Solution-based pressurized metered dose inhaler formulations using HFA134a, HFA152a and HFO1234ze(E) propellants: Analysis of size, aerosolization performance and particle morphology

Nirmal Marasini, Varsha Koala, Lingzhe Rao, Daniel J. Duke, Damon Honnery, Stephen Stein, Benjamin Myatt, Phil Cocks, Hui Xin Ong, Paul Young

Research output: Chapter in Book/Report/Conference proceedingConference PaperResearchpeer-review


The transition of propellants from the traditional pressurised metered-dose inhalers (pMDIs) to low global warming potential (GWP) propellants is challenging for the pharmaceutical industry. A better understanding of how these propellants impact the thermodynamic and physicochemical properties and aerosolization performance of a formulation is required. In this study, we investigate the impact of propellant type on the physicochemical and aerosol properties of a model solution-based formulation containing 2 mg/mL dissolved drug and 8% w/w ethanol cosolvent. After five shots, all formulations had a consistent emitted dose, i.e. within 15% ex-actuator variation of the 500 μg target dose. In general, laser diffraction particle size analysis showed that the formulations prepared with HFA152a produced a significantly larger volume-based particle size distribution than formulations prepared using HFA134a and HFO1234ze(E). Andersen cascade impaction measurements of pMDIs revealed that aerosol aerodynamic particle size distributions were similar in terms of fine particle dose (167-177 μg) regardless of the propellant, with the exception of MMAD [HFA134a- 0.8 μm, HFO1234ze (E)-0.9 μm and HFA 152a -1.5 μm] and GSD [HFA134a- 2.3, HFO1234ze (E)-2.6 and HFA 152a -1.8]. Morphological analysis of the ex-actuator drug particles delivered from HFA134a and HFO1234ze(E) based pMDIs revealed the formation of spherical particles with smooth and irregular surfaces. In conclusion, the HFO1234ze(E) and HFA134a model solution pMDI formulations performed more similarly with respect to aerosol delivery than the HFA152a pMDI formulation.
Original languageEnglish
Title of host publicationProceedings of Drug Delivery to the Lungs Conference 2022
Number of pages4
Publication statusPublished - 9 Dec 2022
EventDrug Delivery to the Lungs Conference 2022 - Edinburgh International Conference Centre, Edinburgh, United Kingdom
Duration: 7 Dec 20229 Dec 2022


ConferenceDrug Delivery to the Lungs Conference 2022
Abbreviated titleDDL 2022
Country/TerritoryUnited Kingdom
Internet address

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