Co-amorphous systems of sulfasalazine with matrine-type alkaloids: Enhanced solubility behaviors and synergistic therapeutic potential.

Autor: Chen X; Innovation Centre for Science and Technology, North Sichuan Medical College, Nanchong, Sichuan 637100, P. R. China. Electronic address: xchen2023@nsmc.edu.cn., Qin Y; Innovation Centre for Science and Technology, North Sichuan Medical College, Nanchong, Sichuan 637100, P. R. China; Institute of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637100, P. R. China., Wang L; Innovation Centre for Science and Technology, North Sichuan Medical College, Nanchong, Sichuan 637100, P. R. China; Institute of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637100, P. R. China., Zhu Y; Laboratory of Pharmaceutical Solid-State Chemistry, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, P. R. China., Zhang H; Laboratory of Pharmaceutical Solid-State Chemistry, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, P. R. China; Interdisciplinary Institute of NMR and Molecular Sciences (NMR-X), School of Chemistry and Chemical Engineering, State Key Laboratory of Refractories and Metallurgy, Wuhan University of Science and Technology, Wuhan 430081, P. R. China., Liu W; School of Pharmacy, North Sichuan Medical College, Nanchong, Sichuan 637100, P. R. China. Electronic address: wh_liu@csu.edu.cn., Zeng M; Innovation Centre for Science and Technology, North Sichuan Medical College, Nanchong, Sichuan 637100, P. R. China; Institute of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637100, P. R. China., Dai Q; Institute of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637100, P. R. China. Electronic address: daiqian@nsmc.edu.cn.
Jazyk: angličtina
Zdroj: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2024 Oct; Vol. 203, pp. 114475. Date of Electronic Publication: 2024 Aug 30.
DOI: 10.1016/j.ejpb.2024.114475
Abstrakt: Sulfasalazine (SULF), a sulfonamide antibiotic, has been utilized in the treatment of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) since its discovery. However, its poor water solubility causes the high daily doses (1---3 g) for patients, which may lead to the intolerable toxic and side effects for their lifelong treatment for RA and IBD. In this work, two water-soluble natural anti-inflammatory alkaloids, matrine (MAR) and sophoridine (SPD), were employed to construct the co-amorphous systems of SULF for addressing its solubility issue. These newly obtained co-amorphous forms of SULF were comprehensively characterized by powder X-ray diffraction (PXRD), temperature-modulated differential scanning calorimetry (mDSC), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). We also investigated their dissolution behavior, including powder dissolution, in vitro release, and intrinsic dissolution rate. Both co-amorphous systems exhibited superior dissolution performance compared to crystalline SULF. The underlying mechanism responsible for the enhanced dissolution behaviors in co-amorphous systems were also elucidated. These mechanisms include the inhibition of nucleation, complexation, increased hydrophilicity, and robust intermolecular interactions in aqueous solutions. Importantly, these co-amorphous systems demonstrated satisfactory physical stability under various storage conditions. Network pharmacological analysis was utilized to investigate the potential therapeutic targets of both co-amorphous systems against RA, revealing similar yet distinct multi-target synergistic therapeutic mechanisms in the treatment of this condition. Our study suggests these drug-drug co-amorphous systems hold promise for optimizing SULF dosage in the future and providing a potential drug combination strategy.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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