Cocrystallization of Curcuminoids with Hydroxybenzenes Pyrogallol and Hydroxyquinol: Investigations of Binary Thermal Phase Behaviors

Abstract

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.

A New Look at the Mechanism of Cocrystal Formation and Coformers Exchange in Processes Forced by Mechanical and/or Thermal Stimuli –ex situandin situStudies of Low‐Melting Eutectic Mixtures

“…Table 1 summarizes the results of interactions of cocrystals with coformers forced by external stimuli (grinding, melting, spinning). As one can see, the ET: EMA cocrystal is the most stable and neither GLU nor MAL can the ideal liquidus lines for ET (black) and the coformer (blue) as well as the predicted cocrystal melting behaviour (dashed red line) calculated using the Schroeder-van Laar and Prigogine-Defay equations, [57] respectively. Experimental points are represented by black diamonds (ET), blue inverted triangles (coformer), red triangles (cocrystal), magenta and orange circles (eutectic), grey squares (metastable eutectic).…”

Development and Characterization of Co-crystals Assisted withIn-silicoScreening for Solubility and Permeability Enhancement of Curcumin

“…The samples were blended with dry potassium bromide, maintaining a weight ratio of 1:100. Subsequently, this mixture was compacted into pellets, and the infrared absorption spectra of the samples were measured in the range of 4000 cm−1 to 600 cm−1 [36][37][38].…”

Accelerated Wound Healing with a Diminutive Scar through Cocrystal Engineered Curcumin

“…Formation of hydrogen bonding between hydroxyl group of phenol and the keto group of CUR is responsible for the emerging cocrystals with pyrogallol (PYR), resorcinol (RES), phloroglucinol (PHL), quinol (HYQ), and hydroxyquinol (HXQ) which has been reported in the literatures. − ,− It has been found that CUR–PYR cocrystal dissolves about 12 times faster than CUR which is the greatest solubility among the reported CUR pharmaceutical solids including polymorphs, cocrystals, and eutectics . Besides, in animal models, CUR–PYR displays less toxicity and more bioavailability during the high dose administration. , PYR, an active ingredient of the native Indian gooseberry Emblica fruit, has been widely used in Asian traditional medicine whose antioxidant and anti-inflammatory properties have been reported in several studies. , Providing that PYR is a potent drug for inhibition in the growth of lung cancer tumor, CUR–PYR has also been considered as a drug–drug cocrystal.…”