How Modern Analytical Chemistry Can Help To Increase Productivity For Unit Dose Level Particle Size Distribution Characterization

The particle size distribution (PSD) characterization measured by means of Andersen cascade impaction (ACI) can be both labor and time intensive using traditional methodologies, due to the fact that a considerable amount of time is spent washing each plate and adjusting the sample to volume. Typically 4 to 5 cascade impaction measurements per day can be performed by one analyst using the standard methodology.

The increase in productivity by eliminating the need to adjust samples to volume when an internal standard (IS) approach is used (IS is added to wash solvent) was previously shown using the next generation impactor. This approach still requires the accurate measurement of wash solvent making it impracticable to use for combination drug products. For example, Advair HFA requires an organic solvent wash to solubilize the drugs followed by the addition of water to make the solvent composition suitable for chromatographic analysis. The purpose of this study was to demonstrate that ACI PSD experiments can be performed for combination drug products, to more than double productivity, when the accurate measurement of wash volume is completely eliminated by the automatic precise addition of IS.