Current Approaches to APSD Measurements of OIPs Based on Inertial Impaction - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 36

Fig. 2.10 Stage collection
efficiency curves for the
full-resolution ACI at 28.3 L/
min, based on the adjusted
calibration data of Vaughan
[ 19 ] ( From [ 42 ] , courtesy of
D L Roberts and J P
Mitchell )
symmetry of each collection efficiency curve about the d 50 value. Under such a
condition, the mass of API that is associated with particles large enough that they
should have been captured is almost counterbalanced by the mass of API contained
in finer particles that should have penetrated the stage in question.
Roberts and Mitchell concluded that these differences would likely be unimport-
ant in understanding the aerosol coming from an OIP [ 42 ]. Their assessment was
based in part on recent industry guidance from the EMA, in which bounds of ±15%
are deemed equivalent from in vitro measurements in regulatory submissions (i.e.,
for target dose and for comparison of CI stage deposition between reference and
test OIP [ 44 ]).
In their follow-on assessment of abbreviated ACI and NGI systems, Roberts and
Mitchell adapted the same approach by comparing abbreviated with full-resolution
CI results calculated from hypothetical aerosols with unimodal and lognormal
APSDs [ 43 ]. It is important to note that the amount of overlap from stage to
neighboring stage in an abbreviated CI is greatly reduced or even abolished com-
pared with the situation that exists in a full-resolution CI of the same design. As a
result, however, even for the same input aerosol, the APSD of the aerosol approach-
ing a given stage of an abbreviated impactor is different to that which exists when
approaching the sequence of individual stages of the full-resolution system. This
situation exists even if some of the stages of the abbreviated CI are identical to those
of the full-resolution CI.
In the case of the ACI operated at 28.3 L/min, the problem was summarized by
comparing the stage collection efficiency curves for the full-resolution CI operated
at 28.3 L/min to the corresponding profiles of the remaining stages of the particular
abbreviated ACI configuration investigated, in which measures of fine and extrafine
particle fractions are sought by retaining just stages 2 and 5 and the final filter from
the full-resolution system (the stage numbering in the abbreviated CI corresponds
with that of the full-resolution impactor for simplicity). Hence, although stage 2 in
the abbreviated ACI was physically the first impaction stage, its construction is that
of stage 2 of a full-resolution ACI. When all the stages were present (Fig. 2.10 ),