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Co-amorphous form of Curcumin-Folic acid dihydrate with increased dissolution rate Jenna Marie Skieneh, Indumathi Sathisaran, Sameer Vishvanath Dalvi, and Sohrab Rohani Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.7b00947 • Publication Date (Web): 12 Oct 2017 Downloaded from http://pubs.acs.org on October 17, 2017
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Crystal Growth & Design
Co-amorphous form of curcumin-folic acid dihydrate with increased dissolution rate Jenna Marie Skieneh1,3, Indumathi Sathisaran2, Sameer Vishvanath Dalvi3 and Sohrab Rohani1,* Chemical and Biochemical Engineering1, Western University, Canada, London, ON, N6A 5B9 Biological Engineering2 and Chemical Engineering3, Indian Institute of Technology Gandhinagar, Palaj, Gujarat 382355, India
*Corresponding author Email:
[email protected] Abstract 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 co-amorphous mixtures, solvates, cocrystals and eutectics, the solubility can be significantly improved. In this study, US 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 co-amorphous 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 one hour, 175 mg/L of curcumin was dissolved from the co-amorphous mixture, while only 45 mg/L was dissolved from curcumin Form I. The co-amorphous mixture is stable as it was shown to keep its amorphous behavior after 24 hours 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. Keywords: Curcumin, Folic Acid Dihydrate, Co-amorphous, Enhanced solubility, Screening
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Crystal Growth & Design
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1. Introduction Curcumin, with many potential applications as an antioxidant1, anti-inflammatory2, colorimetric sensor3, tumor reducer4, holds a high level of interest in food and pharmaceutical industries. Though it is safe for ingestion up to 8000 mg/day5, curcumin is limited in function due to its extremely low water solubility (
