阿司匹林结晶过程的在线分析

晶体的颗粒尺寸分布和形状是结晶产品的两个关键质量指标,不仅影响结晶产品的性质,还影响下游的过滤、干燥及运输存储等过程。利用超声粒度分析仪、衰减全反射傅里叶红外光谱仪、浊度仪与二维成像系统等分析仪器在线测量了不同搅拌速率和不同降温速率下阿司匹林乙醇溶液结晶过程中温度、浓度、颗粒尺寸分布和形状的变化情况。实验结果表明：较低的降温速率或者较大的搅拌速率条件下得到含有大量细晶的阿司匹林结晶产品;较高的降温速率下得到长宽比较大的阿司匹林结晶产品。调节降温速率和搅拌速率是一种有效控制阿司匹林结晶产品尺寸分布与形状的方法。     

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。     

Determination of potash crystallization kinetics in a laboratory-scale continuous cooling crystallizer

Crystallization kinetics of KCl in a 21.8L continuous mixed-suspension-mixed-product-removal (CMSMPR) potash cooling crystallizer are determined using the method of s-plane analysis (Tavare, 1986). Feed saturated in refined potash, nearly saturated in NaCl and containing 0.75 g of MgSO₄ per 100 g of water is cooled from 54°C to 38°C by two concentric cooling coils. The crystallizer is brought to steady-state and then perturbed by a change in the crysallizer temperature from 38°C to 32°C. Samples are withdrawn every 15 minutes by means of a specially devised sample trap which permits representative sample removal. Samples are sized using sieve-analysis. The crystallization kinetics are correlated as B° = 49,618 G^0,982.     

The potential of current high‐resolution imaging‐based particle size distribution measurements for crystallization monitoring

High‐speed, in situ video microscopy is a promising technology for measuring critical solid‐phase properties in suspension crystallization processes. This paper demonstrates the feasibility of high‐resolution, video‐imaging‐based particle size distribution (PSD) measurement by applying image analysis and statistical estimation tools to images from a simulated batch crystallization of an industrial photochemical. The results also demonstrate the ability to monitor important quality parameters, such as the ratio of nuclei mass to seed mass, that cannot be monitored by conventional technologies. General recommendations are given for achieving appropriate sampling conditions to enable effective imaging‐based PSD measurement. © 2009 American Institute of Chemical Engineers AIChE J, 2009     

凝胶对结晶过程影响的研究进展

相比于传统的溶液相结晶,凝胶用作结晶介质时,由于能抑制对流和减慢溶质分子的扩散,除了能提供较大的过饱和度且不会导致爆发成核,以及使溶质分子在生长面上连续地生长之外,还可以通过设计特定的凝胶剂为溶质分子提供模板或者活性成核位点,这使得凝胶相结晶成为了一种有效的结晶控制手段,引起了研究人员的广泛关注。综述了高分子凝胶、超分子凝胶以及无机凝胶如何有效地控制结晶成核和生长的速度,调控晶型、晶习和晶体粒度,简单介绍了微凝胶在溶液相结晶中的作用,以及凝胶相结晶未来的发展趋势。     

反应结晶制备碳酸锂的粒度及形貌控制

碳酸锂的粒度及形貌决定其性能和应用。通过考察反应结晶温度、进料速率、晶种用量和搅拌速率对碳酸锂产品平均粒径的影响以及添加剂的用量对产品形貌的影响,提供了一种经过优化的制备碳酸锂的反应结晶工艺。通过正交实验确定了反应结晶制备碳酸锂的最佳实验条件：200 mL质量浓度为90 g/L的氯化锂溶液一次性加入反应结晶器内,质量浓度为260 g/L的碳酸钠溶液的加料速率为0.5 mL/min,晶种用量为2%（占碳酸锂理论产量的分数）,搅拌速率为400 r/min,反应温度为80 ℃,添加剂六偏磷酸钠用量为2%（占碳酸锂理论产量的分数）。在此条件下制得的碳酸锂为平均粒径为132 μm、变异系数为51.53%的密实球形产品。研究表明,反应温度对晶体粒度的影响最大,添加剂对晶体的粒度和形貌起到调控作用。     

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。     

Inverse phase suspension polymerization of acrylamide in a batch oscillatory baffled reactor

We report, for the first time, our experimental investigation of inverse phase suspension polymerization of acrylamide in a batch oscillatory baffled reactor. In such a reactor, the oscillatory motion is achieved by moving a set of orifice baffles up and down the column at the top of the reactor. The effects of both operational and design parameters on the mean particle size and size distribution of polymer beads were investigated, including oscillation amplitude, oscillation frequency, baffle spacing, baffle free area, and monomer addition time. The experimental results indicated that the mean particle size and size distribution of the polymer beads depended predominantly on the product of oscillation frequency and amplitude, i.e., the oscillation velocity. The size distributions are narrow and of essentially a Gaussian distribution. The level of fines produced is consistently less than 1% for all 100 experiments performed. We demonstrated that the mean particle size and size distribution in an oscillatory baffled reactor can be controlled precisely by simply selecting the appropriate oscillation velocity. The effect of the baffle spacing on the mean particle size is much less compared with that of the baffle free area. The monomer injection time has a noticeable influence on the mean particle size, but the rate of change is relatively small. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 76: 1669–1676, 2000     

氢氧化锂连续冷冻结晶脱硝生产工艺与设备介绍

氢氧化锂冷冻结晶脱硝最早采用的是间歇生产工艺和设备。采用间歇生产工艺和设备,氢氧化锂冷冻母液中硫酸根等杂质含量较高,且芒硝晶体附液量大,锂损失多。介绍了氢氧化锂连续冷冻结晶脱硝生产工艺与设备。通过采用连续生产工艺和设备,使氢氧化锂冷冻母液中硫酸根的质量浓度由45~50 g/L降低到35~40 g/L,芒硝晶体附液质量分数由10%左右降低到5%左右,降低了后续氢氧化锂生产的能耗,提高了锂的回收率。     

Separation of conglomerate forming enantiomers using a novel continuous preferential crystallization process

Providing enantiomerically pure products is of key importance in the fine chemicals, food, and pharmaceutical industries. A continuous preferential crystallization process is presented that allows the separation of conglomerate forming enantiomers in a stable, robust, and flexible way. This is achieved by coupling two continuous crystallizers by exchanging their clear liquid phases. Each crystallizer is connected to a suspension mill responsible for in situ seed generation through particle breakage. The dynamic and steady‐state behavior of this process is extensively analyzed for racemic feed streams through process simulations, and parameter regions, which yield pure enantiomers in both crystallizers, are identified. For enriched feed streams, it is further shown when this novel flow sheet is capable of outperforming an ideal batch process in terms of solvent consumption per unit mass of desired enantiopure product produced. © 2015 American Institute of Chemical Engineers AIChE J, 61: 2810–2823, 2015     

Optimization and control of crystal shape and size in protein crystallization process

Large molecule protein crystals have shown significant benefits in the delivery of biopharmaceuticals to achieve high stability, high concentration of active pharmaceutical ingredients (API), and controlled release of API. However, among the about 150 biopharmaceuticals on the market by 2004, only insulin has been marketed in crystalline form. A major technological challenge is that protein crystallization has a very complicated environment and is affected by many factors. There is currently a lack of knowledge on large scale production of protein crystals. In contrast to the majority of previous work on protein crystallization that was centered on single crystal scale, the current research is focused on computational study of protein crystallization at process scale, investigating the growth behavior of a population of crystals in a crystallizer. Using a newly developed morphological population balance model that can simulate the multidimensional size distributions of a population of crystals, known as shape distribution, an optimization technique is applied to optimize the growth of individual faces with the aim of obtaining desired crystal shape and size distributions. Using a target shape as the objective function, optimal temperature and supersaturation profiles leading to the desired crystal shape were derived. Genetic algorithm was investigated and found to be an effective optimization technique for the current application. Since tracking an optimum temperature or supersaturation trajectory can be easily implemented by manipulating the coolant flowrate in the reactor jacket, the methodology provides a feasible closed-loop mechanism for protein crystal shape tailoring and control.     

Application of ultrasound for start‐up of evaporative batch crystallization of ammonium sulfate in a 75‐L crystallizer

A positive effect of ultrasound on crystallization has been shown for many applications especially on small scale. Predictable scale‐up of sonocrystallization is a challenge due to the inherent dependency of ultrasound on scale. The presented research discusses the experimental application of ultrasound to induce nucleation at low supersaturation for start‐up of evaporative batch‐wise crystallization of ammonium sulfate in a 75‐L draft tube (DT) crystallizer. A comparison is made with a conventional start‐up procedure using primary nucleation or seeding. Ultrasound is applied in two geometrically different vessels of 1.2‐L connected to a 75‐L DT crystallizer. Application of ultrasound for start‐up of a 75‐L DT crystallizer shows that an optimum amount of ground seeds is better capable to suppress nucleation. A challenge for future research is to improve the efficiency of ultrasound to produce a large number of nuclei for start‐up of batch crystallization at larger scale. © 2011 American Institute of Chemical Engineers AIChE J, 2011     

Preparation of magnetic poly(vinyl alcohol) (PVA) materials by in situ synthesis of magnetite in a PVA matrix

An easy method for manufacturing homogeneous inorganic–organic materials, especially composite fibers, was obtained by the in situ synthesis of inorganic particles within polymer matrices. In this article, nanosized magnetite particles were synthesized in situ within poly(vinyl alcohol) (PVA) solutions by precipitating Fe²⁺ ions or a mixture of Fe²⁺ and Fe³⁺ ions with NaOH solution. As a result, magnetite particles with an average diameter of 20 nm were obtained homogeneously within the solutions because of the tridimensional structure and chelating capacities of PVA. Transparent films were obtained by a casting method, and six kinds of magnetic PVA fibers were also prepared by a wet‐spinning method from the solutions containing magnetite nanoparticles. The mechanical properties and the saturation magnetization of the fibers were measured. These fibers, which contain iron ions with a maximum content of 17.63 wt %, can be successfully fabricated by the in situ synthesis and they exhibit excellent magnetization properties (i.e., the largest saturation magnetization is 13.38 emu/g). © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1239–1247, 2003     

分散剂在碳酸钙研磨中的应用

碳酸钙研磨中加入分散剂,既可得到高固含量、低粘度的浆料,又可以降低能耗,节约成本。本文介绍了分散剂在碳酸钙研磨中所起的作用,并分析了研磨碳酸钙的两个主要特性及其相互关系。     

Link between bubbling and segregation patterns in gas‐fluidized beds with continuous size distributions

Experiments involving a bubbling, gas‐fluidized bed with Gaussian and lognormal particle‐size distributions (PSDs) of Geldart Group B particles have been carried out, with a focus on bubble measurements. Previous work in the same systems indicated the degree of axial species segregation varies non‐monotonically with respect to the width of lognormal distributions. Given the widely accepted view of bubbles as “mixing agents,” the initial expectation was that bubble characteristics would be similarly non‐monotonic. Surprisingly, results show that measured bubble parameters (frequency, velocity, and chord length) increase monotonically with increasing width for all PSDs investigated. Closer inspection reveals a bubble‐less bottom region for the segregated systems, despite the bed being fully fluidized. More specifically, results indicate that, the larger the bubble‐less layer is, the more segregated the system becomes. The direct comparison between bubbling and segregation patterns performed provides a more complete physical picture of the link between the two phenomena. © 2011 American Institute of Chemical Engineers AIChE J, 2011