Entry Port Selection for Detecting Particle Size Differences in Metered Dose Inhaler Formulations Using Cascade Impaction

Abstract

Different sized glass entry ports were evaluated for their drug collection efficiency during aerodynamic particle sizing of metered dose inhalers (MDIs) using cascade impaction. A comparison was made between collection efficiency in the entry port, impactor plates, and filter using the 1 L, 2 L, and 20 L glass entry ports and the USP and twin impinger entry ports. Entry port losses were dependent on the size of entry port selected, with 1–2 L ports showing optimal recovery on impactor plates, compared to the USP entry port. The 1 L entry port was further compared with the USP entry port in its ability to discriminate between subtle changes in particle size distribution (PSD) in an investigational hydrofluoroalkane (HFA)‐based MDI formulation. Deliberately induced differences during product manufacture were easily detected using the 1 L entry port with the Andersen cascade impactor. The USP port was unable to distinguish among products with small particle size differences. An alternative entry port such as the 1 L glass entry port used in this study may provide better means of characterizing the PSD during formulation development and stability testing of MDIs.