Device and formulation parameters influencing pressurised Metered Dose Inhaler (pMDI) aerosols using HFO1234ze propellant
Thorne, B. J. A.1, Vaccaro, G.2, Cotton, D. P. J.1, Kirton, S. B.2, Knowles, M.2, Lee, K. C.3, Murnane, D.2, Sapsford, A. I.1
1 Recipharm, Bergen Way, King’s Lynn, PE30 2JJ, U. K., 2 University of Hertfordshire, College Lane, Hatfield, Hertfordshire, AL10 9AB, 3University of East London, Docklands Campus, University Way, London, E16 2RD
Summary
Next generation impactor (NGI) stage-by-stage performance was measured for two pressurised Metered Dose Inhaler (pMDI) device configurations for an ethanolic fluticasone propionate (FP) formulation using the low global warming potential (GWP) propellant HFO1234ze. This was compared with ex-actuator aerosol droplet size distribution measurements captured using a Malvern Spraytec laser diffraction system for an FP solution formulation. The droplet size distributions immediately ex-actuator were also predicted using our 1-dimensional thermofluid mechanic model for both formulations. The simulation predicted only a minimal influence of ethanol on the initial droplet sizes, whereas actuator spray orifice diameter was a much more significant variable. The NGI data showed significant throat deposition for the solution formulation used in conjunction with the larger actuator spray orifice diameter, with a commensurate reduction in subsequent stage deposition. This suggests that the droplets received at the NGI throat had not evaporated fully. The laser diffraction data indicated incomplete evaporation of the solution emitted droplets at a distance of 150 mm from the pMDI actuator. An additional laser diffraction assessment of an FP suspension aerosol indicated complete evaporation of propellant by 150 mm. This highlights the importance of droplet evaporation kinetics on the ultimate destination of the dose in the body.