Microfluidic Continuous Seeded Crystallization: Extraction of Growth Kinetics and Impact of Impurity on Morphology (original) (raw)
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Growth of gamma glycine crystal and its characterisation
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2010
Single crystal of ␥-glycine, an organic nonlinear optical material, has been grown by solvent evaporation technique from a mixture of aqueous solutions of glycine and potassium nitrate, lithium nitrate at room temperature. Gamma glycine crystals have been grown up to the dimension of 20 mm × 15 mm × 12 mm. Powder X-ray diffraction of the grown crystal was recorded and indexed. Single crystal X-ray diffraction studies were carried out and the unit cell parameters were compared with the literature values. The ␥-phase of glycine is confirmed by single crystal XRD and FTIR spectral analysis. The crystals were characterised by UV-vis-NIR transmission spectrum in the range 200-1100 nm. The second harmonic generation conversion efficiency of ␥-glycine crystal was twice the efficiency of KDP crystal. Thermal characteristics of ␥-glycine crystals were determined by thermogravimetric analysis (TGA) and differential thermal analysis, which shows the thermal stability of the grown crystals. Dielectric constant and dielectric loss measurements were carried out at different temperatures and frequencies. The microhardness of the grown crystals has been studied using Vicker's microhardness tester.
Characterization of α and γ polymorphs of glycine crystallized from water-ammonia solution
Crystal Research and Technology, 2011
Crystallization of metastable α and stable γ polymorphs of glycine was carried out from aqueous solution in the presence of ammonia. Pure aqueous solution and solution with lower concentration of ammonia yield α nucleation and solution with a critical concentration of ammonia yield γ nucleation. Variation in the solubility of glycine in double distilled water and pH of the resulting solution due to the ammonia incorporation was studied in a range of temperatures. The induction period for the α and γ nucleation in the solution was determined and its variation due to the ammonia incorporation was also studied. Single crystals of both the polymorphs were grown by slow evaporation method. Effect of ammonia concentration and the resultant pH of the solution on the nucleation, growth and morphology of the grown polymorphs were investigated. The unidirectional growth of the γ polymorph along the polar axis was revealed. X-ray powder diffraction method was employed to distinguish both the polymorphs structurally. Their thermal stability above room temperature was studied by differential scanning calorimetry which revealed that the as-grown γ polymorph transforms to α at 179.6 °C while the as-grown α retains its phase until melting. The optical transmittance of the grown γ polymorph was studied in the UV-Vis-Near IR region. The second harmonic generation (SHG) efficiency of the grown γ polymorph was studied with a Nd:YAG laser source and is about 6.8% higher than that of the inorganic standard KDP.
Crystallization of β-glycine by spray drying
Crystal Research and Technology, 2011
Glycine crystallization during spray drying has been investigated on a laboratory scale. In order to obtain different polymorphs the experiments have been performed at different hot air temperatures, concentrations, different flow of the solution and spraying air. The obtained crystals were analyzed by means of X-ray powder diffractometry, differential scanning calorimetry and the Fourier transform infrared spectrometry. Crystallization mostly resulted with a mixture of αand β-glycine with a small amount of γ-glycine. The glycine polymorphism is affected by the drying air temperature, concentration and the flow of the solution, as well as the spraying air flow. Decrease of the drying air temperature and increase of the solution flow rate causes the increase of the quantity of β-glycine. At room conditions, β-glycine spontaneously transforms into thermodynamically more stable α-glycine.
Glycine Crystallization in Frozen and Freeze-dried Systems: Effect of pH and Buffer Concentration
Pharmaceutical Research, 2007
Purpose (1) To determine the effect of solution pH before lyophilization, over the range of 1.5 to 10, on the salt and polymorphic forms of glycine crystallizing in frozen solutions and in lyophiles. (2) To quantify glycine crystallization during freezing and annealing as a function of solution pH before lyophilization. (3) To study the effect of phosphate buffer concentration on the extent of glycine crystallization before and after annealing. Materials and Methods Glycine solutions (10% w/v), with initial pH ranging from 1.5 to 10, were cooled to −50°C, and the crystallized glycine phases were identified using a laboratory X-ray source. Over the same pH range, glycine phases in lyophiles obtained from annealed solutions (0.25, 2 and 10% w/v glycine), were characterized by synchrotron X-ray diffractometry (SXRD). In the pH range of 3.0 to 5.9, the extent of glycine crystallization during annealing was monitored by SXRD. Additionally, the effect of phosphate buffer concentration (50 to 200 mM) on the extent of glycine crystallization during freezing, followed by annealing, was determined. Results In frozen solutions, β-glycine was detected when the initial solution pH was ≥ 4. In the lyophiles, in addition to β- and γ-glycine, glycine HCl, diglycine HCl, and sodium glycinate were also identified. In the pH range of 3.0 to 5.9, decreasing the pH reduced the extent of glycine crystallization in the frozen solution. When the initial pH was fixed at 7.4, and the buffer concentration was increased from 50 to 200 mM, the extent of glycine crystallization in frozen solutions decreased with an increase in buffer concentration. Conclusion Both solution pH and solute concentration before lyophilization influenced the salt and polymorphic forms of glycine crystallizing in frozen solutions and in lyophiles. The extent of glycine crystallization in frozen solutions was affected by the initial pH and buffer concentration of solutions. The high sensitivity of SXRD allowed simultaneous detection and quantification of multiple crystalline phases.
Crystal Growth & Design, 2005
The control of crystal polymorphism of the trimorphic crystals of glycine (Gly) grown in aqueous solutions in the presence of R-amino acids operating as stereospecific nucleation inhibitors is reported. The presence of enantiopure R-amino acids phenylalanine (Phe), methionine (Met), and tryptophan (Trp) in the crystallizing aqueous solutions induces changes in the morphology of R-Gly leading to the formation of pyramidal instead of bipyramidal crystals. Increased concentrations of racemic Phe and Met inhibit both the R-and-polymorphs of glycine and induce precipitation of the thermodynamically most stable γ-polymorph. R-Amino acids that bear bulky side groups such as racemic tryptophan (Trp), N-CH 3-Trp, and R-naphthylalanine induce precipitation of the least stable-Gly polymorph. Quasi-racemic mixtures of R-Trp and S-Phe (or S-Met), for example, lead to the precipitation of one of the enantiomorphs of-Gly. The roles played by the different R-amino acids in affecting morphology and polymorphism are discussed in terms of their interactions with and stereoselective occlusion in the various sectors of the {010} faces of the-Gly crystals.
Glycine Polymorphism in Nanoscale Crystallization Chambers
Crystal Growth & Design, 2008
Crystallization of glycine by evaporation of aqueous solutions in nanometer-scale channels of controlled-pore glass (CPG) powders and porous polystyrene-poly(dimethyl acrylamide) (p-PS-PDMA) monoliths, the latter prepared by etching polylactide (PLA) from aligned PS-PDMA-PLA triblock copolymers, preferentially results in exclusive formation of the polymorph, which is not observed during crystallization in bulk form under identical conditions. X-ray diffraction (XRD) reveals that the dimensions of the embedded crystals are commensurate with the pore diameter of the matrix.-Glycine persists for at least one year in CPG and p-PS-PDMA with pore diameters less than 24 nm, but it transforms slowly to R-glycine over several days when confined within 55 nm CPG. Moreover, variable temperature XRD reveals that-glycine nanocrystals embedded within CPG are stable at temperatures at which bulk-glycine ordinarily transforms to the R form. XRD and differential scanning calorimetry (DSC) reveal the melting of glycine nanocrystals within CPG below the temperature at which bulk glycine melts with concomitant decomposition. The melting point depression conforms to the Gibb-Thompson equation, with the melting points decreasing with decreasing pore size. This behavior permits an estimation of the melting temperature of bulk-glycine, which cannot be measured directly owing to its metastable nature. Collectively, these results demonstrate size-dependent polymorphism for glycine and the ability to examine certain thermal properties under nanoscale confinement that cannot be obtained in bulk form. The observation of-glycine at nanometer-scale dimensions suggests that glycine crystallization likely involves formation of nuclei followed by their transformation to the other more stable forms as crystal size increases, in accord with Ostwald's rule of stages.
Synthesis, bulk growth, polarizability and nonlinear optical properties of γ-glycine single crystals
Crystal Research and Technology, 2015
The role of sodium acetate, sodium nitrate, sodium hydroxide and malonic acid as additives in assisting the nucleation of γ-polymorph from solution has been investigated. For the first time large dimensional bulk single crystals of γglycine have been grown at the optimized concentration of the additives by the top seeded slow cooling technique. The bulk growth of single crystals elucidates well the unidirectional growth characteristics and the existence of merohedral twinning in γ-glycine. Polarizability, plasmon energy and Fermi energy has been evaluated for the first time for γ-glycine single crystals based on an analytical approach. Structural affirmation of the nucleated polymorph has been carried out by Powder x-ray diffraction and the thermal characteristics of the nucleated polymorph are well revealed by Differential Scanning Calorimetry. The non linear optical characteristics of γ-glycine studied by Kurtz and Perry technique revealed increased SHG efficiency with the highest of about 2.2 in the presence of malonic acid compared to the standard Potassium dihydrogen orthophosphate (KDP).
Reduction of glycine particle size by impinging jet crystallization
International Journal of Pharmaceutics, 2015
The parameters of crystallization processes determine the habit and particle size distribution of the products. A narrow particle size distribution and a small average particle size are crucial for the bioavailability of poorly water-soluble pharmacons. Thus, particle size reduction is often required during crystallization processes. Impinging jet crystallization is a method that results in a product with a reduced particle size due to the homogeneous and high degree of supersaturation at the impingement point. In this work, the applicability of the impinging jet technique as a new approach in crystallization was investigated for the antisolvent crystallization of glycine. A factorial design was applied to choose the relevant crystallization factors. The results were analysed by means of a statistical program. The particle size distribution of the crystallized products was investigated with a laser diffraction particle size analyser. The roundness and morphology were determined with the use of a light microscopic image analysis system and a scanning electron microscope. Polymorphism was characterized by differential scanning calorimetry and powder X-ray diffraction. Headspace gas chromatography was utilized to determine the residual solvent content. Impinging jet crystallization proved to reduce the particle size of glycine. The particle size distribution was appropriate, and the average particle size was an order of magnitude smaller (d(0.5) = 8-35 mm) than that achieved with conventional crystallization (d(0.5) = 82-680 mm). The polymorphic forms of the products were influenced by the solvent ratio. The quantity of residual solvent in the crystallized products was in compliance with the requirements of the International Conference on Harmonization. 2014 Elsevier B.V. All rights reserved.
Factors Affecting the Polymorphic Outcome of Glycine Crystals Constrained on Patterned Substrates
Chemical Engineering & Technology, 2006
The primary goal of crystallization process is to generate particles with controlled size, shape and solid form, and the desired chemical purity. Many different types of approaches including molecular level strategies have been devised and employed to control the final structure of crystals. One promising approach is the utilization of self-assembled monolayers (SAMs) as templates. Recently, we reported that single glycine crystals can nucleate on patterned metallic square islands, with the size and morphology of the particles controlled by the dimensions of the islands or the concentration of the solution. Herein, the effect of the solution concentration on the polymorphic outcome of glycine crystals confined to hydrophilic metallic islands is investigated. Furthermore, we examine how variations in the solvent evaporation rate can impact the polymorph distribution of glycine.
Attainment of unstable β nucleation of glycine through novel swift cooling crystallization process
Journal of Crystal Growth, 2014
The sudden cooling of mother liquor from high temperature to a temperature below the ambient through the recently introduced swift cooling crystallization process yielded the β nucleation of glycine even in the absence of anti-solvents and additives. Experiments were continued at different supersaturation and stirring levels. The nucleation matrix resulted out of these 135 experiments revealed that, even at lower supersaturation and lower stirring rates, the unstable β nucleation could be achieved. This attained result contrasts the existing reports in which β nucleation is achieved only at higher supersaturation levels. The intermediate supersaturation and stirring levels facilitate both the β and α nucleation through solution mediated phase transformation while the higher supersaturation and stirring levels facilitate only the α nucleation of glycine in the system. The swift cooling method adopted declines the energy barrier that inherently exists for β and enables its nucleation in the system. Analytically the nucleation parameters of β and α polymorphs were estimated based on Classical Nucleation Theory. Form of crystallization of the nucleated polymorphs of glycine was confirmed by powder x-ray diffraction analysis. & 2014 Elsevier B.V. All rights reserved. mixtures of water and glacial acetic acid and have studied its calorimetric property [17]. Ferrari et al. have studied the polymorphic transformation from β to α in the presence of varying volumes of ethanol and fixed volumes of aqueous solution of glycine [45]. Weissbuch et al. have studied the solvent effect on Contents lists available at ScienceDirect