A new set of computational tools called CSD-Particle will help academic and industrial researchers understand how particles behave in the manufacture of fine chemicals in an attempt to reduce costs and make the process more efficient.
CSD-Particle is one of many software suites released by the Cambridge Crystallographic Data Center (CCDC), custodians of the Cambridge Structural Database (CSD), based on this valuable data repository. Founded in 1965, the CSD contains a wide range of different crystal structures of chemical compounds and in 2019 surpassed the one million structure mark.
“Some of these suites deal with solid form computing or materials computing, and we wanted to go beyond the solid form and address the mechanical and chemical behaviors of particles,” says Jürgen Harter, Managing Director of the CCDC. “The real trajectory is to go from understanding the molecule and its behavior, to understanding its solid form, and then understanding the behavior of its particles, to determine how the therapeutic product behaves and can be manufactured, developed and produce at best.”
Once a new drug has been developed and approved, it must be manufactured at scale before it can reach patients. Drug developers need to think about this process carefully and early, both in terms of functionality – which formulation will work best for the drug’s mode of action – and production costs – how can they produce the drug from economical way.
“Particle properties are critical to understanding our product performance and manufacturing capability,” says Helen Blade, associate principal scientist in structural science at AstraZeneca, one of the early testers of the software.
“Shape variation, for example, can impact the manufacturability of how things go. Likewise, surfaces can impact performance. Differences in wettability are just one example.
In the past, many physical tests were often required before finding the best formulation for a drug, resulting in high production costs. CSD-Particle has the potential to reduce these costs and the number of experimental tests needed, especially for crystal-structured drugs.
“We can link with our crystallization scientists to be able to help inform particle control strategies, as well as feedback to our materials scientists from a product point of view, to tell what kinds of shapes and surfaces we should expect, and tie that to how the tablet will perform,” says Blade.
“If you can reduce your manufacturing runs from 10 to just a few, that’s already a huge saving,” Harter points out.
CSD-Particle was designed and built in collaboration with academic and industrial partners, including AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline and Pfizer, and is part of the Advanced Digital Design of Pharmaceutical Therapeutics (ADDoPT) project and the Digital Design Accelerator Platform (DDAP) .
Both of these initiatives are helping to shift pharmaceutical development to a “digital first” approach to try to minimize or eliminate non-viable drug candidate formulations as early in the process as possible, which the CCDC also likes objective.
“Computation is cheap compared to experimentation. That’s why we would always prefer to calculate our solution to our problems,” acknowledges medical chemist and drug discovery expert Derek Lowe. He thinks the software has a lot of potential, but scientists and companies will want to test it first before making big changes based on its findings. “At least you can categorize things and say, ‘Here’s where to start. It’s worth knowing, because as you can imagine, there are an awful lot of wording options.
While a key use of CSD Particle will be in drug development, Harter explains that it can also be used to develop agrochemicals such as pesticides and other advanced materials where early knowledge of crystal particle structure could be useful.