膜辅助添加晶种的过硫酸铵冷却结晶在线监测与过程调控

冷却结晶是经典的溶液结晶过程,常用于分离溶解度随温度变化较大的物质,制备高品质晶体产品。直接进行降温会导致成核速率不可控,得到的晶体产品质量差。在工业中通常选择在溶液结晶介稳区内投放适量晶种来诱导成核,但晶种制备过程复杂,而且成功的添加晶种过程取决于晶种的粒度分布、数量、投放时机和操作人员的经验等因素,降低了产品质量的批次重复性。本文利用聚四氟乙烯（PTFE）中空纤维膜组件为结晶溶液和冷却液提供换热界面,结晶溶液温度降低,在膜界面处形成较均匀的过冷度梯度,进而在低过饱和度下发生异相成核,实现膜辅助添加晶种的过硫酸铵冷却结晶过程调控。膜组件中产生的晶种进入结晶釜中继续生长,将成核和生长过程进行解耦。在线结晶检测系统捕捉到的照片证实了通过控制膜组件使用温度和时长两个操作参数便可得到具有较好的形貌、较窄的粒度分布的晶种。相比直接冷却结晶,在相近的降温速率下,膜辅助添加晶种过程制备的晶体产品具有更大的平均粒径,且粒度分布更集中,表面更加光滑。因此,膜辅助冷却结晶呈现了良好的成核控制能力,有望实现晶种自动制备和添加功能,为高附加值晶体产品的冷却结晶过程开发提供了新方向。     

Particle shape manipulation and optimization in cooling crystallization involving multiple crystal morphological forms

A population balance model for predicting the dynamic evolution of crystal shape distribution is further developed to simulate crystallization processes in which multiple crystal morphological forms co‐exist and transitions between them can take place. The new model is applied to derive the optimal temperature and supersaturation profiles leading to the desired crystal shape distribution in cooling crystallization. Since tracking an optimum temperature or supersaturation trajectory can be easily implemented by manipulating the coolant flowrate in the reactor jacket, the proposed methodology provides a feasible closed‐loop mechanism for crystal shape tailoring and control. The methodology is demonstrated by applying it to a case study of seeded cooling crystallization of potash alum. © 2009 American Institute of Chemical Engineers AIChE J, 2009     

高氯酸铵结晶介稳区的研究

研究了温度、降温速率、搅拌速率及Na+存在下对高氯酸铵(AP)在水中介稳区的影响,同时用最大过冷度△Tmax表示了介稳区宽度。结果表明,AP介稳区宽度随温度升高和搅拌速率增大而变窄;随降温速率增大而变宽。研究发现,向原料AP中加入少许杂质Na+,AP在水中的介稳区稍微变宽。AP的介稳性质为其结晶过程选择适宜的操作过饱和度提供了依据。     

基于PBM的L-谷氨酸粒度分布控制优化

针对β型L-谷氨酸冷却结晶过程,为获取期望粒度分布,采用特征曲线法（MOCH）来建立关于粒度相关生长率的种群平衡方程（PBE）,然后通过对种群平衡模型（PBM）参数辨识后确定最优过饱和度及控温曲线。由于辨识模型参数的目标函数具有非线性和非凸型性,因而采用少量经济性的批量冷却结晶实验,结合图像分析晶种和产品粒度分布得到的统计数据,拟合模型参数。根据实际要求的结晶过程时间,为达到目标粒度分布,通过优化结晶过程的过饱和度获得最优调温曲线,实现基于恒定过饱和度的晶体生长过程优化控制。实验结果表明通过优化的控温曲线,实现了基于最优过饱和度控制的期望目标粒度分布。     

On-Line control of supersaturation in a continuous cooling KCL crystallizer

Control of supersaturation in a 1-L continuous cooling KC1 crystallizer was investigated. The supersaturation was determined from on-line measurements of the density and temperature of clear liquor samples. A cascade control scheme was used to control the supersaturation through the manipulation of the co-saturated feed temperature set-point while maintaining the crystallizer temperature at 303.2 K. Experimental results showed that due to the suppression of spontaneous nuclearion, a decrease in the measured supersaturation resulted in a 23% increase in the mean crystal size and a 12% decrease in the amount of NaCl impurity in the KCI crystals.     

Iterative learning control for the systematic design of supersaturation controlled batch cooling crystallisation processes

The paper presents an approach to improve the product quality from batch-to-batch by exploiting the repetitive nature of batch processes to update the operating trajectories using process knowledge obtained from previous runs. The data based methodology is focused on using the linear time varying (LTV) perturbation model in an iterative learning control (ILC) framework to provide a convergent batch-to-batch improvement of the process performance indicator. The major contribution of this work is the development of a novel hierarchical ILC (HILC) scheme for systematic design of the supersaturation controller (SSC) of seeded batch cooling crystallizers. The HILC is used to determine the required supersaturation setpoint for the SSC and the corresponding temperature trajectory required to produce crystals with desired end-point property. The performance and robustness of these approaches are evaluated through simulation case studies. These results demonstrate the potential of the ILC approaches for controlling batch processes without rigorous process models.     

A fed-batch design approach of struvite system in controlled supersaturation

This paper focuses on struvite (MgNH₄PO₄·6H₂O) crystallization in controlled supersaturation. Struvite can be used as a slow-release fertilizer. Crystallization experiments were conducted using supersaturated solutions. The secondary focus of this paper is the design of a struvite recovery system in fed-batch-controlled supersaturation mode. The design and commissioning of fed-batch struvite crystallization included the determination of operating supersaturation of struvite crystallization, suitable seed materials and the composition of feed solution. Determination of operating supersaturation of struvite crystallization was conducted by two steps including thermodynamic simulation using gPROMS² (process simulation software) along with a set of batch experiments. Investigation of suitable seed materials was also conducted using set of batch experiments. Two types of seed materials including quartz sand and struvite seeds were used in the investigation of seed materials. Composition of feed solution included the investigation of struvite solution chemistry using PHREEQC³ thermodynamic modeling package. Based on the previously investigated design approach, struvite crystallization in fed-batch system was conducted using a 44-L of reactor with 15-L of initial reactant volume.     

Determination of the metastable zone and induction time of thiourea for cooling crystallization

The solubility,metastable zone width(MSZW),and induction time of thiourea for cooling crystallization were experimentally determined in the temperature range of 283-323 K. The solubility data could be well described by the Apelblat equation model as lnx=-99.55+1071.66/T+16.27 lnT. The determinations of the effects of various stirring and cooling rates indicated that the MSZW increased with increasing and decreasing cooling and stirring rates,respectively.Furthermore,the induction times at various temperatures and supersaturation ratios were also measured.The results indicated that homogeneous nucleation could occur at high supersaturation,whereas heterogeneous nucleation was more likely to occur at low supersaturation.Based on the classical nucleation theory and induction period data,the calculated solid-liquid interfacial tensions of thiourea in deionized water at 302.46 and 312.58 K were 2.86 and 2.94 mJ·m~(-2),respectively.     

Particle Shape and Purity in Membrane Based Crystallization

Well‐controlled crystallization is the best method for preparing materials that are uniform in shape, size, structure and purity. The driving forces for crystallization are local gradients of supersaturation as the source and desupersaturation as the drain. Very high local supersaturation causes a high growth rate and represents a limiting factor for unstable modifications and product impurities. Hybrid membrane technology provides an interesting tool for controlling and limiting the maximum level of supersaturation due to defined mass transfer across the membrane. In this paper, the level of crystal growth rate in the system NaCl/KCl/water is varied by using different crystallization techniques. Vacuum evaporation crystallization (high growth rate) is compared to membrane based evaporation crystallization (low growth rate) and the results are interpreted in terms of product purity, particle shape and size. Membrane based crystallization in combination with effective solid/liquid separation as well as high performance analytics is suggested as a significant ultrapurification methodology.     

L-酒石酸水溶液结晶介稳区和诱导期的测定

在20~60℃温度范围内,采用激光法测定L-酒石酸在水中的结晶介稳区宽度和诱导期,分别研究了饱和温度、冷却速率和搅拌速率对L-酒石酸结晶介稳区宽度的影响以及过饱和度对L-酒石酸诱导期的影响。结果表明:结晶介稳区宽度随着饱和温度、搅拌速率的增大和冷却速率的降低而变窄,并推算出表观成核级数m,给出了成核速率方程,此外实验测定结晶诱导期随过饱和度S增大而变短,基于经典成核理论和诱导期数据,计算出L-酒石酸在水中20℃和25℃下的固液界面张力。     

A systematic approach for preferential crystallization of 4-hydroxy-2-pyrrolidone: Thermodynamics, kinetics, optimal operation and in-situ monitoring aspects

A systematic approach has been developed and applied to the preferential crystallization of 4-hydroxy-2-pyrrolidone in isopropanol. The concept of critical supersaturation control was introduced for preferential crystallization process. System thermodynamics, crystallization kinetics, optimal operation and in-situ monitoring were combined and integrated to establish the strategy for the critical supersaturation control. Subsequently, the solubility and metastable zone widths of 4-hydroxy-2-pyrrolidone with different compositions in isopropanol under different cooling rates were determined using an automatic lab reactor (Mettler Toledo LabMax) system equipped with Lasentec Focused Beam Reflectance (FBRM) probe. The crystal nucleation and growth kinetics were measured with s-plane analysis. A modified technique was proposed for size-dependent crystal growth. Based on the thermodynamics properties and crystallization kinetics, a simplified cooling profile was proposed and applied to the critical supersaturation control. The final product's high optical purity, good crystal size distribution, SEM imagines and the in-situ observations, all suggested that the critical supersaturation control was essential and the systematic approach was successful and applicable for preferential crystallization.     

抗氧剂BHT结晶工艺研究

BHT结晶采用乙醇作为溶剂。对不同浓度的乙醇,改变溶质与溶剂的物料配比,测定了BHT溶液的出晶点温度。结果表明:在乙醇浓度一定的条件下,出晶点温度随BHT与乙醇配比的增大而降低;而在相同物料配比的条件下,乙醇浓度越低,出晶点温度越高。     

Monitoring the Crystallization Process of Methylprednisolone Hemisuccinate (MPHS) from Ethanol Solution by Combined ATR-FTIR- FBRM- PVM

In-situ Attenuated total reflectance Fourier transform infrared (ATR-FTIR), focused beam reflectance measurement (FBRM) and particle video microscope (PVM) have been used simultaneously in this work to monitor the concentration, supersaturation, chord length distribution, and crystal habit, respectively, during a cooling crystallization process of Methyprednisolone Hemisuccinate (MPHS) from ethanol system. We developed a new calibration method based on peak ratios for the assessment of the concentration, solubility, and supersaturation in the 20–60°C temperature range. The crystallizations were conducted at two concentrations (7.5 and 9.5% w/w) with three different cooling rates (0.3, 0.5, and 0.7 K/min). The lower concentration was chosen within the constructed calibration range while the higher one was outside the calibration range and it was used to examine the extrapolating and predicting ability of the constructed calibration curves. The metastable zone widths (MSZW), supersaturation at nucleation, and the number of fine particle chord length of MPHS were all increased with the cooling rate, while the number of the larger chord length decreased with the increasing of the cooling rate.     

反应-溶析耦合结晶法提纯[（5-噻唑基）甲基]-（4-硝基苯基）碳酸酯

探索了反应-溶析耦合结晶法提纯抗艾滋病药物利托那韦中间体[（5-噻唑基）甲基]-（4-硝基苯基）碳酸酯的工艺过程。选用甲醇作为主溶剂，碳酸钾水溶液作为反应物和析出剂，测定了物系的溶解度关系，研究了结晶温度、析出剂量和加入方式等操作条件时产品收率和纯度的影响。试验表明，在结晶终点温度为20℃，V[碳酸钾水溶液（质量分数5．0％）]，V（甲醇）=3．0的条件下，采用反应-溶析耦合结晶法可从[（5-噻唑基）甲基]-（4-硝基苯基）碳酸酯盐酸盐质量分数为93．42％的原料中，结晶得到纯度为99．81％的[（5-噻唑基）甲基]-（4-硝基苯基）碳酸酯产品，收率可达93．72％。     

Membrane assisted cooling crystallization: Process model,nucleation, metastable zone,and crystal size distribution

The membrane assisted cooling crystallization was proposed and investigated by the simulation and experiments. The developed process model concerned the supersaturation evolution on the membrane interface, the combined nucleation rate in the crystallizer. The impact of different membrane on reducing the nucleation barrier was investigated by introducing the metastable zone width theory. The influence of membrane distillation conditions on the crystal nucleation and growth kinetic was uncovered based on the simulation and experiments results. The experimental results indicated that membrane assisted cooling mode with optimized profiles did improve the crystal size distribution and crystal habit comparing with conventional cooling mode. Terminal coefficient of variation decreased from 55.4 to 33.9 under similar mean crystal growth rate, 2.27 × 10^?7 m s^?1 (conventional cooling) and 1.98 × 10^?7 m s^?1 (membrane assisted cooling). Finally, the brief summary on the advantages and key issues of this propose membrane assisted crystallization operation were concluded. © 2015 American Institute of Chemical Engineers AIChE J, 62: 829–841, 2016     

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。     

环流式碳化塔研究与操作实践

遵循过程不冷却,结晶为控制过程等工艺原则、操作理论和技术路线,在 164×3620环流式碳化塔中分别进行了联合制碱法和氨碱法母液的碳酸化重碱结晶过程模拟试验,介绍了主要条件试验和连续运转120h的试验数据,讨论了晶浆浓度、操作过饱和度、液体环流速度、结晶温度和溶液碳化度等结晶过程工艺参数,考察了二氧化碳吸收传质总系数并比较了塔的二氧化碳吸收容积能力和重碱结晶容积能力,测定了碳酸氢钠平均结疤速度。     

Determination of metastable zone and induction time of analgin for cooling crystallization

The solubility, metastable zone width, and induction time of analgin for unseeded batch cooling crystallization in ethanol–aqueous system were experimentally determined. The solubility data could be well described by the van't Hoff equation model. The metastable zone width at various cooling rates was measured, and some parameters of nucleation kinetic were calculated using the Ny'vlt theory. Furthermore, the induction period of various temperatures and supersaturation ratios was also measured. According to classical nucleation theory, some nucleation parameters and interfacial energy was calculated through the induction time(t_(ind)) data. Homogeneous nucleation tended to occur when the supersaturation is high, whereas heterogeneous nucleation was more likely to occur when the supersaturation is low.     

Multivariable real‐time optimal control of a cooling and antisolvent semibatch crystallization process

This article presents an experimental study of simultaneous optimization with respect to two variables (cooling rate and flow‐rate of antisolvent) in an offline and online (real‐time) manner on a semibatch crystallizer. The nucleation and growth kinetic parameters of paracetamol in an isopropanol‐water cooling, antisolvent batch crystallizer were estimated by nonlinear regression in terms of the moments of the crystal population density. Moments of crystal population were estimated from the measured chord length distribution, generated by the FBRM®, and the supersaturation was calculated from the measured concentration by attenuated total reflectance‐fourier transform infrared spectroscopy. The results of real‐time optimization showed a substantial improvement of the end of batch properties (the volume‐weighted mean size and yield). For the same objective function, the real‐time optimization method resulted in an increase in the volume‐weighted mean size by ～100 μm and 15% of theoretical yield compared with the best result obtained in an offline optimization manner. © 2009 American Institute of Chemical Engineers AIChE J, 2009