Growth and size control in anti-solvent crystallization of glycine with high frequency ultrasound

Antisolvent crystallization of glycine was performed under ultrasonic irradiation of 1.6 MHz. The irradiation enhanced both the growth of α-glycine crystal and the uniformity in the crystal size. The degree of both enhancement effects increased with increasing ultrasonic power. While under the irradiation of 20 kHz ultrasound, no growth enhancement was observed, but the crystal size reduced as was reported in the literature. To elucidate the mechanism of growth enhancement, another experiment was designed and conducted to avoid the effect of nucleation from the sonocrystallization. The result suggests that the ultrasound enhances the incorporation of microcrystals to larger crystals. Probably, the collision between solid particles is intensified by the disturbance characterized by the high frequency ultrasound. The crystal growth was modeled with an apparent reaction of microcrystal and larger crystal. The result of the growth experiment was successfully predicted with a rate equation for pseudo first order reaction with a single parameter of rate constant. The rate constant linearly increased with the ultrasonic power. The analysis enables quantitative evaluation of the ultrasonic effect on the crystal growth.     

Sonocrystallization: effect on lactose recovery and crystal habit

Sonocrystallization is the use of power ultrasound to control the crystallization process, commonly used during the nucleation phase of crystallization. However, in the present study a different approach has been tried, in which the whole process of lactose crystallization from model reconstituted lactose solutions was completed rapidly with the aid of ultrasound, in the presence of 'ethanol' as an anti-solvent, at temperature of 30+/-2 degrees C (ambient temperature). The lactose recovery and crystal properties from sonicated samples were compared with non-sonicated samples. For optimization of sonocrystallization process for rapid lactose recovery, variations in the time of sonication, lactose concentration, protein concentration and pH were tried. A lactose recovery of 91.48% was obtained in 5 min of sonication time, from a reconstituted lactose solution (17.5% w/v, pH 4.2) as against 14.63% under only stirring. Lactose recovery decreased with lowering of pH from 4.2 to 2.8. The protein showed maximum influence on lactose recovery even at concentration of 0.2% w/v. A rapid process of crystallization gave a better uniformity in crystal size distribution of lactose samples.     

功率超声在结晶过程中应用的进展

功率超声在结晶过程中的应用研究促进了结晶技术的发展,丰富了功率超声学和相关学科相互交叉的学术内容。以实例陈述了超声强化溶液结晶过程在化工、食品和制药行业中的应用,从熔融结晶和电结晶两方面阐述了超声改善金属结晶,综述了高分子材料和生物大分子等聚合物结晶过程中超声波的应用,总结了超声波对纳米晶型材料制备和性能的影响,着重说明了功率超声在食品冷冻中冰结晶过程的研究现状和发展方向。最后,总结了超声对结晶的强化机理。     

Polymer-mediated and ultrasound-assisted crystallization of ropivacaine: Crystal growth and morphology modulation

The objective of this research was to modify the crystal shape and size of poorly water-soluble drug ropivacaine, and to reveal the effects of polymeric additive and ultrasound on crystal nucleation and growth. Ropivacaine often grow as needle-like crystals extended along the a-axis and the shape was hardly controllable by altering solvent types and operating conditions for the crystallization process. We found that ropivacaine crystallized as block-like crystals when polyvinylpyrrolidone (PVP) was used. The control over crystal morphology by the additive was related to crystallization temperature, solute concentration, additive concentration, and molecular weight. SEM and AFM analyses were performed providing insights into crystal growth pattern and cavities on the surface induced by the polymeric additive. In ultrasound-assisted crystallization, the impacts of ultrasonic time, ultrasonic power, and additive concentration were investigated. The particles precipitated at extended ultrasonic time exhibited plate-like crystals with shorter aspect ratio. Combined use of polymeric additive and ultrasound led to rice-shaped crystals, which the average particle size was further decreased. The induction time measurement and single crystal growth experiments were carried out. The results suggested that PVP worked as strong nucleation and growth inhibitor. Molecular dynamics simulation was performed to explore the action mechanism of the polymer. The interaction energies between PVP and crystal faces were calculated, and mobility of the additive with different chain length in crystal-solution system was evaluated by mean square displacement. Based on the study, a possible mechanism for the morphological evolution of ropivacaine crystals assisted by PVP and ultrasound was proposed.     

Sonocrystallisation of ZIF-8 in water with high excess of ligand: Effects of frequency,power and sonication time

A systematic study on the sonocrystallisation of ZIF-8 (zeolitic imidazolate framework-8) in a water-based system was investigated under different mixing speeds, ultrasound frequencies, calorimetric powers and sonication time. Regardless of the synthesis technique, pure crystals of ZIF-8 with high BET (Brunauer, Emmett and Teller) specific surface area (SSA) can be obtained in water after only 5 s. Furthermore, 5 s sonication produced even smaller crystals (~0.08 µm). The type of technique applied for producing the ZIF-8 crystals did not have any significant impact on crystallinity, purity and yield. Crystal morphology and size were affected by the use of ultrasound and mixing, obtaining nanoparticles with a more spherical shape than in silent condition (no ultrasound and mixing). However, no specific trends were observed with varying frequency, calorimetric power and mixing speed. Ultrasound and mixing may have an effect on the nucleation step, causing the fast production of nucleation centres. Furthermore, the BET SSA increased with increasing mixing speed. With ultrasound, the BET SSA is between the values obtained under silent condition and with mixing. A competition between micromixing and shockwaves has been proposed when sonication is used for ZIF-8 production. The former increases the BET SSA, while the latter could be responsible for porosity damage, causing a decrease of the surface area.     

Lysozyme crystallization in hydrogel media under ultrasound irradiation

Sonocrystallization implies the application of ultrasound radiation to control the nucleation and crystal growth depending on the actuation time and intensity. Its application allows to induce nucleation at lower supersaturations than required under standard conditions. Although extended in inorganic and organic crystallization, it has been scarcely explored in protein crystallization. Now, that industrial protein crystallization is gaining momentum, the interest on new ways to control protein nucleation and crystal growth is advancing. In this work we present the development of a novel ultrasound bioreactor to study its influence on protein crystallization in agarose gel. Gel media minimize convention currents and sedimentation, favoring a more homogeneous and stable conditions to study the effect of an externally generated low energy ultrasonic irradiation on protein crystallization avoiding other undesired effects such as temperature increase, introduction of surfaces which induce nucleation, destructive cavitation phenomena, etc. In-depth statistical analysis of the results has shown that the impact of ultrasound in gel media on crystal size populations are statistically significant and reproducible.     

Ultrasound-assisted intensified crystallization of L-glutamic acid: Crystal nucleation and polymorph transformation

In this paper, the crystallization of L-glutamic acid with application of ultrasound was explored in detail, including the process of nucleation, polymorphic control and polymorphic transformation. The induction time and metastable zone widths (MSZWs) were measured with and without ultrasound during the nucleation process. The induction time and MSZWs were decreased by ultrasound and the induction time was further decreased by higher ultrasonic power. The calculated nucleation parameters (such as interfacial energy, critical nucleus size and critical Gibbs energy) showed an obvious decrease in the presence of ultrasound, indicating that the nucleation was enhanced with application of ultrasound. By adjusting the ultrasonic power in the quench cooling process, the difference in nucleation temperatures would determine the distribution of polymorphs. In further, the polymorphic transformation was investigated quantitatively, and to the best of our knowledge, it was the first time to study the transformation kinetics with ultrasound using Avrami-Erofeev model. In the transformation process, the crystallization mechanism of the stable form was modified by ultrasound. The ultrasound eliminated the nucleation element in the rate-limiting step and facilitated the crystal growth of stable form. Thus, the ultrasound has a profound influence on L-glutamic acid crystallization.     

Enhancement of lysozyme crystallization under ultrasound field

With the increasing demand for biopharmaceuticals, a method to crystallize biomolecule products with high quality, high yield and uniform size distribution as well as regular crystal habit is needed. In this work, ultrasound was used as a nucleation accelerator to decrease the energy barrier for lysozyme crystal formation. Crystallization experiments on egg-white lysozyme were carried out with and without ultrasound. The effect of ultrasound on induction time, metastable zone width, crystal size and morphology and process yield was investigated in detail. The nucleation-promoting effect produced by ultrasound is illustrated by the reduction of metastable zone width and induction time. By inducing faster nucleation, ultrasound leads to protein crystals grow at lower supersaturation levels with shorter induction time. It was found that ultrasound could result in uniform size distribution of the product due to the preventing of aggregation. However, long time continuous application of ultrasound could result in smaller particle size. Hence, ultrasonic-stop method was found to be a more appropriate strategy to enhance the crystallization process of proteins such as lysozyme.     

Effect of ultrasonic-induced selenium crystallization behavior during selenium reduction

In this work, the crystallization process of selenium was accelerated by ultrasonic wave. The effects of ultrasonic waves and conventional conditions of selenium crystallization were compared to understand the effects of different conditions on crystallization, including ultrasonic time, ultrasonic power, reduction temperature, and H₂SeO₃ concentration. The mechanism of ultrasound affecting selenium crystallization was also investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The experimental results showed that ultrasonic time, ultrasonic power, and reduction temperature significantly influenced the crystallization process and morphology of selenium. Ultrasonic time had a large effect on the completeness (all products have been crystallized) and integrity of the crystallization of the products. Meanwhile, ultrasonic power and reduction temperature had no effect on the completeness of crystallization. However, it had a significant effect on the morphology and integrity of the crystallized products, and different morphologies of the nano-selenium materials could be obtained by changing the ultrasonic parameters. Both primary and secondary nucleation are important in the process of ultrasound-accelerated selenium crystallization. The cavitation effect and mechanical fluctuant effects generated by ultrasound could reduce the crystallization induction time and accelerate the primary nucleation rate. The high-speed micro-jet formed in the rupture of the cavitation bubble generated is the most important reason to influence the secondary nucleation of the system.     

Investigations in physical mechanism of ultrasound-assisted antisolvent batch crystallization of lactose monohydrate from aqueous solutions

Sonication is known to enhance crystallization of lactose from aqueous solutions. This study has attempted to reveal the mechanistic features of antisolvent crystallization of lactose monohydrate from aqueous solutions. Experiments were conducted in three protocols, viz. mechanical stirring, mechanical stirring with sonication and sonication at elevated static pressure. Mechanical stirring provided macroconvection while sonication induced microconvection in the system. Other experimental parameters were initial lactose concentration and rate of antisolvent (ethanol) addition. Kinetic parameters of crystallization were coupled with simulations of bubble dynamics. The growth rate of crystals, rate of nucleation, average size of crystal crop and total lactose yield in different protocols were related to nature of convection in the medium. Macroconvection assisted nucleation but could not give high growth rate. Microconvection comprised of microstreaming due to ultrasound and acoustic (or shock) waves due to transient cavitation. Sonication at atmospheric static pressure enhanced growth rate but reduced nucleation. However, with elimination of cavitation at elevated static pressure, sonication enhanced both nucleation and growth rate resulting in almost complete lactose recovery.     

Intensified recovery of valuable products from whey by use of ultrasound in processing steps – A review

The current review focuses on the analysis of different aspects related to intensified recovery of possible valuable products from cheese whey using ultrasound. Ultrasound can be used for process intensification in processing steps such as pre-treatment, ultrafiltration, spray drying and crystallization. The combination of low-frequency, high intensity ultrasound with the pre-heat treatment minimizes the thickening or gelling of protein containing whey solutions. These characteristics of whey after the ultrasound assisted pretreatment helps in improving the efficacy of ultrafiltration used for separation and also helps in preventing the blockage of orifice of spray dryer atomizing device. Further, the heat stability of whey proteins is increased. In the subsequent processing step, use of ultrasound assisted atomization helps to reduce the treatment times as well as yield better quality whey protein concentrate (WPC) powder. After the removal of proteins from the whey, lactose is a major constituent remaining in the solution which can be efficiently recovered by sonocrystallization based on the use of anti-solvent as ethanol. The scale-up parameters to be considered during designing the process for large scale applications are also discussed along with analysis of various reactor designs. Overall, it appears that use of ultrasound can give significant process intensification benefits that can be harnessed even at commercial scale applications.     

Effect of ultrasound on the kinetics of anti-solvent crystallization of sucrose

The effect of ultrasound on the kinetics of anti-solvent crystallization of sucrose was studied. The influence of temperature, stirring rate, supersaturation and ultrasonic power on the anti-solvent crystallization of sucrose was investigated. The relationship between infrared spectral characteristic band of sucrose and supersaturation was determined with an online reaction analyzer. The crystal size distribution of sucrose was detected by a laser particle-size analyzer. Ultrasound accelerated the crystallization process, and had no impact on the crystal shape. Abegg, Stevens and Larson model was fitted to the experimental data, and the results were the following: At 298.15 K, the average size of crystals was 133.8 μm and nucleation rate was 4.87 × 10⁹ m⁻³·s⁻¹ without ultrasound. In an ultrasonic field, the average size was 80.5 μm, and nucleation rate was 1.18 × 10¹¹ m⁻³·s⁻¹. Ultrasound significantly reduced the average size of crystals and improved the nucleation rate. It was observed that the crystal size decreased with the increase of stirring rate in silent environment. When the stirring rate increased from 250 to 400 rpm, the average size decreased from 173.0 to 132.9 μm. However, the stirring rate had no significant impact on the crystal size in the ultrasonic field. In addition, the activation energy of anti-solvent crystallization of sucrose was decreased, and the kinetic constant of nucleation rate was increased due to the effect of ultrasound. In the ultrasonic field, the activation energy was reduced from 20422.5 to 790.5 J·mol⁻¹, and the kinetic constant was increased from 9.76 × 10² to 8.38 × 10⁸.     

热处理温度对量子点粒度分布的影响

为了明确热处理温度对熔融法制备PbSe量子点玻璃材料的影响, 实验对比了核化时间、晶化温度、晶化时间对晶体大小、粒度分布和吸收光谱特性的影响. 在相同核化温度、不同晶化温度条件下, 各样品的透射电子显微镜图显示都有一定量的晶体形成, 但其晶化程度、尺寸大小及分布有明显不同. 通过计算晶体粒度分布定量地揭示出, 随着晶化温度的提高, 量子点晶体尺寸逐渐增大, 从而提高了晶体颗粒的浓度. 吸收光谱的测量也表明, 随着晶化温度的升高, 吸收峰从无到有不断增强且出现红移现象. 而当晶化温度较低时, 虽有晶体形成, 但无明显吸收峰, 主要是由于晶体尺寸较小, 浓度较低, 晶体颗粒的吸收峰被背景材料所掩盖. 研究结果可为制备具有一定浓度的不同尺寸的量子点晶体, 进而获得多个波段下较强的吸收和辐射的量子点玻璃提供一定的参考.     

Salt crystallization as damage mechanism in porous building materials--a nuclear magnetic resonance study

Salts can damage building materials by chemical reactions or crystallization, which is a serious threat to cultural heritage. In order to develop better conservation techniques, more knowledge of the crystallization processes is needed. In a porous material, the size of a salt crystal is limited by the sizes of the pores. It has been predicted that as a consequence, the solubility of a salt increases with decreasing pore size. This increase seems to be related to an increase of the stress generated by a crystal on the pore wall. It has been suggested that the resulting stress could become high enough to induce failure. We have studied the crystallization of salts in porous materials with well-defined pore sizes. Samples were saturated at 40 degrees C with saturated Na2SO4 and Na2CO3 solutions. Next we have cooled the samples to 0 degrees C and waited for nucleation. After nucleation occurred, the solubility in the porous material was measured with nuclear magnetic resonance (NMR) as a function of the temperature. The measurements on Na2CO3 indeed show an increase in solubility with a decrease in pore size. For Na2SO4, we did not observe a pore size-dependent solubility. However, we have to remark that these results show a metastable crystal phase. The results can be used to calculate the actual pressure exerted by the crystals onto the pore wall.     

Influence of mixing and ultrasound frequency on antisolvent crystallisation of sodium chloride

Ultrasound is known to promote nucleation of crystals and produce a narrower size distribution in a controlled and reproducible manner for the crystallisation process. Although there are various theories that suggest cavitation bubbles are responsible for sonocrystallisation, most studies use power ultrasonic horns that generate both intense shear and cavitation and this can mask the role that cavitation bubbles play. High frequency ultrasound from a plate transducer can be used to examine the effect of cavitation bubbles without the intense shear effect. This study reports the crystal size and morphology with various mixing speeds and ultrasound frequencies. The results show high frequency ultrasound produced sodium chloride crystals of similar size distribution as an ultrasonic horn. In addition, ultrasound generated sodium chloride crystals having a more symmetrical cubic structure compared to crystals produced by a high shear mixer.     

Kinetics of Isothermal and Nonisothermal Crystallization of Poly(ethylene oxide) (PEO) in PEO/Fatty Acid Blends

In this work, isothermal and nonisothermal crystallization kinetics of poly(ethylene oxide) (PEO) and PEO in PEO/fatty acid (lauric and stearic acid) blends, that are used as thermal energy storage materials, was studied using differential scanning calorimetry (DSC) data. The Avrami equation was adopted to describe isothermal crystallization of PEO and nonisothermal crystallization was analyzed using both the modified Avrami approach and Ozawa method. Avrami exponent (n) for PEO crystallization was in the range 1.08–1.32 (10–90% relative crystallinity), despite of spherulites formation, while for PEO in PEO/fatty acid blends n was between 1.61 and 2.13. Hoffman and Lauritzen theory was applied to calculate the activation energy of nucleation (K_g) – the lowest value of K_g was observed for pure PEO, despite of heterogeneous nucleation of fatty acid crystals in PEO/fatty acid blends. For nonisothermal crystallization of PEO in PEO/lauric acid (1:1 w/w) and PEO/stearic acid (1:3 w/w) blends, secondary crystallization occurred and values of the Avrami exponent were 2.8 and 2.0, respectively. The crystallization activation energies of PEO were determined to be ?260 kJ/mol for pure PEO, ?538 kJ/mol for PEO/lauric acid blend, and ?387 kJ/mol for PEO/stearic acid blend for isothermal crystallization and ?135,6 kJ/mol, ?114,5 kJ/mol, and ?92,8 kJ/mol, respectively, for nonisothermal crystallization.     

A study on the primary and secondary nucleation of ice by power ultrasound

Several different investigations have been carried out to study the primary and secondary nucleation of ice by sonocrystallisation. Firstly, the primary nucleation of discrete ice crystals in a supercooled sucrose solution has been observed. For increasing concentrations of sucrose solutions from 0 to 45 wt%, the nucleation temperature consistently occurs at a higher nucleation temperature in the presence of ultrasound. The nucleation temperature also increases as the power output and duty cycle of a commercial ultrasonic horn are increased. Snap shot images of the bubble clouds obtained from the ultrasonic horn also show that the number of bubbles appears to increase as the ultrasonic output is increased. This suggests that the nucleation of ice is related to the power output and number of cavitation bubbles. The effect of a single bubble on the sonocrystallisation of ice is discussed. High-speed movies (1120 fps) have shown that the crystallisation appears to occur in the immediate vicinity of the single bubble. In most cases, many crystals are observed and it is not known whether a single ice crystal is being fragmented by the bubble or whether many crystals are being initiated. The bubble appears to undergo a dancing regime, frequently splitting and rejoining and also emitting some small microbubbles. A study on the secondary nucleation of ice in sucrose solutions has been carried out using a unique ultrasonic cold stage device. Images taken using a microscope system show that the pre-existing ice dendrite crystals can be broken up into smaller fragments by an ultrasonic field. Cavitation bubbles appear to be important during the fragmentation process, possibly melting any ice crystals in their path. Flow patterns around cavitation bubbles have also been observed, and these may be responsible for the fragmentation of ice crystals.     

The application of power ultrasound to reaction crystallization

The action of power ultrasound in controlling the supersaturation, nucleation and crystal growth during the acid-base reaction crystallization of 7-amino-3-desacetoxy cephalosporanic acid (7-ACDA) has been investigated. The experimental results show that ultrasound can mix the reaction more efficiently and uniformly than conventional agitation methods. Insonation leads to the reduction of both the induction period and metastable zone width of the crystallization, so that the process of crystallization can be more efficiently controlled than without insonation. Agglomeration is also greatly reduced. Adjusting the ultrasonic parameters can modulate the crystal size and size distribution. The mechanism of the sonoprocess has been analyzed and comments are made on the potential applicability of sonication in large-scale crystallization practice.     

Ultrasound-assisted solution crystallization of fotagliptin benzoate: Process intensification and crystal product optimization

The ultrasound-assisted crystallization process has promising potentials for improving process efficiency and modifying crystalline product properties. In this work, the crystallization process of fotagliptin benzoate methanol solvate (FBMS) was investigated to improve powder properties and downstream desolvation/drying performance. The direct cooling/antisolvent crystallization process was conducted and then optimized with the assistance of ultrasonic irradiation and seeding strategy. Direct cooling/antisolvent crystallization and seeding crystallization processes resulted in needle-like crystals which are undesirable for downstream processing. In contrast, the ultrasound-assisted crystallization process produced rod-like crystals and reduced the crystal size to facilitate the desolvation of FBMS. The metastable zone width (MSZW), induction time, crystal size, morphology, and process yield were studied comprehensively. The results showed that both the seeding and ultrasound-assisted crystallization process (without seeds) can improve the process yield and the ultrasound could effectively reduce the crystal size, narrow the MSZW, and shorten the induction time. Through comparing the drying dynamics of the FBMS, the small rod-shaped crystals with a mean size of 9.6 μm produced by ultrasonic irradiation can be completely desolvated within 20 h, while the desolvation time of long needle crystals with an average size of about 157 μm obtained by direct cooling/antisolvent crystallization and seeding crystallization processes is more than 80 h. Thus the crystal size and morphology were found to be the key factors affecting the desolvation kinetics and the smaller size produced by using ultrasound can benefit the intensification of the drying process. Overall, the ultrasound-assisted crystallization showed a full improvement including crystal properties and process efficiency during the preparation of fotagliptin benzoate desolvated crystals.     

Skeletonization by crystallization

A skeleton of a planar contour is a set of centres of bitangent circles lying inside the contour. If contour of a planar shape was made up of a spatial distribution of sodium acetate crystals the propagating crystallization patterns would implement distance transformation, or thinning, of the contour. In such a case, boundaries between colliding patterns represent skeleton of the planar shape. In laboratory experiments we demonstrate that a supersaturated solution of a sodium acetate is a massively parallel processor. In this sodium-acetate processor data are inputted as spatial distribution of nucleation sites, information is transmitted via propagating patterns of crystallization and results of computation are represented by boundaries between stationary domains of crystals.