Bis(demethoxy)curcumin (BDMC) is one of the main active components found in turmeric. Major drawbacks for its usage are its low aqueous solubility, and the challenging separation from other curcuminoids present in turmeric. Co-crystallization can be applied to alter the physicochemical properties of BDMC in a desired manner. A co-crystal screening of BDMC with four hydroxybenzenes was carried out using four different methods of co-crystal production: crystallization from solution by slow solvent evaporation (SSE), and rapid solvent removal (RSR), liquid-assisted grinding (LAG), and crystallization from the melt phase. Two co-crystal phases of BDMC were obtained with pyrogallol (PYR), and hydroxyquinol (HYQ). PYR-BDMC co-crystals can be obtained only from the melt, while HYQ-BDMC co-crystals could also be produced by LAG. Both co-crystals possess an equimolar composition and reveal an incongruent melting behavior. Infrared spectroscopy demonstrated the presence of BDMC in the diketo form in the PYR co-crystals, while it is in a more stable keto-enol form in the HYQ co-crystals. Solubility measurements in ethanol and an ethanol-water mixture revealed an increase of solubility in the latter, but a slightly negative effect on ethanol solubility. These results are useful for a prospective development of crystallization-based separation processes of chemical similar substances through co-crystallization.

The binary thermal phase behaviors of the curcuminoids (CURDs) curcumin (CUR), demethoxycurcumin (DMC), and bis-(demethoxy)curcumin (BDMC) with either pyrogallol (PYR) and hydroxyquinol (HYQ) as potential cocrystal formers were investigated. Earlier, it was reported that CUR and BDMC form cocrystals in a 1:1 stoichiometric ratio with the aforementioned coformers. Here, we report for the first time cocrystallization experiments of DMC. Two different cocrystallization techniques, namely, liquid-assisted grinding and cocrystallization from the melt phase, were applied. Analyses of the cocrystallization outcomes were performed using powder X-ray diffraction and differential scanning calorimetry (DSC). A cocrystal phase of DMC with one of the two trihydroxybenzenes could not be found, but a simple eutectic behavior was proven. Binary phase diagrams of all six systems were constructed from DSC measurements revealing distinct thermal behaviors: The CUR cocrystals both melt congruently, while the BDMC cocrystals show an incongruent melting behavior. Together with the eutectic DMC systems, we found three different types of binary phase behaviors for the CURD systems, which can serve as a basis for future crystallization-based purification of structurally similar CURDs.

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