Physical Causes of APSD Changes in Aerosols from OIPs and Their Impact on CI Measurements - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 68

ensembles of aerosol particles, most likely because of the complexity of evaluating
particle behavior while considering both intrinsic charge and size distributions, as
well as the influence of local electric fields, likely of both polarities associated with
charges on nearby surfaces.
There are three mechanisms by which aerosol particles can acquire electrostatic
charge [ 64 ]:
(a) Triboelectrification, whereby charge transfer takes place as each particle is sep-
arated from the bulk material or removed from a surface with different tribo-
electric properties
(b) Diffusion charging, where random collisions between particles and unipolar
ions cause charge accumulation on the particles
(c) Field charging, where particles acquire charge from collisions with unipolar
ions in an applied electric field
Diffusion and field charging are seldom encountered in inhalation therapy, except
with specific liquid electro-hydrodynamic atomization systems, in which an applied
electric field is used to charge the liquid stream containing medication emerging
from an orifice or series of orifices.
Triboelectrification is a widespread phenomenon. It may be further subdivided
into (1) contact charging, where there is an initial attachment between particles or
particle-surface touching, followed by separation without rubbing together, and
(2) frictional charging where relative movement of the two surfaces takes place
while still in contact [ 65 ]. In practice, however, it is difficult to distinguish the two
processes, and the term “triboelectrification” is therefore often applied to include
both forms of static electrification.
The influence of electrostatic charge on the measurement of OIP aerosols is
largest with systems not producing electrically conductive aerosol particles.
Hence, the measurement of aerosols containing physiologically normal saline
that are produced from wet dispersion systems (nebulizers and SMIs) is less
likely to be affected, but charging effects have nevertheless been observed with
nongrounded systems [ 66 ]. However, electrostatic phenomena are a much more
significant issue to contend with when measuring DPI-generated aerosols,
because they acquire bipolar charge during the dispersion process [ 65 , 67 ].
Given that the materials of most DPIs are nonconducting and may therefore
themselves acquire charge by contact electrification, the possibility of subtle
changes in the aerosol dispersion and transport from the inhaler to the measure-
ment apparatus may result in measurable shifts in APSD [ 68 ]. Sensible precau-
tions to minimize the influence of such behavior are (a) controlled ambient
conditions, especially relative humidity, and (b) electrically grounded worksta-
tions and operators undertaking the testing [ 38 ]. Triboelectrification is also a
major consideration when measuring the APSDs of MDI-generated aerosols
[ 69 , 70 ], especially if nonconducting add-on devices are present [ 37 , 71 ].
Similar precautions as those identified for DPI testing therefore apply equally
with MDI-related evaluations.