(330g) A Case of a Twisty Route to First Crystals

Nowadays, polymorph and salt screening are usually conducted in a high throughput (HT) fashion were hundreds of conditions are explored simultaneously. The HT studies are typically conducted by varying solvent systems, temperature programs, ways of creating supersaturation and counter ions. Quite often, HT polymorph and salt screening lead to several crystalline forms and the selection of the crystalline form to progress in development is based mostly on stability and purity attributes. However, in some cases HT polymorph and salt screening results in mostly oiling out and / or solids with poor crystallinity. In that situation, the search of crystalline solids is approached with a focused scientific rationale and conducted under narrower but better targeted conditions. In this presentation we present a case study where a focused scientific approach was utilized to identify and isolate a crystalline salt of a substance for which high throughput salt screening of hundreds of conditions only led to oiling out and/or amorphous solids in the. The presentation describes how a path to 1st crystals can be identified from learnings about the system behavior in terms of solubility and liquid-liquid phase separation (LLPS). The causes leading to oiling out and to the reluctance to crystal nucleation are discussed. In addition, an approach to perform a clarifying filtration when the solublities of both parent and salt do not permit a full dissolution is presented.