Are metastable polymorphs stable solid solutions?

多晶性是一种化合物在一种以上晶体结构中结晶的能力。由于大多数药物化合物是结晶性的，多晶性的发现和控制是药物开发和制造的一个关键方面。在这种情况下，众所周知，亚稳态多晶型通常是首先被发现的，而稳定多晶型最终可能会出现(需要时间和金钱)。通常，这种外观与活性药物成分(原料药)纯度的增加有关。虽然这是结晶科学家共享的常识，但我们目前对其背后的根本原因的了解非常有限。在目前的项目中，我们试图将上述观察结果用于我们的优势。我们有一些实验和计算证据表明，杂质实际上通过插入固体晶格(形成固体溶液)改变了固体形式的热力学稳定性。我们寻求首先测试和确认我们的假设，然后利用这一概念，以便通过实验获得难以捉摸的多态，能够可靠地生产它们，并开发它们的结构和性质。加深对杂质在形成固体溶液和实现固体形式中的影响的了解，将对制药的发展产生重大影响，制药是一项对英国经济非常重要的数十亿英镑的业务。

Polymorphism is the ability of a compound to crystallise in more than one crystal structure. Since most drug compounds are crystalline, discovery and control of polymorphism is a key aspect of drug development and manufacturing.It is well known in this context that metastable polymorphs are usually discovered first and that stable polymorphs may make an appearance eventually (with time and money). Often, this appearance is linked to an increase in the purity of the active pharmaceutical ingredient (API). Whilst this is general knowledge shared by crystallisation scientists, we currently have a very limited understanding of the fundamental reasons behind it. In the current project we seek to utilise the above observation to our advantage. We have some experimental and computational evidence that impurities are in fact changing the thermodynamic stability of solid forms through insertion in their crystal lattices (formation of solid solutions). We seek to first test and confirm our hypothesis to then exploit this concept in order to access elusive polymorphs experimentally, be able to produce them reliably and exploit their structure and properties. Developing a deeper understanding of the impact of impurities in the formation of solid solutions and thus in the realisation of solid forms will have a significant impact in the development of pharmaceuticals, a multi-billion pounds business of great importance to the UK economy.