FINE PARTICLE GENERATION
& PARTICLE SIZE ANALYSIS
Particle size is an important characteristic
for many dosage forms. Stability, flowability, dissolution
rate, and bioavailabilty are among the parameters affected
by the size distribution of particles. Cirrus Pharmaceuticals,
Inc. provides a wide range of services to meet our clients'
particle sizing needs, from formulation development to in-line
process monitoring to quality control and release of finished
product. Our highly trained scientists carry out particle
sizing method development, validation, and routine analysis
under cGMP guidelines to address the complexities of technical
and regulatory challenges.
Applications
Particle size reduction is often used to:
- Generate particles fine enough to be properly delivered
to the lungs (for inhalation product development).
- Enhance bioavailability of oral drugs across the intestinal
epithelium (in the development of tablets and capsules).
- Help enhance absorption of a drug across the skin (in
the development of transdermal products).
- Help with solubilizing poorly soluble compounds as in
the development of emulsions and suspensions or microparticulate
systems.
- Enhance bioavailability.
- Speed the dissolution rate of a drug.
- Enhance flow characteristics of powders.
- Enhance wetting properties to improve solubility.
- Improve drug stability and the taste properties of a
compound.
Particle size is often measured during process
development as part of in-line monitoring of a manufacturing
process, during stability studies, and as part of batch release.
Fine Particle Generation/Milling
Cirrus has the staff and equipment to reduce
compound particle size using a variety of milling machinery.
Milling process development can be conducted and scaled-up
at Cirrus, then transferred to a manufacturing facility as
needed.
Laser Diffraction Analysis
Laser diffraction is a rapid and highly
reproducible means of determining the particle size distribution
of powders, emulsions, suspensions, and sprays over a range
of 0.1 µm to 1000 µm. A wide range of accessories
and lenses allow us to sensitively measure particle and droplet
size distributions of bulk powders and particulate products
as well as emitted doses from devices such as metered dose
inhalers, nasal sprays, and nebulizers. With dry dispersion
and aqueous/non-aqueous wet dispersion capabilities, we have
a wide range of options in optimizing a method for drug product
or in-process samples. We have also perfected techniques for
reducing sample size to the low milligram range for precious
materials. With correctly optimized sample dispersion, method
precision is typically in the 1% range. A Malvern Zetasizer
is used for nanparticle (submicron) measurements.
Inertial Impaction
Inertial impaction methods are widely used
to determine the aerodynamic particle size distribution of
aerosols. Aerosol particles with sufficient inertia impact
upon the collection stage while smaller particles follow the
airflow out of the impaction region. Since each stage represents
a discrete particle size range, a size distribution can be
determined by assaying the drug particles collected on each
stage.
At Cirrus, particle sizing methods are
developed and validated using impactors appropriate to specific
drug products. Our extensive experience in the development
of fast and highly sensitive HPLC/MSD assays enables us to
accurately determine particle size distributions from single
doses of highly potent drugs, while reducing run time and
increasing the sample throughput.
Microscopy
Microscopy can be used as a stand-alone
particle sizing method or as a complement to other methods.
As an absolute method, it can be used to verify results from
other methods; to differentiate between primary particles
and aggregates; and to provide information on particle shape
and morphology.
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