The Formation and Characterization of Multicomponent Crystal Caffeic Acid-Tromethamine Using the Solvent Drop Grinding Technique

Abstract

Caffeic acid is a polyphenol compound with low solubility in water. This study aims to prepare and characterize multicomponent crystals of caffeic acid, using tromethamine as a coformer, to enhance the dissolution rate without lessening its antioxidant effect. Multi-component crystals were prepared by the solvent-drop grinding method. The mole ratio of caffeic acid to tromethamine was 4:6 based on the results of a binary phase diagram showing that it had a eutectic point after which multi-component crystals were formed. Powder X-Ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), FTIR spectroscopy, Scanning Electron Microscopy (SEM), and dissolution tests were used to characterize the multi-component crystals. The antioxidant effect was evaluated by the DPPH test. The characterization results revealed a decrease in intensity and new X-ray diffraction patterns, a lower melting point on the DSC thermogram, a non-significant wavenumber shift on the FTIR analysis, and a new crystal habit of multi-component crystals from the SEM. The dissolution rate of caffeic acid increased 1.23 times (p<0.05). The antioxidant test yielded 11.32 g/mL, 33.11 g/mL, and 28.35 g/mL compared with the IC50 values of gallic acid, caffeic acid, and multicomponent crystals. There was an increase in the antioxidant activity of caffeic acid in the form of multi-component crystals, but not significantly different from the IC50 of pure caffeic acid. Our findings show that after forming multicomponent crystals, the dissolution rate of caffeic acid increased without reducing antioxidant activity.