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首页> 外文期刊>Crystal growth & design >First Crystal Structures of Pharmaceutical Ibrutinib: Systematic Solvate Screening and Characterization
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First Crystal Structures of Pharmaceutical Ibrutinib: Systematic Solvate Screening and Characterization

机译：药物Ibrutinib的第一晶体结构：系统溶剂化物筛选和表征

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摘要

A search for new solid forms of an active pharmaceutical ingredient (API) is an integral part of the drug product development process. The studied compound, Ibrutinib, is a recently approved anticancer drug. The main aim of this study was to search for new solvates of Ibrutinib and to perform their structural characterization. To do so, we performed a tailor-made systematic solvate screening and tested several solution and slurry based methods in the solvate screening for their suitability and success rate. The phase composition of the screening samples was analyzed by Raman spectroscopy and powder X-ray diffraction. From the 11 tested solvents, eight solvates were prepared (with 4-hydroxy-4-methylpentan-2-on, dioxolane, alpha,alpha,alpha-trifluorotoluene, ortho-xylene, meta-xylene, para-xylene, anisole, and chlorobenzene). The crystal structures of all eight solvates were successfully solved from single-crystal X-ray diffraction data, and, to our best knowledge, this work is the first ever crystal structure study of Ibrutinib. The desolvation behavior of the prepared Ibrutinib solvates was studied by thermal methods (differential scanning calorimetry, thermogravimetric analysis, and hot-stage microscopy), and stability tests were performed to determine the strength of the API-solvent interaction. Dissolution experiments showed that the solvate formation can improve the dissolution rate by as much as 8.5 times, compared to the most stable nonsolvated form.
机译：寻找新的活性药物成分（API）的全文形式是药物产品开发过程的一部分。学习的化合物，伊布勒替尼，是最近批准的抗癌药物。本研究的主要目的是寻找伊布勒替尼的新溶剂化物，并进行结构表征。为此，我们在溶剂化物筛选中进行了量身定制的系统溶剂化物筛选，并测试了几种基于溶液和浆料的方法，以获得适合性和成功率。通过拉曼光谱和粉末X射线衍射分析筛选样品的相组成。从11个测试的溶剂中，制备八种溶剂化物（用4-羟基-4-甲基戊烷-2-甲基，二氧戊戊烷，α，α，α-三氟甲苯，邻二甲苯，亚二甲苯，苯乙烯和氯苯）。所有8个溶剂化物的晶体结构从单晶X射线衍射数据成功解决，并且对于我们的最佳知识，这项工作是Ibrutinib的第一个晶体结构研究。通过热方法（差示扫描量热法，热重分析和热阶段显微镜）研究制备的易替尼溶剂化物的脱溶解行为，进行稳定性测试以确定API-溶剂相互作用的强度。与最稳定的非溶剂化形式相比，溶解实验表明，溶剂化物形成可以将溶解速度提高至8.5倍。

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  • 来源
    《Crystal growth & design》 |2017年第6期|共12页
  • 作者

    Zvonicek Vit; Skorepova Eliska; Dusek Michal; Babor Martin; Zvatora Pavel; Soos Miroslav;

  • 作者单位

    Univ Chem &

    Technol Prague Dept Chem Engn Tech 3 Prague 16628 6 Czech Republic;

    Univ Chem &

    Technol Prague Dept Chem Engn Tech 3 Prague 16628 6 Czech Republic;

    Acad Sci Czech Republic Inst Phys Na Slovance 2 Prague 18221 8 Czech Republic;

    Univ Chem &

    Technol Prague Dept Solid State Chem Tech 3 Prague 16628 6 Czech Republic;

    Zentiva Ks U Kabelovny 130 Prague 10237 10 Czech Republic;

    Univ Chem &

    Technol Prague Dept Chem Engn Tech 3 Prague 16628 6 Czech Republic;

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  • 正文语种 eng
  • 中图分类 晶体学;
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