(390c) Application of Process Analytical Technologies (PAT) to Monitor a Continuous Crystallization

A Mixed Suspension Mixed Product Removal Cooling crystallizer with Product Recycle using a heat exchanger was used on a laboratory scale to study the effects of agitation speed, solute concentration and mean residence time on the physical properties of an organic compound. A typical batch cooling crystallization operates at higher levels of supersaturation compared to continuous crystallization systems. Most continuous crystallization studies focus on achieving steady state operation with regards to particle size and size distribution. The monitoring of supersaturation levels during the start-up of a continuous crystallization process and its evolution towards achieving a constant supersaturation level at steady state operation has not received much attention. In many cases, it is possible to achieve steady state operation with regards to particle size but not with regards to supersaturation. On-line Focused Beam Reflectance Monitoring (FBRM) was introduced to monitor how many residence times elapsed in order to achieve steady state chord size and size distribution within the continuous crystallization system. Furthermore, Attenuated Total Reflectance- Ultraviolet (ATR-UV) Spectroscopy in combination with the use of chemometrics was used for the first time to monitor supersaturation on transitioning from a batch cooling to continuous cooling crystallization system including the operational establishment of steady state and constant supersaturation. During the start-up of the continuous crystallization system, an acicular crystal habit was produced, whereas at steady state operation in a continuous crystallization mode, a parallelepiped habit was evident when introducing Process Video Imaging (PVM) and light microscopy. The continuous cooling crystallization system allows for operation at a lower level of supersaturation and can therefore have a profound impact on growth rate on different crystal faces resulting in a change in crystal habit.