Conventional Crystallization Methods Research Articles

Antisolvent crystallization of battery grade nickel sulphate hydrate in the processing of lateritic ores

Lithium-ion batteries are a crucial part in the rapid, on-going electrification of the global vehicle fleet, which is essential in enabling a transition to a society based on renewable energy. By combining metals including lithium, nickel, cobalt, and manganese in different proportions, cathode active materials with different properties can be obtained. Nickel sulphate hexahydrate, which is of great importance to the battery industry, can be produced by hydrometallurgical processing of lateritic and sulphide ores. Antisolvent crystallization is examined as an alternative to conventional crystallization methods for the production of high-grade nickel sulphate hexahydrate in the processing of lateritic nickel ores from Turkey. The ore has been leached under atmospheric pressure followed by purification by ion exchange resulting in a solution enriched with respect to nickel together with a range of impurity metals from which NiSO4·6H2O can be obtained by antisolvent crystallization. Separate antisolvent crystallization experiments have been carried out for nickel, cobalt and iron sulphate systems, which are the main metals present in the solution, and solubility data has been determined for key conditions. Acetone and isopropanol have been evaluated as antisolvents. Antisolvent crystallization experiments have also been carried out using synthetic solutions and the effect of addition rate of antisolvent, addition of diluted antisolvent and seeding on the purity of the crystals has been investigated. Acetone gives the best product quality in terms of purity and shape. Seeding and a slow rate of addition of dilute antisolvent gives the highest purity of the NiSO4·6H2O crystals. Under optimised conditions, crystals containing 22.3% Ni with a purity of 99.8% by mass have been obtained with a crystallization yield of 63.5%.

Quantifying Effects of Active Site Proximity on Rates of Methanol Dehydration to Dimethyl Ether over Chabazite Zeolites through Microkinetic Modeling.

Control of the spatial proximity of Brønsted acid sites within the zeolite framework can result in materials with properties that are distinct from materials synthesized through conventional crystallization methods or available from commercial sources. Recent experimental evidence has shown that turnover rates of different acid-catalyzed reactions increase with the fraction of proximal sites in chabazite (CHA) zeolites. The catalytic conversion of oxygenates is an important research area, and the dehydration of methanol to dimethyl ether (DME) is a well-studied reaction as part of methanol-to-olefin chemistry catalyzed by solid acids. Published experimental data have shown that DME formation rates (per acid site) increase systematically with the fraction of proximal acid sites in the six-membered ring of CHA. Here, we probe the effect of acid site proximity in CHA on methanol dehydration rates using electronic structure calculations and microkinetic modeling to identify the primary causes of this chemistry and their relationship to the local structure of the catalyst at the nanoscale. We report a density functional theory-parametrized microkinetic model of methanol dehydration to DME, catalyzed by acidic CHA zeolite with direct comparison to experimental data. Effects of proximal acid sites on reaction rates were captured quantitatively for a range of operating conditions and catalyst compositions, with a focus on total paired acid site concentration and reactant clustering to form higher nuclearity complexes. Next-nearest neighbor paired acid sites were identified as promoting the formation of methanol trimer clusters rather than the inhibiting tetramer or pentamer clusters, resulting in large increases in the rate for DME production due to the lower energy barriers present in the concerted methanol trimer reaction pathway. The model framework developed in this study can be extended to other zeolite materials and reaction chemistries toward the goal of rational design and development of next-generation catalytic materials and chemical processes.

Miniaturization of the Whole Process of Protein Crystallographic Analysis by a Microfluidic Droplet Robot: From Nanoliter-Scale Purified Proteins to Diffraction-Quality Crystals.

To obtain diffraction-quality crystals is one of the largest barriers to analyze the protein structure using X-ray crystallography. Here we describe a microfluidic droplet robot that enables successful miniaturization of the whole process of crystallization experiments including large-scale initial crystallization screening, crystallization optimization, and crystal harvesting. The combination of the state-of-the-art droplet-based microfluidic technique with the microbatch crystallization mode dramatically reduces the volumes of droplet crystallization reactors to tens nanoliter range, allowing large-scale initial screening of 1536 crystallization conditions and multifactor crystallization condition optimization with extremely low protein consumption, and on-chip harvesting of diffraction-quality crystals directly from the droplet reactors. We applied the droplet robot in miniaturized crystallization experiments of seven soluble proteins and two membrane proteins, and on-chip crystal harvesting of six proteins. The X-ray diffraction data sets of these crystals were collected using synchrotron radiation for analyzing the structures with similar diffraction qualities as conventional crystallization methods.

Comparative Study of Different Crystallization Methods in the Case of Cilostazol Crystal Habit Optimization

The therapeutic usage of cilostazol is limited owing to its poor aqueous solubility and oral bioavailability. Our aim was to produce cilostazol crystals with small average particle size; besides suitable roundness, narrow particle size distribution and stable polymorphic form to increase its dissolution rate and improve processability. Different conventional crystallization methods with or without sonication were compared with impinging jet crystallization combined with cooling, and the optimization of the various parameters was also implemented. The effects of post-mixing time and temperature difference were studied by means of a full factorial design. The physical properties of powder particles were characterized by, i.a., XRPD, DSC and SEM. The dissolution rate and the contact angle of solid surfaces were also determined to elucidate the relationship between wettability and dissolution. It was observed that impinging jet crystallization combined with cooling is a very effective and reproducible method for reducing the particle size of cilostazol. This method resulted in significantly smaller particle size (d(0.5) = 3–5 μm) and more uniform crystals compared to the original ground material (d(0.5) = 24 μm) or the conventional methods (d(0.5) = 8–14 μm), and it also resulted in a stable polymorphic form and enhanced the dissolution rate.

Gas Antisolvent Fractionation: a New Method to Obtain Enantiopure Compounds, a Case Study on Mandelic Acid

Micronization processes involving supercritical carbon dioxide are rapid methods to produce fine particles. They also might offer the possibility of using less organic solvent than conventional crystallization methods leading to an environmentally friendlier processing. The separation capabilities of such processes are now demonstrated on the diastereomeric resolution of mandelic acid using (R)-1-phenylethanamine as a resolving agent, utilizing the batch type gas antisolvent fractionation as the separation method. A detailed study was conducted on the effects of the operational parameters pressure (12-20 MPa), temperature (35-55 °C) and co-solvent concentration (33-99 mg/ml). At 12 MPa, 35 °C and 99 mg/ml methanol concentration, a selectivity of 0.52 and a diastereomeric excess of 62% was reached. The same operational parameters were applied during the investigation of the recrystallization-based further purification of the diastereomeric salts, applying the resolving agent in molar equivalent quantity to a non-racemic mixture of mandelic acid. It has been found that the more stable (R)-1-phenylethylammonium-(R)-mandelate salt can be purified to de>98% through four additional recrystallization steps following the initial, half-molar equivalent resolution step.

Additive Mediated Syn-Anti Conformational Tuning at Nucleation to Capture Elusive Polymorphs: Remarkable Role of Extended π-Stacking Interactions in Driving the Self-Assembly

Understanding the process of prenucleation clustering at supersaturating stage is of significant importance to envisage the polymorphism in crystalline materials. Preferential formation of a thermodynamically stable crystal form suggests energetically favored patterns of interactions which control molecular aggregation during nucleation. Introduction of additives during crystallization is sometimes used as a suitable strategy to obtain metastable polymorphs in cases where it is not easy to capture the same by conventional crystallization methods. Comparative analysis of energy relationships and intermolecular interactions between thermodynamically stable and metastable crystal forms provides valuable clues about the nature of growth synthons at prenucleation clustering and preferential crystallization of the thermodynamic form. Conformationally flexible sulfonamide/sulfoester derivatives constituting electron rich and electron-deficient aromatic rings were synthesized to study the interplay between π-stac...

Effect of nanostructure of mineralized collagen scaffolds on their physical properties and osteogenic potential.

Tissue engineering has enabled development of nanostructured collagen scaffolds to meet current challenges in regeneration of lost bone. In this study, extrafibrillarly-mineralized and intrafibrillarly-mineralized collagen scaffolds were fabricated separately by a conventional crystallization method and a biomimetic, bottom-up crystallization method. Atomic force microscopy (AFM) was employed to examine the nanotopography and nanomechanics of the mineralized collagen scaffolds. The in vitro cell responses to the surface of the mineralized collagen scaffolds were analyzed by laser scanning microscope and field emission scanning electron microscopy. AFM imaging showed that these two mineralized collagen scaffolds exhibited different nanostructure, including the size, morphology and location of the apatites in collagen fibrils. The nanomechanical testing demonstrated that the intrafibrillarly-mineralized collagen scaffold, with bone-like hierarchy, featured a significantly increased Young's modulus compared with the extrafibrillarly-mineralized collagen scaffold in both dry and wet conditions. However, these two mineralized collagen scaffolds had a similar thermal behavior. From the cell culture experiments, the intrafibrillarly-mineralized collagen scaffold showed higher cell proliferation and alkaline phosphatase activity than the extrafibrillarly-mineralized collagen scaffold. The utmost significance of this study is that the nanostructure of the mineralized collagen scaffolds can affect the initial cell adhesion, morphology and further osteogenic potential. The present study will help us to fabricate novel biomaterials for bone grafting and tissue engineering applications.

Simultaneous Spherical Crystallization and Co-Formulation of Drug(s) and Excipient from Microfluidic Double Emulsions

We demonstrate the fabrication of engineered pharmaceutical formulations of drug(s) and excipient as monodisperse spherical microparticles. Specifically, we fabricate monodisperse microparticles of ∼200 μm size containing crystals of a hydrophobic model drug (ROY) embedded within a hydrophilic matrix (sucrose) (DE formulation), which in turn may also contain a hydrophilic model drug (glycine) (D2E formulation). To do this, we dispense the components of the formulation into monodisperse oil-in-water-in-oil (O1/W/O2) double emulsions using capillary microfluidics, to subsequently enable simultaneous crystallization and co-formulation via solvent evaporation. We provide detailed morphological and polymorphic characterization of the particles obtained and highlight how (a) microfluidic methods enable formulations that are nearly impossible to achieve using conventional crystallization methods, and (b) these ‘bottom-up’ methods could potentially circumvent several energy intensive ‘top-down’ processes in tradi...

Hydrothermal synthesis of easy-recycled tobermorite/SiO2/Fe3O4 composites for efficient treatment of phosphorus in wastewater

In this work, tobermorite/SiO2/Fe3O4 composites were designed and synthesized by hydrothermal method for the treatment of phosphorus in wastewater. The composites were characterized by scanning electron microscopy and X-ray diffraction. The removal efficiency of phosphorus on the tobermorite/SiO2/Fe3O4 composites was carried out and investigated under various conditions, such as contact time, sorbent content, and pH. After the multi-run experiments, the phosphorous elimination of the tobermorite/SiO2/Fe3O4 composites was declined slightly comparing with the first-run experiments. Compared with the conventional crystallization methods, tobermorite/SiO2/Fe3O4 composites not only gave high efficiency to remove phosphorus from wastewater without any complicated pretreatment, but also provided excellent magnetic properties for separating the phosphorus from water, which made it easy recycled. Moreover, tobermorite/SiO2/Fe3O4 composites had excellent P-elimination properties even in the strong acidic or basic conditions. Therefore, tobermorite/SiO2/Fe3O4 composites were important candidate for water quality control and protection.

Crystallization of Glycine by Drowning-Out Combined with Fines Dissolution and Cooling Process with in Situ Control using Focused Beam Reflectance Measurement and Attenuated Total Reflection–Fourier Transform Infrared Spectroscopy

The DFC process (a combined process of drowning-out, fines dissolution, and cooling crystallization) was applied for the crystallization of glycine. The DFC process encourages seed crystals to grow further by the dissolution of fines generated by drowning-out. Therefore, glycine crystals obtained through the DFC process have relatively large size and uniform size distribution with high product yield compared with those obtained by conventional crystallization methods. In the present work, an operating strategy of the DFC process with in situ control was proposed. First, antisolvent is injected until generation of fine particles is assumed to be completed. Second, fines dissolution by heating is conducted until fine particles are mostly dissolved. Here, generation and dissolution of fine particles are monitored by focused beam reflectance measurement and attenuated total reflectance–Fourier transform infrared. The main advantage of the in situ controlled approach demonstrated in the present work is no requirement for any predetermined data and a reduction of the operating time compared with the previously proposed DFC process, in which operating profile is predetermined by the mass balance equations.

Crystallization in Unsaturated Glycine/D2O Solution Achieved by Irradiating a Focused Continuous Wave Near Infrared Laser

The crystallization of glycine in unsaturated solution is made possible by laser trapping of its molecular clusters due to photon pressure of a focused continuous wave near-infrared laser beam. Always one single crystal is spatiotemporally formed at a focal spot, and then it undergoes dissolution, eventually leading to repetitive crystallization and dissolution. The polymorph characterization of the crystal formed in unsaturated solution confirmed the γ-form, which is not obtainable by conventional crystallization methods. The preparation probability of the γ-form compared to the α-form is much higher than that in the supersaturated solution.

New directions in conventional methods of protein crystallization

Novel strategies and techniques that are based on conventional crystallization methods for crystallizing proteins are described and discussed. New directions for rendering proteins and protein complexes to become more amenable to crystallization are also presented.

Crystal growth behavior in CuO-doped lithium disilicate glasses by continuous-wave fiber laser irradiation

Crystal growth behaviors in CuO-doped Li2O-2SiO2 glasses by continuous-wave (cw) Ytterbium doped fiber laser (wavelength: 1080 nm) irradiations are examined. The lines (width: ~5 μm) consisting of highly oriented nonlinear optical lithium disilicate (Li2Si2O5) crystals are patterned in various laser powers (1.2-2.4 W) and scanning speeds (2-42 μm/s), and it is found that the crystal growth having the rates of 1 to 32 μm/s gives crystal lines with smooth surface morphologies. The critical (maximum) growth rates of Li2Si2O5 crystals in cw fiber laser irradiations are compared with the crystal growth kinetics (the reference data) in the Li2O-2SiO2 glass system determined by a conventional crystallization method in electric furnaces. It is proposed that the temperature of the fiber laser irradiated region for the Li2Si2O5 crystal growth would be 650-850°C. It is of importance to avoid crystal nucleation during laser irradiations for the patterning of homogeneous crystal lines.

Micronization of the chitosan derivatives d-Glucosamine Hydrochloride and d-Glucosamine Sulphate salts by dense gas anti-solvent precipitation techniques

In the pharmaceutical area, fine particles with a narrow particle size distribution are required to obtain a high surface area. In addition, particle size is one of the critical factors for the determination of appropriate routes of drug administration. In this work, we have used dense-gas anti-solvent crystallization techniques for the straightforward production of micron-sized powders of the chitosan derivatives d-Glucosamine Hydrochloride and d-Glucosamine Sulphate salts, which have increasing interest at present in medicinal research. The use of these crystallization methods permit to avoid the problematic communition and homogenization down-stream processes steps required after conventional crystallization methods. Semi-continuous ASES and batch GAS procedures, which are the two extremes of dense gas anti-solvent precipitation techniques, were successfully used for the micronization of these salts, and the results obtained with both procedures are compared and analysed.

Solution stirring initiates nucleation and improves the quality of adenosine deaminase crystals

Crystals of bovine adenosine deaminase (ADA) grown over a two-week period in the presence of an inhibitor (ADA complex) were found to be of low quality for X-ray diffraction analysis. Furthermore, ADA incubated in the absence of an inhibitor (ADA native) did not form any crystals using conventional crystallization methods. A solution-stirring technique was used to obtain high-quality ADA complex and ADA native crystals. The crystals obtained using this technique were found to be of high quality and were shown to have high structural resolution for X-ray diffraction analyses. The results reported here indicate that the solution-stirring technique promotes nucleation and improves the quality of protein crystals.

Protein Crystallization by Combining Laser Irradiation and Solution-Stirring Techniques

Bovine adenosine deaminase in the absence of an inhibitor (free-ADA) does not form crystals when using conventional crystallization methods. Using a solution-stirring technique, we recently succeeded in generating a small number of free-ADA crystals. In this paper, we demonstrate the combination of laser-irradiated growth and stirring (COLAS). This technique was found to be useful for controlling crystal nucleation and growth, which led to the production of a much larger number of high-quality free-ADA crystals.

Influence of Powder Characteristics of Bulk Substance with Pharmaceutical Processing

The physicochemical properties of crystals can vary with the crystallization procedure employed in their isolation and purification. Moreover, the success of any direct-tableting procedure is directly effected by the quality of the crystals used in this process. We examined the conventional crystallization method employed in the isolation and purification of octotiamine crystals, the active component of the pharmaceutical compound Neuvita®. Our objective was to determine under what crystallization conditions (i.e., supersaturation ratio [pH], temperature, impeller speed) octotiamine crystals with excellent direct-tableting potential could be obtained. Our results indicated that modifications in pH level (from 4.3 to 4.0), i.e., a reduction in the supersaturation ratio, and in impeller speed (from 100 to 78 rpm) are necessary to obtain octotiamine crystals with superior flowability and compressibility compared to the use of the conventional crystallization method.Thus, with these modifications in the conventional crystallization method, octotiamine crystals can be made that show dissolution rates similar to those of the conventionally made crystals, yet which can be manufactured into tablets using a simpler method (i.e., direct tableting). Also, the tableting powder made from the new crystal type proved to be less adhesive than the conventionally made crystal powder. This property attributed to the new crystal type will allow for more stable automated manufacturing than the conventional crystal type would allow.

SODIUM SULPHATE FROM BITTERN BY METHANOL

Sodium sulphate is produced mainly from land ores by conventional crystallization methods of evaporation and dehydration; these sources are fast being exhausted and new processes should be found which do not use the conventional sources. Seawater bittern produced as by-product from solar halite plants contains about 6% by weight of sodium sulphate, the recovery of which by conventional methods, is made difficult by the presence of other salts. Methanol has the property of markedly depressing the solubility of certain inorganic salts while hardly affecting the solubilities of others, because of this property, it can be used to promote various crystallization processes and some double decomposition reactions between inorganic salts. This paper examines one example of the second type of application in which magnesium sulphate and sodium chloride present in the bittern interact in the presence of methanol resulting in the formation and selective crystallization of anhydrous sodium sulphate. Experimental work is described which follows the progress of the reaction under wide range of conditions some given above 94% recovery of high purity sodium sulphate with a crystallizer reactor residence time of 20 minutes. SEM photographs reveal rhombic shapes crystals of size varying between about 1 to 5 μrn. The results presented give promise of forming the basis of a commercially viable process for the fabrication of sodium sulphate.

Solid-state formation of an inclusion compound of cholic acid withp-toluidine

Cholic acid undergoes solid-solid reactions with some aromatic molecules to form inclusion compounds. Simple shaking of a mixture of powdered cholic acid andp-toluidine results in formation of the 1∶1 (host:guest) inclusion compound which has the same structure as that formed by conventional crystallization methods: monoclinic space groupP21 witha=13.577(4),b=8.078(2),c=14.182(6) A, β=114.42(3)°,Z=2 andR 1=0.061 for 2680 unique reflections.