Industrial Crystallization Processes Research Articles

Industrial Crystallization: A Vital Process for the Modern Chemical Industry

AbstractNo abstract.

Solvent Effects on Catechol Crystal Habits and Aspect Ratios: A Combination of Experiments and Molecular Dynamics Simulation Study

This work could help to better understand the solvent effects on crystal habits and aspect ratio changes at the molecular level, which provide some guidance for solvent selection in industrial crystallization processes. With the catechol crystal habits acquired using both experimental and simulation methods in isopropanol, methyl acetate and ethyl acetate, solvent effects on crystal morphology were explored based on the modified attachment energy model. Firstly, morphologically dominant crystal faces were obtained with the predicted crystal habit in vacuum. Then, modified attachment energies were calculated by the molecular dynamics simulation to modify the crystal shapes in a real solvent environment, and the simulation results were in agreement with the experimental ones. Meanwhile, the surface properties such as roughness and the diffusion coefficient were introduced to analyze the solvent adsorption behaviors and the radial distribution function curves were generated to distinguish diverse types of interactions like hydrogen bonds and van der Waals forces. Results show that the catechol crystal habits were affected by the combination of the attachment energy, surface structures and molecular interaction types. Moreover, the changing aspect ratios of catechol crystals are closely related to the existence of hydrogen bonds which contribute to growth inhibition on specific faces.

Improvement of an Industrial Crystallization Process: The Production of Virginiamycin

Virginiamycin is an antibiotic produced by Streptomyces virginiae. The recovery process involves a crystallization step (solvent evaporation and precipitation using an antisolvent). To systematical...

Quantitative Link between Secondary Nucleation and Mixing Hydrodynamics in Batch Cooling Crystallization: A New Approach in Process Development

Precise control of a crystallization process requires a clear understanding of nucleation kinetics. Interpreting secondary nucleation threshold (SNT) of a given crystallization process under optimized hydrodynamic conditions can highlight the impact of critical process variables on product particle size distribution (PSD). In this work, a new approach is proposed in industrial crystallization process development in which a quantitative link was developed between batch cooling crystallization and fluid turbulent shear stress (TSS). The experiments involve solution crystallization of paracetamol in isopropanol. A novel method was adopted in which a large single seed crystal of paracetamol was held stationary in an agitating reactor. Using particle imaging velocimetry, a constant TSS was obtained across different scales which resulted in a constant SNT because of crystal nuclei breeding. This led to better control over the crystallization process which eventually resulted in a consistent PSD, independent of ...

Secondary Nucleation of Sodium Chlorate: The Role of Initial Breeding

Secondary nucleation is the key mechanism behind the creation of new crystals in industrial crystallization processes. Sodium chlorate has widely been used throughout literature as a model compound...

FRACTAL ANALYSIS OF TEMPERATURE TIME SERIES FROM BATCH SUGARCANE CRYSTALLIZATION

Batch crystallization is an important process in many industries, for example, fine chemicals, foods, and pharmaceuticals. Monitoring of the main process variables is essential for process understanding, diagnosis, and for product quality control. It is known that temperature has a critical effect on crystallization. Temperature measurements from crystallization systems display fluctuations with apparently random and complex behavior. Fractal analysis of complex time series has received significant attention in the last few years due to its capability for extraction of hidden useful information of the underlying phenomena behind the time-series complexity. In this work, the potential of fractal analysis of time series for diagnosis of industrial crystallization processes is investigated using temperature measurements from a typical batch sugarcane crystallization system. The crystallizer was operated at different cooling profiles, finding that fractal index is directly related to crystal mean diameter dynamics. Thus, we establish that fractal analysis is a simple and robust alternative for the characterization of batch crystallization.

Unique influence of heating rate on the magnetic softness of Fe81.5Si0.5B4.5P11Cu0.5C2 nanocrystalline alloy

• A finely uniform nano-crystalline structure with α-Fe phase can be obtained after slow annealing. • Small α-Fe crystals precipitated from amorphous matrix by annealing contributes to a low coercivity of 4.8 A/m. • The nano-crystallized mechanism during slow-heating-annealing process is unusual and different with NANOMET. • The simplification of the crystallization process in industry by a one-step annealing. Fe 81.5 Si 0.5 B 4.5 P 11 Cu 0.5 C 2 nanocrystalline alloy with high Fe concentration possesses a finely uniform nanocrystalline structure and numerous α-Fe crystals with a mean grain size of ∼17 nm based on XRD patterns. Such crystals precipitated from the amorphous matrix. Favorable soft magnetic properties, small value of coercivity ( H c ) of ∼4.8 A/m, and high magnetic flux density ( B s ) of ∼1.53 T can be achieved by slow heat treatment (heating rate of ∼10 °C/min). In this case, one-step annealing at a low heating rate is truly antipodal to Fe–Si–B–P–Cu alloy. We analyzed the nanocrystallized mechanism during annealing with various heating rates in Fe 81.5 Si 0.5 B 4.5 P 11 Cu 0.5 C 2 alloy, which inevitably simplified the industrial crystallization process by one-step annealing at a low heating rate.

Study of equilibrium solution and thermodynamic models in correlation with solubility data of rivastigmine tartrate in (H2O + isopropanol), (H2O + ethanol), and (H2O + acetonitrile) binary solvent mixtures

Millions of people around the world have been suffering from Alzheimer’s disease (AD) everyday. Rivastigmine tartrate is a potential AD drug. A crystallization process can enhance purities of rivastigmine tartrate properly. Predictive models for solubilities of rivastigmine tartrate will improve subsequent industrial crystallization process design. In this work, the solubility of rivastigmine tartrate in (H2O + isopropanol), (H2O + ethanol), and (H2O + acetonitrile) binary solvent systems in the temperature range of 278.15–333.15 K under atmospheric pressure was measured and investigated by employing the analytical stirred-flask method. Binary solvent systems of rivastigmine tartrate overcame drawbacks of mono-solvent crystallization systems, such as high viscosity. Three thermodynamic models, including modified Apelblat equation, the general cosolvency model, and the Jouyban–Acree model, were employed to correlate with the obtained experimental solubility data. Moreover, the calculations of apparent thermodynamic properties of rivastigmine tartrate dissolution process involving the Gibbs free energy, enthalpy, and entropy were accomplished by using the van’t Hoff analysis. Among the three models, the modified Apelblat equation is the most suitable one for predicting the solubility behavior of rivastigmine tartrate in binary solvent systems. Based on the data from modified Apelblat equation, a crystallization process of (H2O + ethanol) binary solvent mixture was developed.

Transformation of microstructure and phase of disodium guanosine 5′-monophosphate: Thermodynamic perspectives

Abstract Microstructure and phase transformation of disodium guanosine 5′-monophosphate (5′-GMPNa 2 ) are extremely important for controlling the process and understanding the mechanism of crystallization. In this work, the thermodynamic properties of polymorphous 5′-GMPNa 2 especially the solubility were studied, the solubility results show that 5′-GMPNa 2 is more soluble in ethanol–water (E–W) than in isopropanol–water (I–W). The amorphous form of 5′-GMPNa 2 is more soluble than the crystalline form at the same mole fraction and temperature. Meanwhile, the crystalline forms and morphologies of the residual solids were characterized by PXRD and SEM. The results indicate that solid forms of 5′-GMPNa 2 transformed spontaneously from amorphous to crystalline when the ethanol proportion is ≥ 20%. In addition, increasing the pH facilitates the dissolution of 5′-GMPNa 2 and helps to maintain the crystalline form. The associated Gibbs free energy values were calculated to verify the trend of transformation from amorphous to crystalline 5′-GMPNa 2 . These results should help to guide the industrial crystallization process and to obtain the crystalline form of 5′-GMPNa 2 .

A Generic Polycarbonate Based Microfluidic Tool to Study Crystal Nucleation in Microdroplets

Crystal nucleation is important to control the product properties in industrial crystallization processes. To investigate crystallization phenomena, methods which rely on microscopic volumes have gained relevance over the last decade. Microfluidic devices are suitable for carrying out crystallization experiments based on a large set of individual droplets in the nanoliter range. In this work, we propose a simple method to manufacture such devices from polycarbonate as an alternative to conventional chips made of poly (dimethylsiloxane). The microfluidic device consists of two main functional parts: A T-junction for droplet generation and a section for storage and observation of up to 400 individual droplets. Using these manufactured devices, it is easy to produce and store highly monodisperse droplets of substances that require either a hydrophilic or hydrophobic surface of the microchannel. Since crystal nucleation is a stochastic process which depends on the sample volume, a reproducible droplet volume is of great importance for crystallization experiments. The versatile applicability of the manufactured devices is demonstrated for substances which are used in different crystallization applications, for example, solution crystallization (aqueous potassium nitrate solution) and melt crystallization (ethylene glycol distearate). Finally, we demonstrate that the manufactured microfluidic devices in our experimental setup can be used to conduct crystal nucleation measurements. Based on these measurements we discuss our results with respect to state-of-the-art nucleation models.

Theoretical estimation of mass transfer coefficients in solution crystallization

Generally, diffusion through film thickness is used for correlating data in the industrial crystallization processes. Furthermore, mass transfer is an important phenomenon in most chemical processes and studies involving determination of mass transfer coefficients are necessary for a better estimation of equipment performance. Solid-liquid mass transfer coefficients in stirred systems have received substantial attention in the past due to their practical applications. In contrast, little information is available on solid-liquid mass transfer in crystallization systems, despite the importance of crystallization. In this work, an expression for the mass transfer coefficients in solution crystallization has been developed based on the Stefan problem formulation. The model is able to predict a finite mass transfer coefficient when the layer thickness vanishes. The obtained mass transfer coefficients agree with previously reported experimental data. Furthermore, it is found that the stagnant film for mass transfer has oscillatory behavior, and this behavior is a function of residence time.

The solubility of cefquinome sulfate in pure and mixed solvents

Solid-liquid equilibrium data of cefquinome sulfate is important to develop industrial crystallization processes for cefquinome sulfate. The solubilities of cefquinome sulfate in five pure solvents (methanol, ethanol, ethylene glycol, acetic acid and water) from 277.15 to 305.15 K and in a binary acetone-water solvent from 278.15 to 293.15 K were measured at atmospheric pressure. The pure-solvent solubility data was correlated to the modified Apelblat and Van’t Hoff equations whereas the mixed-solvent system data was correlated to the modified Apelblat, Van’t Hoff, CNIBS/R-K and Jouyban- Acree models. It was found that the solubilities of cefquinome sulfate in all tested solvents decreased with the increasing of temperature. In addition, the thermodynamic properties of the dissolution processes, including standard Gibbs free energy, enthalpy and entropy changes, were calculated using the Van’t Hoff equation. It was found that the dissolution of cefquinome sulfate is exothermic.

Partial Blockage of the Reversible Solid‐Solid Transition of Strontium Succinate

AbstractStrontium succinate, an active pharmaceutical ingredient against osteoporosis, exhibits two polymorphs related by a reversible order‐disorder transformation at about 50 °C. However, during the industrial crystallization process, the transition from the high‐temperature form towards the low‐temperature form was partially inhibited, leading to a mixture of phases at room temperature. The stressful character of the industrial process as demonstrated by in situ X‐ray diffraction and Raman analyses led to defects, constraints, and a coarse mosaicity within crystals. Moreover, thermogravimetric analyses revealed that a non‐negligible amount of water was trapped inside the crystalline solid. The combination of these two factors (stressful crystallization and trapped water) could be at the origin of the partial blockage of the transition.

バッチ冷却晶析プロセスのモデルベース精密温度制御設計ベンチマーク

バッチ冷却晶析プロセスのモデルベース精密温度制御設計ベンチマーク

Simulation of an industrial sodium chloride (NaCl) crystallization process and applications

Crystallization from solution is important industrially because of the variety of materials that are marketed in the crystalline form. To improve the teaching-learning process of this Unit Operation, in this work, performed as a Degree Final Project in Chemical Engineering studies, a simulation program of crystallization has been developed using data of an industrial NaCl crystallization process. The objective was the use of computational tools to simulate and optimize the crystallization, enabling a deeper insight into the crystallization operation and into the use of computational tools.

Effect of Particle Shape on Inline Particle Size Measurement Techniques

AbstractThe influence of the particle shape on the results of different measuring techniques was investigated. Considered were single‐frequency ultrasound technique, 3D optical reflectance measurement (advanced particle analyzing system with multi capture signal technology), and focused‐beam reflectance measurement probes as techniques which are usable inline and in suspension density ranges usually present in industrial crystallization processes. Advantages and shortcomings of these techniques are compared and discussed.

Solubility of Cefotaxime Sodium in Ethanol + Water Mixtures under Acetic Acid Conditions

Aimed at exploring the influence of acetic acid on crystallization thermodynamics of cefotaxime sodium (CTX), the solubility of CTX in ethanol + water mixtures under acetic acid conditions at various temperatures are measured by a gravimetrical method. Different from the solubility curve when acetic acid is absent, the solubility curves of CTX under acetic acid conditions have a maximum value. The maximum solubility drifts as temperature varies, which is related to the dielectric constants of solvent mixtures. A combination of the Jouyban–Acree model and Apelblat equation is used to correlate the solubility data, and the correlation precision is improved when compared with that of the Jouyban–Acree model. By using the Wilson model, the activity coefficients of CTX and the mixing Gibbs free energies, enthalpies, and entropies of CTX solution are also predicted. The data presented in this study explain why the crystallization of CTX in ethanol + water mixtures is difficult and are helpful for guiding the industrial reaction and crystallization process of CTX.

Single-Frequency Ultrasonic Crystallization Monitoring (UCM): Innovative Technique for In-Line Analyzing of Industrial Crystallization Processes

The development, principles, and application of the single-frequency, ultrasonic crystallization monitoring (UCM) technique is discussed. It is shown that the three most important process parameters to control industrial crystallization processes (mean crystal size, suspension density, and liquid concentration) can be monitored simultaneously in-line by means of only one measuring technique holding two sensors. A proof of concept is presented that clearly shows the feasibility and applicability of the UCM method. In demarcation to alternative PAT in the field of industrial crystallization, advantages, potentials, and limits are outlined and discussed with particular reference to the applicability of the technology and the material systems together with the transferability to other substances as well as the scale-up ability of the underlying mathematical model. Additionally, the reliability of the UCM technique is validated by comparing the results with established and commercially available PAT for the solid phase.

Polymorphism Control through a Single Nucleation Event

Recently, we identified that the single nucleus mechanism, in which all crystals in the suspension originate from the same parent single crystal, might occur more generally than is currently recognized, even in larger volumes. This has important implications for the control of industrial crystallization processes of polymorphic compounds. In this paper, we used polymorphism as a tool to validate this single nucleus mechanism. Isonicotinamide (INA) crystallizes as form II in ethanol solutions, form I in nitromethane, and form IV in nitrobenzene solutions. The metastable form I and form IV, furthermore, only very slowly transform to the stable form II in solvent mixtures of ethanol–nitromethane and ethanol–nitrobenzene. We performed multiple crystallization experiments in solvent mixtures of ethanol–nitromethane and ethanol–nitrobenzene which all resulted in the formation of either pure form I or pure form II and either pure form II or pure form IV, respectively. In ethyl acetate, 4-hydroxyacetophenone (4HAP) crystallizes as form II at lower concentrations and as form I at higher concentrations. Crystallization of 4HAP as a function of concentration on a 3 mL scale results in either pure form I or pure form II. This can be well explained by the single nucleus mechanism. In terms of polymorphism, the control can be achieved by controlling the primary nucleation event that leads to the single crystal, which in turn defines the crystal form of the secondary nuclei. Seeding approaches using only a single crystal would then lead to the avoidance of primary nucleation and thus control over the polymorph obtained.

Crystallization in Lactose Refining—A Review

In the dairy industry, crystallization is an important separation process used in the refining of lactose from whey solutions. In the refining operation, lactose crystals are separated from the whey solution through nucleation, growth, and/or aggregation. The rate of crystallization is determined by the combined effect of crystallizer design, processing parameters, and impurities on the kinetics of the process. This review summarizes studies on lactose crystallization, including the mechanism, theory of crystallization, and the impact of various factors affecting the crystallization kinetics. In addition, an overview of the industrial crystallization operation highlights the problems faced by the lactose manufacturer. The approaches that are beneficial to the lactose manufacturer for process optimization or improvement are summarized in this review. Over the years, much knowledge has been acquired through extensive research. However, the industrial crystallization process is still far from optimized. Therefore, future effort should focus on transferring the new knowledge and technology to the dairy industry.