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

TL;DR

This study introduces a novel X-ray fluorescence spectroscopy method to analyze drug deposition in low-GWP propellant inhalers, revealing significant variability in drug distribution that impacts inhaler design and formulation.

Contribution

The paper presents a new application of synchrotron X-ray fluorescence spectroscopy for analyzing drug deposition in opaque inhaler components with low-GWP propellants.

Findings

Significant variability in drug distribution in canister components with new propellants.

X-ray fluorescence spectroscopy effectively assays drug content in opaque parts.

Implications for inhaler formulation and device design with low-GWP propellants.

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.