Validating AIM-Based Instrumentation and Associated Measurement Techniques - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 281

10.3 Proof-of-Concept Experiments Undertaken at Trudell

Medical International: Assessing the Performance
of Systems Based on the Nonviable 8-Stage ACI

In practical terms, abbreviating measurement with the vertical stack design of the
ACI is relatively straightforward, as the early work by Van Oort and colleagues indi-
cated, being simply a matter of configuring the stack with fewer stages and adjusting
the length of the retaining springs to compensate for the shorter configuration.
However, the issue of aerodynamic performance is a critical one; reduced stacks
potentially may exhibit changed air flow patterns that can significantly affect inertial
impaction behavior. Particle bounce, the re-entrainment, the distribution of active
losses to internal surfaces, and the effect of impactor dead volume have all been
shown to be important considerations [ 19 , 20 ]. Furthermore, identifying optimal
stage cut-off diameter values for product QC and also for the potential support of
human respiratory tract (pHRT)-pertinent studies to develop in vitro-in vivo relation-
ships (the latter being the focus of Chap. 12 ) are also topics for practical AIM imple-
mentation with this system as well as other designs of full-resolution CI [ 21 ].
In 2008, two proof-of-concept studies were undertaken by the group at Trudell
Medical International (TMI) in order to validate the performance of two abbreviated
systems for the purpose of improving productivity in testing add-on devices (spac-
ers and valved holding chambers) used with pMDIs. Their work was based on the
full-resolution 8-stage nonviable ACI, the C-FSA and the T-FSA abbreviated sys-
tems also based on the nonviable ACI operating principle [ 19 , 20 ].
The C-FSA is a commercially available (Copley Scientific, UK) two-stage pHRT-
based abbreviated stack, based on the Andersen nonviable CI that divides the incoming
dose into coarse, fine, and extra-fine fractions ( CPF , FPF , and EPF ), respectively
(Fig. 10.3a, b ). In its commercially available formats, a range of stages enables configura-
tion to give stage cut-off diameters ( d 50 values) of 4.7 and 1.1

μ m at 28.3, 60, or 90 L/min,

or alternatively 5.0 and 1.0 m at 28.3 L/min, depending on the specific application.

Similar in design to the C-FSA, the T-FSA was also developed from research into
AIM-based methods at TMI with MDIs delivering “dry particles” of salbutamol (alb-
uterol) following propellant evaporation (Fig. 10.4a ). The T-FSA was a hybrid
C-FSA, which had an upper stage cut-off size of 4.7

μ

m so that data from this stage
could therefore be directly compared with mass deposition of API on stage 2 of the
full-resolution ACI. The d 50 size of the lower stage was 1.0

μ

m.
In a later modification, the T-FSA also included a non-operable (collection sur-
face removed) ACI stage 0 to provide functional dead space before the first size
separating stage, enabling closer mimicry of this potentially important aspect of the
full-resolution ACI.
Two discrete investigations were carried out, each focusing on pMDI-produced
aerosols, one involving dry particles (after HFA-134a propellant evaporation), the
other containing low-volatile liquid ethanol excipient that was associated with the
aerosol particles entering the measurement equipment. In the first study, dry flutica-
sone propionate (FP) particles were produced using a commercially available

μ m, rather than 1.1 μ