Synchrotron X-ray measurements of pressurized metered dose inhaler sprays: enabling improved nozzle design

In order to tailor the performance of pressurized metered dose inhalers (pMDIs) for a desired particle size distribution, the physical processes inside the spray and the nozzle must be understood in great detail. This necessitates non-invasive, in situ particle and droplet size measurements. This article describes several X-ray diagnostic tools developed for this purpose. X-ray radiography measures the mass of liquid in the spray. X-ray fluorescence measures the drug distribution in the spray, independently of the propellant and any co-solvents. A new technique, ultra-small angle X-ray scattering, also provides a quantitative measurement of total surface area of liquid in the spray. These measurements are combined with traditional laser diffraction techniques to estimate important parameters which are difficult to directly measure, such as droplet composition and liquid volume distribution. Combining these measurement techniques allows us to observe the effects of pMDI formulation on the spray in much greater detail than has previously been possible. The measurements reveal the important role that nozzle exit conditions and near-nozzle evaporative effects have on pMDI sprays, as the composition of the liquid droplets is found to vary significantly in the near nozzle region. A deeper understanding of these phenomena opens up new possibilities for the tailored design of pMDI devices for various drug and propellant combinations.