Tranilast-matrine co-amorphous system: Strong intermolecular interactions, improved solubility, and physiochemical stability

There is a great interest to develop co-amorphous drug delivery systems to enhance the solubility of bio-pharmaceutics classification system (BCS) class II and IV drugs. However, most reported systems only resulted in severalfold solubility improvement. Tranilast (TRA) is an anti-allergic drug used to treat bronchial asthma and allergic rhinitis. It is a BCS class II drug and its poor aqueous solubility affects its absorption in vivo. To address this issue, a natural alkaloid matrine (MAR) with interesting biological activities was chosen to form a co-amorphous system with TRA, based on the solubility parameter and phase solubility experiment. The TRA-MAR drug-drug co-amorphous system was prepared by the solvent evaporation method, and further charac-terized by powder X-ray diffraction and modulated temperature differential scanning calorimetry. Fourier transform infrared spectroscopy, FT-Raman, and X-ray photoelectron spectroscopy revealed the formation of salt and the presence of strong intermolecular interactions in the TRA-MAR co-amorphous system, which are also supported by molecular dynamics simulations, showing ionic and hydrogen bonding interactions. This co-amorphous system exhibited excellent physical stability at both 25 degrees C and 40 degrees C under anhydrous silica gel condition. Finally, co-amorphous TRA-MAR showed greatly enhanced solubility (greater than 100-fold) and rapid release behavior in the vitro release experiments. NMR spectroscopy revealed the strong intermolecular interactions between TRA and MAR in both DMSO-d6 and D2O. Our study resulted in a TRA-MAR co-amorphous drug system with significant solubility improvement and showcased the great potential to improve the disso-lution behaviors of BCS class II and IV drugs through the co-amorphization approach.

Automated summary

There is a strong interest in developing co-amorphous drug delivery systems to enhance the solubility of BCS class II and IV drugs. Most reported systems have only resulted in limited improvements in solubility. In this study, a co-amorphous system of tranilast (TRA) and matrine (MAR) was successfully prepared, which showed excellent physical stability and significantly enhanced solubility (over 100-fold) and rapid release behavior in vitro. This study demonstrated the great potential of the co-amorphization approach to improve the dissolution behaviors of BCS class II and IV drugs.