Validating AIM-Based Instrumentation and Associated Measurement Techniques - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 288

Table 10.4 Experiment design with three cascade impactor configurations, six inhalers, three
dosing sets by inhalers, and three replicates of the same inhalers; the values in square parentheses
indicate the order of test on a particular day ( From [ 26 ]— used with permission )
Inhaler Replicate Cascade impactor configuration [dosing set]

1 1 ACI [1] AIM-QC [2] AIM-pHRT [3]

2 AIM-pHRT [5] ACI [6] AIM-QC [4]

3 AIM-QC [9] AIM-pHRT [7] ACI [8]

2 1 AIM-QC [2] ACI [1] AIM-pHRT [3]

2 ACI [4] AIM-pHRT [6] AIM-QC [5]

3 AIM-pHRT [9] AIM-QC [8] ACI [7]

3 1 ACI [1] AIM-pHRT [3] AIM-QC [2]

2 AIM-pHRT [6] AIM-QC [5] ACI [4]

3 AIM-QC [8] ACI [7] AIM-pHRT [9]

4 1 AIM-QC [3] AIM-pHRT [1] ACI [2]

2 AIM-pHRT [5] ACI [6] AIM-QC [4]

3 ACI [7] AIM-QC [8] AIM-pHRT [9]

5 1 ACI [1] AIM-pHRT [3] AIM-QC [2]

2 AIM-QC [5] ACI [4] AIM-pHRT [6]

3 AIM-pHRT [9] AIM-QC [8] ACI [7]

6 1 AIM-pHRT [2] ACI [3] AIM-QC [1]

2 ACI [4] AIM-QC [5] AIM-pHRT [6]

3 AIM-QC [9] AIM-pHRT [7] ACI [8]

systems, respectively. A commercially available HFA-salbutamol pMDI was used
as the test product, and careful attention was made to the design of the experiment
to minimize the influence of possible confounding sources of error (e.g., operator,
environment, inhaler, etc.).
The experiment was conducted using a design with the three impactor configura-
tions already described, six inhalers, with three measurements made per inhaler per
impactor configuration (Table 10.4 ). The specific objective of the study was to
assess the repeatability of the impactor configurations (not to assess inhaler product
performance); consequently, the experiment was conducted so that the following
sources of variability were reasonably controlled:

1. Inhaler-to-inhaler variability over manufacturing run of OIP evaluated
2. Through-life trends of pMDI canister
3. Inter-operator variability
4. Inter-impactor system variability

Another feature of the study design was the inclusion of recurrent testing of each
of the six inhalers on all three impactors. These precautions were taken to enable
estimation of the intrinsic variability (precision) of each impactor system in isolation
from other potentially confounding effects.
The statistical analysis estimated and compared the repeatability of three
impactor configurations side-by-side, based on first quantifying the following