Validating AIM-Based Instrumentation and Associated Measurement Techniques - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 326

Table 10.15 Sealing integrity, apparatus air resistance and interstage API loss for the FSI
compared with the NGI ( From [ 48 ]— courtesy of G. Williams )
(a) Sealing integrity ( Δ Δ P , kPa)

FSI ( n = 5 replicates) NGI ( n = 4 replicates)

Mean 0.3 Mean 0.4

SD 0.07 SD 0.04

(b) Equipment air resistance ( cm

12 /

/ min ) a

L

HO
2

FSI ( n = 3 replicates) NGI ( n = 3 replicates)

Mean 0.12 Mean 0.19

SD 0.00 SD 0.00

(c) Interstage API loss [wall losses] ( μ g)

FSI: 1 actuation ( n = 3 replicates) NGI: 3 actuations ( n = 3 replicates)

Mean 0.6 Mean 1.7

SD 0.33 SD 1.03

n number of replicates
a Sealing integrity verified prior to use

comparable start-up kinetics (pressure drop versus elapsed time) for DPI testing in
general, reinforcing the advice that such considerations should be a key part of
AIM-based method development with this class of OIP.
Rogueda et al . , from Novartis Pharma, also presented a comparison of an FSI
with insert providing a cut point of 5

m aerodynamic diameter at 90 L/min with the
NGI as full-resolution reference impactor [ 49 ]. Their data for various low resistance
DPI products used with lactose-blended powders also confirmed that fine particle
fraction determined by the FSI could be up to 20% higher FPF <5.0μm than equivalent
measures using the NGI (see Fig. 10.53 for DPI “system” C) when the pre-separator
of both devices were used without coating the interior surfaces with an adhesive
agent (i.e., as it would normally be used with the NGI).
Coating the bottom plate of the pre-separator with surfactant in order to reduce
particle bounce resulted in a discernible decrease in FPF <5.0μm with DPI product “C”
(Fig. 10.53 ), with this value almost comparable to that obtained by the reference
NGI (Fig. 10.54 ). However, the FSI-based data for other products “A” and “B” eval-
uated were still marginally lower and higher, respectively, than corresponding val-
ues determined from the NGI (Fig. 10.54 ). Nevertheless, these differences compared
with equivalent values using the NGI were less than the 10% limit that they set as
their acceptance criterion for these measurements.
This group also reported between 35% and 42% savings in time using the FSI
compared with the NGI, based on timed measurements with other similar DPIs,
corresponding to between 22% and 37% time saved on the experimental work
(HPLC analysis excluded).
Confirmatory evidence of the value of the FSI for measuring particles delivered
by pMDIs and nebulizers was also provided in early 2009 by Sheng et al . from MAP
Pharmaceuticals Inc. (California, USA) [ 50 ]. In the first part of their study, two

μ