Characterization of co-amorphous sinomenine-tranilast systems with strong intermolecular interactions and sustained release profiles

Abstract

Drug co-amorphization is an emerging technology to improve the pharmacokinetic properties of drugs and overcome their side effects. Herein co-amorphization of sinomenine (SIN), an anti-rheumatoid arthritis alkaloid, and an antihistamine drug tranilast (TRA) was investigated for the sustained release of SIN and alleviating its histamine-release adverse reactions. The full co-amorphization of SIN-TRA was determined by powder X-ray diffraction and modulated temperature differential scanning calorimetry, while their CO2− and N+–H stretching vibrations in FTIR and protonated nitrogen signals in N 1s X-ray photoelectron spectra suggest the proton transfer between SIN and TRA. These intermolecular interactions could also be observed in their 1D and 2D NMR spectra. All co-amorphous samples exhibited sustained SIN release and excellent physical stability. Therefore, our study not only characterized the strong intermolecular interactions between SIN and TRA, but also discovered a promising drug combination strategy for the sustained release of SIN and reduction of its side effects.