(409a) Crystal Morphology Modification in a Nucleation Dominant Crystallization: A Tool from Traditional Chemistry

Crystal morphology engineering is an important component of process development in the pharmaceutical industry, since the crystal shape or habit directly influences downstream processing, formulation, and the physical properties of the API. Most commonly the desired habits of crystals are prepared through the modification of crystallization process parameters such as temperature, the crystallization solvent, and/or the addition of a co-solvent or an additive. However, in some cases, these methods do not successfully deliver the desired morphology. Here we present the use of Soxhlet extraction conditions as a valuable tool for morphology modification in a nucleation dominant crystallization process. In this case study, the process to produce a cocrystal between Vertex compound A and coformer X resulted in a fibrous morphology in every attempt under various conditions, leading to mixing and filtration issues and low yields. The use of the Soxhlet extraction method provided very slow mixing of the two compounds coupled with temperature cycling close to the solvent’s boiling point to generate a needle morphology, which provided better filtration times, processability and yields, enabling a path forward for further API development.