Solid-state characterization and solubility of a genistein–caffeine cocrystal

• Published in: Journal of molecular structure Vol. 1076; pp. 80 - 88
• Main Authors: Sowa, Michał, Ślepokura, Katarzyna, Matczak-Jon, Ewa
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05-11-2014
• Subjects: Caffeine; Cocrystals; Genistein; Solubility; X-ray crystallography; X-ray crystallography; Cocrystals; Genistein; Solubility; Caffeine
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2014.07.036

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•A 1:1 genistein–caffeine cocrystal was identified via solvent-drop grinding.•The cocrystalline phase was grown from solution and obtained from slurry.•Molecules form a two-dimensional, O−H⋯N and O–H⋯O hydrogen-bonded network.•Cocrystalline phase is stable up to 247°C.•The genistein–caffeine 1:1 cocrystal shows improved solubility as related to parent flavonoid.
Combination of genistein and caffeine leads to a 1:1 cocrystalline phase, which was identified by means of a solvent-drop grinding experiment and isolated afterwards in a solution-evaporation approach. Obtained cocrystal was characterized by X-ray single-crystal and powder diffraction as well as investigated in terms of thermal stability and Hirshfeld surfaces. A scale-up procedure was provided by slurry technique, enabling solubility determination. Neutral forms of both compounds cocrystallize in a common P21/c space group of the monoclinic crystal system. Analysis of packing and interactions in the crystal lattice reveals formation of molecular layers, formed by O–H⋯O, O–H⋯N and C–H⋯O-type contacts between genistein and caffeine molecules, whereas stabilization of the three-dimensional crystal lattice is provided by π⋯π interactions. Dissolution studies in a 50:50 v/v ethanol–water medium revealed that the maximum solubility of the cocrystalline phase reached 0.861mg/mL after 8h, revealing some degree of enhancement as compared to parent genistein, maximum solubility of which was also reached after 8h and equalled 0.588mg/mL.