Validating AIM-Based Instrumentation and Associated Measurement Techniques - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 340

an environmental perspective. The authors concluded that the filter method is
also very feasible for determination of the fine particle dose uniformity (FPDU)
of a product; a parameter that is very difficult and laborious to retrieve from full
NGI measurements. They also observed that it is necessary to size separate the
dose below the first size-fractionating stage in two parts in order to achieve
greater sensitivity in terms of changes in ASPD and dose passing beyond the
impactor inlet. As a next step toward realization of two size fractions (and sam-
ples) in the abbreviated NGI platform, experiments are currently in progress
using a modified NGI in which the stages have been physically interchanged in
combination with the nozzle-filter approach. This approach should enable cap-
ture of the LPM and SPM in a cup and a filter, respectively, thereby resulting in
an elegant abbreviated methodology to implement.

10.9 Short Stack ACI Systems Created by Rearranging

Location of Back-Up Filter

In 2012, Horodnik et al . demonstrated an important alternative arrangement to the
reduced ACI configurations previously described [ 60 ], as their approach avoided the
removal of stages, therefore preserving the internal dead space of the full-resolution
ACI. In their particular configuration, they relocated the back-up filter stage immedi-
ately downstream of the second impaction stage. The equipment was operated at 60 L/
min and active measuring components therefore consisted of stages 1, 0, and filter.
The normal length spring-loaded clamps supplied with the full-resolution ACI
could be used to ensure a tight seal between stages of their configuration, as an
additional benefit [ 60 ]. The physical appearance of their abbreviated ACI was there-
fore comparable with that of the full-resolution system (Fig. 10.68 ).
Horodonik et al. went on to use this arrangement to evaluate a new DPI blend
delivery system containing mometasone furoate intended for use with patients
undergoing mechanical ventilation. The entry to the CI therefore comprised a spacer
designed for use in such an environment with its distal end consisting of a short
length of 22 mm diameter tubing representing part of a ventilator circuit, rather than
the Ph. Eur./USP induction port. The focus of their study was on the proof of con-
cept for a new in vitro method to evaluate how their DPI might perform in the clinic.
They therefore did not present comparative data with the full-resolution ACI.
However values of FPM <ca.6.5μm ( n = 5 replicates at each condition) were consistent
over a wide range of values of recovered mass of this particular API from the filter
stage (Fig. 10.69 ).
This simple-to-configure arrangement may avoid both the need to take mea-
sures to match the flow rate-time profile in DPI testing, already discussed.
Horodonik et al. retained the same number of stages in their short stack ACI by
locating redundant stages below the filter collection stage, so that the internal dead
space was the same as that for a full-resolution ACI. However, although suitable