Good Cascade Impactor Practices - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 91

(j) Cleaning/drying of CI components: It is self-evident that thorough cleaning
and drying of impactor surfaces as part of the maintenance process between
measurements will keep them as close to their specifications as possible [ 2 ].
Appropriate cleaning/drying procedures should therefore be determined
during method development. In this context, users should be aware that varia-
tions in the cleaning/drying procedures, such as the use of a new cleaning
solvent or a move from hand washing to an automated system may potentially
affect variability of APSD measurements. Such an outcome is obvious from
the standpoint of minimizing corrosion in long-term use, as well as maintain-
ing the nozzles fully unobstructed before each measurement in day-to-day
use. At the present time, however, there are no published data systematically
studying the effect of different cleaning/drying regimens on APSD results. For
the new user or for cases where the cleaning regimen is suspected as being the
cause of more than desirable variability in measurements, the EPAG has pub-
lished the results of a survey on CI cleaning methods [ 66 ].
(k) Internal (wall) losses of API within the CI: Mitchell et al . have shown, through
a calibration of an ACI with monodisperse particles of different aerodynamic
diameters in which internal losses were systematically investigated as a func-
tion of particle size, that there is a strong association between these two vari-
ables [ 67 ]. This is especially true when d ae exceeds 5 μm. It follows therefore
that internal losses of API to the non-collection surfaces within a CI (wall
losses) may be an important source of error to be considered in method develop-
ment [ 2 ]. Mitchell et al. further showed that losses in the standard pre-separator
supplied with this impactor for use at 28.3 L/min were especially significant
[ 67 ]. The pharmacopeial compendia have for some time required that internal
losses not accountable for in API mass recovery be <5% of the delivered mass
ex inhaler [ 20 , 21 ]. If this limit is breached, the material from the entire stage
including jets and walls (and not only the impaction plate) should be collected
and added to the total dose recovered from the CI as a compromise position
[ 20 , 21 ]. Since such losses result from grazing interactions between airborne
particles and the internal surfaces not associated with normal collection, their
magnitude almost certainly depends on the physicochemical properties of the
emitted aerosol (linked to the formulation of the product) as well as the CI
preparation method (e.g., coating type, number of actuations delivered per
measurement).
(l) Choice of induction port: The induction port (IP) is particularly important for
MDI testing, due to the need to capture the ballistic component (i.e., the fraction
of the metered dose that is expelled rapidly in projectile-like motion from the
inhaler mouthpiece, due to propellant flash evaporation), separately from the
fraction that is intended to penetrate beyond the oropharynx into the lower
respiratory tract [ 20 , 21 , 68 ]. The IP presents the first impaction surface for the
moving aerosol once it has left the inhaler (and any add-on device), and there-
fore, it strongly affects the proportion of the emitted mass entering the CI.
For this reason, Bonam et al . pointed out that the use of adapters to align the
MDI actuator with the IP is important for ensuring correct angle of entry of the