Discovery and Applications of Novel Solid-State Structures: Water Bridges Salt Forms

新型固态结构的发现和应用：水桥盐形式

• 批准号: 2750753
• 金额: --
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2750753
• 关键词: Discovery; Applications; Novel; Solid; State

The project is designed to improve our ability to identify and exploit crystalline hydrated salt forms that are in a unique solid-state arrangement known as a "water bridge". Currently, we have two salt forms of active molecules in our portfolio that were expected to disproportionate in tablet formulations but showed unexpected solid-state and solution stability. A recent publication by Prof Lynne Taylor and Pfizer researchers highlighted a case study on two solid-state forms of Miconazole mesylate (anhydrous and hydrate) where the salt-hydrate had this same unique "water bridge" arrangement. The research showed that the hydrate form also had resistance to disproportionation. However, sustained solubility in the pH solubility curve was not discussed. This research will seek to build fundamental understanding of salt "water bridge" propensity, creation, stability, and physical property relationships. Collectively, the aim is to develop insights that can inform the targeted selection of water bridge hydrates during salt selection informed by the factors that influence their formation, stability and performance. This will be achieved through the combination of 3 research elements to (1) explore the molecular features that favour water bridge formation in molecular salts, (2) the factors that affect their formation from solution crystallization and (3) the solubility, dissolution and stability of selected water bridge hydrate structures. Using a suite of measurement capabilities of the solid-state (X-ray, thermal, spectroscopic analysis) we will be able to explore the crystal structures and highlight the features that are crucial for water-bridge synthesis. Using in-situ monitoring techniques we will be able to explore the physical properties of the solid under a variety of environmental conditions. These experimental observations will be underpinned by computational efforts to extract energetic information of the systems and how intermolecular interactions may impact on the observed properties.

该项目旨在提高我们识别和开发晶体水合盐形式的能力，这些形式以一种独特的固态排列方式被称为“水桥”。目前，我们的产品组合中有两种盐形式的活性分子，预计在片剂配方中不成比例，但显示出意想不到的固态和溶液稳定性。Lynne Taylor教授和辉瑞（Pfizer）研究人员最近发表的一篇论文，重点介绍了对两种固态甲磺酸咪康唑（Miconazole mesylate）（无水和水合物）的案例研究，其中盐水合物具有同样独特的“水桥”结构。研究表明，该水合物形态还具有抗歧化作用。然而，在pH溶解度曲线中没有讨论持续溶解度。本研究将寻求建立对盐“水桥”倾向、形成、稳定性和物理性质关系的基本理解。总的来说，目标是在盐选择过程中，根据影响其形成、稳定性和性能的因素，为有针对性地选择水桥水合物提供信息。这将通过三个研究元素的结合来实现(1)探索分子盐中有利于水桥形成的分子特征，(2)溶液结晶影响其形成的因素，(3)选定的水桥水合物结构的溶解度、溶解性和稳定性。使用一套固态测量能力（x射线，热，光谱分析），我们将能够探索晶体结构并突出对水桥合成至关重要的特征。利用原位监测技术，我们将能够在各种环境条件下探索固体的物理性质。这些实验观察将由计算工作来支持，以提取系统的能量信息以及分子间相互作用如何影响观察到的性质。