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 369

Fig. 12.3 Silicone cast of an
adult upper airway developed
by 3M Drug Delivery
Systems ( From [ 9 ] —used
with permission )

3M Silicone Cast

90

14

dimensions
in mm

225

16
Volume = 66 mL

As early as the mid-1990s, Berg reported [ 13 ], in a survey of OIP test
methodologies, that casts of human throats of the sort described at that time by
Swift [ 12 ] are better models to mimic the upper respiratory tracts of both adults
and children than a standardized glass inlet having a simplifi ed fl ow channel analo-
gous to that for the USP/Ph.Eur. induction port.
In 1998, Dolovich and Rhem pointed out the wide variety of simplifi ed and ana-
tomically accurate inlets that are available for OIP testing, in the context of demon-
strating the importance of inlet design for both the quantity (mass) and size
distribution of the aerosol that eventually gets to the CI measurement system [ 9 ].
Figure 12.3 is an example of an adult upper airway cast developed around this time
by 3M Drug Delivery Systems for their research. In calibration/validation experi-
ments, Velasquez and Gabrio showed that the collection effi ciency profi le of this
inlet was shifted signifi cantly to fi ner sizes compared with the positions of other
standardized inlet designs [ 14 ], including that of the USP/Ph.Eur. induction port
(Fig. 12.4 ).
On the basis of the data from Velasquez and Gabrio [ 14 ], it might be anticipated
that an AIM-based CI with an anatomically accurate upper airway would allow less
coarse particulate through to the CI entry. In the case of MDI-generated aerosols,
such an airway might also prevent less API mass contained in the ballistic fraction
from reaching the CI system. The ballistic component of the emitted dose comprises
a high-velocity droplet stream that exits from the inhaler mouthpiece as the propel-
lant fl ash evaporates. This idea is taken up later in this chapter when data obtained
in 2011 with the commercialized “Alberta Idealized Throat” (AIT) geometry, devel-
oped by Finlay at the University of Alberta, Canada, are discussed.
The 3M model contained other important refi nements, including a realization
of the upper part of the trachea-bronchial tree together with a fi lter to mimic