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

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方法还由于存在多种晶体形式而变得复杂，这将改变材料的稳定性、可加工性和溶解性。为了帮助加快药物上市的过程，该项目旨在通过研究药物与水在结晶过程中的相互作用来提高其效率，并将其与所得含水晶体形式（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类别。在配制过程中通常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相互作用。确定这些相互作用的化学计量和强度，3.将这些相互作用的强度与它们各自的水合晶体形式的物理稳定性联系起来。提出规则连接溶质-水在溶液中的相互作用与水合物形式的发生和稳定性。该提案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结晶形式的影响，以预测和控制结晶实验。该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日常的配方和制造业务中，例如在制药和精细化工行业。因此，它将通过缩短开发时间和加速新药进入市场的过程而使更广泛的公众受益。

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.