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 half of this talk will focus on impurity retention mechanisms and their identification, starting with a critical view on which mechanisms are most common in industrial development. A discussion will be provided around the accidental formation of crystalline solid solutions between crystallizing products and process impurities, and how those impure crystals behave in contrast with their purified counterparts. 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.
The second half of the talk will cover scalable impurity rejection strategies that leverage thermodynamic understanding on impurity precipitation and solid solution formation, to achieve a desired purity profile in the isolated product. Examples will be given for the successful implementation of those strategies in both academic compounds and industrial crudes.
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 half of this talk will focus on impurity retention mechanisms and their identification, starting with a critical view on which mechanisms are most common in industrial development. A discussion will be provided around the accidental formation of crystalline solid solutions between crystallizing products and process impurities, and how those impure crystals behave in contrast with their purified counterparts. 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.
The second half of the talk will cover scalable impurity rejection strategies that leverage thermodynamic understanding on impurity precipitation and solid solution formation, to achieve a desired purity profile in the isolated product. Examples will be given for the successful implementation of those strategies in both academic compounds and industrial crudes.
