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

Steffi Wünsche,Lina Yuan,Andreas Seidel-Morgenstern,Heike Lorenz

doi:10.3390/molecules26030720

Abstract

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.

Highlights

Turmeric (Curcuma longa L.) originating in South and Southeast Asia, has been used as a spice and in traditional medicine for centuries, e.g., for the treatment of wounds, colds and arthritic disorders among others [1]
Supramolecular are structural units with functional groups that are connected by intermolecular interacsynthons are structural units with functional groups that are connected by intermolecular tions such as hydrogen bonds and π-π stacking [37]
Powder X-ray Diffraction (PXRD) patterns are shown in Figure 4 to 6 for resorcinolincluding (RES), pyrogallol (PYR), and and hydroxyquinol (HYQ), respectively

Summary

Introduction

Turmeric (Curcuma longa L.) originating in South and Southeast Asia, has been used as a spice and in traditional medicine for centuries, e.g., for the treatment of wounds, colds and arthritic disorders among others [1]. The main bioactive constituents of turmeric are the structurally related curcuminoids curcumin (CUR), demethoxycurcumin (DMC) and bis(demethoxy)curcumin (BDMC), differing only in the presence or absence of one or two methoxy groups (Figure 1). It is reported to possess antioxidative, anti-inflammatory, neuroprotective, antibacterial, antifungal, antineoplastic, and proapopotic activity [3,4,8,9,10], which render it a potential drug candidate for the treatment and prevention of cancer and Alzheimer’s disease [5,7]. Available CUR usually used for research and clinical trials contains up to Due to its poor bioavailability caused by low aqueous solubility, slow dissolution rate and rapid metabolism it has not yet been approved as a therapeutic [6].

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