Validating AIM-Based Instrumentation and Associated Measurement Techniques - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 325

Fig. 10.52 Comparison between FSI and DUSA reported by Després-Gnis and Williams (single
dose data) ( From [ 48 ]— courtesy of G. Williams )

Table 10.14 Comparison between FSI and NGI in terms of savings in time per measurement,
HPLC-based analysis time, and API recovery solvent use ( From [ 48 ]— courtesy of G. Williams )

API assay
duration (min)

Solvent
quantity (mL) Apparatus Test duration (min)

NGI 60 140 300

FSI 25 63 200

Gain (%) 58 55 33

to a filter saturated with coating medium, as was done in the follow-on IPAC-RS
precision study to eliminate entirely bias from this source [ 27 ].
In a follow-on study, a dose uniformity sampling apparatus (DUSA, Copley
Scientific Ltd., Nottingham, UK) sampling at 35 L/min with a 4 kPa pressure dif-
ferential and inhalation volume of 2 L was used to compare with single dose FSI
measurements for the same DPI. There was close agreement between the single
actuation TEM results and those measured with the DUSA (Fig. 10.52 ).
Taken together, these results suggest that using the FSI with just a single actuation
is a suitable approach for TEM and FPM <5.0μm measurement in support of screening
during development work, provided precautions are taken to mitigate bias due to
particle bounce and re-entrainment by coating the collection surface of the insert.
The findings of Després-Gnis and Williams support the outcome reported by
Stobbs et al . [ 38 ], in terms of time savings, suggesting gains in excess of 50% may
be possible in both test duration and HPLC analysis time. Reductions in solvent
usage were also quantified at 33%, important in terms of the increasing attention
being paid to so-called green chemistry initiatives (Table 10.14 ).
Finally, additional data relating specifically to the test conditions they employed,
demonstrated that the sealing integrity of the FSI is comparable to that of the NGI,
while the overall pressure drop was considerably lower (Table 10.15 ). Interstage
wall losses were also reduced with the FSI, possibly as the result of needing fewer
inhaler actuations with this system. It is important to note, however, that the lower
pressure drop of the FSI merits careful consideration in the context of achieving