Understanding the performance of pressurized metered dose inhalers formulated with low Global warming potential propellants

Abstract

Switching to low-global warming potential (GWP) propellants for pressurized metered dose inhalers (pMDIs) is crucial in current inhalation product development, as it is crucial to safeguard patient access. This paper provides both theoretical and experimental evidence to advance the understanding of the relative performance of pMDIs using traditional HFA propellants (HFA-134a, HFA-227ea) versus new low-GWP propellant (HFO-1234ze, HFO-1234yf, HFC-152a) across three stages of pMDI actuation: discharge of propellant from the spray orifice, atomization of the bulk liquid into droplets, and interaction with the surrounding environment. The acoustic profiles, which represent the propellant discharge from the spray orifice, revealed that the plume duration and audio amplitude were mostly influenced by the diameter of the orifice and to a lesser extent by propellant type. The initial propellant droplet size produced after atomization of the discharged bulk liquid was evaluated by measuring content equivalent diameters at different ethanol concentrations and spray orifice diameters. Through a 0.32 mm spray orifice, propellant-only pMDIs produced droplets in the 9.0–13.5 µm range, with HFC-152a yielding the largest droplets and HFO-1234yf the smallest, while all exhibited comparable dependence on ethanol concentration and spray orifice size. Modeling of moisture condensation on propellant droplets indicated that the amount of condensed water and droplet lifetime both depend strongly on ambient humidity and ethanol concentration and only weakly on the propellant type. Three suspension formulations in HFA-134a, HFO-1234ze, or HFC-152a, were tested under varying relative humidities to evaluate the impact of ambient humidity on the in vitro aerosol performance of suspension pMDIs.

Copyright © 2024 American Association for Aerosol Research

Editor:

• Darragh Murnane

Acknowledgments

The authors acknowledge the language editing provided by Luba Slabyj.

Disclosure statement

JL, KL, NC, MS, DLB are employees of AstraZeneca Pharmaceuticals, Ltd. and may own stock or stock options.

Additional information

Funding

This work was supported by AstraZeneca Pharmaceuticals, Ltd. and the Natural Sciences and Engineering Research Council of Canada through a Collaborative Research & Development program (Grant CRDPJ 543336–19).