**4. Conclusions**

In this work, the solubility behavior of pure CUR and CUR in presence of the two main impurities DMC and BDMC as well as supersolubilities in acetone, acetonitrile, methanol, ethanol, 2-propanol and their binary mixtures were investigated first. Based on the data obtained, seeded cooling crystallizations in four different process solvents (acetone, acetonitrile and 50/50 (wt/wt) mixtures of acetone/2-propanol and acetone/acetonitrile) were designed and implemented. As a result, the purity of CUR could be increased from initial CUR contents of 67–75% in the curcuminoid mixtures up to values of 90.1–99.4% in a single crystallization step. All crystallization processes provided crystalline curcumin (form I) free of BDMC after this single crystallization step. DMC was significantly depleted from initial contents of 19.2–25.5% in the crude mixtures to residual contents of 0.6–9.9%. Total product yields were significantly enhanced to 70–79% via addition of water and acetonitrile as anti-solvents at the end of the cooling crystallization process.

The presence of crystalline or amorphous DMC in the CUR products could not be detected by XRPD analysis. Whether this is caused by experimental detection limits or by potential formation of CUR/DMC mixed crystals has to be clarified in future studies.

Based on the work presented, a seeded cooling crystallization from a 50/50 (wt/wt) acetone/2-propanol solvent mixture is seen as the best purification strategy providing CUR at highest purity of 99.4%, BDMC free in a single crystallization step. However, there is still space for process optimization in particular with respect to yield. This includes application of a reduced cooling rate and a lowered final cooling temperature to increase both crystallization and total yield. Further, to avoid product losses in downstream processing washing the product with an acetone/anti-solvent mixture (for example acetonitrile) is suggested. No information regarding the maximum admissible limit of BDMC and DMC in the crystalline CUR was found in the literature. However, in any case the CUR purification grade obtained within a simple single crystallization step in this study represents a significant improvement compared to alternative process concepts.

**Author Contributions:** Conceptualization, E.H. and H.L.; investigation, E.H.; supervision, A.S.-M. and H.L.; validation, L.Y., A.S.-M. and H.L.; writing—original draft, E.H. and L.Y.; writing—review and editing, E.H., L.Y. and H.L. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Acknowledgments:** We thank Jacqueline Kaufmann and Stefanie Leuchtenberg (Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany) for supporting the analytical work. We are also grateful to Minh Tan Nguyen and Dinh Tien Vu (Hanoi University of Science and Technology, Hanoi, Vietnam) for motivating this study and providing an extract sample of *Curcuma Longa* L.

**Conflicts of Interest:** The authors declare no conflict of interest.
