Co-amorphous systems of sinomenine with nonsteroidal anti-inflammatory drugs: A strategy for solubility improvement, sustained release, and drug combination therapy against rheumatoid arthritis.
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| Abstract |
Rheumatoid arthritis (RA) is a chronic autoimmune joint disorder that affects about 1% of the world population and may lead to severe disability and comorbidity. Despite breakthroughs in past decades to understand its pathogenesis and the development of transforming disease-modifying antirheumatic drugs, the symptoms of many patients are not substantially improved. Sinomenine (SIN), a natural alkaloid with poor solubility, has been used to treat RA in China for years because of its unique immunoregulative activity. However, its commercial hydrochloride form has a short half-time, which may cause huge fluctuations of blood drug concentration leading to severe adverse reactions. In this study, co-amorphous systems of SIN with three nonsteroidal anti-inflammatory drugs (NSAIDs), including indomethacin, naproxen, and sulindac, were prepared for the combination therapy, as well as the improvement of its aqueous solubility and controlled release. Each co-amorphous sample was characterized by powder X-ray diffraction (PXRD), temperature-modulated differential scanning calorimetry (mDSC), and Fourier transform infrared spectroscopy (FTIR). The CO2- and N+H stretching vibration in the three co-amorphous samples appears in FTIR spectra, suggesting the formation of salts between SIN and NSAIDs. SIN also exhibits sustained release rates in all three co-amorphous samples. These co-amorphous systems show excellent physicochemical stability because no recrystallization was observed at 25 °C and 75% relative humidity (RH) after four months. Our study suggests that SIN-NSAIDs co-amorphous systems represent an affordable and promising treatment against RA.
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| Authors | Xin Chen, Duanxiu Li, Hailu Zhang, Yanwen Duan, Yong Huang |
| Journal | International journal of pharmaceutics (Int J Pharm) Vol. 606 Pg. 120894 (Sep 05 2021) ISSN: 1873-3476 [Electronic] Netherlands |
| PMID | 34280485 (Publication Type: Journal Article) |
| Copyright | Copyright © 2021 Elsevier B.V. All rights reserved. |
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