...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Crystal growth & design >Vemurafenib: A Tetramorphic System Displaying Concomitant Crystallization from the Supercooled Liquid
【24h】

Vemurafenib: A Tetramorphic System Displaying Concomitant Crystallization from the Supercooled Liquid

机译：Vemurafenib：显示从过冷液体中伴随结晶的四晶体系

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The current interest in amorphous forms of active pharmaceutical ingredients stems from their increasing use in enabling formulations for the delivery of poorly water-soluble compounds. Because amorphous drugs are metastable and have a tendency to revert to crystalline forms, their crystallization behavior is an important topic. This study reports the observation of concomitant polymorphs of vemurafenib following crystallization from the supercooled liquid, and their subsequent phase transformations. The crystallization behavior of amorphous vemurafenib was evaluated between the glass transition temperature and melting temperature. Six characteristic crystal morphologies were observed. Based on X-ray diffraction and Raman spectroscopic studies, these morphologies were associated with four polymorphic forms, designated alpha, beta, gamma and delta. The thermodynamic stability is alpha > beta > gamma or delta. Isothermal crystallization between 120 and 240 degrees C resulted in concomitant polymorphs with samples containing either 2 or 3 of the 4 polymorphs depending on the specific temperatures, with the alpha-form or beta-form typically dominating. Crystallization at even higher temperature yielded only the alpha-form. A monotropic relationship was inferred between the alpha- and beta-forms based on calorimetric data. beta-to-alpha, gamma-to-beta, and delta-to-beta phase transformations were observed using hot-stage polarized light microscopy, Raman microscopy, and powder X-ray diffraction. The discovery of three new concomitant polymorphs of vemurafenib following crystallization from the supercooled liquid of vemurafenib highlights the rich polymorphic landscape that can be accessed by evaluating crystallization in supercooled liquids, and underscores the complexity in evaluating the crystallization of amorphous drug forms.
机译：当前对活性药物成分的无定形形式的兴趣源于它们在使用于递送难溶于水的化合物的制剂中的越来越多的使用。由于无定形药物是亚稳态的，并且有恢复为结晶形式的趋势，因此其结晶行为是重要的课题。这项研究报告了从过冷液体中结晶出来的维拉非尼伴随多晶型及其后续相变的观察结果。在玻璃化转变温度和熔融温度之间评估非晶态维拉非尼的结晶行为。观察到六种特征晶体形态。根据X射线衍射和拉曼光谱研究，这些形态与四种多晶型有关，分别命名为α，β，γ和δ。热力学稳定性为α＞β＞γ或δ。在120到240摄氏度之间的等温结晶会导致伴随的多晶型物，根据特定温度，样品包含4种多晶型物中的2种或3种，通常以α形式或β形式为主。在更高的温度下结晶仅产生α-形式。根据量热数据推断出α和β形式之间的单向关系。使用热台偏振光显微镜，拉曼显微镜和粉末X射线衍射观察到β-α，γ-β和δ-β相变。从维拉非尼的过冷液体中结晶后，发现了三个新的维拉非尼伴随的多晶型物，突出了丰富的多晶型态，可通过评估过冷液体中的结晶来获得，并强调了评估无定形药物形式结晶的复杂性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号