  BACKGROUND: The impending transition from high Global Warming Potential (GWP)
propellants such as HFA134a to low-GWP alternatives such as HFA152a and
HFO1234ze(E) in pressurised metered dose inhalers (pMDIs) poses a number of
challenges. Changes in chemicophysical properties will alter spray performance;
this study investigates those differences using matched hardware and
formulations. METHODS AND MATERIALS: Aerodynamic particle size distribution
(APSD) measurements, laser diffraction and high-speed imaging experiments were
used to compare the performance of HFA134a, HFA152a and HFO1234ze(E) solution
formulations of becamethasone dipropionate (BDP). Propellant-only placebos,
cosolvent-free solutions (0.05 mg/mL), 8\% and 15\% w/w ethanol solution
formulations (2.0 mg/mL) were investigated. RESULTS: HFA152a formulations were
found to have increased actuator and throat deposition while HFO1234ze(E)
showed comparable APSD performance to HFA134a. Droplet and particle size
increased for both low-GWP propellants. High-speed imaging revealed that
HFA152a formulations spread more rapidly and were less stable and repeatable
than HFA134a. HFO1234ze(E) formulations were found to spread more slowly than
HFA134a, but converged with HFA134a ex-mouthpiece. Propellant effects were
moderated by the addition of ethanol. CONCLUSIONS: Stability changes were found
to be dominant in the near-orifice region, depending on formulation properties
and ex-orifice flashing behaviour. Shot-to-shot repeatability effects were more
pronounced in the ex-mouthpiece region where mixing with the ambient air is
dominant. As such, modifications to orifice and mouthpiece geometry may provide
a route to improved in vitro bioequivalence for low-GWP PMDIs.
