Study On The Continuous Crystallization Process And Mechanism Of Slug Flow

Crystallization is a fundamental part for a large number of active pharmaceutical ingredient(API)production processes for purification.In recent years,the focus is shifted to the continuous crystallization process in order to overcome the problems such as the inconsistency of batch quality that exists in batch process.Continuous crystallization research focuses currently on mixed-suspension,mixed-product-removal(MSMPR)crystallizers and on tubular crystallizers.In this paper,the continuous crystallization behavior of segmented tubular crystallization process was investigated systematically using glycine as a model compound.Using the air-liquid segmented tubular crystallization process,process parameters such as aspect ratio of the liquid slug,Reynolds number,seed loading,hydrophobicity of the tubing material,tube crystallizer arrangement and ultrasonic were studied experimentally for their effect on the growth rate,size distribution,and morphology of the produced crystals.The wall nucleation of tube crystallizer with different materials was also investigated and obtained the optimal experimental conditions.In order to visualize the crystal particle behavior,an Eulerian liquid-solid two-phase model coupled with a Realizable k–? model in a computational fluid dynamics platform was also used to simulate the suspension state and the flow trajectory of crystals in a liquid slug and the simulation results coincide with experimental results.Based on the optimization conditions of the air-liquid slug flow crystallization system,we studied the liquid-liquid segmented tubular crystallization process and compared and analyzed the difference between the air-liquid and liquid-liquid slug flow crystallization process taking the crystal growth rate,size distribution,and morphology for the main research objects.Ultrasonic was used to study the effect on the liquid-liquid slug flow crystallization process.The static nucleation process of the crystal at the gas-liquid interface and liquid-liquid interface was observed by means of the microscope and the influence of the different supersaturation ratio on the nucleation experiments was discussed.By analyzing the characteristics of the crystals such as the growth rate and crystal habits at the gas-liquid interface and liquid-liquid interface,we can deeply understand the difference of the wall nucleation between the air-liquid and liquid-liquid slug flow crystallization process as well as the growth state of crystals inside the liquid slug.