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 245

Fig. 9.1 Basic changes to hypothetical unimodal APSD; (upper left ) represents a hypothetical
unimodal APSD; (upper right) describes changes in APSD amplitude, refl ected in AUC variations;
(lower left ) describes changes in APSD position on the size axis, refl ected in MMAD movement;
and (lower right) describes changes in both APSD amplitude and position
all the commonly encountered types of a single-mode APSD shift to be detected, as
illustrated schematically by Fig. 9.1 [ 1 ].
At this stage, it is worthwhile reiterating a key message presented in Chap. 3 that
the underlying physical processes that might cause a change in APSD will not lead
to fi ne structure development, defi ned as the appearance of one or more separate
modes encompassing size ranges discernible by one or at most two adjacent stages
of a 7- or 8-stage CI. Instead, changes will take place to an observable extent over a
wide portion of the size range of interest. This understanding is supported by evi-
dence from a Product Quality Research Institute working group survey of patterns
of changes observed in real products [ 2 ].
Table 9.1 is an elaboration of the APSD shifts illustrated in Fig. 9.1 , defi ning the
eight possible scenarios reported by Mitchell et al . , in which the metrics LPM and SPM
(and therefore the ratio metric ( R ) and ISM ) may change with respect to each other [ 3 ].
For scenarios 1 and 2, a change in LPM with approximately the same magnitude
but opposite directional change in SPM will result in a ratio metric ( R ) change but
not a movement in ISM metric and therefore translates to an MMAD change without
an AUC change in the APSD.
For scenarios 3 and 4, a similar directional but proportionate change in LPM and
SPM will result in the same directional change in ISM while maintaining a reason-
ably constant R and R -value and thus translates to an AUC change in the APSD
without a signifi cant change in MMAD .
For scenarios 5 and 6, the ISM and R metrics will show an increasing or decreas-
ing LPM , respectively. In each case, ISM and R will show the same directional
change as LPM . Increased ISM and R correspond to a larger MMAD and an increase