  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.
