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The crystal appearance of industrial grade 2,6-bis(picrylamino)-3,5-dinitropyridine (PYX) was mostly needle-shaped or rod-shaped with an average aspect ratio of 3.47 and roundness of 0.47. To improve the loading density and pressing safety, the crystal shape of PYX was optimized by cooling crystallization method. After recrystallization, the aspect ratio decreased from 3.47 to 1.28, and the roundness value increased from 0.47 to 0.78. XRD data showed that there is no crystal pattern change before and after recrystallization. The friction sensitivity of the explosive decreases from 88% to 56%, and the impact sensitivity decreases from 76% to 12%. Differential scanning calorimeter (DSC) was used to study the thermal decomposition of PYX. The thermal decomposition peak temperature of the samples after recrystallization was 4~7℃ higher than that of raw PYX. The adiabatic induction time (TMRad) and self-accelerating decomposition temperature (SADT) were calculated with AKTS software. In the same adiabatic induction time, the initial temperature of recrystallization PYX is about 30℃~40℃ higher than that of the raw PYX. The SADT is increased by about 50℃~60℃. The thermal safety of recrystallized PYX is improved. [ABSTRACT FROM AUTHOR]

The development of a quantitative in-line UV spectroscopic method for monitoring of solute concentration during the crystallization process of the active pharmaceutical ingredient (API), ceritinib is described. The method is based on artificial neural networks (ANN). A seeded cooling crystallization process of ceritinib from tetrahydrofuran was studied as a model system. The model was constructed from collected ATR-UV spectra and temperature records within the metastable zone. The collected spectra were preprocessed with the first derivative using the Savitzky-Golay filter. ANN models with different architectures were created and the optimal architecture was chosen based on the root mean square error of prediction (RMSEP) criterion. In addition, ANN models were compared with the models obtained by the linear partial least squares regression (PLSR). Due to the nonlinear relationship in the data set, ANN models predict the solution concentration with higher accuracy compared to linear models. The developed models were successfully used in real-time solution concentration measurement during ceritinib crystallization along with a supersaturation control module developed in-house. [ABSTRACT FROM AUTHOR]

Continuous crystallization of pharmaceuticals has been in the center of attention during the past two decades, with a more focus on the large‐scale production of active pharmaceutical ingredients. The increasing demand for pharmaceuticals requires high‐throughput production of drug crystals with different solubilities, stabilities, shapes, habits, polymorphs, and size distributions. With numerous advantages including low cost, ease of scale‐up, and superior control over polymorph and size distribution of drug crystals, antisolvent crystallization is one of the most promising crystallization methods recently attempted. However, it fails to deliver the required characteristic where the crystal systems tend to grow and for the preparation of metastable polymorphs. This review focuses on the most recent efforts to tackle these drawbacks by coupling antisolvent crystallization with cooling, supercritical‐assisted, microfluidics‐assisted, and membrane‐assisted crystallization. This systematic review aims to provide a concise summary of each coupled antisolvent technique and their positive and negative aspects. This review can be used as a guideline for pharmacist, biologists, and chemists, who are interested in the crystal engineering of pharmaceuticals to pave the way for further developments in this field. [ABSTRACT FROM AUTHOR]

The development of a quantitative in-line UV spectroscopic method for monitoring of solute concentration during the crystallization process of the active pharmaceutical ingredient (API), ceritinib is described. The method is based on artificial neural networks (ANN). A seeded cooling crystallization process of ceritinib from tetrahydrofuran was studied as a model system. The model was constructed from collected ATR-UV spectra and temperature records within the metastable zone. The collected spectra were preprocessed with the first derivative using the Savitzky-Golay filter. ANN models with different architectures were created and the optimal architecture was chosen based on the root mean square error of prediction (RMSEP) criterion. In addition, ANN models were compared with the models obtained by the linear partial least squares regression (PLSR). Due to the nonlinear relationship in the data set, ANN models predict the solution concentration with higher accuracy compared to linear models. The developed models were successfully used in real-time solution concentration measurement during ceritinib crystallization along with a supersaturation control module developed in-house.

Introduction: In this article, we demonstrate the application of cooling crystallization to generate novel solid forms of drug-coformer cocrystal complexes. Method: This approach enabled us to replicate several cocrystal phases previously reported for pharmaceutical drugs. Additionally, we successfully produced a new solid mixture comprising the drug luliconazole and coformers such as mannitol and menthol, as well as a potential new crystal form of the cocrystal luliconazole:menthol and luliconazole:mannitol. By utilizing cooling crystallization, we were able to prepare phase-pure LCZ-MNT and LCZ-MNL cocrystals. Result: This study utilized PXRD, thermal methods, and FTIR to analyze cocrystals formed between drug and two coformers, menthol (MNT) and mannitol (MNL). Pure luliconazole showed−345.26 mJ heat of fusion (ΔH) and cocrystals with menthol and mannitol showed−516.19 mJ and−566.46 mJ respectively. The cocrystals showed lower heats of fusion (ΔH) compared to luliconazole, indicating the possibility of increased entropy and solubility for all cocrystals. Both the coformer and drug components showed band shifts in their spectra. A new solid phase was assumed to have formed if the PXRD of the cocrystal product differed from that of the reactants. Pure luliconazole resulted in 6.91 µg/ml solubility and cocrystal with menthol resulted in 26.87 µg/ml solubility. Using cooling crystallization with the menthol coformer resulted in a fivefold increase in cocrystal solubility compared to pure drug. The study also demonstrated improvements in drug dissolution. Conclusion: The DSC analysis showed that the cooling crystallization method resulted in cocrystals with lower heats of fusion. The results of FTIR studies, the drug, and coformer showed only weak interactions, creating the new solid form. PXRD data indicated that the cooling crystallization method modified the crystal habits. Solubility and dissolution studies revealed that cocrystals of luliconazole could be an effective approach for enhancing its solubility. [ABSTRACT FROM AUTHOR]

Preferential crystallization is a method for obtaining a pure enantiomer from a racemic solution However, only a 50% maximum yield is obtained when the chiral molecules are not racemized in the solution. In this study, preferential crystallization of monoammonium glutamate (MAG) was performed in the presence of glutamate racemase, a racemization enzyme. The yield and optical purity of L-MAG were 49.4% and 13.8% ee, respectively, without enzymatic racemization. However, the yield and purity were improved to 97.7% and 97.4% ee, respectively, using glutamate racemase immobilized on chitosan beads. Thus, the combination of preferential crystallization and enzymatic racemization significantly improved the purity and yield. Moreover, a crystallization device with an immobilized enzyme can be expected to become a method for optically resolving chiral molecules with high efficiency.

An industrial side stream containing mainly glucose and galactose was used to crystallize α‐D‐galactose. The dynamic viscosity of samples containing galactose and glucose solutions was measured and compared with pure glucose and galactose solutions. Various crystallization conditions were investigated in terms of temperature range and batch times in cooling crystallization and their influence on the product crystal properties. The obtained results were compared with the results of evaporative crystallization. Several characterization methods were used for studying crystal size and shape, crystal structure, and purity. The overall crystallization time of α‐D‐galactose was shortened by cooling crystallization based on stepwise temperature decrease and the desired crystal properties were achieved. [ABSTRACT FROM AUTHOR]

A new cooling crystallization method is applied to plate copper on SiCp. Cu(NO3)2·3H2O is crystallized on SiCp by decreasing the solution temperature, and is heat‐treated to obtain CuO coating which is finally reduced to copper coating. Based on the optimizing of SiCp content and CuO reduction temperature, the effects of copper plating on SiCp on the spreading and infiltration of AlSi12 alloy melt are studied. The results show that the optimum coating effect is achieved when the SiCp content is 11.63% and the reduction temperature of CuO is 475 °C. The spreading area of AlSi12 alloy melt on the 15 μm copper‐coated SiCp increases by 53.27% compared to the uncoated SiCp when holds at 950 °C for 20 min, indicating that copper plating has a significant improvement on the wettability of AlSi12 melt and SiCp. Additionally, infiltration preparation of copper‐plated SiCp/Al alloy composites is achieved at a pressure of 0.3 MPa, but not under pressureless conditions. The main reason for this is the granular Cu on SiCp cannot form a complete Cu film. Therefore, the formation of complete Cu films on SiCp is presumed to be an important development direction for solving the problem of infiltration preparing ultrathick SiCp/Al composites. [ABSTRACT FROM AUTHOR]

Glucosamine hydrochloride (GAH) is a kind of natural hexose, which is used to promote the synthesis of mucopolysaccharides and improve the metabolism of articular cartilage. In this paper, the solubility of GAH in pure water and aqueous system with the presence of three kinds of additives (HCl, NaCl, KCl) at temperatures ranging from 278.15 K to 323.15 K was determined by gravimetric method. When there are additives in water, the solubility of GAH increases with the increase of temperature and decreases with the increase of concentration of the three kinds of additives. When the additives were at similar mole fractions, HCl led to the lowest solubility of GAH. The modified Apelblat model and van't Hoff model were used to correlate the solubility data. The average relative deviation (ARD) data of Apelblat and van't Hoff models were less than 5%, indicating good fitting results. Based on the thermodynamic data, the cooling crystallization process of GAH was performed. It was found that the additives could affect the crystal morphology, particle size, and yield of GAH products. This study supplemented the thermodynamic data of GAH and studied the cooling crystallization process in the presence of GAH additives, which provided important guidance for the optimization of the crystallization process. [ABSTRACT FROM AUTHOR]

Small-scale continuous apparatuses for solid product manufacturing are receiving increasing interest due to the demand for the fast market availability of specialty chemical products manufactured in integrated and modular processing plants. Relevant unit operations span from crystallization over solid–liquid separation and filter cake washing to drying. For this purpose, the quasi-continuous filter belt crystallizer (QCFBC) was developed and is presented here. The newly integrated unit operations with positive pressure filtration ( Δ p max = 0.8 bar), filter cake washing ( V ˙ wash = 55 mL·min−1), and convection drying ( T dry = 60 °C) have been individually characterized and integrated into the filter apparatus that has been modified for continuous operation. They were synchronized with the flexible cooling crystallization, enabling for a seamless production process. Sucrose in water was used as model substance system. Long-term operations of up to 14 h were successfully performed with dry product filter cakes (22.64 g ± 1.64 g·h−1) of constant quality attributes ( x 50 , 3 = 216.095 ± 14.766, s p a n = 0.347 ± 0.109, Y rel. = 69.9% ± 5%, X RM = 1.64 mg·g−1 ± 1.38 mg·g−1). [ABSTRACT FROM AUTHOR]

Continuous tubular crystallizers that can provide high yield and better control of crystal size would be of great interest to the industrial crystallization process. However, most continuous crystallizer designs face challenges either due to surface fouling or crystal breakage. In this paper, we explore the ability of slug-flow cooling crystallizers to continuously generate acetaminophen crystals using silicone oil as the continuous phase. Each slug acts as a crystallizer, and the crystals formed inside the dispersed phase avoid encrustation. Three crystallizer configurations were studied at a wide range of supersaturation and flow rates. It was found that a narrow crystal size distribution can be achieved at high flow rates and high supersaturation. Additionally, the average crystal size and the crystallization yield increased with supersaturation and residence time. The configuration of the tubular crystallizer was found to influence the crystallization yield by affecting the internal mixing in the slugs. With further studies, slug-flow cooling crystallizer can be developed for continuous crystallization of crystals with a narrow size distribution, polymorphic purity, and good yield. [ABSTRACT FROM AUTHOR]

The control of desired product quality attributes in the crystallization process is one of the major concerns of the pharmaceutical industries due to the established standard limits for active pharmaceutical ingredients in applications. The objective of the present work is to establish the fundamental understanding and methodology of the batch cooling sonocrystallization process to tune the crystal attributes over the range of operating parameters, i.e., ultrasound amplitude, duration of sonication, and cooling rate. For the constant cooling rate, the effect of three levels of ultrasound amplitude has been investigated over the range of durations of insonation. It is observed for a fixed cooling rate that the optimized set of ultrasound parameters shortens the induction time resulting in a finer range of particles increasing the surface area and narrowing the particle size distribution. The performance of the process in terms of thermal characteristics has been analyzed to delineate the effect of operating parameters to be employed as a function of the product characteristics. The simple expressions for temperature profiles during the process have been proposed as a function of saturation temperature to facilitate their applications in the optimization of the operating parameters for the desired product size and size range. [ABSTRACT FROM AUTHOR]

The solubility of 1,1-diamino-2,2-dinitroethylene (FOX-7) in four binary mixed solvents (Dimethyl sulfoxide + Acetonitrile, Cyclohexanone, 1,2-Dichloroethane, 2-Propanol) was determined by using a laser dynamic method at temperatures from 293.15 to 333.15 K under 0.1 MPa. The measured results showed that the experimental solubility of FOX-7 increased with increasing temperature and Dimethyl sulfoxide content in the studied mixture solvents. Solubility data were well correlated by the modified Apelblat model, Yaws model and van't Hoff model, and the modified Apelblat model has the lowest root-mean-square deviation and can be used as the optimal model for data fitting. In addition, the thermodynamic parameters of the dissolution process, the surface tension, and surface entropy factor of FOX-7 were calculated based on the experimental data, which provided basic data for the optimization of crystallization process and industrial amplification of FOX-7. The cooling crystallization experiments were carried out in the investigated mixed solvents. The crystal morphology of FOX-7 obtained in the Dimethyl sulfoxide + Cyclohexanone mixed solvent (xDMSO = 0.3266) was regular, spherical, uniform in particle size, and have better thermal stability. Cyclohexanone could be the excellent non-solvent in the sphericalization of FOX-7. [ABSTRACT FROM AUTHOR]

In the present study, a process of separating high-quality TiO2 from an oxalic-acid leachate of vanadium slag was proposed. It consists of two steps; oxalic acid was firstly recovered from the leachate by the cooling-crystallization method, and subsequently TiO2 was separated from the oxalic-acid recovered leachate by the hydrothermal precipitation method. The experimental results indicate that oxalic acid can be recovered from the leachate by cooling crystallization at 5 °C, and after the recovery of oxalic acid, the purity of final TiO2 product can also be improved. For example, when the leachate was cooled directly at 5 °C for 5 h, about 7% of oxalic acid was recovered, and the purity of final TiO2 product improved from 95.7% to 96.6%. Furthermore, it was found that when some HCl solution was added to the leachate, both the recovery percentage of oxalic acid and the purity of TiO2 product increased. For instance, when 15 vol% of HCl solution relative to pregnant leachate was added, about 35% oxalic acid was recovered by cooling crystallization at 5 °C for 3 h, and the anatase TiO2 product with a purity of 99.2% was obtained by hydrothermal precipitation at 140 °C for 2.5 h. [ABSTRACT FROM AUTHOR]

The characterization of new process equipment often includes tedious experiments, particularly for (cooling) crystallization. This can be cost-intensive and time-consuming when the actual equipment has to be continuously operated to gain new insights. For multi-purpose plants that frequently change the process substance system, this can be especially laborious. In order to accelerate the generation of characterization data for the quasi-continuous filter belt crystallizer (QCFBC), a Peltier-element-driven, simplified experimental benchtop setup is validated in this work using a sucrose/water model substance system. It was shown that the operation conditions during the cooling crystallization on the continuously operated plant can be appropriately emulated; therefore, an actual operation of the entire mini-plant for characterization experiments is no longer necessary. [ABSTRACT FROM AUTHOR]

As an intermediate in the synthesis of pesticide imidacloprid, imidazolidine is easily blended in imidacloprid products, which will lower the purity of the latter, thus affecting the using effects of it. The cooling crystallization method was used to study the distribution of imidazolidine. Taking the imidazolidine removal rate and partition coefficient as assessment criteria, the effect of the cooling rate, final crystallization temperature, crystallization time and addition of seed crystal on the migration of imidazolidine between liquid and solid phases was systematically studied, as well as the separation effect and product quality were evaluated. It was found that imidazolidine was most distributed in the solid phase at a higher cooling rate and a higher final crystallization temperature. The optimal process conditions for cooling crystallization were reached at the cooling rate of 0.2°C/min, the final crystallization temperature 15°C, the crystallization time of 5 h and the addition of seed crystal of 1%, under which the imidazolidine would remained in the liquid phase as much as possible. The final process yield was 83.62%, and the product purity was 99.70%. [ABSTRACT FROM AUTHOR]

Glucosamine hydrochloride (GAH) is a kind of natural hexose, which is used to promote the synthesis of mucopolysaccharides and improve the metabolism of articular cartilage. In this paper, the solubility of GAH in pure water and aqueous system with the presence of three kinds of additives (HCl, NaCl, KCl) at temperatures ranging from 278.15 K to 323.15 K was determined by gravimetric method. When there are additives in water, the solubility of GAH increases with the increase of temperature and decreases with the increase of concentration of the three kinds of additives. When the additives were at similar mole fractions, HCl led to the lowest solubility of GAH. The modified Apelblat model and van’t Hoff model were used to correlate the solubility data. The average relative deviation (ARD) data of Apelblat and van’t Hoff models were less than 5%, indicating good fitting results. Based on the thermodynamic data, the cooling crystallization process of GAH was performed. It was found that the additives could affect the crystal morphology, particle size, and yield of GAH products. This study supplemented the thermodynamic data of GAH and studied the cooling crystallization process in the presence of GAH additives, which provided important guidance for the optimization of the crystallization process.

Continuous tubular crystallizers that can provide high yield and better control of crystal size would be of great interest to the industrial crystallization process. However, most continuous crystallizer designs face challenges either due to surface fouling or crystal breakage. In this paper, we explore the ability of slug-flow cooling crystallizers to continuously generate acetaminophen crystals using silicone oil as the continuous phase. Each slug acts as a crystallizer, and the crystals formed inside the dispersed phase avoid encrustation. Three crystallizer configurations were studied at a wide range of supersaturation and flow rates. It was found that a narrow crystal size distribution can be achieved at high flow rates and high supersaturation. Additionally, the average crystal size and the crystallization yield increased with supersaturation and residence time. The configuration of the tubular crystallizer was found to influence the crystallization yield by affecting the internal mixing in the slugs. With further studies, slug-flow cooling crystallizer can be developed for continuous crystallization of crystals with a narrow size distribution, polymorphic purity, and good yield.

The stirred-tank crystallizer (STC) is the widely used apparatus in industrial crystallization. However, it presents notable challenges, including a broad crystal size distribution (CSD) and fouling. Herein, the twisted hexagonal tube (THT) was employed for thiourea cooling crystallization. The THT exhibited superior heat transfer performance compared to the circular tube (CT) under identical conditions. Furthermore, the THT exhibited longer induction times and wider metastable zone width compared to STC and CT, indicating that the THT can effectively mitigate the nucleation rate. Crystals formed in the THT exhibited elliptical shapes, with a purity of 99.3 % and a target-product (425 μm) proportion of 78 wt%. Thiourea crystallized using the THT met the first-class in China standard HG/T 3454–2013, whereas those crystallized using STC and CT met the second-class standard. Consequently, the THT, as a novel tubular crystallizer, demonstrated considerable potential. [Display omitted] • Twisted hexagonal tube (THT) crystallizer was first time used for cooling crystallization. • THT has a higher heat-transfer efficiency in cooling crystallization compared with circular tube. • THT achieved highest target-product yield of 78 wt% with highest purity 99.3 %. [ABSTRACT FROM AUTHOR]

The control of size distribution is important as it determines the efficiency of downstream processes. The crystalline particles with a narrow size distribution can be produced by controlling the time for the formation of the first crystal. In this study, we investigated the effects of aeration on desupersaturaion to improve size distribution during cooling process. The results show that aeration was able to induce nucleation even in the temperature range where spontaneous nucleation does not occur under certain cooling rate conditions. Furthermore, fine crystals with a narrow size distribution were obtained using aeration. The enhancement effect of desupersaturation was dependent on the aeration start temperature. Therefore, to improve the size and size distribution of crystals, it is important to determine the suitable aeration start temperature. In summary, the characteristics of crystalline particles obtained when aeration is performed could be evaluated based on the changes in the supersaturation of the solution. [Display omitted] • Aeration was introduced into cooling crystallization to improve size distribution. • Aeration allowed the production of fine crystals with a narrow size distribution. • The enhancement effect of desupersaturation depends on the aeration temperature. • A suitable aeration temperature is important to improve the characteristics. [ABSTRACT FROM AUTHOR]

[Display omitted] • >82 % of Al can be transformed into soluble aluminum ammonium sulfate by ammonium sulfate roasting. • The transformed aluminum can be completely separated by water immersion without consuming inorganic acids. • Al can be recovered as ammonium aluminum sulfate from water leachate using cooling crystallization. • Al 2 O 3 with a purity of 99.15 % can be prepared from obtained ammonium aluminum sulfate after calcination. • Ammonium sulfate can be recycled, which not only reduces costs but also avoids environmental pollution. Secondary aluminum dross (SAD), a hazardous waste product generated during the recycling of aluminum-containing electrolytic waste and scrap aluminum products, contains a significant amount of valuable metal aluminum, soluble salts (such as sodium chloride and potassium chloride), and aluminum nitride. Because of its complex phases and chemical composition, approximately 95 % of SAD is disposed of by stockpiling on the spot, resulting in considerable ecological damage and threats to public health. This study proposes a sustainable and green process for selective separation and recovery aluminum oxide, which is a highly valuable material for SAD. The process primarily consists of ammonium sulfate roasting, water leaching, and cooling crystallization. First, ammonium sulfate roasting facilitates the transformation of aluminum into aluminum ammonium sulfate; by employing a roasting temperature of 425 ℃, m((NH 4) 2 SO 4): m(water-washed residue (WWR)) of 6:1, a roasting time of 90 min, a leaching temperature and time of 60 ℃ and 90 min, respectively, and a liquid to solid ratio of 8, over 82 % of Al was transformed into soluble aluminum ammonium sulfate, which is subsequently separated by water leaching. Next, Al was separated from impurities such as Fe, Ca, Si, and Mg in the water leachate using a cooling crystallization method. At the crystallization temperature of 0 ℃ and the crystallization time of 720 min, resulted in an aluminum ammonium sulfate recovery efficiency of 80.5 %. Subsequently, the crystals were calcined at 1200 ℃ for 240 min to obtain Al 2 O 3 with a purity of 99.15 % and an impurity metal content of less than 0.1 %. This process effectively reduces energy consumption, costs, chemical reagent usage, and environmental pollution, thus preventing potential environmental hazards and enhancing process economics. [ABSTRACT FROM AUTHOR]

Ultrasound is a useful method to obtain the stable form for polymorph systems. The stable crystal form of glycine as a model compound in cooling crystallization using ultrasound is studied. The form of the crystal products is characterized by powder X‐ray diffraction. The influences of ultrasound process parameters, including the ultrasound treating timing, treating mode, power density and duration, on the γ‐glycine in cooling crystallization are conducted. The nucleation moment when a "critical size of cluster" is formed is the most effective moment for the ultrasound treatment, and at the same time produces more stable form. Pulse treating mode can effectively solve the ultrasound thermal effect problem. The total energy input and duration has a peak value in promoting the form transformation in practice. The mechanism of the ultrasound in promoting the stable form formation is also discussed. [ABSTRACT FROM AUTHOR]

Volatile markets and increasing demands for quality and fast availability of specialty chemical products have motivated the rise of small-scale, integrated, and modular continuous processing plants. As a significant unit operation used for product isolation and purification, cooling crystallization is part of this trend. Here, the small-scale and integrated quasi-continuous filter belt crystallizer (QCFBC) combines cooling crystallization, solid-liquid separation, and drying on a single apparatus. This contribution shows the general working principle, different operation modes, and possibilities of temperature control with the modular setup. For precise temperature control in cooling crystallization, Peltier elements show promising results in a systematic study of different operation parameters. Sucrose/water was used as a model substance system. The results confirm that seed crystal properties are the most important parameter in crystallization processes. Additionally, an oscillating temperature profile has a narrowing effect on the crystal size distribution (CSD). The integrated, small-scale, and modular setup of the QCFBC offers high degrees of flexibility, process control, and adaptability to cope with future market demands. [ABSTRACT FROM AUTHOR]

In this paper, a crystal image analysis method is presented to measure and predict crystal sizes, based on cooling crystallization of β-form L-glutamic acid (LGA) by using an in-situ non-invasive imaging system. The proposed method consists of image restoration, image segmentation, crystal size measurement, and size prediction. To cope with the effects of noise pollution, uneven illumination and movement blurring, the image processing method is conducted for segmenting crystal images captured from the stirring reactor. Thus, the crystal size distribution for crystal population is obtained by using a probability density function. In addition, a short-term prediction method is given for crystal sizes. An experimental study on the cooling crystallization process of β-form LGA is shown to demonstrate the effectiveness of the proposed method.

In this paper, a new image analysis method based on an in-situ microscopic imaging system is proposed for detecting micro crystals in cooling crystallization. Due to the limitation of measurement technology, it is a challenge to extract the evolutionary information of micro crystals, which are too small to be precisely analyzed by in-situ images, e.g. crystals at the initial crystallization stage. An improved deep-learning model is used to enhance the image resolution of micro crystals, thus more effectively obtaining the crystal shape and size information. In addition, a valid size calibration method by simulating particle motion is proposed. Consequently, image size measurement can be easily performed for crystals by using an axis-based algorithm. Experimental verifications on β-form L-glutamic acid crystallization were performed to demonstrate the effectiveness of the proposed method for detecting micro crystal information.

The sphericity and size of ammonium perchlorate (AP) particles are the most significant properties in composite propellants. In this study, using the Taguchi method, the effects of surfactant type, surfactant concentration, stirring speed, cooling rate, and AP concentration parameters were investigated on the sphericity and size of AP particles in the cooling crystallization process (CCP). The sphericity and size of AP particles were calculated from the scanning electron microscopy (SEM) images by microstructure image processing (MIP) technique. The results showed that the selected parameters have sufficient effect on the sphericity and size of AP particles, based on analysis of variance. In this regards, the most effective parameters for sphericity and size optimization are the stirring speed and the surfactant type, respectively. Also, the AP concentration had the least effect on the sphericity and size of AP particles. Based on analysis of variance; the optimum sphericity and size equal to 0.84 and 21 μm, were predicted in CCP for AP particles, separately. Then, the particle sphericity of 0.84 and size of 23 μm was obtained from the suggested experimental optimal conditions. The differences between the predicted and experimental results are 1.7 and 8% for sphericity and size of AP particles, respectively. [ABSTRACT FROM AUTHOR]

[Display omitted] • Effects of seeding temperature and the purity of seed crystals. • Optimum purity and solvent capacity of curcumin using the azeotrope of ethyl acetate/ethanol. • Recyclable positive azeotropes for reuse in the purification of curcumin. Purification of curcumin (CUR) from crude CUR, which is referred to as curcuminoids, has been conducted by cooling crystallization with the use of two azeotropes of ethyl acetate/ethanol (AZE-EA/EtOH) and ethyl acetate/isopropyl alcohol (AZE-EA/IPA), as compared to the use of single solvents, including acetone, EA, EtOH, and IPA. According to the determination of crude CUR solubility in those solvents, the effects of stirring, crystallization time, and seeding on the induction time, purity, and yield of CUR product were investigated on a small scale. Especially the effects of the purity of CUR seed crystals have a positive trend on the CUR purity. Seeding at a high temperature is suggested. The use of AZE-EA/EtOH shows the optimum purity of 94.0% and solvent capacity of 16.0 mg/mL with a yield of 29.0% by seeded cooling crystallization in a single step. Similar results are observed in the larger scale purification of CUR with a higher purity of 94.9%. After purification, the azeotropes can easily be recovered for reuse without changing their compositions, confirmed by GC, density, and boiling point determination. [ABSTRACT FROM AUTHOR]

Abstract Background Crystallization is used as a purification process in majority of the industries such as pharmaceuticals, food products, chemicals, catalysts, and cosmetics. Crystallization of active pharmaceutical ingredients is carried out to increase the dissolution rate and attain sufficient bioavailability in pharmaceutical industries. It can also enhance the flow properties and drug dosage control of the active pharmaceutical ingredients. Single crystals give us a lucid understanding of the intrinsic properties of a material. A material made up of many crystals will have grain boundaries which do not allow us to measure properties such as thermal and electrical resistance effectively. Single crystals will not have defects or impurities in them. Thus, help us in making comparisons with other materials and contribute to a better understanding of particular behaviors. Therefore, it is important to investigate the growth of single crystals. Sulphanilamide is a sulpha class drug used as an intermediate and starting material for the production of various drugs. It is an antibacterial agent and is often used in pharmaceutics and cosmetics. In this study, we wanted to obtain sulphanilamide crystals by two different crystallization methods and compare the results gathered. Sulphanilamide usually crystallizes in the form of needles, thus is ideal for the purpose of this study. In this work, crystallization of sulphanilamide was carried out by cooling method and solvent evaporation method. In Cooling method as temperature was brought down the crystals separated out. On the other hand, in solvent evaporation method, the solvent evaporated leaving behind the crystals. The process parameters that varied included stirring rate of the solution at a constant temperature, concentration of the solute in a constant volume of solvent, solvent systems chosen-acetone, methanol and ethanol, and time allowed for crystallization. Results Crystals were obtained under the varying conditions. Characterization of the crystals formed was carried out using X-ray diffraction method, scanning electron microscopy, and differential scanning calorimetry. The size and morphology of the crystals formed was observed and the results were compared. It was found that the crystals obtained from using methanol as solvent, with high concentration of solute, gave the most uniform and large-sized cubic crystals under solvent evaporation method. The surface of the crystal was also seen to be smooth with well-defined edges as shown in the SEM images. Stirring reduced the size of crystals formed, and longer time of crystal formation resulted in larger crystals. Solvent evaporation method gave more uniform crystals compared to cooling method. Conclusion This study gives us an understanding of how each parameter affects crystal growth. Thus, optimum conditions for crystal growth can be determined.

The primary motive of the current work is to achieve smaller mean particle size with narrow size distribution that can enhance the bioavailability of azithromycin (ARZ), an essential requirement due to its poor water solubility. Recrystallization of ARZ was evaluated using cooling as well as antisolvent crystallization approaches in the presence of ultrasonic irradiation with detailed study into effect of different parameters such as ultrasonic power, time and temperature. Ultrasound assisted antisolvent crystallization at low temperatures (

1,2-Diphenylethane can be widely used in organic synthesis field because of its particular molecular structure. In order to gain high pure 1,2-diphenylethane, the mainly conventional purification method is vacuum distillation. However, the vacuum distillation exhausts excessive energy, needs heavy tower equipment, and it is not easy to achieve high pure product. To obtain high pure 1,2-diphenylethane, save money, and conserve energy, the cooling crystallization with ethanol is used to purify 1,2-diphenylethane. Firstly, the impact of crystallization temperature, crystal growing time, cooling rate, stirring speed, seed size, and seed weight on the cooling crystallization processes of 1,2-diphenylethane in ethanol were investigated. Then, the orthogonal experiment were also studied. It provides a reference for industrial cooling crystallization of 1,2-diphenylethane. [ABSTRACT FROM AUTHOR]

The characterization of new process equipment often includes tedious experiments, particularly for (cooling) crystallization. This can be cost-intensive and time-consuming when the actual equipment has to be continuously operated to gain new insights. For multi-purpose plants that frequently change the process substance system, this can be especially laborious. In order to accelerate the generation of characterization data for the quasi-continuous filter belt crystallizer (QCFBC), a Peltier-element-driven, simplified experimental benchtop setup is validated in this work using a sucrose/water model substance system. It was shown that the operation conditions during the cooling crystallization on the continuously operated plant can be appropriately emulated; therefore, an actual operation of the entire mini-plant for characterization experiments is no longer necessary.

In the present study, a process of separating high-quality TiO2 from an oxalic-acid leachate of vanadium slag was proposed. It consists of two steps; oxalic acid was firstly recovered from the leachate by the cooling-crystallization method, and subsequently TiO2 was separated from the oxalic-acid recovered leachate by the hydrothermal precipitation method. The experimental results indicate that oxalic acid can be recovered from the leachate by cooling crystallization at 5 °C, and after the recovery of oxalic acid, the purity of final TiO2 product can also be improved. For example, when the leachate was cooled directly at 5 °C for 5 h, about 7% of oxalic acid was recovered, and the purity of final TiO2 product improved from 95.7% to 96.6%. Furthermore, it was found that when some HCl solution was added to the leachate, both the recovery percentage of oxalic acid and the purity of TiO2 product increased. For instance, when 15 vol% of HCl solution relative to pregnant leachate was added, about 35% oxalic acid was recovered by cooling crystallization at 5 °C for 3 h, and the anatase TiO2 product with a purity of 99.2% was obtained by hydrothermal precipitation at 140 °C for 2.5 h.

Nucleation in continuously operated capillary coiled cooling crystallizers is experimentally investigated under the influence of ultrasound. It was found that there is no sharp boundary but rather a transition zone for nucleation under sonication. For this purpose, a tube with an inner diameter of 1.6 mm and a length of 6 m was winded in a coiled flow inverter (CFI) design and immersed into a cooled ultrasonic bath (37 kHz). The CFI design was chosen for improved radial mixing and narrow residence time distribution, which is also investigated. Amino acid l-alanine dissolved in deionized water is employed in a supersaturation range of 1.10 to 1.46 under quiet and sonicated conditions. Nucleation is non-invasive detected using a flow cell equipped with a microscope and camera. Since the interest and demand for small-scale, continuous crystallization increases, seed crystals were generated in a coiled tube via sonication and optically investigated and characterized. No distinct threshold for nucleation could be determined in a wide range of supersaturations of l-alanine in water [ABSTRACT FROM AUTHOR]

This paper reports the solid-liquid phase equilibria of the CoSO 4 -H 2 O and CoSO 4 -H 2 SO 4 -H 2 O systems at low temperatures. Binary and ternary phase diagrams, including the stable solid phases CoSO 4 ·6H 2 O and CoSO 4 ·7H 2 O were established using experimental data and thermodynamic modeling applying the mixed-solvent electrolyte (MSE) model. The results showed that the addition of H 2 SO 4 shifts the eutectic temperature and concentration to lower values for cobalt sulfate and ice crystallization. The trends obtained from the experimental data and the modeling are consistent for the binary CoSO 4 -H 2 O system with good agreement, but the ternary CoSO 4 -H 2 SO 4 -H 2 O system shows some deviations. In general, the MSE model is shown to be reliable for inferring and establishing the phase diagram of the low-temperature system. The phase diagrams are helpful for designing the pathways of cooling crystallization and eutectic freeze crystallization and assessing the performance of the low-temperature crystallization process in the production of CoSO 4 hydrates. In addition, some practical examples of cooling crystallization and eutectic freeze crystallization of CoSO 4 solutions are provided. • Phase equilibria of the CoSO 4 -H 2 O and CoSO 4 -H 2 SO 4 -H 2 O systems at low temperatures • Cooling crystallization of cobalt sulphate hydrates • Eutectic freeze crystallization of cobalt sulphate heptahydrate [ABSTRACT FROM AUTHOR]

Ammonium perchlorate is one of the most important and applicable oxidizers used in solid propellants. Also, the morphology of ammonium perchlorate particles is an effective parameter in the production of propellants. In the current research, the preparation of ammonium perchlorate using the cooling crystallization method was studied. Four parameters including the rate of cooling, mixing patterns, agitator speed, and surfactant were considered in cooling crystallization of ammonium perchlorate. Nine tests were carried out based on the Taguchi experimental design method. The morphology of the obtained crystals was analyzed by optical microscope and MIP 4 student software. The size distribution of the particles was modeled using the Rosin-Rammler method. Obtained results illustrated that the surfactant had the most effect with the value of 70.7% and the agitator speed, flow pattern, and cooling rate had fewer effects on the morphology with the values of 25.8%, 2.9%, and 0.2%, respectively. The optimal amount of sphericity obtained by the Taguchi method was 0.77 which was verified by the experimental result of 0.76. The roundness and aspect ratio values for the optimal crystal were 0.79 and 1.40 respectively. Applying the Rosin-Rammler model showed that the homogeneity factor of size distribution was 2.22 for the optimal crystals. [ABSTRACT FROM AUTHOR]

A four-stage sequential leaching (SL) and subsequently cooling crystallization (CC) techniques have been implemented for the recovery of boron from the clay waste (CW) induced by the borax derivatives production facility located in Kırka district of Eskişehir province, NW of Turkey. Optimum experimental solid-liquid ratio and agitation time for SL tests were determined by preliminary experiments. In the first leaching stage, approximately 85% of boron in the CW was transited to the leachate. A logarithmic decrease in the boron transition efficiency was obtained as a function of stages. After four-stage SL procedure, CC procedure was carried out with the last leachate at 4.0 °C ±0.3 stabilized refrigerator. Approximately 77% of dissolved boron in the last leachate was crystallized by CC as high purity borax crystals. Mineralogical, chemical, and physical definitions of the crystals were determined by X-ray diffraction (XRD), instrumental element analysis following microwave digestion, and scanning electron microscopy (SEM) procedures, respectively. As a result, sequential leaching followed by cooling crystallization system was determined as an effective methodology for the recovery of boron from the CW as high purity borax form. [ABSTRACT FROM AUTHOR]

A novel process for the extraction of vanadium and preparation of sodium vanadate from V–Cr-bearing reducing slag is proposed. This process involves several steps of washing, alkaline leaching, evaporation crystallization and cooling crystallization. The washing procedure ensures that chloride and sulfate ions can be mostly washed away from V–Cr-bearing reducing slag. Subsequently, vanadium can be extracted by alkaline leaching, the leaching rate of vanadium can reach 98%. During this process, vanadium enters the leaching solution, and chromium continues to accumulate in the leaching residue. Finally, most of Na2SO4 can be removed from the alkaline leaching solution by evaporation crystallization, then the Na3VO4·12H2O can be prepared by cooling crystallization. The filtrate of cooling crystallization can be recycled as the new leaching medium with some new alkali added, which greatly reduces the discharge of alkaline wastewater and makes the whole process more environmentally friendly. [ABSTRACT FROM AUTHOR]

Allitol is a kind of rare sugar alcohol with potential application value. An engineered strain, which simultaneously expressed d-psicose-3-epimerase (DPE), ribitol dehydrogenase (RDH), and formate dehydrogenase (FDH) three enzymes, was constructed by cloning above three genes into one plasmid and transformed into the host E. coli strain, and used as the whole-cell catalysts for biotransformation of allitol from the low-cost substrate of d-fructose. The whole cell allitol biotransformation conditions were optimized. The medium, recombinant gene induction conditions, and the substrate feeding rate for cultivation of the catalytic cells were optimized. Then, the fed-batch culture was made and scaled up to 10 L fermentor. Finally, 63.44 g/L allitol was obtained from 100 g/L d-fructose after 3 h of biotransformation, and the allitol crystals of 99.9% purity were obtained by using cooling recrystallization. The allitol production method developed in this research has high product purity, and is highly efficient, easily scaled up, and suitable for large-scale production of highly purified allitol. [ABSTRACT FROM AUTHOR]

A detailed knowledge of the metastable zone width (MSZW) and nucleation kinetics is vital for the design of batch cooling crystallization processes. Factors such as cooling rate and impeller speed affect the MSZW and nucleation kinetics. Crystallization and dissolution temperatures were measured as a function of cooling rate and impeller speed during the batch cooling crystallization of p‐aminobenzoic acid (pABA) from ethanol in a 0.5‐L stirred‐tank crystallizer. The polythermal experimental data were analyzed using the Nyvlt and first principles‐based Kashchiev‐Borissova‐Hammond‐Roberts (KBHR) methods. In all experimental cases, the latter model revealed that the nucleation process of pABA in ethanol was dominated by an instantaneous nucleation mechanism. The Nyvlt and KBHR analyses delivered a range of parameter values associated with a power‐law model describing the nucleation rate as well as the concentration of nuclei. [ABSTRACT FROM AUTHOR]

It was recently demonstrated that the technique of solid hollow fiber membrane-based cooling crystallization can be employed to achieve continuous polymer precipitation from a solution and subsequent polymer coating/encapsulation of sub-micrometer particles/drug crystals as well as nanoparticles in suspension. In this technique, there is no need for high pressure as in supercritical solvent-based anti-solvent crystallization; further, there is easy scale-up and production of free-flowing polymer-coated particles. There is a concern however, whether this crystallization method can be applied for an extended duration since the earlier studies were run for only about 10 min. In this work, the duration of the cooling crystallization-based coating process has been greatly extended from 10 min to 60 min and 120 min. Eudragit RL 100 was chosen as the coating polymer and Cosmo 55 (550 nm silica particles) was the host for the coating process in an acetone solution. Scanning electron microscopy (SEM) and thermogravimetric analysis (TGA) were employed to characterize the coated samples. The results showed that the solid hollow fiber membrane-based cooling crystallization performed successfully as a continuous crystallizer during extended time running operation. Characterization of the products by SEM and TGA indicated a stable product consistent with a uniform spherical shape. The coating thickness of the samples tended to be essentially identical for the extended-duration coating process as long as solvent loss by volatilization and uneven distribution of host particles in the feed solution-suspension was kept to a minimum. Unlabelled Image • Continuous polymer coating of suspended submicron silica particles was demonstrated. • The technique uses solid hollow fiber membrane-based cooling crystallizer. • Coating thickness on silica particles was uniform over a 60 min-long operation. • 550 nm silica particles were coated with ~31.5 nm polymer coating of Eudragit RL100. • There was no evidence of fouling of hollow fiber lumen vis-à-vis coating process. [ABSTRACT FROM AUTHOR]

The cooling crystallization of carbapenem CS-023 was performed at 25 °C in an aqueous solution. Tetrahydrate crystals (form H) were obtained. Hydrate crystals are promising drugs, but there has been problems in manufacturing such crystals. During cooling crystallization, a dissolution process at a high temperature of 70 °C was utilized. The main problem in manufacturing was that the degradation rate of CS-023 at 70 °C was high, as expressed in the half-life period of 2.97 h. Poor solvent crystallization using ethanol was observed at 25 °C. Thus, a different polymorph (Form A) was obtained. Form A comprised CS-023, 5/2 ethanol, and 1/2 H2O. Form A, containing ethanol, is not suitable as a drug. Form A was then transformed to another polymorph of hydrate crystals or tetrahydrate Form H. Another hydrate polymorph, Form B, was obtained through the solid phase transformation of Form A and further transformed to the tetrahydrate Form H, at high humidity over 80% RH. This process, which proceeded at the low temperature of 25 °C, helped to prevent the degradation of CS-023, thereby avoiding wastage. Furthermore, the solid-phase transition could be controlled with vapor composition.

The kinetic rate equation (KRE) model, unlike the population balance equation model, can describe growth, nucleation, and even Ostwald ripening simultaneously. However, the KRE model cannot be applied in cooling crystallization systems. In this work, we propose a modified KRE model to describe cooling crystallization. The modified KRE model can successfully describe crystal growth and nucleation in cooling crystallization systems. In addition, the metastable zone width was simulated using the modified KRE model and compared with the experimental data in references. The results revealed that the modified KRE model could express the effect of overheating prior to cooling on the metastable zone width. As the extent of overheating increases, the metastable zone width becomes wider, which phenomenon can be clearly simulated by the modified KRE model. This modeling capability is attributed to the behavior of particle clusters that are sized less than the size of sub-nuclei. Because the population balance equation model cannot describe the metastable zone width, the modified KRE model has certain competitive advantages in its application to various crystallization systems. [ABSTRACT FROM AUTHOR]

An online concentration monitoring method was established by using attenuated total reflection ultraviolet (ATR‐UV) coupled with a suitable partial least squares regression for a multi‐solute crystallization system, namely, disodium 5'‐inosinate (IMP) and disodium 5'‐guanylate (GMP) in aqueous ethanol. The results indicated that the established method accurately predicted the concentration of IMP and GMP in the solution. The solubility data was measured at various temperatures and ethanol/water mass ratios, and the experimental data was well correlated by applying the modified Apelblat equation and modified Jouyban‐Acree model. The implementation of cooling crystallization demonstrates that the developed calibration model is suitable for online concentration monitoring with reasonable accuracy and precision. [ABSTRACT FROM AUTHOR]

CH 3 NH 3 SnI 3 crystals with largest size up to 10 mm × 6 mm × 6 mm were grown in aerobic environment using cooling crystallization method. XRD analysis of the crystal powder shows that the CH 3 NH 3 SnI 3 crystal grown is of cubic phase with lattice constants a = b = c = 6.2480 Å. XRD and EDX results show that the chemical properties of CH 3 NH 3 SnI 3 crystal are unstable in air, and the oxidation mechanism of CH 3 NH 3 SnI 3 was analyzed. HRTEM shows that the CH 3 NH 3 SnI 3 crystal grown is of good crystallinity. FT-IR spectrum of CH 3 NH 3 SnI 3 crystal was identified. The band gap E g of the CH 3 NH 3 SnI 3 crystal is estimated to be 1.33eV according to the absorption spectrum. First-principles calculation shows the band gap of cubic CH 3 NH 3 SnI 3 crystal is 1.36 eV, which is consistent with the experimental results. The thermal property of CH 3 NH 3 SnI 3 is analyzed by TG/DTG analysis. Our results show that CH 3 NH 3 SnI 3 crystal has potential application prospects in the field of solar cells, however its poor chemical stability in air, leading to the formation of SnI 4 and SnO would limit its application in photoelectric fields. • Large-sized MaSnI 3 crystals were obtained by a cooling crystallization method under aerobic environment. • XRD and EDS analysis show that MaSnI 3 is not stable in aerobic environment. • Band gap obtained by the first-principles calculation is 1.36 eV, which is similar to the experimental results (1.33 eV). [ABSTRACT FROM AUTHOR]