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首页> 外文期刊>Crystal growth & design >Computational Insights into Kinetic Hindrance Affecting Crystallization of Stable Forms of Active Pharmaceutical Ingredients
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Computational Insights into Kinetic Hindrance Affecting Crystallization of Stable Forms of Active Pharmaceutical Ingredients

机译：影响稳定形式的活性药物成分结晶的动力学阻碍的洞察

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A computational investigation of the potential source of kinetic hindrance for the late appearance of pharmaceutically relevant stable forms of ritonavir, rotigotine, ranitidine hydrochloride, and pharmaceutical compound A was performed along the crystallization coordinates of the relative rates of conformational interconversion, crystal nucleation, and growth. Conformational distribution, classical nucleation, and growth morphology theories were utilized, respectively, to compare the results with those of polymorphic systems, famotidine, nimodipine, paracetamol, indomethacin, tolfenamic acid, and mebendazole for which kinetic hindrance of the stable forms was not reported. The results did not support a potential mechanism of kinetic hindering of the stable polymorphic form due to nucleation and growth limited crystallization. However, a low population of crystallographic conformations of the stable forms in solution allowed us to distinguish the behavior of the late appearing stable systems from other polymorphic systems. To account for the low crystallographic conformer population as the potential source for kinetic hindrance, we suggest that self-association of the monomeric active pharmaceutical ingredients molecules precedes over nucleation in solution. As an implication to crystal structure prediction studies, it is suggested to complement the analysis of the lattice energy landscape of conformational polymorphs by the prediction of crystallographic conformers distribution in the gas phase and in solvents of potential interest.
机译：沿着ritonavir，滚石，盐酸甘氨酸盐酸盐，盐酸甘氨酸，盐酸甘氨酸盐酸盐和药物化合物A的潜在动力学障碍潜在的动力学障碍源进行调查，沿着构象相互转化，晶体成核和生长的相对速率的结晶坐标进行。分别使用典型成核和生长形态学理论，将结果与多态性系统，法替辛，尼莫代脂，扑热息痛，吲哚美辛，脱酚酸和兆唑的结果进行比较，没有报道稳定形式的动力学阻力。由于成核和生长有限的结晶，结果不支持稳定多晶形式的动力学阻塞的潜在机制。然而，溶液中稳定形式的低群晶体构象使我们能够区分从其他多晶体系的晚期出现的稳定系统的行为。为了考虑低晶相体群作为动力学障碍的潜在来源，我们表明单体活性药物成分分子的自我关联在溶液中含有成核。作为晶体结构预测研究的含义，建议通过预测气相中的晶体相和潜在兴趣的溶剂的晶体塑壳分布来补充构象多晶型物的晶格能量景观的分析。

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  • 来源
    《Crystal growth & design》 |2020年第3期|共14页
  • 作者

    Abramov Yuriy A.; Zhang Peiyu; Zeng Qiao; Yang Mingjun; Liu Yang; Sekharan Sivakumar;

  • 作者单位

    XtalPi Inc 245 Main Str Cambridge MA 02142 USA;

    Shenzhen Jingtai Technol Co Ltd XtalPi Inc Floor 4 9 Hualian Ind Zone Dalang St Shenzhen Peoples R China;

    Shenzhen Jingtai Technol Co Ltd XtalPi Inc Floor 4 9 Hualian Ind Zone Dalang St Shenzhen Peoples R China;

    Shenzhen Jingtai Technol Co Ltd XtalPi Inc Floor 4 9 Hualian Ind Zone Dalang St Shenzhen Peoples R China;

    Shenzhen Jingtai Technol Co Ltd XtalPi Inc Floor 4 9 Hualian Ind Zone Dalang St Shenzhen Peoples R China;

    XtalPi Inc 245 Main Str Cambridge MA 02142 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 晶体学;
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