Theoretical Basis for the EDA Concept - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 155

7.6 What Constraints Do Various QC Metrics Impose

on CI-Determined APSD?

The cumulative mass-weighted form of the APSD is a unique and direct transformation
of the frequency form of the distribution [ 24 ]. The cumulative form is the best way to
understand how the various metrics attempt to control the APSD. Figure 7.7 illustrates
three different approaches to APSD assessment [EDA, “grouped stages,” and “fine
particle dose” ( FPD )]. In the case of EDA, the ratio metric constrains the (sigmoidal)
cumulative distribution near to its point of inflection, i.e., it controls the measure of
central tendency ( MMAD ). It should be noted that the value of ISM constrains the sig-
moid at its upper asymptote. By comparison, the grouped stages approach and FPD
constrain the amplitude of the APSD at three different chosen size locations and at one
size location defined as 5 μm aerodynamic diameter, respectively. The “grouped
stages” approach indirectly constrains the ISM through the value of the sum of the mass
of API allocated within the groups, while FPD does not.
The logic that drove the selection of the two EDA metrics was as follows [ 11 ]:

1. Both can be easily obtained.
2. The ratio metric, LPM / SPM , is highly correlated with the mass-weighted mean
of the APSD (represented customarily by the MMAD ), but independent of the
AUC of the APSD.
3. The other metric, ISM , is related to the AUC of the APSD, but independent of the
mean of the distribution.

Fig. 7.7 Comparison of constraints to the APSD imposed by various QC approaches