Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 598, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2021.120389
Keywords
Rheumatoid arthritis; Sinomenine; Phenolic acids; Coamorphous systems
Categories
Funding
- National Natural Science Foundation of China [81473123, 21874148]
- Chinese Ministry of Education 111 Project [BP0820034]
- Hunan Provincial Innovation Foundation for Postgraduate [CX20200276]
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In this study, three phenolic acids were used as coformers to prepare binary SIN-phenolic acid coamorphous systems, which showed better physicochemical stability and slower release compared to crystalline SIN and commercial SIN-HCl. This suggests that phenolic acids may be a new type of coformers in the preparation of coamorphous systems for active pharmaceutical ingredients.
Sinomenine (SIN), isolated from Caulis sinomenii, is a benzyltetrahydroisoquinoline-type alkaloid with potent anti-inflammatory and analgesic effects. SIN-HCl has been used in the forms of tablets or enteric-coated tablets in the treatment of rheumatoid arthritis in China for years, while its short half-life leads to attenuated therapeutic effects and serious side effects. In the current study, three phenolic acids, including salicylic acid (SAA), 2,3-dihydroxybenzoic acid (23DHB), and 2,4-dihydroxybenzoic acid (24DHB), were firstly employed as coamorphous coformers to prepare three binary SIN-phenolic acid coamorphous systems. These new coamorphous systems were characterized by powder X-ray diffraction (PXRD), modulated temperature differential scanning calorimetry (mDSC), and Fourier transform infrared spectroscopy (FTIR). The formation of SIN-phenolic acid coamorphous systems are supported by the absence of diffraction peaks in their PXRD spectra, as well as the single T(g)s of three samples (i.e., SIN-SAA, SIN-23DHB, and SIN-24DHB) at 109.5 degrees C, 124.9 degrees C, and 135.3 degrees C. Importantly, the salt formation between SIN and phenolic acids was observed in FTIR. In three coamorphous systems, coamorphous SIN-24DHB shows superior physicochemical stability under both low humidity and accelerated storage conditions. They were also more soluble than crystalline SIN, while were released slower than the commercial SIN-HCl in dissolution experiments. Therefore, our study suggests that phenolic acids may be used as a new type of coformers in the preparation of coamorphous systems for active pharmaceutical ingredients.
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