Good Cascade Impactor Practices - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 90

[ 59 ], including metered liquid inhalers. The choice of the most appropriate coat-
ing material and thickness appears to be inhaler type/drug product-dependant.
At the present time, it is not known whether coating prolongs or shortens
collection surface-life by either preventing or causing corrosion, though
prevention is more likely if the coating presents an impermeable barrier to aque-
ous ionic species. Bonam et al . observed that (semi)-automation or use of a
hand-operated tool that ensures a uniform depth of coating across the collection
surface could be considered as part of CI method development in order to stan-
dardize both coating depth and coverage [ 2 ].
(h) Stage loading and number of actuations of the inhaler into the CI: Kamiya et al .
have shown that it is important to consider potential accumulation of material
on CI stages to the point at which further incoming particles bounce when
working with formulations requiring multiple actuations for CI testing and con-
taining a high mass loading of particulates [ 60 ]. The amount of API mass
depositing on stages needs to be low enough to prevent collected particulate
becoming reentrained in the airflow and transferred to stage(s) further in the CI
system. Furthermore, the mass per stage of excipient (and also carrier particles
for some DPIs) should be taken into account [ 2 ]. In the extreme, excessive
actuations may result in stage overloading that could affect the jet-to-plate dis-
tance. If the number of actuations used per a single CI test is too large, an appar-
ent shift to finer particle sizes will be observed as the result of particle
resuspension from the stage at which they should have been collected and reen-
trainment in the flow to more distal stages of the CI [ 58 , 61 , 62 ]. Merrin et al .
have shown that the type of formulation may also play a role with high unit dose
MDI products emitting >1 mg/actuation [ 63 ]. Such sources of bias should be
studied and eliminated in method development, prior to any method validation,
by undertaking measurements with progressively increased numbers of
actuations.
(i) Collection surface properties: Bonam et al . also considered the fact that differ-
ent roughness of uncoated stage surfaces at the micro-size scale commensurate
with incoming particle dimensions may influence ballistic behavior of aerosol
particles and therefore measured APSD variability [ 2 ]. This effect may depend
on the surface properties of the formulation (i.e., material hardness), wear in use
experienced by a particular CI, as well as the cleaning and drying procedures in
use. From a survey of EPAG users, Mitchell, in 2006, concluded that the use of
collection cups or plates that have surface roughness that is 100% inspected will
assist with uniform coating and that any that are scratched, bent, or dented
should not be used [ 64 ]. Currently, there are no published data in which the
effect of surface roughness on APSD has been systematically investigated, but
both ACI and NGI vendors [ 65 ], as well as the pharmacopeias [ 20 , 21 ], now
describe tolerances for surface roughness. In the case of the compendia, these
are ~0.4 μm for the inner surfaces of the induction port, and entrance cone to the
ACI, and between 0.5 and 2 μm for the collection cups of the NGI. However,
these values are currently informative, rather than normative in nature.