复分解法氯化铵生产中冷却结晶过程研究

研究了硝酸铵和氯化钾复分解法制取氯化铵的冷却结晶过程,考察了降温速率、搅拌速率、晶种添加量等因素对氯化铵产品的纯度及晶体粒度分布的影响。研究结果表明,采取适宜的降温速率、搅拌速率及适宜的晶种添加能有效地改善氯化铵晶体粒度,提高分离效果;氯化铵冷却结晶适宜操作条件为：降温速率为0.3 K/min、搅拌速率为350 r/min、添加晶种粒度为150~180 μm、添加晶种量为1.88%,在此条件下制得的氯化铵产品晶体粒度均一性好,平均粒径更大。     

添加晶种对磷酸二氢钾结晶特性的影响

采用间歇结晶法研究了磷酸二氢钾的添加晶种结晶,考察了添加晶种时的搅拌速率、温度以及添加的晶种粒度、晶种量对结晶产品粒度分布和平均粒径的影响,并与自发成核结晶进行了比较。实验结果表明:添加晶种结晶能有效改善产品粒度分布、增大平均粒径。添加晶种时适宜的结晶条件为:搅拌速率150r/min,温度70℃,晶种粒度40!60目,晶种量1%。产品粒径大于40目的晶体累计质量分数达84.23%,平均粒径为645.37μm。相比自发成核结晶,粒径大于40目的晶体累计质量分数增加了22.46%,平均粒径增大了约100μm。     

氯化钾间歇冷却结晶生长规律及粒度控制实验研究

采用聚焦光束反射测量技术（FBRM）考察了氯化钾（KCl）间歇冷却结晶过程中晶体成核和生长规律,重点研究了降温速率对KCl水溶液冷却时产生过饱和度的影响,以及添加晶种的相关条件（如晶种粒径和添加量等因素）与KCl晶体产品粒度的关系。同时,采用直接冷却刺激起晶产生“晶种”,并控制其生长达到控制晶体产品粒度的目的。结果表明,在添加晶种条件下,程序降温过程产生的低过饱和度不易引起爆发成核,且晶种的添加量决定着晶体产品的平均粒度与理想生长模型的偏差。另外,降温速率是冷却刺激起晶产生“晶种”粒径的关键因素。     

硫酸镍间歇结晶过程的工艺优化

文章采用聚焦光束反射测量仪(FBRM)研究了硫酸镍间歇结晶过程晶体的成核和生长规律,考察了搅拌桨形式、降温方式、搅拌速率、晶种添加量和晶种粒度对结晶过程中结晶动力学的影响。结晶工艺条件优化后,得到了粒径大、晶型好、分布均匀的晶体产品,为硫酸镍间歇结晶过程的工艺优化和工业放大提供了依据。     

酒石酸钾钠结晶工艺的优化

通过控制降温速率和添加晶种优化了酒石酸钾钠结晶工艺,采用简化的降温程序,添加质量分数为8%的晶种时,酒石酸钾钠晶体的结晶形态良好,产品中粒度16~20目的晶体质量分数可达到80%以上。工业实验表明,优化的结晶工艺能有效地改善酒石酸钾钠晶体的粒度分布。     

对二甲苯悬浮熔融结晶动力学

结晶法是工业上生产对二甲苯的主要方法之一。现有对二甲苯结晶动力学参数均单纯由结晶母液的温度和浓度变化通过非线性优化法而获得,未检测对二甲苯的晶体粒度数据,因而其准确性难以得到保证。本文利用超声在线粒度仪(OPUS)检测对二甲苯晶体的粒度分布,通过添加晶种的间歇悬浮熔融结晶实验,应用矩量变换法测定82%（质量）对二甲苯-间二甲苯体系中的对二甲苯结晶动力学。利用最小二乘法对动力学实验数据进行多元线性回归后得到了对二甲苯结晶动力学方程,研究结果表明,在对二甲苯悬浮熔融结晶过程中,溶液相对过饱和度对对二甲苯晶体成核速率的影响大于对晶体生长速率的影响,搅拌速率对成核过程影响明显,而晶浆悬浮密度对成核速率的影响不大。     

卡马西平多晶型结晶工艺研究

通过生物显微镜、X射线粉末衍射(XRD)、马尔文粒度分析仪,差热分析(DSC)及在线聚焦反射测量仪(FBRM)和粒子成像测量仪(PVM)研究了在卡马西平结晶过程中各种操作参数对产品质量特别是晶型的影响,具体考察了溶剂、晶种、结晶方式、干燥、温度、搅拌速率及冷却速率对晶体产品质量的影响。结果表明,不同溶剂中缓慢结晶,高介电常数溶剂(如醇类)中得到卡马西平晶型Ⅲ,乙醇-水混合物中当乙醇摩尔分数低于40%时结晶产物为二水物,四氢呋喃中结晶得到晶型Ⅱ,其他溶剂得到产品为混合晶型;对于醇类溶剂,蒸发结晶一般得到卡马西平晶型Ⅱ,而缓慢冷却得晶型Ⅲ;以正丙醇为溶剂,加大量颗粒较小的晶种可以得到粒度较均一的产品;晶型Ⅱ产品由于特殊的结构,易于有结晶用溶剂包藏在晶体中,加热到约140℃溶剂逸出;温度是影响晶型的重要因素,在较高温度区间(90~76℃)结晶得晶型Ⅱ,而在低温度区间(52~20℃)得晶型Ⅲ;搅拌速率在较低的温度下对晶型没有影响,搅拌速率大可以避免晶体的聚集,形成较均匀的颗粒;3种降温速率结果显示,产品均为卡马西平晶型Ⅲ,但先慢后快的降温速率可以得到更均匀的颗粒晶体。     

磷酸二氢钾结晶工艺控制研究

为了制备形貌规则、粒度分布均匀的磷酸二氢钾晶体颗粒,对磷酸二氢钾结晶过程进行了系统研究,考察了搅拌转速、降温方式、养晶时间、晶种加入量、晶种加入时的温度、晶种加入方式以及晶种颗粒大小对结晶产品的形貌和粒度分布的影响。研究表明,结晶过程条件对晶体形貌、颗粒大小、结晶产品量以及粒径分布等具有较大影响,研究得到的最佳结晶工艺参数为:搅拌速率120～150r/min,降温速率0.3℃/min,养晶时间5h,晶种加入量0.5%～0.8%,晶种加入时溶液温度48℃,晶种加入方式选择分两次加入,晶种颗粒大小70目。在此结晶工艺条件下,磷酸二氢钾晶体形貌规则,粒度分布均匀,平均粒径为1.5mm。     

碳酸氢铵溶液中偏钒酸铵的冷却结晶

针对钒渣空白焙烧-铵化浸出新工艺产生的浸出液,在对NH₄HCO₃-NH₄VO₃-H₂O溶解度数据进行分析的基础上,采用冷却结晶分离方法分离溶液中偏钒酸铵。采用程序控温冷却方式考察了碳酸氢铵浓度、降温速率、搅拌速率、晶种添加量等因素对偏钒酸铵从70℃冷却结晶至40℃时结晶率、产品粒度、形貌等的影响,明确了偏钒酸铵冷却结晶规律,建立了偏钒酸铵从碳酸氢铵母液中高效结晶分离方法,获得了结晶最佳工艺条件。在碳酸氢铵浓度10g/L、降温速率0.36℃/min、搅拌速率200r/min、晶种添加量1.0%时偏钒酸铵结晶率可达94.28%,得到的偏钒酸铵晶体纯度为99.5%,产品粒度均匀,平均粒径约为152μm,晶体成规则棱柱状结构。     

五水柠檬酸钠连续结晶动力学研究

研究了五水柠檬酸钠的连续结晶过程。利用马尔文激光粒度分析仪对不同温度和停留时间下连续结晶过程产品的粒度分布进行分析。通过实验数据和粒度无关生长模型,分别计算了连续结晶过程中五水柠檬酸钠晶体生长与成核速率方程。研究表明,在33.3℃的连续结晶过程中,五水柠檬酸钠的成核速率较生长速率对溶液的过饱和度变化更敏感,增加溶液过饱和度更易形成较小粒度的晶体。     

Industrial batch crystallization of a plate-like organic product. In situ monitoring and 2D-CSD modelling. Part 2: Kinetic modelling and identification

The batch seeded cooling solution crystallization of a fine organic material, exhibiting a platelet-like habit, was investigated and a model of the time variations of the crystal size distribution (CSD) was designed using two-dimensional population balance equations. Activated surface secondary nucleation and attrition secondary nucleation mechanisms were considered, coupled with growth mechanisms of two main dimensions of the crystal, resulting in a set of eight kinetic parameters. The model relates the effects of the main batch operating conditions: seeding temperature, cooling rate and total area of the seed particles, on both the supersaturation profile and bi-dimensional CSD. Surface secondary nucleation occurs first since it is promoted by the introduction of seeds and remains active as long as the relative supersaturation exceeds a threshold value of about 16%. It vanishes below which could be expected as we deal with an activated mechanism. Contact secondary nucleation occurs later when the concentration of solid is sufficient. It is spread over time until supersaturation disappears at the end of the batch process. This contact secondary mechanism is assumed to be the dominant nucleation mechanism as it generates about two-thirds of the final crystal number. Sharp desupersaturation profile following the introduction of seeds, which was observed experimentally, is shown to be quantitatively described through the growth of seed particles. The termination of the batch process is more difficult to represent. Due to crystal attrition, distinct growth rates between initial and secondary crystals or growth rate dispersion might explain such difficulty.     

Internally generated seeding policy in anti-solvent crystallization of ceftriaxone sodium

A promising seeding strategy of internally generated seeds in producing ceftriaxone sodium with a uni-modal crystal size distribution (CSD) was experimentally investigated in batch anti-solvent crystallization. Effects of different seeding policies on product CSDs, both external seeding and internally generated seeding, were experimentally determined. A uni-modal product CSD was obtained without obvious nucleation at high external-seed loadings, while a bi-modal CSD was obtained with plenty of secondary nuclei at low external-seed loadings. The internally generated seeds, prepared by adding pure acetone into the non-seeded saturated solution of ceftriaxone sodium, were fine crystals with a uni-modal, narrow CSD, irrespective of the amount of the added diluent. These fine crystals were grown continuously as seeds by slowly adding a relatively low concentration diluent. The product CSD was uni-modal with relatively large mass-weighted mean size, and the product quality was as good as the one obtained by external seeding. Therefore, such an internally generated seeding policy is expected to be a favorable seeding technology to hopefully substitute for the external seeding policy in the pharmaceutical industry, where external seeding is not welcome because the external seeding policy would destroy the axenic conditions in crystallizer and lead to unstable quality of different batches.     

Modeling of crystal growth and nucleation rates for pentaerythritol batch crystallization

The kinetics of crystallization – nucleation and crystal growth – was determined for a seeded batch cooling process. Several experiments were done utilizing always the same condition: initial concentration, seed mass and size distribution, and cooling rate. From one experiment to other the agitation speed was varied. As the utilized reactor is able to measure torque of the impeller, the power dissipated in agitation was monitored during the crystallization, as well as reactor temperature and turbidity of the suspension. Turbidity monitoring and the measurement of particle size distribution from seeds and final product allowed obtaining the evolution of the second moment of the particles during the crystallization. The crystallization process was modeled utilizing the Method of Moments and the nucleation and crystal growth kinetics were obtained from least-square minimization of calculated second moments of the crystals. A crystal growth kinetic was determined and the secondary nucleation rate was described as a function of dissipated power and as functions of impeller tip speed. Additional experiments were done, in which cooling rate, seed mass and seed size were varied. The calculated kinetics could satisfactorily describe the results of the additional experiments, corroborating the quality of the modeling.     

Modeling batch crystallization processes: Assumption verification and improvement of the parameter estimation quality through empirical experiment design

In this work, experimental data of different batches was used for estimation of the kinetic parameters for the secondary nucleation framework of Gahn and Mersmann [Gahn, C. and Mersmann, A., 1999. Brittle fracture in crystallization processes. Chem. Eng. Sci. 54, 1273–1292].An empirical experiment design procedure was used to design an informative batch experiment through optimization of the seed quality, size and mass and process conditions at seeding. The parameters estimated using the data of the designed experiment showed smaller magnitudes of the confidence ellipsoids and standard deviations as compared to those obtained by using the data of conventional (un)seeded batch experiments. It was shown that the designed experiment allowed reducing uncertainty in the initial conditions, namely, the mass and crystal size distribution of the initial population of crystals and the initial supersaturation.It was also demonstrated that the main reason for the model/process mismatch was the origin of nuclei. Dynamic experimental data could be described better if the state of the crystals forming the crystallization system corresponded to the assumptions of the used kinetic model. Differences in the crystal surface properties, shape, and strain content could be responsible for a divergent nucleation and growth behavior in batches that were initiated either by primary nucleation, seeding with small ground seeds or seeding with coarse crystals from the product of the previous batch.     

Industrial batch crystallization of a plate-like organic product. In situ monitoring and 2D-CSD modelling: Part 1: Experimental study

Experimental results obtained during the batch cooling solution crystallization of a fine organic compound in aqueous ethanol solvent are presented. The process monitoring was ensured through in-line, in situ ATR FTIR spectroscopy, providing continuous solute concentration estimates. Off-line image analysis was also performed to yield discrete-time measurements of the 2D-crystal size distribution (CSD) of the platelet-like particles. The decisive effect of secondary nucleation on both the course of supersaturation and CSD was highlighted through the qualitative analysis of selected batch runs, particular attention being focused on the seeds size and weight. At least two nucleation mechanisms allow explaining the experimental results: the introduction of seeds causes a significant burst of surface nucleation and the continuation of the cooling process, through the generation of continuous supersaturation, allows activated secondary nucleation to take place.     

A novel hollow fiber membrane-assisted antisolvent crystallization for enhanced mass transfer process control

Herein, a novel hollow fiber membrane-assisted antisolvent crystallization (MAAC) was proposed to enhance the mass transfer control over the antisolvent crystallization. A polyethersulfone membrane module was introduced as the key device for antisolvent transfer and solution mixing. An antisolvent liquid film layer was formed on the membrane surface and mixed with the solution. The liquid film also prevented the membrane from directly contacting with crystallization solution. By controlling both the shell side flow velocity and the antisolvent transfer, the antisolvent permeation rate achieved sensitive, stable, and accurate control during long-term and repeated utilization. The interfacial mass transfer rate of MAAC was 0.66 mg cm⁻² s⁻¹, which was only 1/50 that of conventional droplet antisolvent crystallization. MAAC also provided crystal products with better morphologies and narrower size distributions than the conventional process. The stable performances of MAAC in terms of its accurate antisolvent mass transfer and antifouling capabilities were also highlighted. © 2018 American Institute of Chemical Engineers AIChE J, 65: 734–744, 2019     

苊冷却结晶动力学的间歇动态法研究

通过添加晶种的间歇冷却结晶实验研究了苊在乙醇中的结晶动力学。由苊晶体的粒数密度数据,通过矩量变换法按粒度无关生长模型求解粒数衡算方程,采用多元线性最小二乘法回归动力学数据,得到苊在乙醇中晶体生长及成核速率方程。对动力学方程的理论分析表明:搅拌速率对二次成核影响显著,随搅拌速率增加,晶体的成核速率明显增加。同时适宜的过饱和度及较低的悬浮密度,有利于苊晶体生长。该研究为苊冷却结晶特性的辨识、粒度分布的控制及工业放大提供了重要的理论指导。     

Modelling of crystallization process and optimization of the cooling strategy

To obtain a uniform and large crystal in seeded batch cooling crystallization, the cooling strategy is very important. In this study, an optimal cooling strategy is obtained through simulation and compared to linear and natural cooling strategies. A model for a crystallization process in a batch reactor is constructed by using population balance equation and material balance for solution concentration, and a prediction model for meta-stable limit is formulated by the dynamic meta-stable limit approach. Based on this model, an optimal cooling strategy is obtained using genetic algorithm with the objective function of minimizing the unwanted nucleation and maximizing the crystal growth rate. From the simulation results, the product from the optimal cooling strategy showed uniform and large crystal size distribution while products from the other two strategies contained significant amount of fine particles.     

Effect of cooling mode on product crystal size in seeded batch crystallization of potassium alum

Potassium alum was crystallized by seeding in a batch crystallizer under controlled and natural cooling modes. Regardless of the cooling mode, the product crystal size distribution (CSD) became bi-modal at low seed concentrations because of enormous secondary nucleation. The mean mass size of the product was smaller for the natural cooling mode compared to that for the controlled cooling mode with more intensive secondary nucleation. On the other hand, at high seed concentrations, the product CSD became uni-modal with the same mean mass size for both cooling modes, where the crystallization was dominated by seed growth. The low supersaturation caused by the growth of enough seeds plays a key role to produce uni-modal size distribution with suppressed nucleation. Adhering of small crystals (secondary nuclei) to growing seed crystals is also considered to be another mechanism for generating uni-modal CSD.