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

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

Mechanical & Aerospace Engineering

Research output: Contribution to journal › Article › Research › peer-review

2 Citations (Scopus)

Abstract

A challenge in pressurised metered-dose inhaler (pMDI) formulation design is management of adhesion of the drug to the canister wall, valve and actuator internal components and surfaces. Wall-material interactions differ between transparent vials used for visual inspection and metal canister pMDI systems. This is of particular concern for low greenhouse warming potential (GWP) formulations where propellant chemistry and solubility with many drugs are not well understood. 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 sulphate in propellants HFA134a, HFA152a and HFO1234ze(E) using aluminium canisters and standard components. Preliminary results indicate that through unit life drug distribution in the canister valve closure region and actuator can vary significantly with new propellants. For solution formulations HFO1234ze(E) propellant shows the greatest increase in local deposition inside the canister valve closure region as compared to HFA134a and HFA152a, with correspondingly reduced actuator deposition. This is likely driven by chemistry changes. For suspension formulations HFA152a shows the greatest differences, due to its low specific gravity. These changes must be taken into consideration in the development of products utilising low-GWP propellants.

Original language	English
Article number	123569
Number of pages	12
Journal	International Journal of Pharmaceutics
Volume	648
DOIs	https://doi.org/10.1016/j.ijpharm.2023.123569
Publication status	Published - 15 Dec 2023

Keywords

Deposition
Fluorescence
Green propellants
Metered dose inhaler
Sedimentation
X-ray

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10.1016/j.ijpharm.2023.123569

Cite this

@article{7520eae610364388973338aaa398c96d,

title = "Canister valve and actuator deposition in metered dose inhalers formulated with low-GWP propellants",

abstract = "A challenge in pressurised metered-dose inhaler (pMDI) formulation design is management of adhesion of the drug to the canister wall, valve and actuator internal components and surfaces. Wall-material interactions differ between transparent vials used for visual inspection and metal canister pMDI systems. This is of particular concern for low greenhouse warming potential (GWP) formulations where propellant chemistry and solubility with many drugs are not well understood. 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 sulphate in propellants HFA134a, HFA152a and HFO1234ze(E) using aluminium canisters and standard components. Preliminary results indicate that through unit life drug distribution in the canister valve closure region and actuator can vary significantly with new propellants. For solution formulations HFO1234ze(E) propellant shows the greatest increase in local deposition inside the canister valve closure region as compared to HFA134a and HFA152a, with correspondingly reduced actuator deposition. This is likely driven by chemistry changes. For suspension formulations HFA152a shows the greatest differences, due to its low specific gravity. These changes must be taken into consideration in the development of products utilising low-GWP propellants.",

keywords = "Deposition, Fluorescence, Green propellants, Metered dose inhaler, Sedimentation, X-ray",

author = "Duke, {Daniel J.} and Lingzhe Rao and Alan Kastengren and Benjamin Myatt and Phil Cocks and Stephen Stein and Nirmal Marasini and Ong, {Hui Xin} and Paul Young",

note = "Funding Information: The authors acknowledge the support of the Australian Research Council (grants LP190100938 & DP200102016 ). Use of the Advanced Photon Source, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357 . The authors thank Brandon Sforzo and Aniket Tekawande (Argonne National Laboratory) for their support. We gratefully acknowledge the computing resources provided on Bebop, a high-performance computing cluster operated by the Laboratory Computing Resource Center at Argonne National Laboratory. The authors also acknowledge the use of the National Computational Infrastructure (NCI), which is supported by the Australian Government. Funding Information: The authors acknowledge the support of the Australian Research Council (grants LP190100938 & DP200102016). Use of the Advanced Photon Source, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357. The authors thank Brandon Sforzo and Aniket Tekawande (Argonne National Laboratory) for their support. We gratefully acknowledge the computing resources provided on Bebop, a high-performance computing cluster operated by the Laboratory Computing Resource Center at Argonne National Laboratory. The authors also acknowledge the use of the National Computational Infrastructure (NCI), which is supported by the Australian Government. Publisher Copyright: {\textcopyright} 2023 The Author(s)",

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doi = "10.1016/j.ijpharm.2023.123569",

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AU - Duke, Daniel J.

AU - Rao, Lingzhe

AU - Kastengren, Alan

AU - Myatt, Benjamin

AU - Cocks, Phil

AU - Stein, Stephen

AU - Marasini, Nirmal

AU - Ong, Hui Xin

AU - Young, Paul

N1 - Funding Information: The authors acknowledge the support of the Australian Research Council (grants LP190100938 & DP200102016 ). Use of the Advanced Photon Source, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357 . The authors thank Brandon Sforzo and Aniket Tekawande (Argonne National Laboratory) for their support. We gratefully acknowledge the computing resources provided on Bebop, a high-performance computing cluster operated by the Laboratory Computing Resource Center at Argonne National Laboratory. The authors also acknowledge the use of the National Computational Infrastructure (NCI), which is supported by the Australian Government. Funding Information: The authors acknowledge the support of the Australian Research Council (grants LP190100938 & DP200102016). Use of the Advanced Photon Source, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357. The authors thank Brandon Sforzo and Aniket Tekawande (Argonne National Laboratory) for their support. We gratefully acknowledge the computing resources provided on Bebop, a high-performance computing cluster operated by the Laboratory Computing Resource Center at Argonne National Laboratory. The authors also acknowledge the use of the National Computational Infrastructure (NCI), which is supported by the Australian Government. Publisher Copyright: © 2023 The Author(s)

PY - 2023/12/15

Y1 - 2023/12/15

N2 - A challenge in pressurised metered-dose inhaler (pMDI) formulation design is management of adhesion of the drug to the canister wall, valve and actuator internal components and surfaces. Wall-material interactions differ between transparent vials used for visual inspection and metal canister pMDI systems. This is of particular concern for low greenhouse warming potential (GWP) formulations where propellant chemistry and solubility with many drugs are not well understood. 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 sulphate in propellants HFA134a, HFA152a and HFO1234ze(E) using aluminium canisters and standard components. Preliminary results indicate that through unit life drug distribution in the canister valve closure region and actuator can vary significantly with new propellants. For solution formulations HFO1234ze(E) propellant shows the greatest increase in local deposition inside the canister valve closure region as compared to HFA134a and HFA152a, with correspondingly reduced actuator deposition. This is likely driven by chemistry changes. For suspension formulations HFA152a shows the greatest differences, due to its low specific gravity. These changes must be taken into consideration in the development of products utilising low-GWP propellants.

AB - A challenge in pressurised metered-dose inhaler (pMDI) formulation design is management of adhesion of the drug to the canister wall, valve and actuator internal components and surfaces. Wall-material interactions differ between transparent vials used for visual inspection and metal canister pMDI systems. This is of particular concern for low greenhouse warming potential (GWP) formulations where propellant chemistry and solubility with many drugs are not well understood. 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 sulphate in propellants HFA134a, HFA152a and HFO1234ze(E) using aluminium canisters and standard components. Preliminary results indicate that through unit life drug distribution in the canister valve closure region and actuator can vary significantly with new propellants. For solution formulations HFO1234ze(E) propellant shows the greatest increase in local deposition inside the canister valve closure region as compared to HFA134a and HFA152a, with correspondingly reduced actuator deposition. This is likely driven by chemistry changes. For suspension formulations HFA152a shows the greatest differences, due to its low specific gravity. These changes must be taken into consideration in the development of products utilising low-GWP propellants.

KW - Deposition

KW - Fluorescence

KW - Green propellants

KW - Metered dose inhaler

KW - Sedimentation

KW - X-ray

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DO - 10.1016/j.ijpharm.2023.123569

M3 - Article

AN - SCOPUS:85175877048

SN - 0378-5173

VL - 648

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

M1 - 123569

ER -

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

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Enabling precise droplet control in hydrofluorocarbon free sprays

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

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Enabling precise droplet control in hydrofluorocarbon free sprays

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