抗肿瘤药物吉非替尼的晶型研究进展

本文调研了与吉非替尼晶型有关的大量文献，从晶型种类、晶型制备、晶型表征以及晶型讨论4个方面进行了综述。吉非替尼现已发现有8种晶型，各种晶型物质可通过直接或间接的制备方式来获得，已应用于对这些晶型进行分析表征的技术有单晶X射线衍射分析、粉末X射线衍射分析、差示扫描量热分析、热重分析、红外光谱分析、熔点分析等分析方法。通过对表征结果的比较总结，对吉非替尼多晶型形成原因进行了分析，并在已有研究基础上探讨了选择Form 1成为药用晶型的原因。本文对部分实验结果提出了质疑，指出了现有文献对于吉非替尼多晶型的的研究缺乏系统性，现有研究数据并不完整，特别是缺乏关于吉非替尼各晶型的溶解度、生物学等关键数据。因此，对吉非替尼的多晶型研究还需要更系统更深入。

This article gives a review on the description,preparation,characterization and discussion of crystalline forms based on the literatures. Totally 8 crystalline forms which can be obtained directly or indirectly have been found. The techniques adopted to characterize the polymorphic materials include single crystal X-ray diffraction,powder X-ray diffraction,differential scanning calorimeter,thermogravimetric analysis,infrared spectroscopic analysis and melting point analysis. The reasons of polymorphs formation and choosing Form 1 as predominant crystalline form are dissected by comparing the characterizing results. Some data of the experimental results have been questioned. The article pointed out some remaining problems in the research on gefitinib polymorphs,such as lack of systematicness and incompleteness of experimental data,whic is especially so for the solubility and some other biological data. At length,further study on gefitinib polymorphs developing in the future is indicated.