In the pharmaceutical industry, process development is a long-term activity which extends beyond laboratory scale. Work initiated during the pre-clinical phase continues through the three clinical phases and the outcomes are constantly checked during the commercial phase to ensure that patients are dosed with the right quality medicines.
For the crystallization processes of Active Pharmaceutical Ingredients (APIs), solid form and particle properties are typically the most impacted. Not all powders behave in the same way and uncontrolled physical attributes can increase the formulation manufacturability risks through, for example, poor flow properties or undesirable particle sizes. Understanding the solid state diversity of the Crystalline API is a critical activity. In addition the different crystallization mechanisms should ideally be deconvoluted and managed as far as possible.
In this context a crystallization process development framework starts with small-scale experiments to identify suitable solvents and processes. These initial processes are then scaled-up further in the laboratory environment to be evaluated and hence identify critical process parameters. This structured framework facilitates the understanding of crystallization mechanisms, thus enabling the development of a scalable crystallization process to manufacturing plant.
The presentation showcases the mentioned framework and the different approaches and tools used to support crystallization process development by enhancing our understanding. These range from experimental to predictive and some examples from the AstraZeneca portfolio will be presented.
