PharmTech: Can you offer any best practices for those beginning to apply a QbD approach to tableting and granulation?
Freeman (Freeman Technology):
QbD relies heavily on engineering an optimized, well-understood process. It is therefore important, from the outset, to work
out how to gather analytical data that will accurately reflect process performance. Effective powder handling is central to
the success of tableting, granulation and a wide range of other pharmaceutical unit operations. Appropriate powder characterization
techniques are, therefore, an essential prerequisite.
The number of powder testing techniques available reflects both the importance of such testing and its difficulties. When
choosing which techniques to apply for QbD studies, I would suggest assessing against a number of criteria including:
- reproducibility and sensitivity
- process relevance
- ease of use.
Levoguer (Malvern Instruments):
One of the biggest challenges for those applying QbD is how to access and gather the necessary information. The full implementation
of QbD demands a comprehensive understanding of process and product, and the identification of an effective control strategy
for the manufacturing process. Choice of analytical instrumentation is therefore crucial.
With well-established techniques such as laser diffraction particle-size measurement, customers can rightly expect the highest
levels of automation and analytical productivity. Some systems can extend the efficiencies of dry measurement to more samples
and combine rapid measurement times with assured data quality, to push analytical productivity to high levels for all users.
Of equal importance, however, are continuous laser diffraction particle size analyzers that offer real-time measurement for
pilot-scale studies and commercial plant monitoring and control. These systems can significantly accelerate QbD studies. Running
a pilot plant with real-time monitoring in place enables consistent control at the experimental conditions of interest and
makes the impact of changes in operating variables instantly obvious.
For some types of analysis, the technology is newer, but it is vital to recognize what can now be achieved. Returning to
the example of morphologically directed imaging, these systems involve considerable investment but can deliver significant
value over the long term. Being able to measure not just size and shape but also the distribution of different chemical species
within a dispersed sample, such as a disintegrated tablet, can be invaluable when trying to really understand how the process
works and how to optimize it.
1. X. Fu et al., Particuology
10 (2), 203–208 (2012).
2. J. Khoo et al., "Use of Surface Energy Heterogeneity to Relate the Effect of Surface Modification to Powder Properties"
(Freeman Technology website, 2012),
http://www.freemantech.co.uk/goto.php?link=ART_POSTER_02/, accessed Apr. 16, 2012.