This study aims at easing the design of crystallization and the cake washing step of cocrystals. It is assessed if solvent systems can be classified based on the dissolution behavior of the cocrystal by leveraging on the solubility of its pure components. Solubility data of pure components are typically readily accessible data in the pharmaceutical industry at an early stage of development. For the three model systems considered in this study, the composition of eutectic liquid phases was determined at 20 °C in numerous solvent systems and compared with the solubility of pure components at the same conditions. In the solvent systems in which the cocrystal dissolves congruently, the solubilities of the pure components are similar. Incongruent dissolution behavior is in turn consistently observed if the solubilities of the pure components differed by at least one order of magnitude. For these solvent systems, the eutectic liquid phases are consistently enriched in the more soluble component. Comparison of the solubilities of the pure components thus enables determination of the component that needs to be charged in excess to reach thermodynamic stability of the cocrystal, which is particularly relevant for the design of screening and solubility experiments. Finally, highly asymmetric phase diagrams, which are not suitable for crystallization and cake washing purposes, are easily identifiable by highly dissimilar solubilities of pure components.

中文翻译：

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快速识别用于共晶结晶的潜在溶剂系统的方法

本研究旨在简化共晶的结晶设计和滤饼洗涤步骤。评估是否可以通过利用其纯组分的溶解度，根据共晶的溶解行为对溶剂系统进行分类。纯组分的溶解度数据通常是制药行业早期开发阶段容易获得的数据。对于本研究中考虑的三个模型系统，低共熔液相的组成在 20 °C 下在许多溶剂系统中确定，并与相同条件下纯组分的溶解度进行比较。在共晶完全溶解的溶剂系统中，纯组分的溶解度相似。如果纯组分的溶解度相差至少一个数量级，则会依次一致地观察到不一致的溶解行为。对于这些溶剂系统，低共熔液相始终富含更易溶解的组分。因此，比较纯组分的溶解度可以确定需要过量充电以达到共晶热力学稳定性的组分，这与筛选和溶解度实验的设计特别相关。最后，不适合结晶和滤饼洗涤目的的高度不对称相图很容易通过纯组分的高度不同的溶解度来识别。低共熔液相始终富含更易溶解的成分。因此，比较纯组分的溶解度可以确定需要过量充电以达到共晶热力学稳定性的组分，这与筛选和溶解度实验的设计特别相关。最后，不适合结晶和滤饼洗涤目的的高度不对称相图很容易通过纯组分的高度不同的溶解度来识别。低共熔液相始终富含更易溶解的组分。因此，比较纯组分的溶解度可以确定需要过量充电以达到共晶热力学稳定性的组分，这与筛选和溶解度实验的设计特别相关。最后，不适合结晶和滤饼洗涤目的的高度不对称相图很容易通过纯组分的高度不同的溶解度来识别。