Phase Diagram-Enabled Curcumin Isolation and Purification by Utilizing Resorcinol as Cocrystal Former and Additive.

In this study, cocrystallization was explored as a method for purifying a compound from a complex mixture. Using the case of curcumin purification, resorcinol was selected as the additional component due to its propensity to form a cocrystal with curcumin in a mole ratio of 1:1. To enable a proper process design, a ternary phase diagram of curcumin-resorcinol-ethanol at 25 °C was constructed. However, it was found that resorcinol can only be suitably used if the curcumin content in the crude powders is at least 70 wt %, otherwise complete solubilization would occur. By taking this into account, starting from raw turmeric powders, the following operations were carried out: (1) extraction, (2) solid-liquid equilibration, and (3) two stages of cocrystal formation-dissociation. Finally, 96.06 ± 1.19 wt % curcumin purity with an overall yield of 0.26 ± 0.02 wt % was obtained. Furthermore, coformer recycling was carried out by antisolvent addition and evaporative crystallization of the mother liquor, with a recovery yield of up to 80.6 ± 1.40 wt %. Interestingly, the coformer could also be used directly as an additive to the curcumin-ethanol suspension, thereby entirely skipping the cocrystal formation-dissociation steps. Starting from raw material with 70 wt % curcumin purity, this method could produce a superior curcumin purity of 85.3 ± 2.0 wt % against 78.5 ± 1.6 wt % without any resorcinol addition, both at similar yield values.