Canister valve and actuator deposition in metered dose inhalers formulated with low-GWP propellants

Daniel J Duke; Lingzhe Rao; Alan Kastengren; Benjamin Myatt; Phil Cocks; Stephen Stein; Nirmal Marasini; Hui Xin Ong; Paul Young

doi:10.1016/j.ijpharm.2023.123569

arXiv · 2309.16999

Canister valve and actuator deposition in metered dose inhalers formulated with low-GWP propellants

Daniel J Duke·Lingzhe Rao·Alan Kastengren·Benjamin Myatt·Phil Cocks·Stephen Stein·Nirmal Marasini·Hui Xin Ong·Paul Young

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Abstract

A challenge in pressurised metered-dose inhaler formulation design is management of adhesion of the drug to the canister wall, valve and actuator internal components and surfaces, especially for sedimenting or creaming suspensions. Visual analysis of drug solubility and suspension behavior is typically performed in transparent vials. If the results are affected strongly by wall-material interactions, they may not be replicable in typical metal canister pMDI systems. This is of particular concern in low-greenhouse warming potential (GWP) propellant formulations where the chemistry of the new propellants and solubility with many drugs is not yet fully understood. The same can be extended to deposition in actuator and valve components, which are generally opaque. In this study, we demonstrate a novel application of X-ray fluorescence spectroscopy using synchrotron radiation to assay the contents of surrogate solution and suspension pMDI formulations of potassium iodide and barium sulfate in propellants HFA134a, HFA152a and HFO1234ze(E) using standard components. Through unit life drug distribution in the canister valve closure region and actuator can vary more significantly with new propellants. These effects must be taken into consideration in the development of products utilising low-GWP propellants.

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Daniel J Duke, Lingzhe Rao, Alan Kastengren, Benjamin Myatt, Phil Cocks, Stephen Stein, Nirmal Marasini, Hui Xin Ong, Paul Young. 2023-09-29. Canister valve and actuator deposition in metered dose inhalers formulated with low-GWP propellants. https://doi.org/10.1016/j.ijpharm.2023.123569

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