Effects of ultrasonic radiation on induction period and nucleation kinetics of sodium sulfate

The effects of ultrasound on crystal nucleation and particle size distribution of sodium sulfate were investigated via determining the induction period and particle size. Crystal nucleation parameters and equations for primary nucleation were calculated. The experimental results show that the induction time decreases under the ultrasound irradiation, therefore, we can get a shorter induction period at a higher supersaturation level. Based on these observations, the growth mechanism of sodium sulfate is continuous growth because the value of the surface entropy factor f is smaller than 3. The induction period was observed shorter and particle size was smaller when the ultrasonic radiation time increased. Crystal growth improved with the longer crystallization time.     

头孢氨苄连续结晶研究及应用

头孢氨苄的传统生产方法多为间歇结晶,存在效率低、能耗高等弊端。为节约能耗、提高生产效率、缩短工时、降低成本,针对头孢氨苄等电点结晶的特点,本文设计了两级连续结晶工艺。采用单因素法系统研究了头孢氨苄水溶液初始浓度、停留时间、搅拌速率、结晶终点pH、晶种策略等因素对头孢氨苄连续结晶过程产品的收率、晶习及粒度分布的影响。单因素实验结果显示头孢氨苄水溶液质量分数为14%、最佳停留时间为12min、结晶终点pH控制在4.8附近、晶种添加量为5%时其产品收率、粒度分布均达到了理想的效果。该工艺能将结晶过程的过饱和度有效地控制在介稳区内,避免了爆发成核。与间歇结晶相比,两级连续结晶工艺的工时缩短30%。产品晶习完整,粒度分布均匀,收率可以达到96%。目前该工艺已成功实现单条生产线规模为500t/a的产业化应用。     

超声波对阿洛西林酸晶体形态的影响

针对阿洛西林酸（ALPC）生产中存在晶形差、产品聚结的问题,研究了超声波对ALPC晶体形态的影响。首先测定了纯水中的介稳区,分析了超声波影响产品晶习的机理,然后考察了超声波下初始浓度、流加速率和搅拌速率对阿洛西林酸反应结晶过程的影响,从而确定出了最适宜结晶工艺条件。结果表明：超声波可以改善阿洛西林酸产品的晶习、粒度分布并能降低产品聚结程度,实验所得符合厂家的要求。     

环丙沙星在溶液中固液表面能的测定

采用激光法测定了环丙沙星在纯水和水－乙醇溶液（水体积分数23％）中的溶解度，介稳区和不同条件下的诱导期。根据经典成核理论和诱导期理论，推导了固液表面能与诱导期的理论关系，应用该理论关系计算了环丙沙星在溶液中的固液表面能，为环丙沙星初级成核与晶体生长研究提供了重要的参数。     

Continuous crystallization of adipic acid with ultrasound

The application of a novel continuous cooling crystallization system coupled with ultrasound technology to crystallize adipic acid from an aqueous solution was investigated. Both continuous ultrasound irradiation and silent (control) regimes were used in order to elucidate the effects of unstable cavitation on the duration of the transient period, steady state operating conditions, crystal habit, and particle size distribution.The results reveal that under continuous ultrasonic irradiation the steady state particle size distribution is achieved after shorter times, with a consistent reduction of the steady state supersaturation resulting in increased product yields relative to silent continuous crystallization experiments. Continuous crystallization with ultrasonic irradiation results in significantly smaller crystal sizes, reduced agglomeration and an improved habit of crystals. Furthermore, the influence of mean residence time using continuous ultrasound produces a smaller change in particle size and size distribution. Finally, the experiments reveal a noticeable reduction of the fouling on non-cooling surfaces and underline the need for intermittent discharge to prevent classification on withdrawal product.     

一水盐酸环丙沙星初级成核机理的研究

A general expression for the ralationship between induction period and supersaturation was developed based on polynuclear approach.Different mechanism of primary nucleation in solution can be illustrated by the expression.The results of induction period determined by laser scatering method shows that the crystallization of ciprofloxacin hydrochloride monohydrate in water/ethanol or aqueous solution is by the mechanism of primary nucleation followed by one-dimensional diffusion growth,and then one-dimensional continuous or “birth and spread” growth on crystal face. The growth mechanism on the crystal face is affected by temperature and solvent.     

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.     

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。     

莱鲍迪苷A溶解度与介稳区宽度的测定及其结晶过程研究

莱鲍迪苷A是极为重要的新型甜味剂,由于缺乏合理的溶解度数据且其成核机理不明确,导致现存的结晶工艺得到的结晶产品存在细晶多、粒度分布不均等问题。为此,首先利用激光动态法测定了莱鲍迪苷A在甲醇-水、乙醇-水、正丙醇-水、丙酮-水中的溶解度及在甲醇-水中的介稳区宽度,并利用Wilson方程对溶解度进行模型验证;研究了溶剂组成、饱和温度、搅拌速率与冷却速率对介稳区宽度的影响,研究表明,莱鲍迪苷A的介稳区宽度随溶剂中甲醇含量与冷却速率的增加而变宽,随饱和温度与搅拌速率的增加而变窄;基于经典成核理论与相关模型,计算了莱鲍迪苷A的固液界面能γ与临界Gibbs自由能\mathrm{\Delta }{G}_{\mathrm{c}\mathrm{r}\mathrm{i}\mathrm{t}}等成核参数;根据表观成核级数m分析可知,初始温度高于318.15 K时,连续成核是莱鲍迪苷A主导的成核方式;基于上述研究优化了莱鲍迪苷A冷却结晶过程,得到了粒度分布均一的结晶产品。     

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。     

Sonocrystallization and crystallization with gassing of adipic acid

Sonocrystallization is widely used to control nucleation and, therewith, improve the product quality. For this purpose, power ultrasound is turned on within the metastable zone during the crystallization process. But the mechanism by which power ultrasound induces nucleation is still unclear. Efforts have been made to identify the mechanism. It is assumed that nucleation is induced due to the bubble surface provided acting itself as nucleation center so that the mechanism seems to be a heterogeneous one. To prove this assumption, gassing has been investigated to induce nucleation during batch cooling crystallization. The gas bubbles are just expanding not collapsing. This study focuses on the investigation of the crystallization behavior of adipic acid during sonocrystallization and, furthermore, during the crystallization with gassing. During sonocrystallization experiments the insonation period, the ultrasonic frequency and the initial supersaturation ratio were varied. The results show that the metastable-zone width can be reduced and the crystal-size distribution, which turns out to be bimodal, can be narrowed the longer the insonation period and the higher the initial supersaturation ratio is. The crystals formed were identified as agglomerates, whereas the agglomeration can be reduced by power ultrasound. The gassing experiments demonstrated that the crystallization behavior of adipic acid can be affected similar to the application of power ultrasound. It can be concluded that gassing is an alternative to power ultrasound.     

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     

Surface Properties – A Key for Nucleation in Melt Crystallization Processes

Numerous organic products which are commercially refined by crystallization exhibit wide metastable zones, for example, xylene, bisphenol‐A, isocyanates, or pyridine derivatives. The practical meaning for layer crystallization processes is that a high degree of subcooling on crystallization surfaces is necessary to start nucleation at the beginning of a crystallization stage. The subsequent crystallization runs then uncontrolled, at much higher rates than designed until the subcooling has been dissipated. As a consequence dendritic crystal growth sets in, which is disadvantageous in terms of the separation efficiency of the crystallization process. A practicable countermeasure is seeding which, however, requires more complex equipment and generates additional process steps, resulting in additional costs. In this work an alternative way of reducing the negative impact of subcooling on crystallization, which is based on the reduction of the metastable zone itself rather than on the bypassing it, has been investigated. The width of the metastable zone depends on the activation energy for nucleation which in turn depends on the interfacial surface tension between the melt and the surface of the crystallization element. It has been shown in this work that the activation energy for nucleation and so the supercooling in a xylene isomer mixture can be considerably reduced when replacing stainless steel by PTFE as a material for the crystallization surface. In follow‐up trials it was found that the crystallization surfaces do not need to be wholly covered by PTFE but that just small PTFE nucleation zones on steel surfaces have the same positive effect on the separation by crystallization. Applied in industrial equipment such nucleation zones might contribute to the cost optimization of commercial layer crystallization processes.     

Determination of Metastable Zone Width and Nucleation Induction Period of Palm Oil and its Olein/Stearin in Melting Layer Crystallization

Measurement methods of metastable zone width (MZW) and nucleation induction time for melting layer crystallization of palm oil (PO) and its olein/stearin (POL/PST) were established, and the effects of cooling rate (corresponding to various supercoolings) on MZWs and induction time for melting layer crystallization of PO, POL, and PST were determined. The results indicated that the MZW coherently rose with increasing cooling rates with respect to PO and POL, while it declined with higher cooling rates for PST. The induction period results demonstrated that the nucleation induction periods of PO, PST, and POL decreased with increasing supercoolings, and the lag time for nucleation negatively correlated to the melting point of oils at the same supercooling. These data could offer significant instruction in designing and controlling the melting layer crystallization process for palm oil.     

头孢他啶双股进料结晶工艺的研究

针对头孢他啶结晶产品聚结、晶习差、粒度分布不均匀等问题，设计了双股进料结晶工艺，并将结晶环境控制在介稳区，有效避免自发成核，操作简单，容易控制。采用单因素法研究了结晶液初始浓度、料液流加速率、搅拌速率、温度以及养晶时间对结晶产品收率、晶习及粒度分布的影响，确定了优化的工艺参数：结晶液初始浓度(溶质质量/溶剂质量) 0.33 g·g^-1,料液流加速率0.14 mL·min^-1,温度27℃,养晶时间60 min,搅拌速率为250 r·min^-1可以得到均匀的片状头孢他啶晶体，晶习完整，中值粒径达到184μm,径距为1.290,收率可以达到80%。     

超声波对甘氨酸溶析结晶过程的影响

以甘氨酸水溶液的丙酮溶析结晶为对象,探讨了超声波对结晶过程的影响. 在超声波作用下,结晶过程经历空泡形成、超声波诱导成核、二次成核多个阶段;在不同的阶段施加超声波,或在相同时刻引入超声波但持续不同的时间,都可能影响晶体的粒径大小和分布. 在自然均相成核点之前施加超声波并持续较短时间,使晶核以超声波诱导成核为主时,可获得较大颗粒的晶体;在接近均相成核点处施加超声波,将产生更多的晶核,使晶体平均粒径降低. 在晶体生长过程中继续使用超声波,因超声波的破碎效应,也将降低晶体的平均粒径.     

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.     

SAPO-34分子筛晶化机理及晶化动力学研究

对SAPO-34分子筛晶化过程中预相形成、诱导期内晶核生成、晶体生长和晶化过程的研究进行综述。SAPO-34分子筛晶化过程首先形成不稳定的层状预相结构,进而发展为具有有序排列晶格骨架的晶核。结晶热力学控制晶相结构,晶化动力学控制晶体成核和生长速率。影响晶化动力学的关键因素是温度和浓度,成核速率和晶体生长速率互相竞争控制晶粒大小。晶化过程的Si取代机理和Si分布影响分子筛酸性。晶化动力学研究结果表明,温度升高,结晶速率增加,成核时间缩短。     

头孢拉定双股进料结晶新工艺

针对头孢拉定反应结晶工艺,设计了双股进料结晶体系,将结晶环境控制在介稳区,有效避免自发成核,操作简单,容易控制。采用单因素法研究了结晶液初始浓度、料液流加速率、搅拌速率、结晶pH值范围、晶种添加量以及养晶时间对结晶产品收率、晶习及粒度分布的影响,确定了优化的工艺参数：结晶液初始浓度（溶质质量/溶剂质量）0.43 g/g,料液流加速率2 mL/min,pH值2.5~2.7,晶种添加量按公式计算,养晶时间60 min,搅拌速率为140 r/min可以得到均匀的棒状晶体,搅拌速率为70 r/min可以得到均匀的簇状聚结体,晶习完整,粒度分布均匀,收率可以达到92%。     

磷酸二氢铵结晶介稳区及诱导期的测定

采用激光测定装置研究了温度、降温速率、磷酸三丁酯（TBP）对磷酸二氢铵（ADP）的介稳区的影响,重点研究了其介稳区的变化规律,计算了不同条件下磷酸二氢铵的介稳区和表观成核级数。测定了磷酸二氢铵在磷酸三丁酯存在下的诱导期,并应用经典成核理论计算成核参数。研究结果表明：磷酸二氢铵的介稳区宽度在高温区狭窄而在低温区较宽,介稳区宽度随着降温速率的增大而变大,磷酸三丁酯的加入增大了介稳区、诱导期和成核参数。