Effect of seeded surface area on crystal size distribution in glycine batch cooling crystallization: a seeding methodology

In batch cooling crystallization, if the seeding process is not carefully carried out, the crystal size distribution (CSD) is dispersed. The aim of this work is to determine the optimal conditions for seeding operations. Results show that the CSD is controlled if the seed surface area reaches a specific value called critical surface S_c. Nevertheless, S_c is not the only parameter to be considered. The mean crystal size of the product obtained actually depends on the size of the seeds used because of the growth rate distribution. In fact, seeds behave differently according to their crystal sizes, which accounts for the difference in crystal growth rates. Rules are proposed for seeding with the view to obtain a uni-modal CSD and a final product size predefined by the seed crystals.     

Efficient solution of a batch crystallization model with fines dissolution

In this paper, an efficient and accurate numerical method is proposed for solving a batch crystallization model with fines dissolution. The dissolution of small crystals (fines dissolution) is useful for improving the quality of a product. This effectively shifts the crystal size distribution (CSD) towards larger crystal sizes and often makes the distribution narrower. The growth rate can be size-dependent and a time-delay in the dissolution unit is also incorporated in the model. The proposed method has two parts. In the first part, a coupled system of ordinary differential equations (ODEs) for moments and solute mass is numerically solved in the time domain of interest. These discrete values are used to get growth and nucleation rates in the same time domain. In the second part, the discrete growth and nucleation rates along with the initial CSD are used to construct the final CSD. The analytical expression for CSD is obtained by applying the method of characteristics and Duhamel's principle on the given population balance model (PBM). A Gaussian quadrature method, based on orthogonal polynomials, is used for approximating integrals in the ODE-system of moments and solute mass. The efficiency and accuracy of the proposed numerical method is validated by a numerical test problem.     

Morphology analysis of magnesium hydroxide prepared by magnesium oxide hydration within seawater

In order to investigate the microstructure of magnesium oxide hydration product within seawater, two reaction conditions (liquid‐solid and gas‐liquid‐solid) and two solutions (seawater and deionized water) were adopted for magnesium oxide hydration. The characterization of the hydration product using X‐Ray diffraction and scanning electron microscope was performed. Experimental results indicate that cations and anions in seawater promote the hydration. Most of the hydration products within seawater system display flower‐like morphology, but the agglomeration phenomenon is not obvious within deionized water system, especially for the supernatant layer products within deionized water system under gas‐liquid‐solid reaction condition. There was no stratification phenomenon occurred when MgO hydrated with seawater under three‐phase reaction condition.     

Crystallization of mefenamic acid and polymorphs

The crystallization of Mefenamic Acid, (MA), which has a prevalent usage in drug formulation, was investigated. MA is a high‐dose, anti‐inflammatory, analgesic agent used for pain in menstrual disorders. Some negative properties of MA are a high hydrophobicity and propensity to stick to surfaces, which cause great problems during granulation and tabletting. To facilitate tabletability, enhance dissolution rates, and develop a stable and reproducible dosage form, investigation of the physicochemical properties of mefenamic acid is necessary. Pharmaceutical drugs are commonly crystalline materials and are therefore subject to polymorphism. Polymorphism, the ability of a substance to exist in more than one crystalline form, is a significant phenomenon in the field of chemical engineering sciences, including pharmaceutical development. Establishing the polymorphic behaviour of a drug molecule early in development minimizes the number of unsuitable candidates developed and reduces the risk of encountering issues later which may have a major financial and time impact. Mefenamic acid crystals were recrystallized from five different solvents of N, N‐dimethylformamide (DMF), acetone, N, N‐dimethylacetamide (DMA), Dimethylsulfoxide (DMS) and Ethyl Acetate (EA). In order to characterize the Mefenamic Acid crystal structure and the polymorphic forms of the crystals obtained by recrystallization, the scanning electron microscopy (SEM), Raman diffractometry and X‐ray pattern were used. From the industrial crystallization point of view, the crystal size distribution (CSD), the crystal shape, the polymorphic form and the crystallization steps are important factors that affect the quality and bioavailability of a drug. For the determination of crystal size distribution of MA, The Focused Beam Reflectance Measurement (FBRM) technique was practiced and CSD profiles were obtained. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Advancements (and challenges) in the study of protein crystal nucleation and growth; thermodynamic and kinetic explanations and comparison with small-molecule crystallization

This paper reviews advancements and some novel ideas (not yet covered by reviews and monographs) concerning thermodynamics and kinetics of protein crystal nucleation and growth, as well as some outcomes resulting therefrom. By accounting the role of physical and biochemical factors, the paper aims to present a comprehensive (rather than complete) review of recent studies and efforts to elucidate the protein crystallization process. Thermodynamic rules that govern both protein and small-molecule crystallization are considered firstly. The thermodynamically substantiated EBDE method (meaning equilibration between the cohesive energy which maintains the integrity of a crystalline cluster and the destructive energies tending to tear-up it) determines the supersaturation dependent size of stable nuclei (i.e., nuclei that are doomed to grow). The size of the stable nucleus is worth-considering because it is exactly related to the size of the critical crystal nucleus, and permits calculation of the latter. Besides, merely stable nuclei grow to visible crystals, and are detected experimentally. EBDE is applied for considering protein crystal nucleation in pores and hydrophobicity assisted protein crystallization. The logistic functional kinetics of nucleation (expressed as nuclei number density vs. nucleation time) explains quantitatively important aspects of the crystallization process, such as supersaturation dependence of crystal nuclei number density at fixed nucleation time and crystal size distribution (CSD) resulting from batch crystallization. It is shown that the CSD is instigated by the crystal nucleation stage, which produces an ogee-curve shaped CSD vs. crystal birth moments. Experimental results confirm both the logistic functional nucleation kinetics and the calculated CSD. And even though Ostwald ripening modifies the latter (because the smallest crystals dissolve rendering material for the growth of larger crystals), CSD during this terminal crystallization stage retains some traces of the CSD shape inherited from the nucleation stage. Another objective of this paper is to point-out some biochemical aspects of the protein crystallization, such as bond selection mechanism (BSM) of protein crystal nucleation and growth and the effect of electric fields exerted on the process. Finally, an in-silico study on crystal polymorph selection is reviewed.     

Study of phosphoric acid crystallization using a focused beam reflectance measurement method

A way for restoring the crystal size distributions (CSD) from measured chord length distributions (CLD) was reported in this paper. The kinetics of phosphoric acid crystallization process was investigated in cooling mode using focused beam reflectance measurement (FBRM) and digital photo technique. In order to restore the CSD from measured CLD and verify the reliability of FBRM data, digital photo technique in real time and optical microscope were applied in large crystal size and small range, respectively. Results indicated a converting constant A existed between CLD and CSD when crystal growth follows size‐independent growth (Mcabe's ΔL law) law. It was verified by Malvern particles size analysis method. The converting constant A varied with crystal morphology. The crystal growth order increased with the stirring increasing speed during phosphoric acid crystallization process. The trend was especially notable at higher speed situations. It can illustrate that the state of phosphoric acid hemihydrate crystal growth was controlled by both diffusion and surface‐integration with the increasing stirring speed. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Studies on large uniaxially grown benzophenone single crystals

〈110〉, 〈010〉 and 〈100〉 oriented uniaxial benzophenone crystals were grown by uniaxially solution‐crystallization method of Sankaranarayanan ‐ Ramasamy (SR). The experimental parameters involved in the present study were investigated in detail and a constant growth rate was achieved by compensating the loss of growth units in the solution. A transparent uniaxial benzophenone crystal having dimension of 500 mm length and 55 mm diameter was grown at room temperature for the first time in the literature. In contrast to the conventional solution growth method, the growth rate along each direction was measured at ease during the respective growth experiment by monitoring the elevation of the solid‐liquid interface and found to be 2, 4 and 6 mm/day along the 〈110〉, 〈010〉 and 〈100〉 directions respectively for a chosen supersaturation. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Preparation of lithium carbonate hollow spheres by spray pyrolysis

Lithium carbonate (Li₂CO₃) hollow spheres were prepared by spray pyrolysis of lithium bicarbonate (LiHCO₃) in this research. The products were characterized by X‐ray diffraction (XRD), scanning electron microscope (SEM), crystal size distribution (CSD) analysis and BET surface area measurement. The XRD figure of the product is nearly the same as the standard pattern, indicating the product achieved by spray pyrolysis has pure Li₂CO₃ crystalline phase. The SEM images show the self‐assembly hollow spheres are composed of about 200 nm primary particles. While the CSD analysis shows the macro‐volume mean crystal size ranges 4‐9 μm depending on the experimental conditions. The BET surface area of the product reaches 7.24 m²/g, which is much higher than the best value reported in the literature. The product prepared in this work has great potential application prospect in the lithium‐battery industry. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Synthesis,morphology and structure of the dense (Y1‐xEux)2O3 spherical shape particles

The method to decrease of the porosity (densification) of crystalline spherical particles of the solid substitution solution, obtained by the method of precipitation from aqueous solution followed by low temperature crystallization of the amorphous intermediate product was proposed. The comparative analysis of morphology and structure of the particles before and after densification have been carried. It has been established that porosity of (Y_1‐xEu_x)₂O₃ particles has decreased 5 times compared to their initial state. It has been shown that densification process of the (Y_1‐xEu_x)₂O₃ spherical particles changes their morphology and structure: the size of the crystals doubles, the number and area of crystalline boundaries decrease, the intercrystalline spaces, which forming pores, are almost absent.     

Crystallization of potassium sulfate by cooling and salting‐out using 1‐propanol in a calorimetric reactor

A study was made on a isothermal process for the crystallization of potassium sulfate as an alternative to the cooling process. The process employs addition of 1‐propanol to aqueous salt solutions to achieve the “saltingout” of the K₂SO₄. This work was carried out using an automated Mettler Toledo model RC1 reactorcrystallizer with 800 ml capacity, and controlled isothermally at 25 °C to test the crystallization of K₂SO₄ by addition of the alcohol, and from 50 to 10 °C for the cooling crystallization. In both systems, the line of nucleation points was shown to be approximately parallel to the saturation curve, with an average width of 13°C or 3 % mass for crystallization by cooling, compared with 0.2 to 1 % by salting‐out. In experiments on crystallization by cooling, the K₂SO₄ crystals were 0.27 mm in mean size, showed 7 % agglomeration, and contained 8.5 % moisture. Crystals obtained by salting‐out had a mean size of 0.79 mm, 28 % agglomeration, and 9‐10 % moisture content. A crystal shape factor of approximately of 0.7 was obtained in both systems, apart from the agglomeration.     

Raman and ATR FTIR spectroscopy in reactive crystallization: Simultaneous monitoring of solute concentration and polymorphic state of the crystals

Batch-reactive crystallization of the two polymorphs of l-glutamic acid was studied using in-line Raman and ATR FTIR spectroscopy. It was observed that the barrier to the nucleation of the stable β-form was higher, and thus the occurrence of β-form nucleation requires a higher supersaturation level. The local supersaturation level inside the reactive crystallizer is significantly affected by the feeding manner of the reactant. When the reactant was fed to a poorly mixed zone, such as the surface of the liquid, a high local supersaturation level was generated near the feeding point. This high local supersaturation level drastically increased with the increase in the concentrations of the reactants. As a consequence, the fraction of the β-form increased with the increase in reactants concentrations. On the other hand, feeding the reactant to a well-mixed zone near the impeller can avoid the occurrence of high local supersaturation, and therefore the dependence of the polymorphic composition of the final product on the concentration of the reactants can be reduced. The information obtained from the spectroscopy leads to improved understanding of the precipitation process and offers great potential for process optimization and control of crystalline quality.     

Synthesis of high purity calcium carbonate micro‐ and nano‐structures on polyethylene glycol templates using dolomite

This research paper describes the synthesis of nano‐ and micro‐structures of high purity precipitated calcium carbonate (PCC) on poly(ethylene glycol)(PEG) templates for broad‐range industrial applications, using readily available and cheap impure dolomitic marbles. In the method, calcium components of impure dolomitic marbles are extracted as calcium sucrate which is then bubbled with carbon dioxide gas using a carbonation column in the presence of PEG. The effects of concentration of PEG, pH of calcium sucrate solution and temperature on the final yield, morphology and polymorphism of PCC have been studied. Vaterite and calcite are the crystalline forms of calcium carbonate found in final PCC products. The vaterite is observed as hollow spheres with particle diameter of 1.5‐2 μm which is formed by aggregation of vaterite nanoparticles with particle size of 20 nm on PEG templates. Optimum conditions for the highest PCC yield of 79.94% are 0.4 mol dm⁻³ of PEG, pH of 6.5 and temperature of 80 °C. The purity of PCC products is about 99%. Therefore, the synthesized PCC products are of required purity and quality for industrial applications.     

Ultrasound assisted crystallization for the recovery of lactose in an anti‐solvent acetone

Continuous worldwide increase in high‐scale production of dairy products leads to the constant generation of vast amounts of liquid by‐product, whey. Disposal of liquid whey is costly due to its high biological oxygen demand (BOD) and water content. More than 90% of whey BOD is due to lactose. Recovery of lactose from whey solves both the problems of improving economics of whey utilization and pollution reduction as lactose recovery itself can reduce BOD of whey by more then 80%. Commercial effluent treatment techniques focus on degradation rather than recovery of useful by‐products like lactose. Also, these techniques are time consuming and hence not effective enough. Sonocrystallization is the use of power ultrasound to control the crystallization process during the nucleation phase. In the present study, the process of lactose crystallization has been studied for the recovery of lactose from reconstituted lactose solutions with the aid of ultrasound, in the presence of ‘acetone’, as an anti‐solvent. The crystallization is found to be completed with excellent yields in the range of 80 – 92% within 4 minutes of sonication. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Melting and Crystallization Processes of EBBA I. Thermal Analysis

Melting and crystallization processes of EBBA (N-p-Ethoxybenzylidene-p'-butylaniline) have been studied by the method of thermal analysis and measurement of light transmittance. When the sample is cooled down from the nematic phase at a rapid cooling rate, solid phase (solid S) is formed directly. Solid S contains two solid modifications (solid S₁ and solid S₂. By heating the solid S, some amount of Solid S₁ is transformed into the nematic phase through the process of (melting of solid S₁ → crystallization to solid S₂ → melting of solid S₂). After the melting of solid S₁, some liquid crystalline state appears transiently. Solid S₁ is stabilized by the heat treatment at low temperature. The quantity of solid S₁ in solid S increases with the heat treatment time and/or with cooling at a low temperature.     

Optimization of the local crystallization processes of preparing chiral drugs in periodic crystallizers

The regularities of periodic processes of local crystallization of enantiomers and the kinetics of nucleation and growth of crystals are considered. The criteria for optimization of technological processes of preparing chiral drugs with the aim of attaining the maximum yield of final products with a required optical purity are formulated on the basis of experimental data.     

Influence of Nature of Silica Source on Template‐Free Synthesis of ZSM‐5

Synthesis of ZSM‐5 from template‐free batches which preceded the preparation of template‐free ZSM‐5 layers on porous supports was studied to ascertain the effect of nature of silica source on the purity of template‐free ZSM‐5. Silicic acid and two colloidal silica sols were used as silica sources to prepare the template‐free batches with a molar composition of 6.5Na₂O:Al₂O₃:80SiO₂:3196H₂O. One of the colloidal silica sols contained methanol as stabilizer while the other did not. The product purity and rate of crystallization increased when colloidal silica sols were used as silica source, however, use of silicic acid led to low purity and slow crystallization rate. The methanol in the colloidal silica sol appeared to act as template to promote the crystallization and was occluded in the resultant ZSM‐5 pores. The dissolution of the meta‐stable ZSM‐5 phase and formation of quartz was observed regardless of the nature of the silica source in case of prolonging the crystallization time more than 90 h at 200°C.     

Application of Rosin–Rammler model for analysis of CSD in sugar crystallization

Crystal‐size distribution (CSD) is one of the most important parameters in sugar production. The objective is to grow crystals of uniform sizes or narrow CSD. CSD appears to be determined by the growth‐rate history of the crystals and the relative supersaturation (SS) of the solution from which crystals growth takes place. Three methods for preparation of nucleation seeds were described and used for industrial crystallization of raw and white sugars; these are wet milling filtered sugar (ML), agitating saturated solution (AS) and powdered sugars (PD). Rosin–Rammler (RR) and mathematical models were adopted to investigate CSD and the uniformity of the produced crystals. Higher uniformity coefficients were reported for the AS seeded crystals than the other two seeding methods. Furthermore, higher crystal contents were obtained for the AS seeded white sugar batches in comparison.     

Determination of reactive crystallization kinetics of 5‐(difluromethoxy)‐2‐mercapto‐1H‐benzimidazole in a batch crystallizer

5‐(difluromethoxy)‐2‐mercapto‐1H‐benzimidazole (DMB) was crystallized via the reaction between sodium salt of DMB and acetic acid. In this work, we firstly measured the solubility data of DMB in binary ethanol‐water mixture at different temperatures. Then, the reactive crystallization kinetics of DMB was determined in the batch crystallizer. Based on the population balance and mass balance, the kinetics model of reactive crystallization process of DMB was established. And the nucleation rate, size‐independent crystal growth and agglomeration kernel were determined by method of classes. Finally, based on the population balance, numeric simulation was done using the above crystallization kinetics in order to verify its reliability.     

Detection of the II–I Etiracetam solvent-mediated polymorphic transformation through the online monitoring of the suspension apparent viscosity

Although going to complex techniques can be useful at some stage of process development of crystallization processes, the goal of this article is to show that process control can also be achieved with relatively simple measurements, depending of course on what type of control is needed. Focusing on the Etiracetam crystallization process, this work demonstrates the potential of the online monitoring of the power dissipated in the suspension, a property that can be directly related to the suspension apparent viscosity for the detection of the solvent-mediated polymorphic transformation from form II to form I. Even if the work presented in this paper focused on a specific crystallization process, this easy-to-use method seems promising for the control of other crystallization processes exhibiting solvent-mediated polymorphic transformations with similar characteristics: (i) significant difference in the PSD of the crystals of the stable and the metastable forms, (ii) solid volumetric fraction in the suspension higher than 40% and (iii) absence of phenomena (breaking, attrition, agglomeration, secondary nucleation, etc.) interfering with the polymorphic transformation and affecting the PSD of the crystals.     

Inversion of the Temperature Field in Optical Crystals

This article is devoted theoretical and experimental researches of temperature fields which are formed in area semi‐transparent, diffusely transmitting and scattering boundary of two optical environments. It is revealed, that thus can arise non‐monotonic or at certain conditions completely an inverse temperature field. The phenomenon of inversion of a stationary temperature field is revealed theoretically and subsequently is experimentally confirmed. The specific conditions of occurrence of the phenomenon of inversion are determined. During the crystal growth process behind the front of crystallization there can be a congestion of impurities or micro‐bubbles which are grasped by the moving front of crystallization. It results in occurrence diffusely transmitting and scattering boundary on which the radiating thermal flux going from the melt is dissipated in a growing crystal. In turn under the certain conditions it could result in non‐monotonic of temperature field in area of phase boundary and even in full inversion. The experimental equipment was developed and results of experimental measurements which completely confirm theoretical conclusions are given. The described phenomenon could be meet in growing of such optical crystals as sapphire, ruby, fluorides etc. It is specified, that the similar conditions can arise as well on boundary of solid‐gas and liquid‐gas.