Biomedical Engineering Reference
In-Depth Information
de-aggregate and disperse the particles that then provide an effi cacious lung
dose [
19
]. Therefore, the air fl ow start-up kinetics may profoundly infl uence the
APSD that is achieved [
20
]. If either the inlet and/or stage confi gurations of the
AIM apparatus are different from those of the full-resolution CI, then it is
possible that different APSD data will be obtained in comparison between the
two systems. It is a concern, especially to those charged with pharmacopeial
method development, that these divergences can eventually turn out to be
inhaler-measurement system dependent. Sponsors therefore need to provide
detailed methodology descriptions in submissions to have particular AIM-
based confi gurations adopted into the compendia, in order to minimize the risk
of inadvertently introducing such confounding effects. In particular, attention
needs to be paid to the dimensions of the inlet port, internal dead space, and the
stage confi gurations themselves. In summary, it cannot be assumed that an AIM
apparatus is automatically suitable for a particular inhaled dosage form just
because its acceptability has been reported elsewhere, most likely from investi-
gations having limited scope.
(d) Comparative data for full-resolution CI and AIM apparatus:
Without doubt, the most obvious question that will be asked in connection
with an application to include an AIM-based method into the compendia will
be “
How does the APSD data using AIM apparatus compare to that acquired
with a full stage CI?
”
The acquisition of copious data with both full-resolution and AIM CI sys-
tems will be a key requirement, as will be the subsequent demonstration of
comparative performance in statistically robust terms. It is also reasonable that
demonstration of system suitability through the API mass balance be provided
[
21
]. Furthermore, cumulative undersize plots and API mass values should be
demonstrated to be substantially comparable at selected cut-point sizes within
the range of interest (0.5-10
m aerodynamic diameter). Given that the basic
physical aerodynamic particle sizing processes are occurring in both full-
resolution and AIM CI systems (see Chap.
3
), qualitatively “similar” results are
to be expected as the norm. However, as already illustrated in Chap.
μ
10
, one or
more of several experimental factors may require attention in order to achieve
the desired goal of quantitative comparability. Therefore, it should not come as
a surprise if initial data comparisons between AIM and full-resolution CIs are
not always identical. The important thing is to be able to explain why such dif-
ferences exist and mitigate identifi able cause(s), wherever possible. Furthermore,
it may be possible to demonstrate a consistent relationship, even though the
ideal correlation between full-resolution CI and AIM-based data that is directly
proportional to the magnitude of API mass may not always be achieved.
It follows that the presentation to a regulatory agency as justifi cation for
using AIM as a product quality test would require comparative APSD data from
the full CI together with associated metrics derived from an AIM-based appara-
tus of choice, in support of the proposed specifi cation.
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