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)     

Effect of process parameters on crystal size and morphology of lactose in ultrasound‐assisted crystallization

α‐lactose monohydrate is widely used as a pharmaceutical excipient. Drug delivery system requires the excipient to be of narrow particle size distribution with regular particle shape. Application of ultrasound is known to increase or decrease the growth rate of certain crystal faces and controls the crystal size distribution. In the present paper, effect of process parameters such as sonication time, anti‐solvent concentration, initial lactose concentration and initial pH of sample on lactose crystal size, shape and thermal transition temperature was studied. The parameters were set according to the L₉‐orthogonal array method at three levels and recovered lactose from whey by sonocrystallization. The recovered lactose was analyzed by particle size analyzer, scanning electron microscopy and differential scanning calorimeter. It was found that the morphology of lactose crystal was rod/needle like shape. Crystal size distribution of lactose was observed to be influenced by different process parameters. From the results of analysis of variance, the sonication time interval was found to be the most significant parameter affecting the volume median diameter of lactose with the highest percentage contribution (74.28%) among other parameters. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

On the interpretation of metastable zone width in anti‐solvent crystallization

Considering nonlinear dependence of solute concentration on anti‐solvent–solvent composition a modified Nývlt‐like equation based on traditional power‐law relation between nucleation rate and developing supersaturation and a new equation based on the classical theory of three‐dimension nucleation are proposed to explain the dependence of anti‐solvent addition rate on metastable zone width defined as excessive anti‐solvent composition in anti‐solvent crystallization. The experimental data on the metastable zone width in anti‐solvent crystallization of benzoic acid are analyzed and discussed from the standpoint of these equations. It is found that the new approach based on the classical nucleation theory provides better insight into the processes involved in anti‐solvent crystallization. Analysis of the experimental results on anti‐solvent crystallization of benzoic acid [D. O'Grady, M. Barret, E. Casey, and B. Glennon, Trans. IChemE A 85 , 945, (2007)] revealed that: (1) the value of metastable zone width for a solvent–anti‐solvent system is determined by the solute–solvent and solute–anti‐solvent interactions, (2) the dependence of the metastable zone width on stirring is associated with the enthalpy of mixing, and (3) the new approach predicts a threshold anti‐solvent addition rate associated with the setting up of an equilibrium between solvent and anti‐solvent and a maximum anti‐solvent addition rate connected with the induction period t_ind for the onset of crystallization. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Anti‐solvent effect of crystallization by feeding ethanol under microwave radiation

The nucleation and crystal growth of sodium chloride in aqueous solution during crystallization by ethanol droplet feeding were investigated by determining the suspension density and crystal size distribution. Crystallization was conducted in a microwave reactor, and the effect of the power, stirring speed, and ethanol concentration were investigated to clarify the anti‐solvent effect under microwave radiation. Molecular diffusion was accelerated by fine particle production due to microwave radiation when the stirring speed was low and ethanol concentration was high. However, moderate microwave power and stirring speed were required for efficient molecular diffusion.     

Solvent freeze out crystallization of lysozyme from a lysozyme‐ovalbumin mixture

Hen egg white lysozyme (HEWL) crystallization conditions from an ovalbumin‐lysozyme mixture were found by screening tests and further located in pseudo‐phase diagrams. This information was used to set up the initial conditions for the solvent freeze out (SFO) process. The process uses the freezing of ice to create the supersaturation for the proteins to crystallize out of the solution. The crystallization of HEWL (15 mg/mL) out of a lysozyme‐ovalbumin mixture (1.7 mg/mL) is carried out by SFO. Under the reported conditions, a crystallization yield of 69 % was obtained. A mean crystal size of 77.8 µm was enhanced in a crystallization time of 15.1 h. The lysozyme nature of the crystals is proven by SDS PAGE and enzymatic activity tests. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Study of lactose crystallization in water‐acetone solutions

This paper describes a study on the process of lactose crystallization using a water‐acetone solution. The selection of lactose was based on its significance for the pharmaceutical and food industries and on the fact that the crystallization of this organic compound has been little studied and is, unlike inorganic compounds, complex. The objective was to achieve lactose batch crystallization of solutions by analyzing the crystal growth under different operating conditions. To determine solubility curves, the experiments were carried out based on gravimetric methods. All the crystallization experiments were performed according to the methodology proposed by Nývlt in 1985, who uses the temperature at which the first crystals appear (nucleation) to establish the width of the metastable zone and the induction time. The results showed that crystals with different average diameters, shape factors, and recovered mass were obtained for different water‐acetone compositions. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Influence of various factors on the liquid/liquid diffusion crystallization of proteins

From a numerical simulation of pre-nucleation solute transport in the liquid/liquid diffusion crystallization of proteins, it is derived that there are various factors influencing the spatial and temporal distributions of supersaturation. They include the ratio of the length of the protein solution to that of the salt solution in a tube crystallizer, the initial concentrations of protein and salt, and the initial salt concentration in the protein solution. Their influences on the protein crystallization have been demonstrated by the corresponding experiments of gel crystal growth. It may be deduced that the experimental conditions for the liquid/liquid diffusion growth of protein crystals could be optimized under given conditions in order to develop the advantages of this method.     

Crystallization of silicalite‐1 from clear synthesis solutions: Effect of template concentration on crystallization rate and crystal size

Synthesis of silicalite‐1 powders and membranes from initially clear solutions with different tetrapropylammonium hydroxide or bromide concentrations was studied. While tetrapropylammonium bromide acts only as template, tetrapropylammonium hydroxide provides both the template and hydroxyl ions to the synthesis medium. The effects of template and hydroxyl ion concentration on the product yield, crystallization rate and crystal size were investigated. Pure and highly crystalline silicalite‐1 was obtained with all compositions. The nucleation time decreases from 100 h to 20 h and the crystal size decreases from 3.5 μm to 0.35 μm as the template amount x is increased from 5 to 30 moles at a batch composition of 80SiO₂.xTPAOH.1500H₂O at 95 °C. Yield of silicalite‐1 passes through a maximum at intermediate TPA concentration. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Electrical properties of PbxSn1‐xS thin films prepared by hot wall deposition method

The Pb_xSn_1‐xS (x = 0 – 0.25) thin films were prepared on glass substrates by hot wall vacuum deposition. The films were polycrystalline monophase in nature and had orthorhombic crystal structure. The thickness of the films was about 2‐3 μm. The temperature dependences of the conductivity were measured in the temperature range from 150 to 420 K. The films revealed p‐type of conductivity. The Seebeck coefficient and conductivity values of the films was in the range of α = 6 – 360 μV/K and σ = 4.8×10^‐5 – 1.5×10^‐2 Ω^‐1·cm^‐1, respectively, at room temperature depending on concentration of the lead in the films. The lead atoms created the substitution defects Pb_Sn in the crystal lattice of the Pb_xSn_1‐xS. These defects formed the donor energy levels in the band gap. The activation energy of the films increased in the range ΔE_a = 0.121 – 0.283 eV with increasing of the lead concentration. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Influence of solvent and crystallization method on the crystal habit of metronidazole

In the present study, metronidazole was crystallized in several solvents, according to both the “cooling crystallization” and the “crystallization by non‐solvent addition”. Particle properties, such as crystal habit, elongation ratio, and mean particle size, were determined by SEM analysis. Structural changes and development of polymorphic forms were excluded by both Differential Scanning Calorimetry (DSC) and X‐Ray Powder Diffractometry (XRPD). Crystal habit (and thus elongation ratio) was typically influenced by both the solvent polarity index and the crystallization method: solvents with higher polarity index tended to promote acicular or stick‐shaped crystals with a high elongation ratio, while isodimensional crystals were promoted by decreasing the polarity index, as was particle aggregation. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Study on crystallization kinetics and the crystal internal defects of HMX

In this paper, the solubility data of HMX (1,3,5,7‐tetranitro‐1,3,5,7‐tetrazocane) in acetone from 323.15 K to 293.15 K were accurately measured by use of the laser‐monitoring observation technique. Intermittent dynamic method was utilized to study crystallization kinetics of HMX in acetone. The data of crystallization kinetics were obtained by moment analysis, and the parameters of the growth rate and nucleation rate equations were derived by using multiple linear least squares method. Subsequently, growth rate and nucleation rate at different conditions were calculated according to these equations. In addition, Optical Microscopy Images (qualitative) and Particle Apparent Density (quantitative) experiments were applied to study the crystal internal defects of HMX under different crystallization conditions. It can be found that the crystal apparent density of HMX is in the range of 1.8993 g·cm⁻³ to 1.9017 g·cm⁻³, very close to the theory density of HMX; the internal defects and the crystal size do not increase after 25 °C, from which we predict that the HMX crystal growth reaches the steady growth segment. These results suggest that the nucleation rate is a significant factor influencing the crystal internal defects, and larger nucleation kinetics can reduce crystal internal defects.     

Effect of CuCl2 on hydrothermal crystallization of calcium sulfate whiskers prepared from FGD gypsum

Using purified flue‐gas desulfurization (FGD) gypsum as raw material, effects of CuCl₂ on crystal morphology, phase structure, aspect ratio and crystallization of hydrothermal products prepared via hydrothermal crystallization in H₂SO₄‐H₂O solutions were investigated. The results show that dosage of CuCl₂ has a significant effect on the morphology, aspect ratio and crystallization of calcium sulfate whiskers (CSWs), but no effect on their phase transformation . At a dosage of 15 g CuCl₂/kg FGD gypsum, the produced calcium sulfate whiskers had diameters ranging from 1 to 3 μm with average aspect ratio greater than 200 . Transmission electron diffraction patterns and highly magnified surface morphology of CSWs were found different from those of self‐assembly crystals. Compared to self‐assembly crystals, the produced CSWs showed a single crystal structure and their surface was very smooth.     

Spontaneous crystallization of potassium chloride from aqueous and aqueous‐ethanol solutions; Part 3: Model of the crystallization process

A model of spontaneous crystallization process was proposed. The model describes kinetics of the crystallization process after the end of the induction period. To test the model the published earlier data on crystallization and aggregation kinetics of potassium chloride at its spontaneous crystallization from supersaturated aqueous and aqueous‐ethanol solutions were used. It was found excellent coincidence of the experimental and theoretical data on concentration of the salt and the total number of crystals in solution at crystallization. Somewhat change for the worse was at the theoretical calculations of crystal size distribution at the end of the crystallization process. It indicated that the ways of calculation of size of crystals and their weight fraction in deposit were very approximate. The model allows predicting with satisfactory accuracy kinetics of crystallization using such general parameters of potassium chloride as the specific surface energy and the height of the nucleus‐bridges between crystals at coalescence. It needs further test of the model for other salts. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

In situ determination of metastable zone width by a simple optical probe

The metastable zone width (MSZW), which denotes the region between the solubility curve and the onset of nucleation, is an important control parameter for successful operation of a solution crystallization process as it defines an operating boundary for the crystallization process. The MSZW can be approximated as the gap between the loci of cloud points that correspond to onset of nucleation and clear points that closely represent solubility. This work presents the design and application of a simple optical probe consisting of a line laser source, a light‐dependent resistor, and a simple processing circuit for in situ determination of onset of nucleation of a crystallization process. Three different crystallization processes, namely, cooling crystallization of glycine, cooling crystallization of L‐asparagine monohydrate, and anti‐solvent crystallization of glycine, are investigated to assess the performance of the in situ probe. In all the cases, the cloud points and clear points are conveniently detected by sharp changes in output voltage of the probe with reasonable accuracy. The presented optical probe can be used as a simple and inexpensive alternative tool in the area of crystallization process monitoring.     

Crystal growth and solubility studies of Aspergillus niger acid proteinase A in the presence of both a salt and an organic solvent

The quality of proteinase A crystals improves considerably, as judged from the X-ray diffraction limit, in the presence of an organic solvent, dimethylsulfoxide (DMSO). The effects of DMSO have therefore been studied through the observation of crystallization and protein concentration versus time. It was found that DMSO increases the nucleation rate, and decreases the crystal solubility as does ammonium sulfate. It is suggested that organic solvents may be used to alter the protein crystal growth usually obtained by salting-out.     

Effects of forced solution flow on lysozyme crystal growth

In order to study quantitatively the effects of forced solution on crystal growth, we designed a new set of experimental equipment, in particular, a microchannel mixer was used as crystallization container so that the consumption of protein samples was much reduced and thus an exact syringe pump could be used for precise control of the flow rates. Since the mixer's section was designed to be rectangular, the solution velocity in its center was steady and constant, and thus repeatable experiments were facilitated. Experimental results showed that the effects of forced solution on protein crystal growth were different under different levels of supersaturation, and new results were obtained for cases of high supersaturation. When the supersaturation is σ = 2.3, with increasing flow rates the growth rates of the lysozyme crystal's (110) face hardly change when the flow rates are lower than 1300 μm/s, and decrease quickly afterwards. When the flow rate reaches 2000 μm/s, the crystal nearly ceases to grow. When the supersaturation is σ = 2.7, with increasing flow rates the (110) face growth rates increase at the beginning then reach the maximum values at 1700 μm/s – 1900 μm/s and decrease afterwards, approaching zero or so when the flow rate reaches 12000 μm/s. The higher the supersaturation, the larger the flow rate at which the crystal ceases to grow. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

A novel growth method for ZnAl2O4 single crystals

ZnAl₂O₄ is a well‐known wide band gap compound semiconductor (E_g=3.8eV), ceramic, opto‐mechanical, anti‐thermal coating in aero‐space vehicles and UV optoelectronic devices. A novel method for the growth of single crystals of a ternary oxide material was developed as a fruit of a long term work. Material to be grown as metal incorporated single crystal was taken as precursor and put into a bath containing acid as reaction speed up reagent (catalyst) as well as solvent with a metal foil as cation scavenger. Using this method, ZnAl₂O₄ crystals having hexagonal facets are prepared from a single optimized bath. Structural and compositional properties of crystals were studied using Philips, Xpert ‐ MPD: X‐ray diffractometer and Philips, ESEM‐TMP + EDAX. Thus technique was found to be a new low cost and advantageous method for growth of single crystals of ternary oxide a material. We hope that these data be helpful either as a scientific or technical basis in material processing. Dedicated to Prof. P. Ramasamy © 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim     

Comparison Study of Mixing Effect on Batch Cooling Crystallization of 3‐Nitro‐1,2,4‐triazol‐5‐one (NTO) Using Mechanical Stirrer and Ultrasound Irradiation

The insensitive explosive 3‐Nitro‐1,2,4‐triazol‐5‐one (NTO) has been recrystallized from water in an effort to prepare crystals with smaller size and narrower distribution in a batch cooling crystallizer. Two mixing devices, i.e., a mechanically stirred system with and without ultrasound in aqueous media were employed to compare the mixing effect on the crystallization. Under ultrasound irradiation, the metastable zone width was significantly reduced by more than 2 fold and the crystal size was shifted from 140∼160 μm to 50∼70 μm with a narrower CSD compared to the mechanically stirred system. However in the mechanical stirrer, the mixing effect on NTO crystallization was negligible if the impeller speed was sufficient to suspend all crystals in the crystallizer. It was found that the crystal growth was not influenced by mixing. We suggest that the NTO crystals were formed by primary heterogeneous nucleation that is common in batch cooling system. Finally, the population balance model (PBM), with the empirical nucleation and growth kinetic expressions, was solved numerically to predict the crystal size and the CSD with batch time, and the results were in good agreement with the experimental data.     

Influence of emulsion types on nucleation kinetics and growth habit in the cooling crystallization

Experiments on unseeded batch cooling crystallization were made to investigate the influence of emulsion [solution in non‐solvent (S/NS) emulsion and non‐solvent in solution (NS/S) emulsion] on crystal size and growth habit of various materials such as hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine, ammonium sulfate, potassium dihydrogen phosphate (KDP), and γ‐glycine. Size of crystals obtained from the S/NS emulsions was found to be significantly larger than that obtained from the NS/S emulsions. Those results were explained by broad induction time distribution of nucleation in the isolated solution droplets and subsequent seeding effect by free movement of early‐induced crystals by vigorous agitation. As a result, the population density of crystals was shown to be smaller in the S/NS emulsions than that in the NS/S emulsions. In the S/NS emulsions, desupersaturation rate should be slow and high supersaturation is subsequently generated during crystal growth stage. Therefore, it may be concluded that crystal morphology of the materials with supersaturation dependent growth habit, such as ammonium sulfate, KDP and γ‐glycine, can be controlled by selection of emulsion type.     

Continuous reaction crystallization of struvite from phosphate(V) solutions containing calcium ions

Continuous reaction crystallization of struvite from water solutions containing phosphate(V) (1.0 mass%) and calcium ions (from 0.01 to 0.20 mass%) was investigated. Process was carried out in temperature 298 K in continuous DT MSMPR type crystallizer with internal circulation of suspension. Influence of pH (from 9 to 11) and mean residence time of suspension in crystallizer (from 900 to 3600 s) on product crystal size distribution, mean size, population homogeneity and shape of crystals, as well as chemical composition of solid phase was tested. Within the investigated process parameter ranges struvite crystals of mean size from 18 to ca. 50 μm were produced. With the increase in calcium ions concentration in a feed mean crystal size decreased from 34.2 to 18.4 μm (pH 9, τ 900 s). Coexistence of struvite and hydroxyapatite crystals in the solid product was confirmed analytically (Ca content in solid product from 0.3 to 8.4 mass%). Presence of calcium ions favoured crystallization of struvite in a form of tubular crystals, characterized by lengthwise cracks and irregular edges. Co–precipitated hydroxyapatite particles showed relatively small sizes, even below 1 μm, forming agglomerates on the surface of larger struvite crystals and individual agglomerates. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)