Improvement of the Thermal Stability and Aqueous Solubility of Three Matrine Salts Assembled by the Similar Structure Salt Formers

Abstract

Matrine (MAT), a natural Chinese herbal medicine, has a unique advantage in the treatment of various chronic diseases. However, its low melting point, low bioavailability, and high dosage restrict its subsequent development into new drugs. In this study, three kinds of MAT salts, namely, MAT-2,5-dihydroxybenzoic acid (MAT-25DHB), MAT-2,6-dihydroxybenzoic acid (MAT-26DHB), and MAT-salicylic acid-hydrate (MAT-SAL-H2O), were designed and synthesized to improve the drugability of MAT. The three salts were characterized by using various analytical techniques, including single-crystal X-ray diffractometry, powder X-ray diffractometry, differential scanning calorimetry, thermogravimetry, and infrared spectroscopy. The results of the thermal stability evaluation showed that the formation of salts improved the stability of MAT; MAT-25DHB is the most stable salt reported at present. The results of aqueous solubility showed that the solubility of MAT-25DHB was higher than that of MAT, while that of MAT-26DHB and MAT-SAL-H2O were less. Given that the MAT-25DHB salt further improved the solubility of MAT, it is expected to be subjected to further research as an optimized salt. Lattice energy and solvation free energy are important factors affecting the solubility of salts; the reasons for the changes of solubility and stability of three kinds of salts are explained by calculating them.

Keywords

• matrine
• salt
• stability
• solubility
• theoretical calculation