Automated in-line technique using FBRM to achieve consistent product quality in cooling crystallization

An in-line technique involving focused beam reflectance measurement (FBRM) for control of crystal product quality in unseeded systems is proposed. The method consists of nucleation detection followed by a holding time to internally generate seeds through primary nucleation and then controlled conditioning of these seeds using FBRM measurement of the particle size distribution (PSD). The technique has been successfully implemented for the cooling crystallization of glycine and paracetamol in water. Results showed that the crystal product consistency using our technique was comparable to that of externally seeded crystallizations.