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Optimizing Spray Formation in Solution and Suspension Low GWP Metered Dose Inhalers

Duke DJ, Myatt BJ, Rao L, Vutlapalli S, Marasini N, Dowdle H, Cocks P, Schmidt D, Ong H, Young PM.

Respiratory Drug Delivery 2023. Volume , 2023: 81-92.

Abstract:

The transition from HFA134a and HFA227ea propellants in pressurized metered dose inhalers (pMDIs) to low global warming potential propellants such as HFA152a and HFO1234ze(E) requires a comprehensive understanding of how these new gases behave. Conventionally measured outcomes are mixed, as the physical causes of the changes in spray behavior are multifaceted, depending on turbulent mixing ex-orifice, droplet size distribution, and changes in saturated vapor pressure. In this study, we present aerodynamic particle size distributions and geometric particle size measurements for model solution and suspension formulations containing up to 15% w/w ethanol, using conventional pMDI hardware. High-speed imaging and droplet sizing is used to reveal the various drivers of differing pMDI performance due to a complex range of competing factors involving spray mixing, spray width and droplet size. These differences are small enough that they may be managed through optimization of co-solvent concentration and actuator orifice length. With this insight, promising routes for optimization of HFA152a and HFO1234ze(E) based pMDIs are proposed.