Medical and Pharmaceutical Aerosols - Aerosols: Measurement, Dosimetry, and Health Effects - page 16

Currently, optical particle sizing techniques are useful tools in evaluating pharmaceutical aero-
sols. In general, these techniques are not accepted as pharmacopeial methods because, from a regu-
latory point of view, they suffer from representative sampling issues and an absence of chemical
analysis. 164
1.4.2 o tHer I n V Itro M easureMent t ecHniques c oMMonly
e MPloyed For P HarMaceutical a erosols
From a development and regulatory viewpoint, particle size is a dominant analytical method used to
characterize medical and pharmaceutical aerosols. However, regulatory agencies also recommend
that other characteristics of medical aerosols be measured. 75 These include dose content uniformity
of the emitted aerosol, 53 spray pattern and geometry measurements, 165 and the effect of storage con-
ditions (temperature, relative humidity, duration), low rates, and stability challenges. 53
1.4.2.1 Angle of Repose
The angle of repose of a powder employed in a DPI is useful in determining the relative lowability
of the sample. Highly cohesive powders tend to have larger angles of repose, whereas minimally
cohesive powders have a very small angle of repose. Several methods are used in determining this
value and most methods employ forming a cone of powder and measuring the angle formed between
the horizontal surface and the side of the cone. This property relates to the now defunct USP <1174>
standard.
A fairly new piece of equipment, the rotating drum 166 (e.g., the Revolution Powder Analyzer by
Mercury Scientiic Inc.), allows the measurement of the dynamic angle of repose, as well as many
other properties. A drum with clear sides is partially loaded with powder, and the drum is rotated at
a desired rate while a camera captures the avalanching of the powder. These images are then used
in determining the average time to avalanche, the avalanche energy, the dynamic angle of repose,
and many other useful properties which can be related to low. 87 The luidization, packing, and
granulation behavior of these powders can also be analyzed with the Revolution Powder Analyzer.
1.4.2.2 Atomic Force Microscopy
Atomic force microscopy (AFM) is a relatively new characterization technique, invented in 1986,
which uses a microscopic cantilever to determine such features as surface topology and adhesion
forces. Force measurements have been used to probe the interaction between pMDI surfactants and
solvents 167 or drugs and pMDI components. 168 The cohesive-adhesive balance (CAB) approach has
shown that the ratio between the cohesion of the drug and the adhesion of the drug to carrier can
inluence the performance of DPIs. 169,170 These measurements are performed by attaching a probe,
such as the drug of interest, to an AFM cantilever and then measuring the forces between this probe
and different surfaces. The CAB approach can potentially help during the formulation process to
optimize drug-drug and drug-carrier interactions.
1.4.2.3 Electrostatics
Electrostatics can play an important role in several aspects of aerosol formulation and delivery, and,
thus, measuring these forces can provide some insight into how they will affect the inal product. In
particular, triboelectric charging due to contact between particles may increase the lung deposition
due to charge attraction between the particles and the lung tissue. 171 The electrostatic charge can be
measured by a Faraday pail or Faraday cup, which essentially consists of an electromagnetically
shielded and insulated metal collection pail connected to either an electrometer or a series of ampli-
iers to measure the total charge delivered from the powder to the pail. The powder is either manu-
ally added to the pail, or it impinges on the pail from the aerosol device itself. 172-174 A newer method
includes coupling particle sizing with charge measurement, by either modifying a Berner multi-jet