Are metastable polymorphs stable solid solutions?

多态是指化合物结晶成一种以上晶体结构的能力。由于大多数药物化合物是结晶的，因此发现和控制多态性是药物开发和生产的一个关键方面。众所周知，亚稳态多晶通常首先被发现，而稳定多晶可能最终出现（需要时间和金钱）。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共有的常识，但我们目前对其背后的基本原因的理解非常有限。在目前的项目中，我们试图利用上述观察到的优势。我们有一些实验和计算证据表明，杂质实际上通过插入其晶格（形成固溶体）来改变固体形态的热力学稳定性。我们寻求首先测试和确认我们的假设，然后利用这个概念，以便通过实验获得难以捉摸的多晶，能够可靠地生产它们并利用它们的结构和性质。更深入地了解杂质在固体溶液形成过程中的影响，从而实现固体形态，将对药品的发展产生重大影响，这是对英国经济至关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.