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 381

Table 12.3 Values of CPM >4.7 µm , FPM <4.7 μm , and EPM <1.1 µm ex MDI metering valve from AIM-
pHRT and full-resolution ACI confi gurations evaluated with MDI-delivered 100 µ g/actuation

salbutamol ( From [ 42 ] —used with permission )
Metric
(mean ± SD)

AIM-pHRT with AIT
inlet (µg/actuation)

ACI with AIT inlet
(µg/actuation)

ACI with USP/Ph.Eur.
inlet (µg/actuation)

CPM >4.7 μm 59.2 ± 4.2 58.4 ± 2.4 65.6 ± 5.8

FPM <4.7 μm 41.3 ± 4.2 38.7 ± 3.0 35.9 ± 3.8

Table 12.4 Values of CPF >4.7 µm , FPF <4.7 µm , and EPF <1.1 µm ex MDI metering valve from AIM-
pHRT and full-resolution ACI confi gurations evaluated with MDI-delivered 100 µ g/actuation

salbutamol based on TM exMVM ( From [ 42 ] —used with permission )
Measure of
total mass

Metric
(mean ± S.D.)

AIM-pHRT with
AIT inlet (%)

ACI with
AIT inlet (%)

ACI with USP/
Ph.Eur. inlet (%)

TM exMVM CPF >4.7 μm 58.9 ± 1.8 60.2 ± 1.5 64.7 ± 0.6

FPF <4.7 μm 41.1 ± 1.8 39.8 ± 1.5 35.3 ± 0.6

EPF <1.1 μm 1.7 ± 0.2 2.0 ± 0.4 2.1 ± 0.4

Values of the various mass fractions ( CFF >4.7 μm , FPF <4.7 μm , and EPF <1.1 μm ) calcu-
lated based on the total mass recovered from the inhaler mouthpiece, inlet, and
impactor ( TM exMVM ) are presented in Table 12.4 . The values of C-of-V associated
with CPF >4.7 μm and FPF <4.7 μm were all highly reproducible at <5 %, with corre-
sponding values in the range from 11.8 to 20.0 % for EPF <1.1 μm , refl ecting less
absolute mass of API associated with this subfraction. Differences in all of these
measures from one confi guration to another were small, as the result of the large
absolute mass associated with the ballistic fraction that was collected by the appro-
priate inlet relative to the corresponding values of IM (Table 12.1 ).
When values of CPF >4.7 μm , FPF <4.7 μm , and EPF <1.1 μm were determined based only
on the mass captured in the impactor ( IM in Table 12.4 ), the outcomes were found to
be more discriminating of differences in confi guration between the systems.
Thus, CPF >4.7 μm , which was now based solely on the mass collecting upon either
impactor stages 0-2 for the two ACI confi gurations or on the fi rst stage of the AIM-
pHRT system, was substantially greater for the ACI-Ph.Eur./USP system
(22.8 ± 1.4 %), compared with the same measure obtained by ACI-AIT confi gura-
tion (12.5 ± 1.0 %).
The value of 9.8 ± 0.6 % for CPF >4.7 μm obtained with the AIM-pHRT system was
also slightly lower than that obtained with ACI-AIT confi guration. However, such a
difference could potentially be anticipated from a theoretical analysis of the effect
of removing intermediate stages on performance as the result of the imperfect size
selectivity of practical impactor stages, refl ected by deviations in their collection
effi ciency-particle aerodynamic size profi les from step functions at the effective