Particle-characterization data is central to the development, manufacture, and quality control of pharmaceutical products.
The characteristics of a pharmaceutical's composite particles can affect the product in many ways, including by influencing
drug efficacy and stability, as well as how the product behaves during processing. When considering the importance of particle
characterization, the International Conference on Harmonization's (ICH) Q6A guideline on specifications (1) is a useful starting
point because it identifies potentially important particle variables, including polymorphic form, enantiomeric purity, and
particle size and distribution. The guideline also provides a decision tree to help determine when related testing is required.
IMAGE: INFLUX PRODUCTIONS, PHOTODISK, GETTY IMAGES
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Historically, industry has paid greater attention to control of particle size and distribution, which, according to ICH Q6A,
can significantly affect the dissolution rates, bioavailability, and stability of drug substances in both solid and suspension
products. Today, particle characteristics are attracting even greater focus as industry strives to increase manufacturing
efficiencies. This drive has been largely influenced by the growing emphasis on quality by design (QbD), which encourages
pharmaceutical companies to use an information- and risk-based approach to optimize product development and manufacture. Using
particle characterization to understand how a product behaves during processing supports this initiative.
This article takes a brief look at what factors have driven innovations in particle-characterization techniques and how technology
may advance in this area in the coming years.
Innovations in particle characterization
Two of the earliest particle-sizing techniques were manual microscopy and sieving. These methods are still used today, but
both have drawbacks. For instance, microscopy is slow and manually intensive, while sieving is unsuitable for fine or cohesive
materials. As such, industry has sought more advanced particle-sizing techniques.
One such approach that is gaining popularity is laser diffraction. "Although laser diffraction methods have been used for
the last 30 years, continuous development has resulted in much more accurate and reproducible measurements between manufacturers,"
explains Graham Rideal, founder of and a senior scientist at Whitehouse Scientific, which specializes in particle-sizing methods.
Paul Kippax, product group manager at Malvern Instruments, a producer of analytical equipment, agrees that laser diffraction
is an important technology, particularly because its measurement range (0.1 to 3000 μ) covers the vast majority of particle-sizing
applications used by industry. In addition, laser diffraction is capable of high-speed size distribution sampling (typically
less than 20 s, according to Kippax), is nondestructive, and is suitable for automation. "Today's laboratory laser diffraction
analyzers have been automated to the point of push-button operation, with sample loading being the only remaining routine
manual task," says Kippax.
Imaging and microscopy are not being left behind, however. Some recent advances have been made with these analytical techniques.
"The continuous and concomitant development of imaging technology and high-speed computers has transformed the humble microscope
from a predominantly qualitative instrument into one of the most potent quantitative tools available today," explains Rideal.
"This development has extended the definition of a particle from that of a simple equivalent spherical diameter into a comprehensive
shape analysis where length, width, and perimeter can be measured at tremendous speeds."
