Current Approaches to APSD Measurements of OIPs Based on Inertial Impaction - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 21

The use of CIs in conjunction with breathing simulators is at first sight at odds
with the constant flow rate limitation. However, as will be discussed in Chap. 12 ,
various groups have found ways to effect such an interface, enabling the OIP to be
operated either through a half cycle (i.e., inspiration only) for DPIs or in conjunc-
tion with a continuously varying flow rate cycle associated with mimicking tidal
respiration. At the same time, the CI is simultaneously sampling the resulting aerosol
at a fixed flow rate. In general, these arrangements are complex [ 9 ] and have there-
fore thus far not been incorporated into the compendial methods. There are also
limited validation data available, so that caution is urged before implementing such
an approach.
A further limitation of the CI technique is its relatively limited size-resolving
capability compared with that obtainable by optical particle detection methods,
such as TOF, OPC, LD, PDPA, and even microscopy image analysis [ 8 ]. The resolu-
tion of a CI is restricted by the finite size range within which a given stage operates,
as will be seen in the next section of this chapter. The NGI, designed to optimize
resolution, is capable of providing an APSD with at most five measurements of
mass within the important range from 0.5- to 5.0- m aerodynamic diameter [ 14 ].

Attempts to develop a CI with greater than this size resolution will fail because the
resulting APSDs will inevitably contain intrinsic bias brought about through sub-
stantial overlap of the collection efficiency-size profiles of adjacent stages.

μ

2.4 Fundamentals of Inertial Size Fractionation Affecting

Multistage CI Performance

The principles of multistage CIs in the context of in vitro testing of OINDPs were
reviewed in 2003 by Mitchell and Nagel [ 9 ]. Little of a fundamental nature in terms
of the underlying theory has changed since this date, although there has been a con-
certed effort to acquire a more robust understanding of the processes associated with
calibration and validation of full-resolution cascade impaction systems [ 14 , 15 ].
Key aspects of cascade impaction theory are presented in this chapter to familiar-
ize the reader with sufficient background information to understand the advantages
and, perhaps more importantly, the limitations of the AIM-based techniques that are
introduced in Chap. 5 .
A typical CI used for OIP testing comprises several stages (Fig. 2.5 ), each of
which functions as a size fractionator of the incoming aerosol in a gas stream mov-
ing at constant velocity [proportional to volumetric flow rate ( Q )]. In concept, a
single-stage impactor comprises a jet or nozzle plate containing one or more circu-
lar or slot-shaped orifices located a fixed distance from a collection surface that is
usually horizontal. The stage functions by classifying incoming particles of various
sizes ( d ae ) on the basis of their differing inertia, the magnitude of which reflects the
resistance to a change in direction of the laminar flow streamlines.