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.