Validating AIM-Based Instrumentation and Associated Measurement Techniques - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 279

where Q 1 and Q ref represent the calibration flow rate and reference flow rate of
60 L/min, respectively, and d ae,50,1 and d ae,50,ref are the cut-off sizes at the calibration
and reference flow rates, respectively.
In retrospect, it is clear that the study carried out by Miller et al . [ 7 ] fuelled
uncertainty as to the ability of the TI to differentiate between OIP aerosols with
markedly different APSDs, making the simplification that they are unimodal and
lognormal, and therefore using MMAD and GSD to represent measures of central
tendency and spread, respectively. By concluding that because the instrument only
separated into two size fractions, and, moreover gave a broad rather than sharp sepa-
ration, the impression was given that it could not distinguish between aerosols that
fell within the same MMAD/GSD “family”. It was possible that a discrete range of
MMAD/GSD combinations would give the same results when analyzed using just
two size fractions, and broad separation between fine/coarse size boundary and
MMAD appeared to exacerbate the problem. Referring to the recent work by Tougas
et al . [ 11 ], it is now clear that the sensitivity of this apparatus for APSD-related
shifts will vary considerably according to the location of the MMAD of the product.
The MMAD of many currently marketed pMDIs and DPIs is likely to be located in
the region from 1 to 3 m, and this separation is likely to be too far from the stage

cut-off size for the unmodified TI, therefore potentially impairing its precision.
A further drawback of both the TI (and also the Copley-Fisons 2-stage metal
impactor) is that, as they are currently supplied, neither instrument has an easily
varied stage cut-off size. However, despite these disadvantages, in the near future as
AIM research progresses, there may be cause to reexamine the potential role of this
apparatus, possibly with a modified stage cut-off diameter, since the impinger
design is attractive from the point of view of its ability to eliminate size-related bias
caused by particle bounce and re-entrainment [ 12 ]. It would be a relatively easy
modification to move the cut point for the TI to 5.0

μ

m aerodynamic diameter in the
flow rate range from 30 to 100 L/min within which most OIPs are evaluated, by
modifying the diameter of the tube entering the upper stage, in accordance with the
relationship (Chap. 2 ):

μ

12 /

=

9
4

ph
r Q

W

3

C d St

(10.2)

c, 50 50 50

0

in which St 50 is the dimensionless Stokes number at the size where the stage collec-
tion efficiency is 50%, W = tube diameter, d 50 = stage cut size, Q = volumetric flow
rate, h = air viscosity, r 0 = unit density (i.e., 1 kg/m 3 ), and C c,50 is the Cunningham
slip correction factor for a particle of size d 50 [ 13 ]. However, the practicality of mak-
ing this change so that this apparatus could be used at close to 30 L/min to evaluate
pMDIs has not, to the authors' knowledge, yet been addressed.
The issue of flow rate sensitivity to stage d 50 size with CIs, which is discussed in
more detail in Chap. 2 , highlights an important potential limitation to the AIM con-
cept in the case of DPI testing. In contrast with MDI or nebulizer performance