Process Parameters in the Purification of Curcumin by Cooling Crystallization

Abstract

Purification of crude curcumin by up to four successive cooling crystallizations has been investigated for a wide variety of process conditions. For each crystallization step the influence of various processing conditions on crystal purity, polymorphic outcome, and crystal size and shape is reported. By an extensive number of experiments according to a statistical experimental design, the influence on cooling rate, seeding, seed polymorph, and agitation conditions has been identified. Slow cooling and seeding, particularly with the metastable Form II seed, significantly improves the purification. A correlation between product crystal size and purity is found. By tuning the crystallization parameters the number of recrystallization steps required to reach a certain purity can be reduced, which significantly increased the overall curcumin yield from 28% to 50%.

Solvate Formation of Bis(demethoxy)curcumin: Crystal Structure Analyses and Stability Investigations

“…In the past twenty years, around half of the approved drugs are based on natural compounds 17,18 . Prominent examples are curcuminoids, extracted from rhizomes of the bis(demethoxy)curcumin (BDMC), which makes the purification quite challenging (issue 1) 19,20 .…”

Solvate Formation of Bis(demethoxy)curcumin: Screening and Characterization

“…BDMC is more soluble in the polar solvents (except water) compared to the nonpolar solvents. This rough estimation of solubility could provide information when performing purification experiments of curcuminoids by recrystallization from solvents [17,30].…”

“…Commercially available curcuminoids consist of three main components: curcumin (CUR), demethoxycurcumin (DMC) and bis(demethoxy)curcumin (BDMC) [14][15][16]. The three components are structurally similar (Figure 1), which makes the separation and purification quite challenging [17,18]. The method of using the property of solvate formation might be helpful for the separation.…”

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).…”