Verification of the EDA Concept Through an Assessment of Theoretical Failure Modes, Failure Mode Analysis, and Case Studies with Real Data - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 246

Table 9.1 Eight possible scenarios associated with APSD shifts

Summary of APSD
changes Scenario Δ MMAD a Δ AUC b Δ LPM Δ SPM Δ R c Δ ISM d

1
2

MMAD change with
no change in AUC

↑
↓

≈
≈

↑
↓

↓
↑

↑
↓

≈
≈

3
4

AUC change with no
change in MMAD

≈ ↑ ↑ ↑ ≈ ↑

≈ ↓ ↓ ↓ ≈ ↓

5
6
7
8

MMAD and AUC
change

↑ ↑ ↓ ( ≈ ↓ ) ↑ ↑

↓ ↓ ↓ ( ≈ ↓ ) ↓ ↓

↓ ↑ ( ≈ ↓ ) ↓ ↓ ↑

↑ ↓ ( ≈ ↓ ) ↓ ↑ ↓

a Δ MMAD = shift in MMAD
b Δ AUC = shift in area under differential mass-weight APSD profi le
c R = Ratio = LPM
SPM

d ISM = LPM + SPM

in AUC . Likewise, decreased ISM and R correspond to a smaller MMAD and a
decrease in AUC .
For scenarios 7 and 8, the SPM metric will show an increase or decrease, respec-
tively, with ISM and R moving in opposite directions with respect to each other. In
each case, the ISM change will be in the same direction as the SPM movement. An
ISM decrease with an increase in R corresponds to an AUC decrease associated with
a larger MMAD . Conversely, an ISM increase associated with a decrease in R cor-
responds to an increase in the AUC with a smaller MMAD .
In summary, an increase in MMAD without a change in the AUC should be read-
ily evident when the value of R increases while at the same time, the ISM does not
exhibit change. For four of the scenarios, both the MMAD and the AUC of the APSD
change at the same time, while for the remaining four scenarios, two result in a
change only in the median value and two result in an area only movement.
The next question to ponder is how these scenarios play out if the magnitude of
total mass ex-inhaler that enters the CI system ( TM ) is allowed to vary. TM includes
the non-sizing as well as the sized component of the aerosol emitted by the inhaler.
It is conceivable that a change in the former alone might go undetected by EDA
because movements in either or both R and ISM may not occur as the result of
changes in the non-sized component.
The outcomes from this type of behavior are examined for various sub-scenarios.
Hypothetical APSDs described in terms of TM, ratio of NISM to ISM, LPM, SPM,
Ratio of LPM to SPM and ISM were compared to the baseline APSD characteristics
representing conditions commonly encountered with OIP aerosols:

Total Mass (TM) = 100 mass units
Non-impactor-sized (NISM) mass component = 65 mass units,
Impactor sized mass (ISM) component = 35 mass units,