The AIM and EDA Concepts: Why They Are Needed and How They Fit Together - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 120

The description of the approaches taken to obtain the most appropriate in vitro
OIP performance metrics for these different purposes forms the main topic for the
remainder of the handbook. At this introductory stage, though, it is important to
appreciate that the provision to stakeholder confi dence that the inhaler will deliver
medication safely and effi caciously is common to all these types of laboratory
evaluation.

5.4 AIM Applied in OIP Quality Assessment

Tougas et al. have claimed that an approach involving an abbreviated CI measure-
ment has the potential to offer at least equivalent and possibly greater sensitivity
than that achievable by multistage impactor in the OIP quality control environment
[ 18 ]. In the so-called AIM-QC approach, they recommended that the process of
measurement be simplifi ed to its maximum extent (Fig. 5.5 ), namely, the determina-
tion of the size fractions related to large ( LPM ) and small particle mass ( SPM ) that
are sensitive to shifts in the APSD.
In the example shown, the size boundary between small and large mass fractions
does not necessarily have to be fi xed at a physiologically relevant particle size, such
as 5 m, that is defi ned as the bound between fi ne and coarse fractions in the

European Pharmacopoeia [ 19 ]. In fundamental terms, changes in a mass-weighted
APSD obtained from full-resolution CI measurements can be reduced to those asso-
ciated with position of the mass distribution profi le on the abscissa (size) scale and
with its area under the curve or amplitude position of the mode(s) on the ordinate
(mass) scale [ 18 ]. Tougas et al. showed that two metrics, namely, the ratio, LPM / SPM
and the sum, LPM + SPM , are foundational to the EDA concept [ 18 ], explained in
more detail in Chap. 6 . It is important to note that the sum, LPM + SPM , is identical
with the impactor-sized mass ( ISM ) and is the total mass of API collected by size-
fractionating stages of the CI that have a defi ned upper bound size limit.
An essential aspect of the EDA approach is that it is as applicable to full-
resolution CI data as to the assessment of results from an abbreviated system.
In addition to reducing measurement complexity, it was realized that there is the
potential to undertake more determinations in a given time period of a batch being
QC tested, thus achieving greater coverage, associated with increased statistical
power. This benefi t, of course, only applies if the time saved is allocated to making
more replicate determinations.
Importantly, due to elimination of confounding variables, EDA-based measures
of OIP aerosol APSD should be less prone to method and analyst error (which may
lead to wrong decision-making) [ 20 ]. This benefi t of EDA is expanded upon in
Chap. 7 .
As well as its more obvious use in OIP QC, the AIM-EDA approach should also
be an excellent tool in exploratory stability studies which are performed at the early
product and formulation development stages. This aspect is discussed further in
Chap. 6 , and some case studies are presented in Chap. 9 . Since the identifi cation of

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