Identifying mistakes in cocrystal structure determination
What is it about?
Pharmaceutical drugs can exist in different solid forms, such as salts and cocrystals. Even though these forms may differ by just one hydrogen atom, they have different regulations. To help distinguish them, we tested a computational method based on quantum chemistry (DFT). We tested this method on a large dataset of 404 cocrystal models and confirmed that most were correctly classified. However, we found 16 that might actually be salts instead of cocrystals. We investigated these 16 cases further, growing single crystals for seven of them and using X-ray analysis to check their structures. We also compared different computational approaches and found that the r2SCAN method is the best choice for accurately distinguishing salts from cocrystals.
Why is it important?
Distinguishing between salts and cocrystals is very important in the pharmaceutical industry for regulations and quality control. The U.S. Food and Drug Administration (FDA) has set clear rules for correctly identifying pharmaceutical phase in its 2018 guidelines.