In this work three active pharmaceutical compounds were assessed for stability using a combination of CCDC tools, to select the most stable solid form for further development.
As well as supporting and validating lab work, in one case this "healthcheck" assessment raised the possibility of a significant weakness with an existing form that was not identified in initial experiments.
Follow up experimental work confirmed the healthcheck findings, and a new form, with better characteristics, was found to form in certain conditions.
Changes in conditions can produce different polymorphic forms of a crystalline material - with potentially big impacts in solubility, stability and more. In pharmaceutical development it is therefore vital the solid form is fully understood - unforeseen polymorphs have cost drug companies hundreds of thousands of pounds in the past, for example the case of Ritonavir (Bauer et al, Pharm Res, 2001).
The "healthcheck" assessment described in this work is a collection of in silico analyses which complement and add to experimental work already done to address this risk. By combining experimental and informatics results in this way, scientists can have greater confidence in their decision to take a structure on to further development.
The team employed a range of informatics analyses to fully characterise the intermolecular interactions, intramolecular geometry, chirality, Z' and more - and coined the term "healthcheck" to encompass this complete review of the structure. This work is done in addition to laboratory work, to strengthen and support findings there.
Across the three molecules studied here;
- Crizotinib - healthcheck in agreement with experimental work.
- Pain candidate drug - healthcheck confirmed which of two experimental forms was more stable.
- Maraviroc - healthcheck suggested a more stable form could be possible. Additional lab work later confirmed this.
Read the Journal of Pharmacy and Pharmacology paper here.
Learn more about the CSD-Materials suite, containing all the tools to perform a Healthcheck analysis, here.
See more examples of CCDC tools in action here.