Cocrystal production method reducing deposition risk of undesired single component crystals in anti-solvent cocrystallization

• The new strategy of cocrystal production method was developed.
• The reduction of the risk of undesired crystals was successful.
• A domain without the deposition risk of undesired crystals was determined on the phase diagram.

The cocrystallization operation has the deposition risk of undesired crystals. In this study, the strategy of cocrystal production method considering the risk reduction of undesired single component crystal deposition was investigated. The anti-solvent cocrystallization was carried out in four-component system of carbamazepine (CBZ), saccharin (SAC), methanol and water. The undesired single component crystals precipitated depending on the solution addition sequences. Considering the driving force for each component, a domain without the deposition risk of the undesired crystals was determined on the phase diagram. It is important to keep the operation point in this domain for production of desired cocrystals.

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