Good Cascade Impactor Practices - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 89

(e) Environmental conditions, temperature, and humidity: It is widely known that
the local environmental conditions surrounding the aerosol as it is generated by
the inhaler may influence variability of the aerosol and thereby contribute to
measured product variability. However, local temperature and relative humidity
also may influence the aerosol APSD during the process of measurement. The
first type of influence is not considered in this chapter because it is product-
specific. The second type of effect could, however, be categorized as CI
(method)-related variability. In particular, the relative humidity will influence
electrostatic (i.e., triboelectric) effects that are discussed later. Together with
temperature, local humidity will also affect droplet growth or evaporation
throughout the CI system [ 35 - 39 ], especially for aqueous droplets such as those
produced by SMIs and the various types of nebulizer. Unless corrected for,
ambient temperature variations may additionally bias measured volumetric
flow rate through the system and thus further affect the APSD measurement.
Bonam et al . observed that usually, temperature and nowadays relative humidity
are both normally monitored and controlled to minimize these effects [ 2 ]. The
extent of environmental influences and the needed controls depend on the prod-
uct type (API, carriers, propellants, cosolvents, etc.), as well as on the CI sys-
tem and its other operating conditions (e.g., whereas the flow rate may affect the
rate of particle growth and evaporation, the CI temperature may affect heat
transfer and droplet evaporation).
(f) Electrostatic charge and triboelectrification: Several groups have demonstrated
that aerosolized particles acquire and carry intrinsic electrostatic charges (of
either sign). This acquisition of electric charge is chiefly by triboelectric effects
(contact electrification). It takes place always during aerosol formation from
either DPIs [ 40 - 45 ] or MDIs [ 45 - 52 ]. However, triboelectrification is unlikely
with aerosols from SMIs and nebulizers, as the preparations used with these
classes of OIP nearly always contain physiologically normal saline which is
fully ionized. Horton et al . have shown that electrostatic charge may also be
acquired by CI components that are nonconducting or electrically insulated and
can significantly influence particle collection behavior [ 53 ], thereby adding to
the variability of the measured APSD and MB. Unless the OIP is a nebulizer,
exploratory studies are likely to be warranted to optimize the CI method.
(g) Collection surface coating material and coating thickness: Several groups,
including Nasr et al . [ 54 ], have shown that grease-coating CI plates reduces or
eliminates particle bounce and reentrainment altogether. At the micron-size
scale, the addition of a tacky coating modifies the impaction surface such that the
incoming kinetic energy associated with the particles whose trajectories inter-
sect with the surface is absorbed more efficiently than would be the case with a
smooth and hard surface that has a relatively high coefficient of restitution. In
2003, Mitchell surveyed EPAG member organizations, reporting that almost all
practice some form of collection surface coating to reduce bias and variability of
CI measurements [ 55 ]. This effect is particularly important for DPI formulations
[ 56 , 57 ] and may also occur with some MDI products [ 58 ]. However, it may be
unimportant for the collection of liquid droplets arising from nebulizing systems