Current Approaches to APSD Measurements of OIPs Based on Inertial Impaction - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 48

Fig. 2.22 Valved holding
chamber with face mask as
patient interface for use with
pressurized metered-dose
inhaler
Given the lack of guidance in the (then) compendial methods, about 10 years
ago, a group of Canadian stakeholders met to develop a national standard that for
the first time set out detailed methods for the evaluation of these add-on devices,
including sections on the simulation of delayed inhalation following inhaler
actuation [ 62 ]. This standard retains the CI as the apparatus of choice for the evalu-
ation of emitted aerosol APSD but contains the following extensions to existing
methodology [ 63 ]:
(a) Measurements are made initially with the MDI alone following the compendial
method to provide benchmark data.
(b) The VHC is then evaluated simulating a 2 s delay following inhaler actuation,
chosen to mimic the behavior of a typical uncoordinated user; testing at other
delay intervals is also possible.
(c) The flow rate chosen should be appropriate for the intended age range of the
VHC; for example, an infant VHC might be evaluated at close to 5 L/min, an
add-on for a small child at 12 L/min and a product for adult use at ca. 30 L/min.
This approach has recently been proposed for adoption as a future informative
chapter in the USP through the publication of a Stimulus to Revision article in
Pharmacopeial Forum , in which the pharmacopeial organization publishes pro-
posed revisions to USP-NF for public review and comment. [ 64 ]. This proposal has
been partly driven by the recommendation from at least one regulatory agency that
new MDI applications should contain in vitro data with a nominated spacer/VHC
[ 65 ].
Although the Canadian Standard describes the framework for testing by CI, it
does not contain any detail concerning suitable apparatus(es) to undertake measure-
ments simulating delayed inhalation. At the present time, there is therefore no stan-
dardized “delay” apparatus. However, work undertaken at Trudell Medical
International shortly after the standard was developed resulted in the apparatus
shown in Fig. 2.23 , seen in conjunction with a model 150P MMI [ 66 ].
The use of the NGI at 15 L/min, the lowest flow rate for which calibration data
are available, would, in principle, also be suitable at least for testing VHCs intended
for use by small children. In the so-called delay apparatus [ 67 ], simulation of the