(646a) Simultaneous Lattice Incorporation and Co-Precipitation of Impurities in Solution Crystallization

Incorporation of impurities in a crystallizing suspension is a common challenge during crystallization of small organic molecules. Process development methods tend to characterize the product’s purity as a single metric, representing an average value that does not inform about a specific incorporation mechanism. However, multiple impurity incorporation mechanisms can simultaneously occur during crystallization, sometimes for the same impurity, and knowledge of those mechanisms is the first step for the design of preventive and corrective actions.

In this talk, we will discuss two academic and industrial case studies presenting simultaneous lattice incorporation and impurity co-precipitation in solution crystallization. The focus is first on the diagnosis of the incorporation mechanisms, and how the contributions of each mechanism on the average powder purity were quantified using widely available technologies. The second half of the talk will focus on preventive and corrective strategies, rooted on the acquired mechanistic knowledge, for the rejection of those impurities during and after crystallization. The cost, time and resource benefits of adopting an effective diagnosis are contrasted with current standard practices in the pharmaceutical and chemical industries.