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 252

that might occur as the result of locally induced shear stress in turbulent fl ow will
cause mass migration to the fi ner end of the APSD as a smooth process in terms of its
size-dependency, rather than a sudden cutoff located precisely at the SPF / LPF bound-
ary. These shifts in APSD are therefore all detectable by EDA through changes in
LPM / SPM and, in the case of removal processes, by a decrease in ISM .
Other processes Mitchell et al. [ 3 ] deemed worthy of consideration are the
following:

1. Brownian diffusion as a removal process from the aerosol phase to the walls of
the CI system would selectively reduce the concentration of the fi ner particles,
resulting in a smooth but steadily decreasing effect as particle size increases.
Such changes, if signifi cant at the size range typical of currently marketed OIPs
(from 0.5 to 10

m aerodynamic diameter), would be detectible by EDA as an
increase in LPM / SPM .
2. Phoretic processes (i.e., thermophoresis, diffusiophoresis) are generally size
independent, so that an LPM / SPM change might not be anticipated. However, for
thermophoresis to be effective as a removal process, a temperature gradient
would need to exist along the axis perpendicular to the cooler walls of the CI
system. The phenomenon can be readily avoided by operating the CI system
under controlled temperature conditions, thereby preventing the presence of
thermal gradients. Diffusiophoresis would require the presence of a condensing
vapor to the CI walls. Since OIP aerosols are typically not present with this type
of atmosphere and the water vapor content of the air containing the emitted aero-
sol is usually well below saturation, this type of removal process would not be
expected to occur.
3. The effect of electrostatic charge on APSD is linked with electric charge distribu-
tion of the aerosol being sampled [both positive and negative charges (Chap.

μ

3 )].
It is theoretically more complex and therefore diffi cult to predict. Signifi cant loss
of particles by attraction to charges on the walls of the CI can be avoided with the
use of conducting metal surfaces, but some charge may reside on the surface of
stage-coating materials, such as silicone oil that are insulators. The use of electri-
cally conducting tacky substrates is an obvious solution to the problem. However,
in the authors' experience, particle removal from the aerosol phase due to this
cause is not so size selective as to account for changes solely within the mea-
sured LPF .
4. Particle fragmentation (de-agglomeration) or more likely the introduction of
increased numbers of larger particles into the APSD that is sized by the CI by
changes to the way they are bound to larger carrier particles might conceivably
result in a shift within only the LPF component of an APSD for DPI-based
assessments. This outcome would most likely be the result of a transfer of
mass retained in the non-sizing components (induction port and pre-separator
(if used)) into the aerosol reaching the CI. However, such a change would be
detected by an increase in both LPM and ISM and therefore be detectable by
EDA. Even if in the extremely unlikely case where a simultaneous and exact
amount of mass transfer also takes place from the LPF to the SPF component
thereby maintaining LPM constant, SPM and therefore ISM would increase in
response, making the change detectable.