By Dr. Gerard Capellades,
Assistant Professor, Rowan University


  Industrial crystallization is heavily used as a purification step and to isolate valuable products with the desired solid-state properties. Consequently, it plays a major role in the production of fine and commodity chemicals, food products, and pharmaceuticals. However, the development of robust crystallization processes is often hindered by the lack of fundamental understanding on the mechanisms driving kinetics, polymorphism, and impurity retention.
A highly complex yet underexplored area of crystallization deals with the incorporation of process impurities in crystalline products, as well as the effect of those impurities on major crystal quality attributes. Impurities, as process raw materials, intermediates, by-products, and even solvents, are unavoidable in a crystallization process. Their retention in crystallized powders leads not just to the presence of a potentially toxic molecule in a product meant for human/animal consumption, but also to a change in properties including solubility, dissolution behavior, and polymorphic stability.
The first part of this talk will focus on impurity retention mechanisms and their diagnostics. Multiple mechanisms have been identified in academic literature, and workflows have been developed for the identification of those mechanisms. This talk will present a critical view on which mechanisms are most common and/or concerning for industrial development, and which common diagnostics may have been misdirected by our limited understanding on how impure crystals behave. Alternative diagnostic tools will be discussed, backed by data on more than 50 product-impurity pairs of industrial relevance.
In the second part of the talk, the effects of lattice impurities on crystal behavior will be discussed beyond the potentially toxic effects of foreign molecules. Dyes will be used as model impurities to visualize and compare the dissolution behaviors of pure and impure crystals, the effects of lattice impurities on solubility and crystal fragility will be discussed, and examples of solid solutions with structurally similar impurities will be provided as evidence of a changing polymorphic landscape.