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 multi-component 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 multi-component 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 multi-component crystals, the dissolution rate of caffeic acid increased without reducing antioxidant activity.