Sinapic Acid Co-Amorphous Systems with Amino Acids for Improved Solubility and Antioxidant Activity

Abstract

The objective of this study was to obtain co-amorphous systems of poorly soluble sinapic acid using amino acids as co-formers. In order to assess the probability of the interaction of amino acids, namely, arginine, histidine, lysine, tryptophan, and proline, selected as co-formers in the amorphization of sinapic acid, in silico studies were carried out. Sinapic acid systems with amino acids in a molar ratio of 1:1 and 1:2 were obtained using ball milling, solvent evaporation, and freeze drying techniques. X-ray powder diffraction results confirmed the loss of crystallinity of sinapic acid and lysine, regardless of the amorphization technique used, while remaining co-formers produced mixed results. Fourier-transform infrared spectroscopy analyses revealed that the co-amorphous sinapic acid systems were stabilized through the creation of intermolecular interactions, particularly hydrogen bonds, and the potential formation of salt. Lysine was selected as the most appropriate co-former to obtain co-amorphous systems of sinapic acid, which inhibited the recrystallization of sinapic acid for a period of six weeks in 30 °C and 50 °C. Obtained co-amorphous systems demonstrated an enhancement in dissolution rate over pure sinapic acid. A solubility study revealed a 12.9-fold improvement in sinapic acid solubility after introducing it into the co-amorphous systems. Moreover, a 2.2-fold and 1.3-fold improvement in antioxidant activity of sinapic acid was observed with respect to the ability to neutralize the 2,2-diphenyl-1-picrylhydrazyl radical and to reduce copper ions, respectively.

Keywords: amino acid; co-amorphous; lysine; sinapic acid.

Figure 1

The XRPD diffraction patterns of SA (a), co-amorphous systems of SA with TRP and the physical mixture (b), co-amorphous systems of SA with ARG and the physical mixture (c), co-amorphous systems of SA with LYS and the physical mixture (d).

Figure 1

The XRPD diffraction patterns of SA (a), co-amorphous systems of SA with TRP and the physical mixture (b), co-amorphous systems of SA with ARG and the physical mixture (c), co-amorphous systems of SA with LYS and the physical mixture (d).

Figure 2

Scanning electron microscopy images of SA (a), LYS (b), co-amorphous system of SA with LYS in molar ratio 1:1 obtained by ball milling (c), co-amorphous system of SA with LYS in molar ratio 1:2 obtained by ball milling (d), co-amorphous system of SA with LYS in molar ratio 1:1 obtained by solvent evaporation (e), co-amorphous system of SA with LYS in molar ratio 1:2 obtained by solvent evaporation (f), co-amorphous system of SA with LYS in molar ratio 1:1 obtained by freeze drying (g), co-amorphous system of SA with LYS in molar ratio 1:2 obtained by freeze drying (h).

Figure 3

Dissolution profiles of SA and SA co-amorphous systems with LYS in molar ratio 1:1 in water (a) and HCl 0.1 N (b).

Figure 4

Antioxidant activity of SA and SA co-amorphous systems with LYS in molar ratio 1:1 evaluated using the DPPH (a) and CUPRAC (b) models. Mean values with the same letter are not significantly different at p < 0.05 using Duncan’s multiple range test. “a” stands for the highest values, “b” and “c” stand for the statistically significant decreasing values.