(324c) Purity Reigns Supreme over Stability and Processibility!! .. but Wait, Why Can’t I Have My Cake and Eat It Too?

Typically, a small molecule crystallization process is tasked with producing solids that meet the desired purity and crystal form specifications. In addition to having good processibility (i.e. good filtration/drying characteristics for slurries and flow properties of solids), being robust and scalable, the crystallization process is also expected to deliver high yields in short cycle times. Achieving all this in one crystallization sometimes becomes challenging. In such cases, generally, purity of the solids is prioritized over the physical or chemical stability as the latter could be mitigated through enhanced packaging and storage conditions.

In this presentation, we highlight a system with two forms: a mixed solvate/hydrate and an anhydrate. The mixed solvate/hydrate could reject a key impurity and had better processibility; however, it was physically unstable upon storage, resulting in product assay variability. On the other hand, the anhydrate had good stability, but could not reject the key impurity and had poor processibility due to its morphology and particle size.

Through detailed understanding of the form landscape, focus on fundamentals, and extensive use of Process Analytical Technology (PAT) to interrogate the crystallization kinetics and impact of crystal form on impurity rejection, a more robust process was developed which achieved best of both worlds. The resulting product had good/adequate processibility, physical stability and purity with a minimal impact on the cycle time.

All authors are employees of AbbVie and may own AbbVie stock. AbbVie sponsored and funded the study; contributed to the design; participated in the collection, analysis, and interpretation of data, and in writing, reviewing, and approval of the final publication.