Relative Precision of Inhaler Aerodynamic Particle Size Distribution (APSD) Metrics by Full Resolution and Abbreviated Andersen Cascade Impactors (ACIs): Part 1

Abstract

The purpose of this study was to compare relative precision of two different abbreviated impactor measurement (AIM) systems and a traditional multi-stage cascade impactor (CI). The experimental design was chosen to provide separate estimates of variability for each impactor type. Full-resolution CIs are useful for characterizing the aerosol aerodynamic particle size distribution of orally inhaled products during development but are too cumbersome, time-consuming, and resource-intensive for other applications, such as routine quality control (QC). This article presents a proof-of-concept experiment, where two AIM systems configured to provide metrics pertinent to QC (QC-system) and human respiratory tract (HRT-system) were evaluated using a hydrofluoroalkane-albuterol pressurized metered dose inhaler. The Andersen eight-stage CI (ACI) served as the benchmark apparatus. The statistical design allowed estimation of precision with each CI configuration. Apart from one source of systematic error affecting extra-fine particle fraction from the HRT-system, no other bias was detected with either abbreviated system. The observed bias was shown to be caused by particle bounce following the displacement of surfactant by the shear force of the airflow diverging above the collection plate of the second impaction stage. A procedure was subsequently developed that eliminated this source of error, as described in the second article of this series (submitted to AAPS PharmSciTech). Measurements obtained with both abbreviated impactors were very similar in precision to the ACI for all measures of in vitro performance evaluated. Such abbreviated impactors can therefore be substituted for the ACI in certain situations, such as inhaler QC or add-on device testing.