Development and in vitro evaluation of solution-based pressurized metered-dose inhaler formulations using green propellants

OBJECTIVES: Pressurized metered-dose inhalers (pMDIs) are currently being transitioned from hydrofluoroalkanes HFA134a (1,1,1,2-tetrafluoroethane), HFA 227, and HFA227ea (1,1,1,2,3,3,3-heptafluoropropane) to low-GWP (global warming potential) propellants such as HFO1234ze(E) (1,3,3,3-tetrafluoropropene) and HFA152a (1,1-difluoroethane). This study aimed to investigate the impact of different propellants on the behaviour of maturated beclomethasone dipropionate (BDP) particles. METHODS: Physicochemical analysis and a dissolution methodology were also used to observe the influence that low-GWP propellants had on the behaviour of maturated BDP particles following pMDI aerosolization. KEY FINDINGS: Aerodynamic particle size distributions produced by all three formulations were broadly comparable [mass median aerodynamic diameter (MMAD) = 1.25 μm]. Morphological analysis of maturated BDP particles collected on stage 5 of the Anderson Cascade Impactor showed that HFA134a produced a higher ratio of irregular-shaped particles (53.0 ± 3.0%) with smaller geometric size (1.45 ± 0.43 μm). The in vitro dissolution rate of the collected maturated particles from the different propellant-based formulations followed the rank order HFA134a > HFO1234ze(E) > HFA152a, which correlated with the morphological analysis, suggesting smaller, more irregular-shaped maturated BDP particles exhibited increased wetting and higher specific surface area. CONCLUSIONS: Morphological assessment of the maturated BDP particles collected from ACI stage 5 with different propellants suggested some differences in particle shape and geometric particle size which may influence the dissolution behaviour.