Conclusions - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 404

Chapter 3 : Changes in OIP aerosol APSD both during and following formation
arise from many physical causes; the more important ones are exam-
ined in this chapter. Particle-particle agglomeration/coagulation is
continuously acting on the formed aerosol cloud after actuation of the
inhaler and will tend to result in a time-dependent increase in both
MMAD and GSD . Agglomeration/coagulation is important when
particle concentration is at its highest during the initial formation
stage. Inertial impaction processes will decrease both MMAD and
GSD by preferentially removing the largest particles at obstructions or
bends during transport; this mechanism is important in connection
with the transfer of the aerosol from the inhaler to the CI system in
product performance testing or to the patient in use. Gravitational
sedimentation, like agglomeration, is continuously present, selectively
removing the largest particles from the formed aerosol with elapsed
time. Hence, delayed aerosol inhalation/sampling by CI will result in
a reduced aerosol mass concentration compared with optimal condi-
tions in which no delay is present. Like agglomeration and gravita-
tional sedimentation, molecular diffusion operates continuously on
the formed aerosol; however, diffusion is important only for the fi nest
particles that are in the submicron size range. This process will there-
fore have minimal impact on either MMAD or GSD from a typical
OIP-generated aerosol. Electrostatic charge on either or both the
aerosol particles and surrounding surfaces can have a major and
unpredictable impact on the aerosol before it is inhaled or sampled;
since the effects on APSD properties are variable, its mitigation or
better avoidance altogether is therefore highly recommended when
making CI measurements. Evaporative processes require the presence
of a volatile component to the aerosol; the process is highly time
dependent, resulting in a reduction in both MMAD and GSD , the latter
by potential elimination of the fi nest particles that may comprise only
volatile species. Finally, the condensation of ambient water vapor,
also a time-dependent process, can be signifi cant with hygroscopic
particles, resulting in increases in both MMAD and GSD .
Chapter 4 : The cascade impaction technique is both complex and exacting in
terms of the skills required for successful measurement outcomes,
leading to reproducible results. This chapter is a review of the under-
lying causes of variability associated with these measurements, aris-
ing from four main causes: man, machine, measurement, and material.
Factors to be considered when implementing a CI-based measurement
regimen are summarized, both for OIP method development and in
routine (i.e., day-to-day) use, and a method failure diagnostic tree is
presented, based on the good cascade impactor practice (GCIP) prin-
ciple. The second part of this chapter explores the potential to simplify
full-resolution CI measurements, introducing the AIM concept for the