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首页> 外文期刊>Crystal growth & design >Hepatoprotective Cocrystals and Salts of Riluzole: Prediction, Synthesis, Solid State Characterization, and Evaluation
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Hepatoprotective Cocrystals and Salts of Riluzole: Prediction, Synthesis, Solid State Characterization, and Evaluation

机译：Riluzole的肝脏保护碳酸酯和盐：预测，合成，固态表征和评估

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摘要

Riluzole is a drug, used to slow the course of amyotrophic lateral sclerosis. Due to its unique structure and functionalities, it is able to form both salts and cocrystals. This is a BCS class II drug with poor solubility and causes hepatotoxicity which limits its application. The present study aims toward development of novel solid forms of riluzole to address the said limitations. Apart from this, an attempt has been made to develop a prediction model using software tools to identify the appropriate synthons for formation of cocrystals. It was observed that out of 33 coformers selected, prediction results were in agreement with the experimental outcome for 25 coformers, which demonstrated the potential of the model developed. Seven new solid forms of riluzole, five cocrystals with ferulic acid, syringic acid, vanillic acid, cinnamic acid, and proline, and two salts with 2,4 dihydroxybenzoic acid and fumaric acid were successfully developed. All the solid forms were characterized by DSC, powder XRD, FTIR, and single crystal XRD. Single crystal X-ray analysis of the all solid form shows R_(2)~(2)(8) motif between riluzole and coformers through N–H···O and O–H···N bond except riluzole-proline zwitterionic cocrystal. In riluzole-fumaric acid, partial proton transfer of O to N due to acidic H atom disorder has been observed. Dissolution profiles of all the solid forms were comparable to that of plain riluzole, and complete drug release was observed within 60 min for all systems. In vivo hepatotoxicity study with riluzole-ferulic acid and riluzole-syringic acid in mice model revealed its potential hepatoprotective effect to counterattack the hepatotoxic adverse effects of riluzole.
机译：Riluzole是一种药物，用于减缓肌营养的侧面硬化的过程。由于其独特的结构和功能，它能够形成盐和池组。这是一个具有差的溶解度和肝毒性，这是一种BCS类药物，并限制其应用。本研究旨在开发新型固体形式的Riluzole，以解决所述限制。除此之外，已经尝试使用软件工具开发预测模型，以识别用于形成COCrystals的适当合成器。观察到，选定33种CoFormers中，预测结果与25个CoFormers的实验结果一致，这表明了模型的开发潜力。七种新的固体形式的Riluzole，五种与阿魏酸，注射酸，香草，肉桂酸和脯氨酸和脯氨酸的盐，以及2,4二羟基苯甲酸和富马酸的盐。所有固体形式的特征在于DSC，粉末XRD，FTIR和单晶XRD。所有固体形式的单晶X射线分析显示Riluzole和Coformers之间的R_（2）〜（2）（8）个主题通过N-H···o和O-H···以外的Riluzole-脯氨酸两性离子Cocrystal。在Riluzole-umaric acid中，已经观察到由于酸性H原子病症的o至n的部分质子转移。所有固体形式的溶解谱与普通的瑞洛唑相当，并且在所有系统的60分钟内观察到完全的药物释放。在小鼠模型中使用柠檬唑 - 阿魏酸和瑞洛唑酸和柠檬腈酸的体内肝毒性研究显示其潜在的肝脏保护作用，以抵抗Riluzole的肝毒性不良反应。

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  • 来源
    《Crystal growth & design》 |2018年第2期|共15页
  • 作者

    Balvant Yadav; Sridhar Balasubramanian; Rahul B. Chavan; Rajesh Thipparaboina; V. G. M. Naidu; Nalini R. Shastri;

  • 作者单位

    Solid State Pharmaceutical Research Group (SSPRG) Department of Pharmaceutics and Department of Pharmacology National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad 500037 India;

    X-ray Crystallography Division CSIR-Indian Institute of Chemical Technology Hyderabad Telangana 500007 India;

    Solid State Pharmaceutical Research Group (SSPRG) Department of Pharmaceutics and Department of Pharmacology National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad 500037 India;

    Solid State Pharmaceutical Research Group (SSPRG) Department of Pharmaceutics and Department of Pharmacology National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad 500037 India;

    Solid State Pharmaceutical Research Group (SSPRG) Department of Pharmaceutics and Department of Pharmacology National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad 500037 India;

    Solid State Pharmaceutical Research Group (SSPRG) Department of Pharmaceutics and Department of Pharmacology National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad 500037 India;

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  • 正文语种 eng
  • 中图分类 晶体学;
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