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.
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."