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 254

Fig. 9.5 Situation 3 for
potential failure of EDA:
simultaneous change of shape
in LPF and SPF but the same
absolute SPM and LPM
before and afterwards ( From
[ 3 ] —used with permission )

APSD, the signifi cance in terms of medication delivery of such a change would
likely be minimal, given that most extra-fi ne particles do not deposit in the HRT as
effi ciently as larger fi ne particles [ 7 ], unless combined with a breath-holding
maneuver [ 8 ].
Turbulent diffusion is not particularly size selective in the range of interest for
the sized-portion of the OIP-generated aerosol, although this phenomenon is likely
to be more important than Brownian diffusion in the associated non-sizing compo-
nents of the CI system.

9.3.3 Simultaneous Change of Shape in LPF and SPF But the

Same Absolute LPM and SPM Before and Afterwards

Mitchell et al . [ 3 ] considered that two different processes must happen simultane-
ously for the third situation to occur (Fig. 9.5 ). One of these must take place entirely
within the SPF , thereby unaffecting SPM and the other entirely within the LPF ,
thereby unaffecting LPM .
Realistically, the probability of such an event is vanishingly small, given the
stringency of the criteria for EDA to fail. Nevertheless, considering potential mech-
anisms further, particle-particle agglomeration could increase LPM but would also
decrease SPM , as has been explained in connection with scenario 1, making the
effect detectible by EDA. This process always gives rise to peak broadening as well
as an overall shift in APSD to larger sizes. Note that the mass in the SPF would
always decrease in proportion to the gain in the mass of LPF , because there is no
further input of fi ne particles to compensate for the shift in APSD.
APSD shifts towards fi ne particle sizes brought about either by gravitational
sedimentation and/or inertial (turbulent) deposition to the walls of the CI system
would always result in a reduction in LPM that is larger than any corresponding