Validating AIM-Based Instrumentation and Associated Measurement Techniques - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 314

Fig. 10.35 Pressure drop-elapsed time profiles for DPI combinations studied by Russell-Graham
et al . ( From [ 40 ]— courtesy of D. Russell-Graham )
Their start-up kinetics for each DPI, shown by the time-dependent variation in
pressure drop at the mouthpiece for each device-impactor combination (Fig. 10.35 ),
show that the set flow (as measured via pressure drop) is not experienced instanta-
neously by the product and that the pressure drop profile varied depending on both
the device resistance and choice of abbreviated or full-resolution impactor.
The plateau (equilibrium) pressure drop attained, which would be expected to
depend on the device resistance, was also observed to differ between the two measure-
ment apparatuses, particularly for Product 3. This was an unexpected observation, but
was not thought to be large enough to account for the differences in FPF observed,
particularly for Products 1-3 which are not known to be highly flow dependent. An
alternative explanation provided by this group involved the observation that the initial
acceleration of the pressure drop experienced by each DPI product varied substan-
tially comparing abbreviated with full-resolution apparatus (Fig. 10.36 ).
In the initial 0.1-0.2 s period, which may be critical for the de-agglomeration of the
powder to generate the fine particle fraction delivered from the DPI, the pressure drop
measured with the FSI was almost double that measured with the NGI. This effect
appeared most pronounced for the product with the highest device resistance (Product
4) which was, perhaps coincidentally, the most flow dependent of the group of devices.
This work lends support to the hypothesis that the different internal volume of the FSI
may be significant in considering its comparability to the NGI for the testing of DPI
products, but further work, including the introduction of additional extra-impactor
volume to the FSI apparatus, needs to be done to provide confirmatory data.
More recently, Pantelides et al. have reported further assessments of pressure
drop-elapsed time profiles for the FSI, exploring the influence of dead space, sys-
tematically increasing the internal volume of the FSI in 500 mL steps by the addi-
tion of glass vessels of varying volume and shape configurations (Fig. 10.37 ), in