(508h) Solubility Measurements of Coumarin Derivatives and Search of Their Co-Solvents

Bioactive compounds in natural products have attracted great interest because of their pharmacological activity antioxidant, e.g., anti-inflammatory, and potential cancer chemopreventive activities, and so on. Thus, they are expected to the applications to pharmaceuticals or functional foods. The solubilities of bioactive compounds are important properties in the development of their applications. Also, the major problem with the bioactive compounds is its extremely low solubility in aqueous solution and poor bioavailability. If addition of a suitable co-solvent makes an enhancement of solubilities of them, it would be useful for the development of drug or functional food which an efficient systemic absorption is available. Previously, we have studied an enhancement of solubilities of poorly water-soluble pharmaceutical compounds by adding co-solvents, e.g., ethanol, polyethylene glycol (PEG), surfactant, and cyclodextrin (CD) or its derivatives [1, 2].

In this work, we selected several coumarin derivatives, i.e., 6-methylcoumarin, 4-hydroxycoumarin, and 7-diethylamino-4-methylcoumarin as a bioactive compound. 6-Methylcoumarin is often used as a natural flavoring agent of cosmetic [3], which was given GRAS (generally recognized as safe) status by the Flavor and Extract Manufacturers Association (FEMA). 4-Hydroxycoumarin is one of important ingredients of anticoagulant. Coumarin derivatives are also used as an organic fluorescent dye. The solubilities of them in several alcohols were determined using the synthetic-visual method [4]. Next, several β-cyclodextrin (β-CD) derivatives were investigated as a co-solvent. The solubilities of 6-methylcoumarin in water + β-CD derivative mixed solvents, and a suitable co-solvent for an enhancement of the solubilities in 6-methylcoumarin was examined. The solubilities of 6-methylcoumarin in water + β-CD derivative mixed solvents at 298.15 K were determined using high-performance liquid chromatography (HPLC).

References
[1] H. Matsuda, S. Matsumoto, K. Kaburagi, K. Kurihara, K. Tochigi, and K. Tomono, Fluid Phase Equilibria 302 (2011) 116-123.
[2] Y. Naito, H. Matsuda, K. Shimomura, K. Kurihara, K. Tochigi, and K. Tomono, Fluid Phase Equilibria 357 (2013) 59-65.
[3] A. Jos, G. Repetto, J. C. Rios, A. del Peso, M. Salguero, A. M. Camean, Arch. Environ. Contam. Toxicol. 56 (2009) 52-59.
[4] H. Matsuda Y. Ohashi, K. Kurihara, K. Tochigi, K. Ochi, Fluid Phase Equilibria 479 (2019) 17-24.