Are metastable polymorphs stable solid solutions?

多晶型现象是化合物以一种以上晶体结构结晶的能力。由于大多数药物化合物都是晶体，发现和控制多晶型是药物开发和生产的一个关键方面。众所周知，亚稳态多晶型通常首先被发现，而稳定的多晶型最终可能出现（随着时间和金钱的推移）。通常，这种外观与活性药物成分（API）纯度的增加有关。虽然这是结晶科学家的常识，但我们目前对它背后的基本原因了解非常有限。在目前的项目中，我们试图利用上述观察结果。我们有一些实验和计算的证据表明，杂质实际上是改变热力学稳定性的固体形式，通过插入其晶格（形成固溶体）。我们试图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晶型物，能够可靠地生产它们并利用它们的结构和性质。深入了解杂质在固溶体形成中的影响，从而实现固体形式，将对制药业的发展产生重大影响，这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.