Validating AIM-Based Instrumentation and Associated Measurement Techniques - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 296

Fig. 10.17 Comparison of values of FPM <5.0μm achieved by aerosolizing BDP (100 μ g per actua-

tion/50 L metered volume) with novel prototype actuators A-D: series 1 and 2 refers to the two

ACI measurements ( n = 2) shown separately: series 3 refers to the rFSA measurements ( n = 3), in
which mean ± SD is illustrated for group ( From [ 28 ]— used with permission )

μ

In the second phase of their investigation, four prototype actuators were assessed
using a standard procedure ( n = 2; ACI) and rFSA method ( n = 3) in order to deter-
mine the screening capability of the rapid method. The trend in FPM <5.0μm observed
between prototypes A-D was found to be independent of the impactor method, with
prototype B delivering the optimal dose (Fig. 10.17 ).
Keegan and Lewis observed that their rFSA method reduced the time taken to
obtain replicate ACI measurements by 50%. This time saving was in addition to
other reported benefits such as reduced solvent consumption, analysis time, and
data processing. They concluded that their AIM-based methodology represents a
sufficiently precise method for determining key particle distribution metrics such as
FPM <5.0μm for the purpose of screening and design optimization studies.
In their second investigation [ 29 ], Keegan and Lewis turned their attention to the
use of their FSA as a tool for the rapid screening of solution pMDIs containing
increasing concentrations of ethanol. The effect of adding 1.3% w/v glycerol was
also investigated with the preparation containing 13% ethanol. The general test pro-
cedure used by Keegan and Lewis was similar to that for the full FSA method
described in their first study [ 28 ].
An additional spacing stage was included above the first impaction stage in the
FSA, as recommended by Mitchell et al . (see Fig. 10.4 ) [ 20 ] for some measure-
ments. In this modified FSA (mFSA) configuration, more time was allowed for
ethanol to evaporate, with the aim of achieving closer agreement with full-resolution
benchmark ACI measurements for these MDI products. However, this annular
spacer stage differed from the approach adopted by Mitchell et al . , in that it con-
sisted of a metal ring without the nozzle plate (Fig. 10.18 ).
The MDIs, again containing BDP as API (100

L metered
volume), were manufactured containing 8%, 13%, and 26% w/w ethanol in HFA134a
propellant. Each MDI was equipped with the same actuator as used in their first
study. Values of CPM >5.0μm , FPM <5.0μm , and EPM <1.0μm obtained from each of the

μ g per actuation/50 μ