A Contribution to the Solid State Forms of Bis(demethoxy)curcumin: Co-Crystal Screening and Characterization

Area of Science:

• Pharmaceutical Chemistry
• Materials Science
• Crystallography

Background:

• Bis(demethoxy)curcumin (BDMC), a key turmeric component, suffers from poor water solubility and difficult separation from similar compounds.
• Co-crystallization offers a viable strategy to modify physicochemical properties, including solubility and processability.

Purpose of the Study:

• To investigate the co-crystallization of BDMC with hydroxybenzenes to enhance its properties.
• To explore different co-crystal production methods for BDMC-hydroxybenzene systems.
• To characterize the resulting co-crystals and assess their solubility.

Main Methods:

• Co-crystal screening of BDMC with four hydroxybenzenes using solution crystallization (SSE, RSR), liquid-assisted grinding (LAG), and melt crystallization.
• Characterization of co-crystals using infrared spectroscopy and melting point analysis.
• Solubility measurements in ethanol and ethanol-water mixtures.

Main Results:

• Two novel co-crystal phases were successfully obtained: pyrogallol-BDMC (PYR-BDMC) and hydroxyquinol-BDMC (HYQ-BDMC).
• PYR-BDMC co-crystals were formed exclusively from the melt phase, while HYQ-BDMC co-crystals were produced via melt crystallization and LAG.
• Both co-crystals exhibited equimolar composition and incongruent melting behavior. Infrared spectroscopy indicated different tautomeric forms of BDMC in each co-crystal.
• Solubility studies showed increased solubility in ethanol-water mixtures but a slight decrease in ethanol.

Conclusions:

• Co-crystallization is an effective method for improving BDMC solubility and developing separation processes for chemically similar compounds.
• The distinct formation conditions and tautomeric states of PYR-BDMC and HYQ-BDMC co-crystals offer tunable properties for potential applications.
• These findings provide a foundation for advanced crystallization-based separation techniques for complex natural product mixtures.