(437g) Control of Batch Cooling Crystallization of Glycine

Crystallization is often the most important step in isolation and purification in the manufacture of pharmaceuticals and fine chemicals. Good control of the crystallization process is crucial to ensure the end product possesses the desired properties, such as downstream processability and bioavailability. Once a process has been developed and is in operation, batch-to-batch consistency is of paramount concern.

Traditionally, temperature control strategies are used for cooling crystallization, whereby the temperature of the solution is controlled to follow a pre-set cooling profile determined in the laboratory from small scale crystallization experiments. In recent years, with the advancement in in-line technologies for measuring particles and solution concentrations, more sophisticated control strategies have been proposed by various researchers. The benefits claimed for such new approaches are more consistent product and easier scale-up. Therefore, the main purpose of this paper is to evaluate the benefits, or lack thereof, of new methods for controlling crystallizations over conventional methods using temperature control. The present work uses glycine-water as a model system to demonstrate the effects of the various modes of crystallization process control and of scale-up.

In-line sensors, including FTIR-ATR, FBRM and turbidity probe, have been used to monitor the cooling crystallization of glycine. Making use of information from the sensors, different control strategies have been implemented. Industrial applicability, especially with regards to practicality and robustness, has been taken into account; and questions involving scale-up and seeding will be discussed.