Curcumin is a naturally occurring compound derived from turmeric. Despite its many medicinal properties, such as being an antioxidant, anti-inflammatory, tumor reducer, etc., applications of curcumin are restricted due to its low aqueous solubility and consequently its poor bioavailability. By converting the solid state of poorly water-soluble active pharmaceutical ingredients to coamorphous mixtures, solvates, cocrystals, and eutectics, the solubility can be significantly improved. In this study, U. S. Food and Drug Administration approved excipients were screened for their ability to form novel solid states with curcumin to increase its aqueous solubility. Excipients were screened based on their molecular complementarity with curcumin, using Mercury software. Folic acid dihydrate (FAD), suberic acid, and dextrose are the three coformers that are investigated in this study. It was found that a coamorphous mixture can be formed between curcumin and FAD. FAD has potential as a prenatal or a women’s health drug due to its use in pre-eclampsia and ovarian cancer treatments. This mixture was found to have an increased dissolution rate when compared with curcumin. After 1 h, 175 mg/L of curcumin was dissolved from the coamorphous mixture, while only 45 mg/L was dissolved from curcumin Form I. The coamorphous mixture is stable as it was shown to keep its amorphous behavior after 24 h in solution at elevated temperatures. Curcumin formed a eutectic with suberic acid at a mole fraction of 0.2, whereas it remained as a physical mixture with dextrose. Also, solution crystallization of curcumin with dextrose at a mole fraction of 0.5 resulted into a form II curcumin polymorph.

Curcumin is a potentially viable pharmaceutical ingredient obtained from the rhizome of a turmeric plant, Curcuma longa. It is a polyphenolic compound which is known to possess antibacterial, anti-inflammatory, antitumor, and anticancer properties. Its use in pharmaceutical applications has been limited because of its poor aqueous solubility and hence poor bioavailability. In this work, attempts were made to formulate new solid forms of Curcumin with several coformers, mainly to enhance the dissolution rate of curcumin in aqueous medium. Ibuprofen, succinic acid, paracetamol, carbamazepine, ethyl paraben, glycine, tyrosine, N-acetyl D,Ltryptophan and biotin are the coformers investigated in this study. Binary phase diagrams were constructed for each binary system which helped in identifying the nature and the composition of the solid phase. All binary systems except curcumin−ibuprofen exhibited eutectic formation. The curcumin−ibuprofen system resulted in a physical mixture. These solid phases were further characterized through powder X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy and Raman spectroscopy. Dissolution studies conducted for eutectics showed enhanced dissolution rates as compared to raw curcumin. The results obtained were compared with the literature reports to present a consolidated account of research being conducted to enhance aqueous solubility of curcumin by developing new solid forms of curcumin such as eutectics, coamorphous solids, and cocrystals. Further, attempts have been made to understand how molecular geometry and intermolecular interactions influence the formation of a specific solid form.

Abstract:The molecular structure of esomeprazole magnesium derivative in the solid-state is reported for the first time, along with a simplified crystallization pathway. The structure was determined using the single crystal X-ray diffraction technique to reveal the bonding relationships between esomeprazole heteroatoms and magnesium. The esomeprazole crystallization process was carried out in 1-butanol and water was utilized as anti-solvent. The product proved to be esomeprazole magnesium tetrahydrate with two 1-butanol molecules that crystallized in P6 3 space group, in a hexagonal unit cell. Complete characterization of a sample after drying was conducted by the use of powder X-ray diffraction (PXRD), 1 H-nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), infrared spectroscopy (IR), and dynamic vapor sorption (DVS). Investigation by 1 H-NMR and TGA has shown that the solvent content in the dried sample consists of two water molecules and 0.3 butanol molecules per esomeprazole magnesium molecule. This is different from the single crystal X-ray diffraction results and can be attributed to the loss of some water and 1-butanol molecules stabilized by intermolecular interactions. The title compound, after drying, is a true solvate in terms of water; conversely, 1-butanol fills the voids of the crystal lattice in non-stoichiometric amounts.

Curcumin is an active pharmaceutical ingredient (API) present in the Indian spice turmeric, Curcuma longa. Among the several solid-state properties of an API, dissolution has an immediate effect on its bioavailability. Inspite of its medicinal properties, curcumin has very low aqueous solubility. Efforts have been already made for increasing solubility and bioavailability of curcumin by preparing various solid forms. In this work attempts have been made to investigate cocrystallization of curcumin with various coformers. The work focused on understanding curcumin cocrystallization with coformers namely N-acetyl D, L-Tryptophan, tyrosine, glycine, biotin, paracetamol, carbamazepine, ibuprofen, folic acid, suberic acid, succinic acid, ethyl paraben and dextrose. The coformers chosen belong to different categories like amino acids, API, acids and sugars. Binary Phase diagrams were constructed for the investigated systems. The relationship between melting point and dissolution properties has been analyzed in detail. With the obtained phase diagrams, attempts have been made to correlate the dissolution properties of each system with curcumin. Cocrystallization of curcumin with ethyl paraben (Eutectic melting temperature: 110.3 °C) and succinic acid (Eutectic melting temperature: 154.2 °C) resulted in formation of eutectic mixtures whereas with ibuprofen and dextrose, curcumin resulted in a physical mixture. In depth understanding of the explored systems are being developed by characterizing the physical mixtures, eutectic mixtures or cocrystals by FTIR analysis, solid-state NMR and single crystal X-RD analysis. This will be followed by investigating the extent of dissolution achieved by the solid forms. This kind of thorough investigation will enable us to fine-tune the solubility of curcumin by choosing structurally-related coformers that can potentially enhance solubility of curcumin.