Continuous Cooling Crystallization in a Coiled Flow Inverter Crystallizer Technology—Design, Characterization, and Hurdles

Abstract

Continuous small-scale production is currently of utmost interest for fine chemicals and pharmaceuticals. For this purpose, equipment and process concepts in consideration of the hurdles for solids handling are required to transfer conventional batch processing to continuous operation. Based on empirical equations, pressure loss constraints, and an expandable modular system, a coiled flow inverter (CFI) crystallizer with an inner diameter of 1.6 mm was designed. It was characterized concerning its residence time behavior, tested for operation with seed crystals or an ultrasonic seed crystal unit, and evaluated for different purging mechanisms for stable operation. The residence time behavior in the CFI corresponds to ideal plug flow behavior. Crystal growth using seed crystals was demonstrated in the CFI for two amino acids. For fewer seed crystals, higher crystal growth rates were determined, while at the same time, secondary nucleation was observed. Feasibility for the interconnection of a sonicated seeding crystal unit could be shown. However, the hurdles are also identified and discussed. Prophylactic flushing combined with a photosensor for distinguishing between solvent and suspension phase can lead to stable and resource-efficient operation. The small-scale CFI technology was investigated in detail, and the limits and opportunities of the technology are presented here.

Detecting Crystals in Suspensions: Convolutional Neural Networks vs. Gravity‐Based Approach for Size Distribution Detection

“…However, a stretching of the curve to the right can be seen as some found crystal diameters are above 125 mm. This stretching can also be seen in the evaluation of Schmalenberg et al The evaluation with CNN shows good results in the middle and especially in the high size ranges, which are clearly below the results of Schmalenberg et al [12,13,20] On the other hand, the evaluation with CNN in the low value ranges of the PSD is far from the results of the sedimentation analysis. This can be explained by the effects of watershed and roundness described above.…”

P48 - Design of an AI-supported Sensor for Process Relevant Parameters in Emulsification Processes

“…Due to the similar refractive index of water (1.3312 -1.3372) [4] and FEP (1.3380 -1.334) [5] a distortion-free observation of a water-based emulsion is carried out. Several further investigations confirm this experience [3,6,7]. A peristaltic pump (LabDos Easy-Load, HiTec Zang GmbH, Germany) pumps the emulsion through the analytic bypass, where it returns to the emulsion vessel.…”

Continuous Miniaturized Draft Tube Baffle Crystallizer with Particle Screw for Supportive Suspension Discharge

“…Another reason might be the substance system itself because, for the crystallization investigations without the particle screw, the purity of the L-alanine was higher. Other investigations showed that purity influences this substance system regarding nucleation behavior, 43 which is probably the case for the growth kinetics. Another possibility could be that the particle screw causes a faster suspension discharge and that the crystals in the investigations made without the particle screw grew in the product tube because they settled and stayed there so that they could grow longer.…”

“…The same thermogravimetric method as described in ref and used already in refs and was used to determine the solid weight fraction ( w i ) of the suspension and to calculate the relative yield ( Y rel ) (eq ), which indicates how well the solubility line was reached and supersaturation was reduced. The relative yield needs the mass loading ( X i ) for determination.…”