhalers (pMDI) with low global warming potential (GWP) propellants is challenged by wide-ranging changes to their chemicophysical properties such as vapor pressure, density and latent heat. The effect of low-GWP propellants on spray pattern and plume geometry for suspension pMDIs are not fully understood. There is a lack of data regarding the role of propellant choice and potential interactions with suspended drugs, which may explain performance variations between products and guide development of in-silico models. In this study, high speed imaging was used to measure the plume morphology and optical density of sprays containing HFA134a, HFA152a and HFO1234ze(E) propellants. Propellant-only placebo controls were compared to suspension formulations containing 2 mg/mL salbutamol sulphate. It was found that the presence of suspended particles has a significant effect on plume structure, reducing correlations between propellant thermophysical properties and cone angle, targeting angle, and optical center of mass by 6-7 times. These effects vary depending on propellant type due to variations in flash-evaporation behavior, which is less pronounced in low-GWP propellants compared to HFA134a. HFA152a sprays have a 23% reduction in Jakob number compared to HFA134a; plume width at the mouthpiece exit is commensurately increased by 40%. Equivalent HFO1234ze(E) sprays have less pronounced differences in Jakob number (13% reduced) and plume width (25% increased) compared to equivalent HFA134a sprays. Empirical models and standards which implicitly incorporate the flash-evaporation effects commonly observed in high-GWP HFA propellants may require adjustment to be suitable for use with low-GWP formulations.