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

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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.