Applying the AIM Concept in Support of Developing Improved In Vitro–In Vivo Relationships for OIPs - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 366

Chapter 12
Applying the AIM Concept in Support
of Developing Improved In Vitro-In Vivo
Relationships for OIPs
Jolyon P. Mitchell , Mark Copley , and Derek Solomon
Abstract The previous chapters have focused primarily on the application of
AIM-EDA in the quality control part of an OIP lifecycle. An AIM-based approach
would also be desirable for comparing and ideally correlating in vitro APSD-derived
metrics with the likely particle deposition profi le in the HRT that in turn should be
linked with clinical effects. In addition to selection of appropriate size boundaries
between coarse and fi ne particle mass fractions, there is the consideration of modi-
fying the reduced impactor to add a third subfraction that relates to the measurement
of the fraction of the dose ex-inhaler that comprises extra-fi ne submicron-sized par-
ticles. Furthermore, adapting the AIM concept to an alternative approach in which
more clinically pertinent measures of in vitro performance are obtained raises the
prospect of making the aerosol transport system more realistic in terms of human
anatomy. An obvious move in this direction would be to replace the USP/Ph.Eur.
induction port that was designed primarily to support OIP QC-based testing with an
inlet that more appropriately models aerosol fl ow through the human oropharyn-
geal/nasopharyngeal region, depending upon patient age being studied. This chap-
ter describes key features of how so-called AIM-pHRT systems might be constructed.
The prefi x “p” refers to the potential application of this alternative AIM-based
approach. It will be for sponsors of this type of CI-based measurement application
to undertake validation studies with their products. Such studies will likely compare