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Understanding the effect of impurities in the crystallization of pharmaceutical polymorphs

了解杂质对药物多晶型物结晶的影响

基本信息

批准号：
2240338
负责人：
金额：
--
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2019
资助国家：
英国
起止时间：
2019 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2240338
关键词：
Understanding effect impurities crystallization pharmaceutical

项目摘要

Polymorphism is the ability exhibited by organic molecules to crystallise in more than one structure. There has been considerable interest in this phenomenon in the last 20 years or so, especially because of the impact it has in solid form development of pharmaceuticals. This project will attempt to understand the effect of impurities on the crystallisation of pharmaceuticals with a special view on polymorphism.The research questions addressed are the following: Why do impurities act different on different polymorphs of the same compound? What is the impact of the amount of impurities in crystallization outcomes of pharmaceuticals? What is the critical amount of impurity needed to switch polymorphic outcomes? What is the mechanism of action of such impurities.In order to address this questions, the student will: Carry out a literature review to compile examples of polymorphic systems obtained in the presence of impurities. Perform experimental nucleation and crystal growth studies in three model systems in the presence of variable amounts of impurities. Characterise the obtained crystals with complementary techniques. In collaboration with a simulations expert, propose mechanism of actions of the impurities. Design a new impurity for one of the systems and test it.The novelty of this project lies in the molecular level detail that we wish to understand as to how the impurities impact crystallization and polymorphism. Understanding and controlling this will have an impact in the way we design additives in the futures and will have a positive impact in the manufacturing processes of pharmaceuticals.

多晶型现象是有机分子以一种以上的结构结晶的能力。在过去20年左右的时间里，人们对这种现象产生了相当大的兴趣，特别是因为它对药物的固体形式发展产生了影响。该项目将试图了解杂质对药物结晶的影响，特别是对多晶型的影响。研究问题如下：为什么杂质对同一化合物的不同多晶型有不同的作用？杂质含量对药品结晶结果有何影响？转换多态结果所需的临界杂质量是多少？这些杂质的作用机制是什么？为了回答这些问题，学生将：进行文献综述，以汇编在杂质存在下获得的多晶型体系的实例。在三个模型系统中进行实验性成核和晶体生长研究，其中存在不同量的杂质。用互补技术表征所获得的晶体。与模拟专家合作，提出杂质的作用机制。为其中一个系统设计一种新的杂质并进行测试。该项目的新奇在于我们希望了解杂质如何影响结晶和多晶型的分子水平细节。了解和控制这一点将对我们设计未来添加剂的方式产生影响，并将对药品的制造过程产生积极影响。