Investigation of dry powder inhaler (DPI) resistance and aerosol dispersion timing on emitted aerosol aerodynamic particle sizing by multistage cascade impactor when sampled volume is reduced from compendial value of 4 L.

Compendial methods determining dry powder inhaler (DPI)-emitted aerosol aerodynamic particle size distribution (APSD) collect a 4-L air sample containing the aerosol bolus, where the flow, which propagates through the cascade impactor (CI) measurement system from the vacuum source, is used to actuate the inhaler. A previous article described outcomes with two CIs (Andersen eight-stage cascade impactor (ACI) and Next-Generation Pharmaceutical Impactor (NGI)) when the air sample volume was ≤4 L with moderate-resistance DPIs. This article extends that work, examining the hypothesis that DPI flow resistance may be a factor in determining outcomes. APSD measurements were made using the same CI systems with inhalers representing low and high flow resistance extremes (Cyclohaler® and HandiHaler® DPIs, respectively). The ratio of sample volume to internal dead space (normalized volume (V*)) was varied from 0.25 to 1.98 (NGI) and from 0.43 to 3.46 (ACI). Inhaler resistance was a contributing factor to the rate of bolus transfer; the higher resistance DPI completing bolus relocation to the NGI pre-separator via the inlet when V* was as small as 0.25, whereas only ca. 50% of the bolus mass was collected at this condition with the Cyclohaler® DPI. Size fractionation of the bolus from either DPI was completed within the ACI at smaller values of V* than within the NGI. Bolus transfer from the Cyclohaler® capsule and from the HandiHaler® to the ACI system were unaffected by the different flow rise time observed in the two different flow controller systems, and the effects the ACI-based on APSD measurements were marginal.

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 µm 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 µg/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 (µg/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.