Identifying and choosing the best solid form of an API is crucial in a drug’s development. Therefore, it is always best to conduct a thorough search to identify as many solid forms of the API as possible (polymorphs, salts and cocrystals) to allow the selection of the form with the most desired physical and chemical properties as well as for generation of IP. Once the desired form has been chosen and the API progresses through the development pipeline, the design of a robust and scalable crystallization must be undertaken.
However, as crystallization is not only governed by thermodynamics but also heavily influenced by kinetics, unexpected issues can arise during process scale-up, such as the appearance of previously unseen and undesirable solid forms, the formation of transient polymorphs, and or the phenomena of oiling out. These latter phenomena are often too short-lived to be observed at lab scale but can become process-limiting on a multi-kilogram scale. However, with the arrival of high-resolution process analytical technology (PAT), such phenomena can be observed at a reduced scale. The use of PAT, modelling and design of experiment studies, coupled with expert understanding of the solid form landscape, means that crystallization development can be driven by a Quality by Design (QBD) approach to give a scalable, robust process yielding the desired outcome at an early stage of development.
Ruth Lunt joined Johnson Matthey almost two years ago after gaining her PhD from the University of Bath as part of CMAC, a national centre for Continuous Manufacturing and Crystallization. As part of her PhD, she completed industrial secondments at two large multi-national pharmaceutical companies focusing on crystallization development in batch and continuous platforms. Since joining JM, Ruth has continued to work on challenging crystallization development projects alongside solid form screening.