Understanding the effect of solvent polarity on the habit modification of monoclinic paracetamol in terms of molecular recognition at the solvent crystal/interface

The habit change of monoclinic paracetamol crystallized from solutions with different solvents such as water, ethanol, methanol, acetone, isopropyl alcohol, tetrahydrofuran, cyclohexanone, acetonitrile and 1, 4 ‐ dioxane was investigated. Change in solubility, pH and nucleation time of paracetamol in these solvents at ambient condition was studied. The polymorphic form of the nucleated paracetamol was observed under in‐situ optical microscopy. Solutions with different solvents having different chemical nature and polarity yielded paracetamol crystals with different habits: columnar morphology from polar protic water and prismatic morphology from other selected polar protic, aprotic and in non‐polar solvents. The significant differences on the growth rate of various crystal habit faces of the monoclinic paracetamol grown from different solvents are attributed in context with the solubility of the solute, solvent polarity, evaporation number of the solvent, rate of generation of supersaturation and the role of hydrogen bonding interaction between the solvent molecules and protruding solute molecules on the crystal surface. Among the solution with different solvents, bulk monoclinic paracetamol single crystal was grown from ethanolic solution using seed rotation technique by controlled cooling method.     

软X射线分光晶体琥珀酸氢十四酯的合成及结晶习性研究

本文合成了软X射线分光晶体琥珀酸氢十四酯(THS).通过红外光谱、差示量热扫描等手段对所合成样品进行表征和鉴定.对THS在苯、甲苯、二甲苯、异丙醇等溶剂中的自发成核和结晶形态进行了研究,结果表明THS在苯、甲苯和二甲苯中表现出良好的结晶习性.采用平衡法测定了THS在苯、甲苯和二甲苯中的溶解度曲线.综合考虑结晶习性和溶解度情况,可选择甲苯作为晶体生长的溶剂进行单晶生长实验.     

Behavior of LiOH·H2O crystals obtained by evaporation and by drowning out

In the present work, the behavior of crystals derived from two different crystallization methods applied in a concentrated aqueous lithium salt solution was studied. The LiOH·H₂O crystals obtained by a simple evaporation (Crystal I) differed in terms of morphology and solubility from those precipitated from lithium hydroxide solutions by addition of ethanol as a co‐solvent (Crystal II). Solubility of Crystal II at different temperatures (15 to 35°C) and mass ratios of ethanol to water (0 to 0.1) was determined. Polymorphic like behavior of these crystals was evidenced from X‐ray diffraction patterns. Measurement of density, refractive index, absolute viscosity and electrical conductivity of saturated solutions are reported. A thermodynamic analysis in terms of the Chen model for the calculation of activity coefficients, indicate that the polymorphic system in water and in water + ethanol (ethanol/water ratio 0.1) is enantiotropic. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Effect of different solvents on the habit of meta‐nitroaniline single crystals

The habit of the organic non‐linear optical material meta‐nitroaniline (mNA) crystallized from different organic solvents such as acetone, benzene, ethyl acetate, n‐hexane, methanol and toluene were studied. Solubility of mNA in these solvents at various temperatures in the range between 288 and 323 K was determined by gravimetric method. Crystals were grown by restricted evaporation of solvents method. Solutions with different solvents having different chemical nature and polarity yielded crystals with different habits: one‐dimensional needles, two‐dimensional rhombic platelets and three‐dimensional octahedral. In addition, the mNA crystals show unidirectional growth behaviour along its polar [001] direction irrespective of the solvents used. All the grown crystals were found to be orthorhombic system with point group mm2 and space group Pbc2₁ which was confirmed by powder X‐ray diffraction study. Optical transmittance study showed that the grown mNA single crystals have optical transparency in the wavelength range between 430 and 1550 nm. SHG efficiency of the grown mNA crystal was 3 times grater than KDP. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Characterization of L‐ascorbic acid single crystals grown from solution with different solvents

Single crystals of L‐ascorbic acid, popularly known as vitamin‐C, were grown from solutions with different solvents and solvent combinations by low temperature solution growth methods. The suitability of different solvents and solvent combinations such as acetone, ethanol, methanol, isopropyl alcohol, water, water + acetone (1:1), water + ethanol (3:1), water + isopropyl alcohol (3:1) and isopropyl alcohol + methanol (1:1) for crystal growth of L‐ascorbic acid was found out by assessing the solubility and crystallization behaviours. Solubility of L‐ascorbic acid in selected solvents and solvent combinations in a range of temperatures was determined by gravimetric method. Solution prepared with water, water + acetone (1:1), water + ethanol (3:1) and water + isopropyl alcohol (3:1) were yielded crystals with tabular, columnar and prismatic habits and their morphologies were evaluated by goniometry. Grown single crystals were characterized with various instrumental techniques such as powder X‐ray diffraction, Fourier infrared spectroscopy, optical transmittance study, differential scanning calorimetry and second harmonic generation studies. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Improvement of growth habit and optical properties of rapidly grown KDP crystal by adding diethylene triamine pentacetate acid in growth solution

By altering the concentration of a new additive ‐ diethylene triamine pentacetate acid (DTPA) in the growth solution, a series of KDP crystals were obtained by the “point seed” rapid growth method. The growth rates up to about 20 mm/day. Effects of DTPA on the growth habit and optical properties of these as‐grown KDP crystals were investigated. The results reveal that, with the increase of DTPA concentration in growth solution, the contents of impurity metal ions incorporated into crystal and aspect ratio of crystal morphology were both decreased gradually, while the UV transmittance of crystal was enhanced continually. In the presence of moderate concentration of DTPA (100–200 ppm), the solution stability was increased and optical properties of crystal (including optical homogeneity, light scattering and laser damage threshold) were all improved. However excessive doping (>500 ppm) has opposite effects. The impact mechanism was also analyzed combining with the structure of KDP crystal and chemical characteristics of DTPA molecular.     

Crystallization shelves for laboratory furnaces

Several designs of air coolers (modular bilateral “crystallization shelves”), installed in laboratory furnaces are presented. The setup allows easy regulation and simultaneous crystallization of several substances at different temperature gradients, shapes of crystallization fronts and rate intervals, with the purpose of obtaining crystals. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Agglomeration of NTO on the surface of HMX particles in water‐NMP solvent

A sensitive explosive was coated with a less sensitive explosive in order to improve stability while maintaining explosion performance. Agglomeration of 3‐nitro‐1,2,4‐triazole‐5‐one (NTO) on the surface of cyclotetramethylene tetranitramine (HMX) crystals in water‐N ‐methyl‐2‐pyrrolidone (NMP) solvent was performed by cooling crystallization. Phenomena for coating by crystallization and agglomeration were studied by in‐situ measurement. The agglomeration kinetic for the coating of NTO on HMX crystals was correlated with the 3rd power of the solution supersaturation and the 2nd power of the number of the suspended particles. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Cooler for obtaining crystals

A modular air‐cooled tube, with a series of movable Tamman test tubes or plugs (modular unilateral and bilateral “crystallization comb”), installed in a laboratory tube furnace is presented. The setup allows easy regulation and simultaneous crystallization tests of a series of different crystallization parameters in crucible columns, enabling rapid acquisition of crystals. The relationship between the crystallization parameters has been given and numerically analyzed. This method can also be applied in crucible and chamber furnaces. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

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.     

Preparation and characterization of superfine ammonium perchlorate (AP) crystals through ceramic membrane anti-solvent crystallization

In this paper, a novel ceramic membrane anti-solvent crystallization (CMASC) method was proposed for the safe and rapid preparation ammonium perchlorate (AP) crystals, in which the acetone and ethyl acetate were chosen as solvent and anti-solvent, respectively. Comparing with the conventional liquid anti-solvent crystallization (LASC), CMASC which successfully introduces ceramic membrane with regular pore structure to the LASC as feeding medium, is favorable to control the rate of feeding rate and, therefore, to obtain size and morphology controllable AP. Several kinds of micro-sized AP particles with different morphology were obtained including polyhedral-like, quadrate-like to rod-like. The effect of processing parameters on the crystal size and shape of AP crystals such as volume ratio of anti-solvent to solvent, feeding pressure and crystallization temperature were investigated. It is found that higher volume ratio of anti-solvent to solvent, higher feeding pressure and higher temperature result in smaller particle size. Scaning electron microscopy (SEM) and X-ray diffraction (XRD) were used to characterize the resulting AP crystals. The nucleation and growth kinetic of the resulting AP crystals were also discussed.     

KDP single crystal growth via three‐dimensional motion growth method

A novel system for rapid crystal growth, namely three‐dimensional motion growth method (“3D MGM”) was proposed. Using this system, a potassium dihydrogen phosphate (KDP) seed was grown to a single crystal with a final size of 50×55×85 mm³. The KDP crystal was characterized by Raman spectroscopy, UV‐vis‐NIR spectroscopy, extinction ratio, laser damage threshold, and etching studies. Raman spectrum shows KDP crystal grown by “3D MGM” maintains good crystallinity as that grown by rotating‐crystal method (“RCM”). The “3D MGM” grown KDP crystal has much better transmittance, higher extinction ratio, higher damage threshold and less dislocation density, compared to “RCM” grown crystal.     

Structural and microhardness studies of pure and thiourea doped glycine phosphite single crystal

Ferroelectric Glycine Phosphite (GPI) crystal have been grown from aqueous solution employing the slow cooling technique. As the crystal solubility in water depends on temperature, single crystals were grown. Transparent, colourless crystals with habit morphology weighing about 8g were obtained with in a month. The same procedure was used to grow single crystals of 10 wt% of Thiourea doped GPI (TUGPI). Formation of a new crystal was confirmed by Powder X‐ray diffraction studies as well as FTIR studies. Crystalline quality were found using rocking curve for both the crystals. Due to the presence of Thiourea in TUGPI, it improves the crystalline perfection and also enhances the growth rate. The variation of hardness on (010) faces of monoclinic GPI and TUGPI crystals, with load were studied.Vickers hardness numbers, H_v were found to decrease with the increase in load. The value of Mayer's index, ‘n ’ was found to be greater than 1.6 for GPI and TUGPI showing soft‐material category. The results are discussed in detail. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Investigation of the Conditions for the Production of Calcium Magnesium Acetate (CMA) Road Deicer in an Extractive Crystallization Process

Calcium magnesium acetate (CMA) is considered as the best road deicer to replace the environmentally unacceptable NaCl and CaCl₂. However, the high cost of CMA prohibits its widespread use. The present study is dealing with the investigation of a crystallization method for the production of deicing CMA crystals of desired physical properties and the elucidation of the conditions under which such a product can be formed. Extractive crystallization is promising for the low cost production of CMA crystals considering that acetic acid is produced by a biochemical method and removed from the fermentation broth in situ by organic extractant systems. In this method, this organic phase, which contains the acetate ions is contacted with an aqueous phase which is the source of calcium and magnesium ions. The extractive crystallization process resulted in the production of well‐formed, large, and non‐spherical crystals of calcium acetate (CA), magnesium acetate (MA), and calcium magnesium acetate double salt (CMADS). The crystal size was affected by the concentration of acetic acid in both the organic and aqueous phases, whereas the crystal type and hydration level were determined primarily by the acetic acid concentration in the aqueous phase. The molar ratio of the precursor salts (CaCO₃/MgCO₃) in the reaction mixture was found to be the major factor for determining the habit and Ca/Mg content of crystals. Crystallization of CMADS was favored at high concentrations of acetic acid in the aqueous phase and at higher temperatures as shown from supplementary evaporation‐to‐dryness experiments.     

Growth and properties of dyed KDP crystals

Potassium dihydrogen phosphate (KDP) crystals doped with xylenol orange (XO) and methylthymol blue (MTB) are grown from aqueous solutions by the method of solvent evaporation at room temperature under the conditions of natural convection and by the method of temperature lowering. Studied is the influence of the mother solution acidity on the character of the crystal coloration. The color and coloration intensity of the grown crystals are shown to strongly depend on the solution's pH. It is revealed that the crystal habit changes in the presence of organic dyes. The optical transmission spectra and the luminescence spectra of KDP:XO solutions and of the grown crystals are measured. The effect of thermal treatment and UV‐irradiation on the coloration stability of the crystals is studied. It is found that the laser damage threshold in the prismatic impurity rich colored sectors of KDP:XO is the same as that in the prismatic sectors of pure KDP crystals. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

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.     

Synthesis and characterization of 4,4′‐dihydroxy‐α‐methylstilbene crystal

4,4′‐dihydroxy‐α‐methylstilbene (DHAMS) was synthesized by condensation reaction with chloroacetone and phenol in the presence of concentrated sulfuric acid, and has been successfully grown by solution growth technique. This is the first report in the literature on the crystallization of DHAMS and exhibited the birefringent melt (liquid crystal property) of the optical properties. FTIR and FTNMR studies are in accordance with the structure. Good quality crystals were grown by slow evaporation technique by acetone as solvent. A transmission spectrum of the crystal was obtained in the region of 285 nm. The structural and optical properties were studied. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Crystallization of mefenamic acid and polymorphs

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

The combined effects of supersaturation and Ba2+ on the batch cooling crystallization of potassium dihydrogen phosphate

The combined effects of supersaturation and Ba²⁺ on potassium dihydrogen phosphate (KDP) were investigated in batch cooling suspension crystallization. Growth size, morphology, and impurity Ba²⁺ adsorbed in the KDP crystals were measured with changing Ba²⁺ concentration and supersaturation. Significant changes in shapes and volume of the grown crystals have been observed. The results further confirmed that the size and shape of crystals were greatly determined by supersaturation. Ba²⁺ ions significantly modified the growth habit of KDP crystals. The concentration of Ba²⁺ ions adsorbed in the crystals increases with the increasing Ba²⁺ ions in the solutions and supersaturation. The foggy phenomena caused by the addition of Ba to the KDP solution were also described. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Synthesis,growth and characterization of single crystals of pure and thiourea doped L‐glutamic acid hydrochloride

L(+)Glutamic acid hydrochloride [HOOC (CH₂)₂CH(NH₂) COOH·HCl], a monoamino dicarboxylic acid salt of L‐Glutamic acid was synthesized and the synthesis was confirmed by FTIR analysis. Solubility of the material in water was determined. Pure and Thiourea doped L‐Glutamic acid hydrochloride crystals were grown by low temperature solution growth using solvent evaporation technique. XRD, UV‐Vis‐NIR analyses were carried out for both pure and thiourea doped crystals. The crystals were qualitatively analyzed by EDAX analysis and the presence of thiourea was confirmed. The cell parameters of L‐Glutamic acid hydrochloride have been determined as a = 5.151 Å, b = 11.79 Å, c = 13.35 Å by X‐ray diffraction analysis and it crystallizes in orthorhombic space group P2₁2₁2₁. UV‐Vis‐NIR spectra analysis showed good optical transmission in the entire visible region for both pure and doped crystals. Micro hardness of both pure and doped crystals has been determined using Vickers micro hardness tester. The SHG efficiencies of both pure and doped crystals were determined using Kurtz powder test and pure L‐Glutamic acid hydrochloride crystal was found to possess better efficiency than thiourea doped L‐Glutamic acid hydrochloride crystals. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)