The effect of mouthpiece shape and size on low-GWP metered dose inhaler performance

Design of the mouthpiece of a pressurised metered dose inhaler is generally informed by patient needs, followed by manufacturing and product differentiation considerations. However, relatively few studies have investigated whether the size and shape of the mouthpiece might be altered to adjust drug deposition. The motivation for such adjustment is the impending switch to low-global warming potential (GWP) propellants with differing plume geometry and deposition characteristics. In this study we investigate how the size and shape of the mouthpiece affects aerodynamic particle size distribution and spray plume geometry for a model solution formulation of 2 mg/mL beclomethasone dipropionate in 8% w/w ethanol. Six mouthpiece designs were investigated for a control formulation with HFA-134a propellant. A partial parametric study was also conducted for formulations in HFA-152a and HFO-1234ze(E) propellants. The mouthpiece shape had a statistically significant effect on mouthpiece and throat deposition as expected, but with no statistically significant change at smaller particle sizes, since aerosol maturation is primarily influenced by formulation and actuator orifice design. Significance was reduced for low-GWP propellants using the larger mouthpiece designs. Analysis of ex-mouthpiece plume geometry revealed that the mouthpiece shape and size had no significant effect on the ensemble-average plume geometry, but did have an effect on the degree of shot-to-shot variation between actuations. These results show that mouthpiece design may be a useful means of adjusting the balance between throat and mouthpiece deposition without altering APSD at the respirable size range when formulating low-GWP pMDIs to achieve equivalent APSD outcomes to existing systems.