Co-amorphous Systems of Sinomenine with Platensimycin or Sulfasalazine: Physical Stability and Excipient-Adjusted Release Behavior

There is strong interest to develop affordable treatments for the infection-associated rheumatoid arthritis (RA). Here, we present a drug-drug co-amorphous strategy against RA and the associated bacterial infection by the preparation and characterization of two co-amorphous systems of sinomenine (SIN) with platensimycin (PTM) or sulfasalazine (SULF), two potent antibiotics. Both of them were comprehensively characterized using powder Xray diffraction, temperature-modulated differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The co-amorphous forms of SIN-PTM and SIN-SULF exhibited high Tgs at 139.10 +/- 1.0 and 153.3 +/- 0.2 degrees C, respectively. After 6 months of accelerated tests and 1 month of drug-excipient compatibility experiments, two co amorphous systems displayed satisfactory physical stability. The formation of salt and strong intermolecular interactions between SIN and PTM or SULF, as well as the decreased molecular mobility in co-amorphous systems, may be the intrinsic mechanisms underlying the excellent physical stability of both co-amorphous systems. In dissolution tests, two co-amorphous systems displayed distinct reduced SIN accumulative releases (below 20% after 6 h of release experiments), which may lead to its poor therapeutic effect. Hence, we demonstrated a controlled release strategy for SIN by the addition of a small percentage of polymers and a small-molecule surfactant to these two co-amorphous samples as convenient drug excipients, which may also be used to improve the unsatisfactory dissolution behaviors of the previously reported SIN co-amorphous systems. Several hydrogen bonding interactions between SIN and PTM or SULF could be identified in NMR experiments in DMSO-d6, which may be underlying reasons of decreased dissolution behaviors of both co-amorphous forms. These drug-drug co-amorphous systems could be a potential strategy for the treatment of infection associated RA.

Automated summary

This study presents a drug-drug co-amorphous strategy against infection-associated rheumatoid arthritis (RA) by preparing and characterizing two co-amorphous systems of sinomenine (SIN) with platensimycin (PTM) or sulfasalazine (SULF). Both systems exhibit satisfactory physical stability but reduced SIN release, which may lead to poor therapeutic effect. A controlled release strategy for SIN is demonstrated by adding a small percentage of polymers and a small-molecule surfactant to improve the dissolution behavior. These drug-drug co-amorphous systems could be a potential strategy for the treatment of infection-associated RA.