Hydrates in Solution - Interactions of drug compounds with water in pre-nucleation clusters

溶液中的水合物 - 药物化合物与成核前团簇中的水的相互作用

• 批准号: EP/P002870/2
• 负责人: Katharina Edkins
• 金额: $ 9.52万
• 依托单位: Queen's University Belfast
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FP002870%2F2
• 关键词: Hydrates; Solution; Interactions; drug; compounds

One of the bottlenecks of a new pharmaceutical drug entity reaching the market is its formulation into a safe and effective medicine. This cost- and time-intensive process is furthermore complicated by the presence of multiple crystal forms, which will alter the stability, processability and solubility of the material. In order to help speed up the process of a drug getting onto market, this project aims to improve the efficiency of this by investigating the interaction of drug with water during crystallisation and relate this to the physical stability of the resulting water-containing crystal forms (hydrates). This knowledge will then help to predict the occurrence and stability of these pharmaceutical materials, which present an especially challenging class to deliver to the pharmacological target due to their low water solubility and, thus, bioavailability. Hydrates are generally avoided during formulation wherever possible.The project will:1. Investigate the molecular interactions between drug compounds and water molecules in solution,2. Determine the stoichiometry and strength of these interactions,3. Connect the strength of these interactions with the physical stability of their respective hydrated crystal form,4. Propose rules to connect solute-water interactions in solution with occurrence and stability of resulting hydrate forms.This proposal is part of an overarching project aiming to understand the influence of solution structure and solute aggregation before crystallisation on the resulting crystal form in order to predict and control crystallisation experiments.The results of this project will further our fundamental understanding of crystallisation. This knowledge can be immediately implemented into the day-to-day business of formulation and manufacturing, e.g. in the pharmaceutical and fine-chemical industries. It will thus benefit the broader public by shortening development times and accelerating the process of new medications reaching the market.

新药实体进入市场的瓶颈之一是将其配制成安全有效的药物。这种成本和时间密集的过程由于多种晶体形式的存在而变得更加复杂，这将改变材料的稳定性、可加工性和溶解度。为了帮助加快药物进入市场的过程，该项目旨在通过研究药物在结晶过程中与水的相互作用来提高效率，并将其与所得到的含水晶体形式（水合物）的物理稳定性联系起来。这些知识将有助于预测这些药物材料的发生和稳定性，这些药物材料由于其低水溶性和生物利用度而呈现出特别具有挑战性的一类，以传递到药理学目标。在配方过程中尽可能避免使用水合物。该项目将：1；研究药物化合物与水分子在溶液中的分子相互作用；确定这些相互作用的化学计量和强度；将这些相互作用的强度与它们各自水合晶体形态的物理稳定性联系起来。提出将溶液中溶质-水相互作用与生成的水合物形式的发生和稳定性联系起来的规则。该建议是一个总体项目的一部分，旨在了解结晶前溶液结构和溶质聚集对所得晶体形式的影响，以便预测和控制结晶实验。这个项目的结果将进一步加深我们对结晶的基本理解。这些知识可以立即应用到配方和制造的日常业务中，例如制药和精细化工行业。因此，通过缩短开发时间和加速新药进入市场的过程，它将使更广泛的公众受益。

项目成果

Pre-nucleation aggregation based on solvent microheterogeneity.

基于溶剂微异质性的预成核聚集。

• DOI: 10.1039/c9cc01455a
• 发表时间: 2019
• 期刊: Chemical communications (Cambridge, England)
• 作者: Jones CD

The solid state of pharmaceuticals

药物的固态

• DOI: 10.1039/c9ce90044f
• 发表时间: 2019
• 期刊: CrystEngComm
• 影响因子: 3.1
• 作者: Edkins K

Extensive Sequential Polymorphic Interconversion in the Solid State: Two Hydrates and Ten Anhydrous Phases of Hexamidine Diisethionate

• DOI: 10.1021/acs.cgd.9b01170
• 发表时间: 2019-12-01
• 期刊: CRYSTAL GROWTH & DESIGN
• 影响因子: 3.8
• 作者: Edkins, Katharina;McIntyre, Garry J.;Steed, Jonathan W.
• 通讯作者: Steed, Jonathan W.