In-Vitro Evaluation of pMDI Spray Development of HFA134a, HFA152a and HFO1234ze(E)  

Lingzhe Rao1, Anesu J Kusangaya1, Nirmal Marasini2, Hui Xin Ong2,3, Ben Myatt5, Phil Cocks5, Damon Honnery1, Paul Young2,4, Daniel J Duke1

1Laboratory for Turbulence Research in Aerospace and Combustion (LTRAC), Department of Mechanical and Aerospace Engineering, Monash University, Clayton Campus, Melbourne, VIC 3800, Australia

2Respiratory Technology, Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia

3Macquarie Medical School, Faculty of Medicine, Healthy and Human Sciences, Macquarie University, Sydney, NSW 2109, Australia

4Department of Marketing, Macquarie Business School, Macquarie University, NSW 2109, Australia

5Kindeva Drug Delivery Limited, Charnwood Campus, 10 Bakewell Road, Loughborough, LE11 5RB, UK


To assist the transition to alternative low GWP pMDI propellants, the current study performed high-speed imaging and droplet sizing of the near-orifice spray development of HFA-152a and HFO-1234ze(E) based formulations. Conventional HFA-134a propellant was tested as the control. Placebo (pure HFA/HFO) and model solution (2 mg/mL drug dissolved in 8%w/w ethanol) formulations were measured, for each propellant. The results indicate larger droplets produced by HFA-152a and HFO-1234ze(E) based placebo formulations at the near-orifice locations. HFA-152a also showed a wider and denser spray profile as compared to that of HFA-134a due to its low vapour pressure and density. The temporal spray development was also less stable and repeatable. HFO-1234ze(E) showed a similar spray profile and a more stable spray development compared to that of HFA-134a, however with reduced spray repeatability. The impact of changing propellants on spray development was reduced in model solution formulations. Both HFA-152a and HFO1234-ze(E) showed comparable spray profiles and measured droplet size to that of HFA-134a. The issue of low spray stability and repeatability persists in solutions, particularly for HFA-152a. These early results indicate that the transition to low GWP propellants is feasible, but further optimisation of the actuator design and formulation composition is needed.

Key Message

HFA-152a and HFO-1234ze(E) show higher similarity with HFA-134a in spray width and extinction profile, and droplet size in model solution-based formulations than propellant placebo models of suspension formulations. The two alternative low GWP pMDI propellants also show reduced spray stability and repeatability. Between the two, HFA-152a is more different from HFA-134a.