Solid-State Phase Transformations and Storage Stability of Curcumin Polymorphs

Abstract

Curcumin crystallizes in three polymorphic forms. Form 1 exists as a monoclinic structure, whereas Forms 2 and 3 exist as orthorhombic structures. The aim of this work was to understand the polymorphic behavior of curcumin and the stability of the forms of curcumin. Liquid antisolvent precipitation of curcumin in the presence of ultrasound and additives results in the precipitation of curcumin in orthorhombic forms (Form 2 or Form 3), whereas raw curcumin and curcumin particles precipitated without ultrasound and without additives exist in monoclinic form. Differential scanning calorimetery (DSC) experiments reveal that both of the orthorhombic forms (Forms 2 and 3), which precipitated in the presence of ultrasound and additives, transform to a monoclinic form (Form 1) upon heating. The orthorhombic form (Form 3) in particles, which precipitated in the presence of ultrasound only (no additives), transforms directly to a monoclinic form (Form 1) upon heating. On the other hand, the orthorhombic form (Form 3) in particles, which precipitated in the presence of additives such as HPMC and BSA along with ultrasound, first transforms to Form 2 before finally converting to Form 1 upon heating. All of these transformations occur below the melting points of all three forms. These polymorphic transformations also result in a visible change in particle morphology from rice seed-like or spherical to acicular. While Form 2 and Form 3 were found to be unstable at higher temperatures, these forms, when stored in aqueous suspensions at room temperature (25°C), were found to be stable even after 3 years, with no significant change in particle size or morphology.

Effect of high pressure homogenization on physicochemical properties of curcumin nanoparticles prepared by antisolvent crystallization using HPMC or PVP

“…In addition, the enthalpy of fusion in 2 nd peak of CUR-CRS sample reduced from 82 J/g for untreated CUR to 74 J/g for newly prepared sample. This may be due to a slight reduction in the crystallinity of the sample which also has been reported elsewhere for curcumin when antisolvent crystallization was applied [31,36,38]. PM samples showed a broad melting endothermic peak near melting point of CUR.…”

High Amplification of the Antiviral Activity of Curcumin through Transformation into Carbon Quantum Dots

“…The two phenolic groups at the two ends of each curcumin molecule and the keto and enols are the centers of hydrogen bonding . The intermolecular hydrogen bonding among the curcumin molecules gives rise to different conformations in the crystals, including linear, planar, curved, and twisted . All the purified Cur‐CQDs exhibit some sharp peaks that can be ascribed to the high order of pyrolytic curcumin molecules or polymers on the surfaces of the CQDs because their sharp peak profiles are similar to that of pure curcumin in the solid state.…”

“…[30] The intermolecular hydrogen bonding among the curcumin molecules gives rise to different conformations in the crystals, including linear, planar, curved, and twisted. [30,32] All the purified Cur-CQDs exhibit some sharp peaks that can be ascribed to the high order of pyrolytic curcumin molecules or polymers on the surfaces of the CQDs because their sharp peak profiles are similar to that of pure curcumin in the solid state. The interactions among the curcumin molecules are changed through dehydration and condensation, followed by the formation of cross-linked, polymer-like curcumin.…”

Polymorphs of Curcumin and Its Cocrystals With Cinnamic Acid

“…22 There is a possibility of phase transformation of Form 2 to Form 1 at pH above 3, leading to the precipitation of Form 1 alone. 44 The p-XRD spectra in Figure 3 The spherical aggregate structure of curcumin crystals at lower solvent-to-anti-solvent ratio, changes to fine needle-like crystals at 3:10 solvent to anti-solvent ratio. At this ratio, the crystals are fiber like, which are loosely but regularly connected to form a mesh like structure (Figure 4 (d)).…”