Co-amorphous form of curcumin-folic acid dihydrate with increased dissolution rate

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 watersoluble 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.