Preparative Protein Crystallization

Preparative protein crystallization can possibly replace one or more chromatographic steps in downstream processing. The development of such crystallization processes is demanding: first, promising principal crystallization conditions must be identified; second, details about the process must be defined; and third, the crystals have to be separated from the mother liquor without putting harm of their crystalline integrity. State‐of‐the‐art about these three steps is developing fast by (i) employing new screening methods which are based on fundamental understanding of the interaction of the protein molecules, (ii) application of existing concepts of technical bulk crystallization of small molecules to preparative protein crystallization, and (iii) making available specific gentle separation machinery.     

聚甲醛及其纤维的热分析研究

用Ozawa法和Mo法对聚甲醛(POM)的非等温结晶动力学进行研究。采用双螺杆纺丝机熔融纺得POM初生纤维,再用水浴拉伸方法制得POM纤维,研究拉伸倍数、水浴温度对POM纤维结晶性能的影响。结果表明:在不同的降温速率下,随着降温速率的提高,POM结晶峰峰值温度降低,半结晶时间缩短,结晶速率加快;采用Mo法研究POM的非等温结晶过程比较理想,而Ozawa法不适用;水浴拉伸有利于纤维的结晶,而随着水浴温度的提高,POM纤维的结晶度提高。     

Significantly enhanced energy‐storage density in the strontium barium niobate‐based/titanate‐based glass‐ceramics

Two‐step crystallization process was employed to improve microstructure and energy‐storage density of the strontium barium niobate‐based/titanate‐based glass‐ceramics. By using two‐step crystallization process, the optimum nucleation temperature was obtained to improve dielectric breakdown strength. Compared to the breakdown strength by one‐step crystallization process, the breakdown strength by two‐step crystallization process is increased about 1.89 times with the optimum nucleation temperature. Energy‐storage density of 7.73 ± 0.26 J/cm³ is significantly improved by two‐step crystallization process and is about 2.9 times of 2.63 ± 0.17 J/cm³ by one‐step crystallization process. This result is attributed to the homogeneous nucleation improving the microstructures of glass‐ceramics. Identification and quantification of crystalline phases by using Rietveld refinement reveals the difference of dielectric constants for one‐step and two‐step crystallization processes.     

Process Optimization and Profitability Calculations

Beginning with a typical example of cost control, key parameters are suggested in order to judge the effect of optimization efforts on costs. Each optimization process automatically has some effect on productivity and production figures; however, the safety factor – expressed in terms of shading and redyeing operations – must not be left out of consideration. The influence of these factors on the costs as well as on the production figures is shown. By means of these factors the dyeing processes optimized for the machines used up to now are compared with the processes for new machines (high performance) as far as costs are concerned. The prerequisites which must be satisfied when optimizing dyeing processes in order to achieve low costs are emphasized. Furthermore, non-optimized processes on existing machines are compared with the so-called rapid-dyeing processes.     

Antisolvent crystallization: Model identification, experimental validation and dynamic simulation

This paper is concerned with the development, simulation and experimental validation of a detailed antisolvent crystallization model. A population balance approach is adopted to describe the dynamic change of particle size in crystallization processes under the effect of antisolvent addition. Maximum likelihood method is used to identify the nucleation and growth kinetic models using data derived from controlled experiments. The model is then validated experimentally under a new solvent feedrate profile and showed to be in good agreement. The resulting model is directly exploited to understand antisolvent crystallization behavior under varying antisolvent feeding profiles. More significantly, the model is proposed for the subsequent step of model-based optimization to readily develop optimal antisolvent feeding recipes attractive for pharmaceutical and chemicals crystallization operations.     

Trockene Mehrfachfraktionierung — Ein kostengünstiges Umwandlungsverfahren

Dry Multiple Fractionation – A Low Cost Modification Process Originally regarded as unaccurate or inconsistent, dry fractionation technology saw its development boosted by that of palm oil. Since then, it hasn't stopped improving and it is now considered as an important step in edible oil and fat refineries, margarine plants and even in dairies. This paper updates the state of the technology developped by Tirtiaux, including both crystallization and separation sections. The theory of crystallization is also reviewed with examples taken from palmoil, milkfat, tallow, hardened fish and soyabeanoil etc. Finally, emphasis is made on the lower cost when replacing hydrogenation with a process involving multiple fractionation.     

Zur optimierung der Polymerfraktionierung auf der Grundlage von Lösungsgleichgewichten in Lösungsmittel-Fällungsmittel-Systemen

The phase separation behavior of dilute polydisperse polymer solutions primarily depends on the partial concentration of each polymer component. So the equilibrium data obtained by turbidimetric titration with “calibration” fractions and their mixtures can be used for the construction of a solubility diagram (Claesson-diagram) which generally allows to describe fractionation processes. It can be shown that the characteristic features of precipitation fractionations can well be derived from the solubility diagram. This diagram then offers the possibility for a complete discussion of parameter variation (concentration, step of γ-variation, process-scheme, temperature, solvent/nonsolvent-system) on the efficiency of a fractionation step. On one hand these results correspond – as for the concentration variation – to well known experimentell experiences. On the other hand it is possible for the first time to give definite predictions for the influence of temperature and the solvent/nonsolvent system. The temperature selection can be shown to be inconsiderable for the separation effect. The usual characterization of solvents and nonsolvents as “good” or “poor” is absolutely insufficient, if not misleading, for there is no connection between these properties and the shape of the solubility diagram. Based on the analysis of the single parameters the optimum conditions for the preparation of narrow preparation of narrow precipitation fractions can be derived.     

Reducing the mean size of API crystals by continuous manufacturing with product classification and recycle

A continuous crystallization process is proposed that can produce active pharmaceutical ingredients with a small mean size and narrow distribution. The process flowsheet consists of a new product classifier configuration where the large crystals from the classifier are recycled to a dissolver along with the mother liquor from the filter. Crystallizer stability is explored and regions of sustained limit cycles are identified for the proposed kinetic models. Most industrial crystallizers are operated at low supersaturation; however, with this methodology the continuous crystallizer must be operated at high levels of supersaturation to promote nucleation and increase the number of small crystals in order to maintain a fixed desired production rate. The design and operating strategies presented can be implemented by simple modifications to most conventional continuous crystallization processes. This particle micronization technique may offer significant cost savings over other size reduction methods that utilize mechanical means.     

强化碳酸化固定CO2反应过程分析与机理探讨

以乙酸为媒质的间接碳酸化固定CO₂工艺路线,主要包括乙酸媒质浸出钙镁离子形成乙酸盐,碳酸化过程乙酸盐转化成碳酸钙产品,同时生成乙酸媒质循环利用。然而在碳酸化过程碳酸化反应结晶转化率低,从而制约该工艺路线的进一步工业应用。采用有机溶剂TBP萃取乙酸与碳酸钙结晶过程耦合,可以实现碳酸化反应结晶转化率的大幅度提高。通过实验研究了体系达到平衡时初始乙酸钙浓度对碳酸化过程的影响,结果表明碳酸化反应结晶转化率都在40%以上,比文献报道的高出一倍。基于强化碳酸化过程的机理分析,初步进行了耦合过程的热力学平衡计算。研究结果表明：由于有机溶剂TBP的加入,体系的酸性条件得到改善,有利于碳酸钙结晶析出;然而高浓度条件下,乙酸根与钙离子之间强烈的相互作用成为进一步提高碳酸化反应结晶转化率的主要障碍。     

Feststoffbildung durch Kristallisation und Fällung

Formation of solids by crystallization and precipitation. Formation of solids from solutions can take place by crystallization or precipitation. The principal factor is the relationship between solubility and supersaturation. In crystallization, the solubility of the crystallising substance is so high that the formation of solids occurs largely in the metastable zone in the immediate vicinity of the solubility limits. Crystal growth and nucleation are functions of supersaturation. If a high supersaturation is required at low substance-specific growth rates for an adequate crystal growth, high nucleation rates and hence small crystals will result. On this basis, the authors present information for the specific design of crystallization processes. In contrast, the solubility of the precipitated product must be very low for precipitation. Direct crystal formation is possible only for substance systems of high solubility. As a rule, however, the precipitated substance is so insoluble that solids are formed via amorphous intermediates. The results of a large number of experiments show the influence of various parameters of the precipitation process on the filtrability of the precipitated product.     

Grenzflächeneffekte bei der Fest/Flüssig-Trennung

Interfacial effects in solid-liquid separations. In this survey the nature and origin of interfacial effects in finely dispersed suspensions are explained. Their influence upon conventional process steps in solid-liquid separation is discussed. Examples of technical applications of electrokinetic effects in separation processes are reviewed. The state-of-the-art in solid-liquid separation is characterized by qualitative knowledge about the effects of interfacial phenomena and empirically based electrokinetic separation processes. Knowledge is still insufficient for quantitative calculation of real processes or proper design of technical equipment. The field between interfacial physics, physical chemistry of surfaces and chemical or process engineering is interesting and far-reaching. If the preceding step of particle generation by precipitation or crystallization is included in a comprehensive research program, a better understanding and a systematic use or prediction of electrokinetic interfacial phenomena in solid-liquid systems can be expected.     

Physicochemical Parameters of Nitramines Influencing Shock Sensitivity

TNO Prins Maurits Laboratory has actively followed and contributed to the research on the development of insensitive munitions (IM). One of the initial research topics at TNO focused on the improvement of the shape of RDX crystals and its relation to the shock sensitivity. The variation of crystal shape has been studied by crystallization from different solvents and/or by post‐treatment of the crystals. The role of the mean particle size on shock sensitivity was also included in these analyses. The decrease in shock sensitivity is even more pronounced when controlling the internal quality of crystals. In the meantime research has shifted to other energetic materials as well – in particular HMX and CL‐20 – in this way revealing step by step the important physicochemical parameters which play a role in determining the shock sensitivity of formulations containing these types of nitramines. Various characterization techniques, to determine the internal and external quality of crystals will be discussed, and their relation to shock sensitivity in PBXs will be shown. Two different grades of I‐RDX have been subjected to different characterization tests. The objective is to gain more understanding about which of the physicochemical parameters enables one to discriminate between a reduced sensitivity RDX and normal RDX.     

Efficient preparation of substituted 5,6,7,8-tetrahydroquinolines and octahydroacridine derivatives

The reaction of the enamine 4 with different β-amino ketone hydrochlorides 3a – e affords the diketones 5a – e which can be cyclized to the corresponding mono- and disubstituted tetrahydroquinolines 6a – e . Furthermore the preparation of the octahydroacridines 8f and 8g by using a straightforward multi step sequence is described.     

Auslegungsgrundlagen von Kristallisatoren

Design principles of crystallizers . Numerous processes in the chemical, heavy chemical, and food industries involve a crystallization step. Most commonly, a crystalline product is to be obtained from solution. Crystallizers are designed with the aim of cost-effective isolation of the product in the desired quality, i.e. in the necessary particle size and purity, while minimizing encrustation.     

PET卷绕丝预取向对后加工拉伸性能和纤维结构、性能的影响

应用ＷＡＸＤ、ＤＳＣ、声速法、密度法、双折射等，讨论了在提高卷绕丝纺速与喷丝头拉伸比后，纤维的预取向增大，对其在后加工中的拉伸性能及其结构、性能的影响。结果表明，预取向高的卷绕丝，在后加工一道拉伸过程中，除了非晶取向外，还产生了“应变结晶”（取向诱导结晶）。由此造成晶态、取向非晶态结构差异大，而导致强度、伸长不匀率上升，产生毛丝、缠辊，但可得到高强度纤维。调整拉伸浴槽温度、拉伸速度，可改变卷绕丝的拉伸性能。     

降膜结晶法在高纯硫酸制备中的应用

现行高纯硫酸生产工艺复杂、能耗大且成本高。降膜结晶法具有绿色环保、节能和工艺简单的优势。采用减压蒸馏、降膜结晶工艺对工业硫酸进行净化提纯,可以制备出达到BV-Ⅲ级的高纯硫酸。最佳工艺条件：1）通过减压蒸馏将工业硫酸中的大部分杂质除去;2）通过降膜结晶获得粗晶体,结晶条件为初始结晶温度-5 ℃、降温步长每10 min降温0.6 ℃、结晶时间80 min、料液流量20 mL/min;3）对粗晶体进行发汗提纯,发汗条件为发汗终温 6 ℃、升温速度3 ℃/h、升温方式每10 min升温0.5 ℃。该工艺在高纯硫酸的制备方面有着广阔的应用前景。     

Positron Emission Particle Tracking for Liquid-Solid Mixing in Stirred Tanks

Mixing in stirred tanks is vital to a wide range of industrial processes, typically requiring solids to be fully suspended and evenly distributed. The quality of suspension and mixing is typically measured visually. Such measurements are thus subject to human interpretation and can only feasibly be conducted in transparent systems – an uncommon condition in industrial systems. Visual measurements of homogeneity must also infer full 3D distributions of particles solely from the observation of a limited section thereof. This work details methods by which a system's homogeneity and state of suspension may be measured and quantified with no human interpretation, which can extract information from opaque systems and consider full 3D data acquired throughout the interior of a given system.     

Concomitant crystallization for in situ encapsulation of organic materials

Concomitant crystallization leads to process intensification through the synergistic combination of the partial processes of particle formation and encapsulation within a single process step. Both cooling and electrospray crystallization in multi-component solutions were used to create (sub-)micron sized particles of different crystalline materials. Concentrations were varied to control core and shell material. Depending on the relative initial concentrations used, concomitant electrospray crystallization of isonicotinamide and caffeine leads to encapsulated particles. Only limited encapsulation was achieved during concomitant cooling crystallization. Concomitant cooling crystallization of cyclotrimethylenetrinitramine (RDX)–2,4,6-trinitrotoluene (TNT) resulted in separate RDX and TNT particles. Using electrospray crystallization, spherical nano-particles were produced, for which the component distribution within the particles could not be determined. Whereas crystallization from bulk solvent starts with a nucleus that grows gradually outward, whereby heterogeneous growth of a coating material on this core particle is not guaranteed, it appears that crystallization from evaporating solvent droplets starts at the surface of the droplets, and moves gradually inward. The resulting RDX–TNT powders have been tested for impact and friction sensitivity. The impact sensitivity has decreased compared to the raw materials, and the friction sensitivity did not change.     

Waschverfahren partikulär‐disperser Systeme – Verfahrensspektrum und Aspekte der Verfahrensauswahl

Washing of Disperse Solid Systems – Existing Washing Processes and Guidelines for Choosing the Appropriate Washing Procedure Washing of disperse solid systems is a widely used and complex operation. Since the washing‐step is mostly integrated into other process operations, it is subject to numerous demands, which exceed the primary demands like a good separation result and a low specific wash liquid demand. Because of the phenomenology and limits of different washing procedures it is difficult to choose an appropriate washing process. Additionally, the acting transport mechanisms of some washing procedures are not yet sufficiently understood. This work shows a broad overview over the existing washing processes, the numerous parameters and the demands they have to fulfill. A categorization of washing procedures as well as a classification of the processes concerning their macroscopic transport phenomena are the base for a broad decision chart which compares and evaluates existing washing processes and shows their individual limits. The work can be seen as a rough guideline for choosing the appropriate washing procedure.