Adapting the Abbreviated Impactor Measurement (AIM) Concept to Make Appropriate Inhaler Aerosol Measurements to Compare with Clinical Data: A Scoping Study with the Alberta Idealized Throat (AIT) Inlet

Background: The Abbreviated Impactor Measurement (AIM) concept simplifies determination of aerodynamic size metrics for inhaler quality control testing. A similar approach is needed to compare in vitro particle size distribution metrics with human respiratory tract (HRT) deposition. Methods: An abbreviated impactor based on the Andersen eight-stage cascade impactor (ACI) was developed having two size-fractionating stages with cut-points at 4.7 and 1.1 mu m aerodynamic diameter at 28.3 L/min, to distinguish between coarse (CPM), fine (FPM), and extra-fine (EPM) mass fractions likely to deposit in the oropharynx, airways of the lungs, or be exhaled, respectively. In vitro data were determined for pressurized metered dose inhaler (pMDI)-delivered salbutamol (100 mu g/actuation ex valve) with an Alberta idealized adult upper airway (throat) inlet (AIM-pHRT). Corresponding benchmark data for a full resolution Andersen eight-stage cascade impactor with Alberta idealized throat (ACI-AIT) and ACI-Ph. Eur./USP inlet were obtained with the same product. Results: Mass recoveries (mu g/actuation; mean +/- SD) were equivalent at 100.5 +/- 0.7; 97.2 +/- 4.9 and 101.5 +/- 9.5 for the AIM-pHRT, ACI-AIT, and ACI-Ph. Eur./USP induction port, respectively [ one-way analysis of variance (ANOVA), p=0.64]. Corresponding values of CPM were 59.2 +/- 4.2; 58.4 +/- 2.4, and 65.6 +/- 5.8; the AIT captured larger particles more efficiently than the Ph.Eur./USP induction port, so that less large particle mass was apparent in the upper stages of the ACI-AIT (p <= 0.037). Equivalent values of FPM were similar regardless of inlet/abbreviation at 41.3 +/- 4.2; 38.7 +/- 3.0, and 35.9 +/- 3.8 (p=0.054), and EPM measures (1.7 +/- 0.3; 2.0 +/- 0.5; 2.1 +/- 0.3) were also comparable (p=0.32). Conclusions: The AIT inlet significantly increased the capture of the coarse fraction compared with that collected by the Ph.Eur./USP induction port. Measures obtained using the AIM-pHRT apparatus were comparable with those obtained with the ACI-AIT.