Medical and Pharmaceutical Aerosols - Aerosols: Measurement, Dosimetry, and Health Effects - page 14

1.4.1.1 Inertial Methods
1.4.1.1.1 Cascade Impactor
Cascade impactors are commonly used to characterize environmental materials such as pollutants;
however, this chapter will focus on the use of the instrument for characterizing particles designed
for delivery to the lung. The cascade impactor has been a tool to determine the particle size of
pharmaceutical aerosol dispersions for over 30 years. The impactor applies the principles of inertia
discussed earlier in this text to separate particles by size. Particles are dispersed and travel through
multiple stages with sequentially decreasing jets. Each stage plate should be thinly coated in oil to
avoid particle bounce and blow-off. 145
There are multiple impactor systems currently on the market and their size speciications can be
seen in Table 1.4. 76 The Next Generation Impactor (MSP, Inc., Niwot, CO) was developed to make
particle size testing more eficient. It has low internal particle loss and requires minimal washing
between tests. 146-148
There are some differences in the setup of the apparatus when sampling for pulmonary delivery
as opposed to environmental testing. First, a throat is added to the impactor to model the anatomy
of the human body so as to catch the larger aerodynamic particles. 149 Second, the low rate of air
through the impactor differs from that of environmental sampling. 150 When performing impac-
tions of aerosols intended for pulmonary delivery, airlow rates of 28.3-90 L/min are typically
employed.
1.4.1.2 Optical Methods
Optical particle size analysis techniques are commonly used in pharmaceutical aerosol
development and testing. Due to the unstable and transient nature of emitted aerosols, these
methods frequently perform dynamic measurements. Particle size characterization of pharma-
ceutical aerosols by static measurements (i.e., microscopy) is also essential during formulation
development. 151-153
Phase Doppler anemometry (PDA) is an open laser system and can sample the aerosol from the
point of generation to the extremities. 154,155 Accordingly, PDA has been most often used to character-
ize the development of nebulizers and MDI aerosols. 154 Time-of-light (TOF) particle size analyzers
are real-time optically based and are used frequently in medical and pharmaceutical aerosols. 156,157
Particles are separated on the basis of their inertia by accelerating the particles through a well-
deined low ield and measuring the particle TOF across a split laser beam. TOF analyzers measure
single particles and collect distributions by collecting size data on a statistically valid number of
particles. Powder dispersion, DPIs, MDIs, and nebulizers have all been investigated using this type
of instrument. 157,158
Laser diffraction as a method of particle size analysis for pharmaceutical aerosols has also been
reviewed. 159-161 Laser diffraction techniques are widely used in the characterization of pharmaceuti-
cal aerosols due to the rapid nature of data collection. The laser light scattering patterns of an aero-
sol passing through the laser region allow instantaneous evaluation of multiple particles. Original
systems used the principle of Fraunhofer diffraction, although newer laser diffraction equipment
relies on Mie scattering theory that more accurately allows the sizing of particles near the same size
as the wavelength of the laser. 162 Like PDA systems, various regions and time points of an aerosol
produced from an inhaler can be sampled. 159
A new system currently being investigated for pharmaceutical aerosol measurements is the opti-
cal particle counter (OPC). A white light aerosol spectrometer can measure single particle sizes on
the order of 0.3-40 μm, although typically it requires very dilute sample conditions. A welas (Palas
GmbH) sensor, however, in conjunction with an appropriate dilution mechanism, can be used to
measure particle sizes of pMDIs comparable to laser diffraction or cascade impactor values. The
aerosol amount can also be accurately measured with such a system, possibly saving some time dur-
ing the characterization of pMDI aerosols. 163