Hot stuff: CSD-based co-crystal design

We are pleased to announce that a recently published scientific communication involving researchers at the Pfizer Institute of Pharmaceutical Materials Science and CCDC has appeared as a CrystEngComm hot-article. The article summarises exciting results assessing the potential of the Mercury Solid Form Suite’s hydrogen bond propensity tool in screening potential co-crystal formers, and is available to view free of charge for 4 weeks from 20th March.

The published study describes the co-crystal screening of the anti-malarial drug pyrimethamine with various pharmaceutically acceptable adducts. Co-crystals offer completely new physical properties compared to a pure active ingredient and are viewed as a rich source of novel solid forms in the pursuit of a stable candidate for drug or agrochemical product development.  Co-crystallising pairs of actives with different or complementary pharmacological effects is also an elegant potential route to multi-drug therapy. Developing methods to better suggest successful co-crystallisation experiments is, therefore, of great interest.


The article is the second in a series in which the collaborators used the Solid Form Suite to compare the hydrogen bonding potential between molecules of the Active Ingredient (AI) on its own versus potential interactions involving the AI and a second component (a co-crystal former). The results confirmed their hypothesis that highest propensity interactions between AI and co-former signal a favourable configuration over the pure forms on their own, and a cocrystal product is likely. However, if AI-AI interactions are preferred, then a co-crystallisation reaction is not likely to be seen. The authors were also able to hypothesise the occurrence of a salt from as a result of proton transfer between AI and co-former, and predict their occurrence as well.

Of the eight attempted experiments, two new co-crystals and four salt forms were obtained. Seven of those eight outcomes were in line with the authors’ expectations, whereas in one experiment no firm case for the occurrence of a co-crystal or a pure form could be made.
About the authors: Dr. Elna Pidcock is a Principal scientific investigator at CCDC; Dr. Peter Galek is a Senior Software Developer at CCDC; Dr. Amit Delori held a post-doctoral position with Prof. Bill Jones at the Pfizer Institute of Pharmaceutical Materials Science, University of Cambridge, and has since moved to University of Strathclyde; Mohit Patni was a University of Cambridge research intern and is now studying at the Indian Institute of Technology, Guwahati.