Solubility and Crystal Nucleation in Organic Solvents of Two Polymorphs of Curcumin

Abstract

Two crystal polymorphs of 1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (curcumin) have been obtained by crystallization from ethanol solution. The polymorphs have been characterized by DSC, IR spectroscopy and XRPD and shown to be the previously described forms I and III. The solubility of both polymorphs in ethanol and of one polymorph in ethyl acetate has been measured between 10°C and 50°C with a gravimetric method. Primary nucleation of curcumin from ethanol solution has been investigated in 520 constant temperature crystallization experiments in sealed, magnetically stirred vials under different conditions of supersaturation, temperature and agitation rate. By a thermodynamic analysis of the melting data and solubility of form I, the solid state activity is estimated from 10°C up to the melting point. The solubility is lower in ethanol than in ethyl acetate, and in both solvents a positive deviation from Raoult's law is observed. Form I has lower solubility than form III and is accordingly thermodynamically more stable over the investigated temperature interval. Extrapolation of solubility regression models indicates that there should be a lowtemperature enantiotropic transition point, below which form I will be metastable. By slurry conversion experiments it is established that this temperature is below -30°C. All nucleation experiments resulted in the stable form I. The induction time is observed to decrease with increasing agitation rate up to a certain point, and then increase with further increasing agitation rate; a trend previously observed for other compounds. By correlating the induction time data obtained at different supersaturation and temperature, the interfacial energy of form I in ethanol is estimated to be 3.0 mJ/m 2 .2

Recent advances in emulsion-based delivery approaches for curcumin: From encapsulation to bioaccessibility

“…Polymorphism of crystal structures of curcumin depends on the crystallization conditions. Curcumin crystals can adopt different shapes, such as monoclinic (acicular), orthorhombic (rice seed like), and amorphous (Liu, Svärd, Hippen, & Rasmuson, 2015;Mishra, Sanphui, Ramamurty, & Desiraju, 2014;Sanphui, Goud, Khandavilli, Bhanoth, & Nangia, 2011) Using scanning electron microscopy (SEM), to analyze curcumin particles, in our laboratory has revealed interesting morphological characteristics, that was dependent on the solvent in which curcumin was dispersed. Figure 2a presents a SEM image of the curcumin particles dispersed in methanol.…”

Rationalising crystal nucleation of organic molecules in solution using artificial neural networks

“…1. [16][17][18][19][21][22][23][24] The solvents include polar protic, polar aprotic, and non-polar molecules, although the majority of the systems feature fairly polar solvents. The solutes differ significantly with regard to properties such as molar mass, the number of rotatable bonds, intermolecular interactions, and melting properties.…”

“…The solvent parameters are: molar mass (9); Reichardt polarity (10), which is an empirical polarity value; dynamic viscosity (11); density (12); boiling point (13); enthalpy of vaporisation (14); topological polar surface area (15); XLogP3 (16); molecular complexity (17); melting point (18); and refractive index (19). The solution parameters are: the number of solute-solvent hydrogen bonds (20) and the solid-liquid solubility (21).…”

Purification of Curcumin from Ternary Extract-Similar Mixtures of Curcuminoids in a Single Crystallization Step

“…The used separation methods were implemented as multi-step processes consisting of at least two successive sub-steps. It is reported that the main part of BDMC could be depleted after the first separation step, full removal was achieved after the second crystallization step [33,34]. DMC was always present in the final Studies show that CUR can be potentially used to treat over 25 diseases due to its anti-oxidative, immunosuppressive, wound-healing, anti-inflammatory and phototoxic effects [6][7][8].…”

“…In the last decade, crystallization as a single separation technique was studied to purify CUR from the ternary mixture of curcuminoids [32][33][34]. Processes were described exploiting anti-solvent Crystals 2020, 10, 206 3 of 16 addition or system cooling, using methanol, ethanol and 2-propanol as process solvents and water as anti-solvent (Table 1).…”