柳氮磺胺吡啶与麻黄碱类生物碱的共晶系统:增强的溶解行为和协同治疗潜力

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-08-30 DOI:10.1016/j.ejpb.2024.114475
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引用次数: 0

摘要

磺胺类抗生素柳氮磺胺吡啶(Sulfasalazine,SULF)自发现以来一直被用于治疗类风湿性关节炎(RA)和炎症性肠病(IBD)。然而,由于其水溶性较差,患者每天需要服用大量的磺胺类药物(1--3 克),这可能会导致无法忍受的毒副作用,从而影响类风湿性关节炎和炎症性肠病的终生治疗。在这项工作中,我们采用了两种水溶性天然抗炎生物碱--马钱子碱(MAR)和槐定碱(SPD)--来构建SULF的共晶体系,以解决其溶解性问题。我们通过粉末 X 射线衍射 (PXRD)、温度调制差示扫描量热法 (mDSC)、傅立叶变换红外光谱 (FTIR) 和 X 射线光电子能谱 (XPS) 对这些新获得的共晶型 SULF 进行了全面表征。我们还研究了它们的溶解行为,包括粉末溶解、体外释放和内在溶解速率。与结晶 SULF 相比,两种共晶体系都表现出更优越的溶出性能。此外,还阐明了共晶体系溶出行为增强的内在机制。这些机制包括抑制成核、络合、亲水性增强以及水溶液中分子间的强相互作用。重要的是,这些共晶体系在各种储存条件下都表现出令人满意的物理稳定性。我们利用网络药理学分析研究了这两种共晶系统对 RA 的潜在治疗靶点,发现了治疗 RA 的相似但又不同的多靶点协同治疗机制。我们的研究表明,这些药物-药物共晶体系有望在未来优化SULF的剂量,并提供一种潜在的药物组合策略。
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Co-amorphous systems of sulfasalazine with matrine-type alkaloids: Enhanced solubility behaviors and synergistic therapeutic potential

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.

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来源期刊
CiteScore
8.80
自引率
4.10%
发文量
211
审稿时长
36 days
期刊介绍: The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.
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