Bulk Video Monitoring for Nucleation Detection and Metastable Zone Determination for Pharmaceutical Applications

Metastable zone identification is the first step during the design of crystallization systems. The accurate determination of the metastable zone and nucleation onset allows improved supersaturation control policies, it helps to avoid secondary nucleation, ensures maximal productivity and the desired particle size distribution (PSD) at the end of the batch.

This work presents the application of the bulk video monitoring (BVM) and digital image processing for nucleation detection and metastable zone determination. The proposed BVM approach requires low cost hardware instrumentation.

The BVM method is able to detect the nucleation onset with comparable accuracy to the focused beam reflectance measurement probe (FBRM, from Mettler-Toledo) and faster than the UV/Vis spectroscopy (Zeiss).

The comparison is carried out on the caffeine and palm oil crystallization.