Determination of the metastable zone and induction time of thiourea for cooling crystallization

The solubility,metastable zone width(MSZW),and induction time of thiourea for cooling crystallization were experimentally determined in the temperature range of 283-323 K. The solubility data could be well described by the Apelblat equation model as lnx=-99.55+1071.66/T+16.27 lnT. The determinations of the effects of various stirring and cooling rates indicated that the MSZW increased with increasing and decreasing cooling and stirring rates,respectively.Furthermore,the induction times at various temperatures and supersaturation ratios were also measured.The results indicated that homogeneous nucleation could occur at high supersaturation,whereas heterogeneous nucleation was more likely to occur at low supersaturation.Based on the classical nucleation theory and induction period data,the calculated solid-liquid interfacial tensions of thiourea in deionized water at 302.46 and 312.58 K were 2.86 and 2.94 mJ·m~(-2),respectively.     

L-酒石酸水溶液结晶介稳区和诱导期的测定

在20~60℃温度范围内,采用激光法测定L-酒石酸在水中的结晶介稳区宽度和诱导期,分别研究了饱和温度、冷却速率和搅拌速率对L-酒石酸结晶介稳区宽度的影响以及过饱和度对L-酒石酸诱导期的影响。结果表明:结晶介稳区宽度随着饱和温度、搅拌速率的增大和冷却速率的降低而变窄,并推算出表观成核级数m,给出了成核速率方程,此外实验测定结晶诱导期随过饱和度S增大而变短,基于经典成核理论和诱导期数据,计算出L-酒石酸在水中20℃和25℃下的固液界面张力。     

DMT甲醇溶液结晶介稳区性质的研究

研究了对苯二甲酸二甲酯（ＤＭＴ）甲醇溶液的结晶特性。测定了ＤＭＴ在甲醇中的溶解度、ＤＭＴ甲醇溶液于不同降温速率、搅拌转速下的结晶介稳区宽度以及不同过饱和度下的结晶成核诱导期。结果表明：ＤＭＴ在甲醇溶液中的溶解度随温度升高而增加;溶液的结晶介稳区随降温速率的增加变宽,随搅拌转速的增加而变窄,且ＤＭＴ甲醇溶液的结晶诱导期随相对过饱和度的增加而缩短。     

季戊四醇水溶液结晶介稳区性质的研究

用激光自动检测法测定了季戊四醇水溶液在不同降温速率、搅拌转速下的结晶介稳宽度以及不同过饱和度下的结晶成核诱导期。实验还采用折射率法测定了季戊四醇在水中的溶解度     

表面活性剂对光卤石中氯化钾结晶介稳区和诱导期的影响

利用在线监测系统测定了光卤石中氯化钾的溶解度,并采用Van′t Hoff方程对其溶解度数据进行拟合。探讨了不同类型的表面活性剂及其含量对光卤石中氯化钾结晶介稳区宽度的影响以及在不同过饱和度下表面活性剂对诱导期的影响,并结合诱导期数据计算了固-液界面张力γ值。结果表明：Van′t Hoff方程能够对氯化钾溶解度很好地拟合;3种不同类型的表面活性剂都使介稳区宽度变宽;加入阴、阳离子表面活性剂,随着其含量的增大介稳区变宽,而加入非离子表面活性剂,其含量对介稳区宽度的影响不大。在恒定温度下,随着过饱和度增大,结晶诱导期时间变短,而加入表面活性剂使诱导期时间变长。     

有机酸杂质对乳酸锌初次成核速率的影响

引言 溶液结晶作为一种高效、低能耗、少污染的分离和提纯技术,在医药、食品、生物等工业生产中的应用非常广泛.特别在医药行业,溶液结晶是主要的单元操作,85%以上的医药产品的生产过程中含有结晶单元[1].结晶过程涉及成核和生长两个阶段,成核和生长的热力学和动力学决定最终晶体产品的粒度分布以及产品质量,是进行结晶器分析、设计、操作和优化的主要依据[2].     

磷酸二氢铵结晶介稳区及诱导期的测定

采用激光测定装置研究了温度、降温速率、磷酸三丁酯（TBP）对磷酸二氢铵（ADP）的介稳区的影响,重点研究了其介稳区的变化规律,计算了不同条件下磷酸二氢铵的介稳区和表观成核级数。测定了磷酸二氢铵在磷酸三丁酯存在下的诱导期,并应用经典成核理论计算成核参数。研究结果表明：磷酸二氢铵的介稳区宽度在高温区狭窄而在低温区较宽,介稳区宽度随着降温速率的增大而变大,磷酸三丁酯的加入增大了介稳区、诱导期和成核参数。     

甲醇-水溶剂中L-苯丙氨酸结晶热力学

在293.15~322.15 K温度范围内，研究L-苯丙氨酸无水物在甲醇-水混合溶剂中溶解度和超溶解度特性，得到L-苯丙氨酸无水物结晶介稳区，计算了成核级数及成核速率，考察了不同初始温度和降温速率对介稳区宽度的影响，并通过研究L-苯丙氨酸297.15 K和302.15 K的转晶水活度，依据溶解度特性绘制L-苯丙氨酸-甲醇-水在该温度下的三元相图。溶解度数据用Apelblat方程、λh方程关联、van t Hoff方程拟合。结果表明，L-苯丙氨酸无水物溶解度随温度的升高而增大，随甲醇体积分数的增加而减小；L-苯丙氨酸无水物结晶介稳区宽度在相同条件下，随初始温度的升高，降温速率的降低变窄；L-苯丙氨酸转晶水活度随温度的升高而增大。     

Crystallization and Precipitation: The Optimal Supersaturation

In this article optimal supersaturation for cooling and evaporation crystallization are presented. This information is based on a simplified model which describes the metastable zone width of activated nucleation. The model assumes that the nucleation step is very fast and the occurrence of the shower of nuclei which is used to define the metastable zone width is caused by the growth of activated nuclei. In future new sensors for the measurement of supersaturation will help to operate batch crystallizers at the optimal supersaturation during the entire batch time.     

Crystallization and Precipitation: The Optimal Supersaturation

In this article the optimal supersaturation for cooling and evaporation crystallization are presented. This information is based on a simplified model which describes the metastable zone width of activated nucleation. The model assumes that the nucleation step is very fast and the occurrence of the shower of nuclei which is used to define the metastable zone width is caused by the growth of activated nuclei. In future new sensors for the measurement of supersaturation will help to operate batch crystallizers at the optimal supersaturation during the entire batch time.     

莱鲍迪苷A溶解度与介稳区宽度的测定及其结晶过程研究

莱鲍迪苷A是极为重要的新型甜味剂,由于缺乏合理的溶解度数据且其成核机理不明确,导致现存的结晶工艺得到的结晶产品存在细晶多、粒度分布不均等问题。为此,首先利用激光动态法测定了莱鲍迪苷A在甲醇-水、乙醇-水、正丙醇-水、丙酮-水中的溶解度及在甲醇-水中的介稳区宽度,并利用Wilson方程对溶解度进行模型验证;研究了溶剂组成、饱和温度、搅拌速率与冷却速率对介稳区宽度的影响,研究表明,莱鲍迪苷A的介稳区宽度随溶剂中甲醇含量与冷却速率的增加而变宽,随饱和温度与搅拌速率的增加而变窄;基于经典成核理论与相关模型,计算了莱鲍迪苷A的固液界面能γ与临界Gibbs自由能\mathrm{\Delta }{G}_{\mathrm{c}\mathrm{r}\mathrm{i}\mathrm{t}}等成核参数;根据表观成核级数m分析可知,初始温度高于318.15 K时,连续成核是莱鲍迪苷A主导的成核方式;基于上述研究优化了莱鲍迪苷A冷却结晶过程,得到了粒度分布均一的结晶产品。     

过硫酸铵冷却结晶过程研究

针对工业生产中过硫酸铵从硫酸铵的电解液中结晶分离过程,研究了过硫酸铵在硫酸铵水溶液中的结晶热力学和动力学。首先,测定了(NH₄)₂S₂O₈-(NH₄)₂SO₄-H₂O体系在不同温度下的三元相图,为优化过硫酸铵冷却结晶工艺提供了热力学依据;此外,采用激光动态法测定了(NH₄)₂S₂O₈的结晶介稳区,研究了降温速率和搅拌速率对介稳区宽度的影响,计算了相关的成核动力学参数;最后,测定了(NH₄)₂S₂O₈在纯水中不同温度下的诱导期,并探究了诱导期与过饱和度之间的相关性。     

Ultrasound assisted crystallization of cephalexin monohydrate:Nucleation mechanism and crystal habit control

With the high-quality requirements for cephalexin monohydrate,developing a robust and practical crys-tallization process to produce cephalexin monohydrate with good crystal habit,appropriate aspect ratio and high bulk density as well as suitable flowability is urgently needed.This research has explored the influence of ultrasound on crystallization of cephalexin monohydrate in terms of nucleation mechanism and crystal habit control.The results of metastable zone width and induction time measurement showed the presence of ultrasound irradiation can narrow the metastable zone and shorten induction time.Cavitation phenomena generated by ultrasound were used to qualitatively explain the mechanism of ultrasound promoting nucleation of cephalexin monohydrate.Furthermore,on the basis of classical nucleation theory and induction time data,a series of nucleation-related parameters (such as crystal-liquid interfacial tension,radius of the critical nucleus and etc.) were calculated and showed a decreasing trend under ultrasound irradiation.The diffusion coefficient of the studied system was also determined to increase by 72.73％ under ultrasound.The changes in these parameters have quantitatively confirmed the mechanism of ultrasound influence on the nucleation process.In further,the calculated surface entropy factor has confirmed that the growth of cephalexin monohydrate follows continuous growth mechanism under the research conditions of this work.Through the exploration of crystallization conditions,it is found that suitable ultrasonic treatment,seeding,supersaturation control and removal of fine crystals are conducive to improving the quality of cephalexin monohydrate product.Optimizing the crystalliza-tion process coupled continuous ultrasound irradiation with fine-crystal dissolution policy has achieved the controllable production of monodisperse cephalexin monohydrate crystal with good performance.     

Validation of Models Predicting Nucleation Rates from Induction Times and Metastable Zone Widths

Three approaches for estimation of nucleation rates from induction time and metastable zone width (MSZW) were validated based on directly measured nucleation rates for paracetamol in ethanol. To quantitatively predict nucleation kinetics using Kubota's methods it is necessary to know the minimum detectable number concentration of nuclei. This was found by determination of light transmission of a series of diluted suspensions of newly nucleated crystals where the size had already been assessed by optical reflection measurement (ORM). The measured nucleation rates strongly depended on both temperature and supersaturation. The Nyvlt method predicted nucleation rates in this system reasonably well; however, it gave slightly low estimates for all temperatures. The methods of Kubota provided nucleation rates that were low by an order of magnitude.     

光卤石中氯化钾溶解度、介穏区、诱导期测定

采用变温溶解动态法测定了光卤石中氯化钾的溶解度,并用简化固液平衡方程对溶解度数据做了拟合。研究了搅拌速度、降温速率对介穏区宽度以及不同过饱和度对诱导期的影响。结果表明：简化固液平衡方程能够对氯化钾溶解度拟合良好;介穏区宽度随降温速率的升高而变宽,随搅拌速度增大而变窄;诱导期随过饱和度的增大而变短,且在不同温度下,相同过饱和度下的诱导期相近。应用经典Nyvlt理论方程和3D成核原理,结合实验介穏区及诱导期数据,计算了光卤石中氯化钾的成核级数为2.46~2.51,在283.15、293.15、303.15 K条件下,氯化钾在该体系中表面张力γ为0.019 8~0.556 0,表面能因子f<3,结晶连续生长。     

环丙沙星在溶液中固液表面能的测定

采用激光法测定了环丙沙星在纯水和水－乙醇溶液（水体积分数23％）中的溶解度，介稳区和不同条件下的诱导期。根据经典成核理论和诱导期理论，推导了固液表面能与诱导期的理论关系，应用该理论关系计算了环丙沙星在溶液中的固液表面能，为环丙沙星初级成核与晶体生长研究提供了重要的参数。     

基于逆溶解度性质的硫酸钠-水体系成核动力学的研究

以逆溶解度性质的硫酸钠-水体系为研究对象,通过聚焦光速反射测量技术对硫酸钠-水体系升温结晶成核行为进行了研究,考察了升温速率、饱和温度对介稳区宽度的影响,通过经典成核理论模型确定了成核动力学参数,探讨了化学势和成核温度对成核速率的影响。结果表明：较小的升温速率、较高的饱和温度都会使介稳区宽度变窄;溶质在固液两相中的化学势差是结晶过程的驱动力,但它并不总是有利于成核过程。以上研究不仅为硫酸钠升温结晶工艺过程开发提供了基础物性数据,还有助于深入理解此类逆溶解度类型升温结晶的成核行为。     

SUPERSATURATION, INDUCTION PERIOD, AND METASTABLE ZONE WIDTH OF CaCl2—Na2C03—HCl SYSTEM

The supersaturation, induction period, and mctastablc zone width ofan aqueous supersaturated solution of CaC₂—Na₂C0₃—HCl system are studied in the present paper. The supersaturation is varied and predicted within a reasonable accuracy when a specified amount of HCl(_aq) is added into the aqueous supersaturated CaC₂—Na₂C0₃—HCl solution. It is found that the decrease of solution supersaturation at low pH is caused mainly by the decrease of carbonate ions. Then, the induction periods are estimated by using the coagulation theory and they can be expressed as a function of supersaturation alone, which results from different values of reagent concentration and pH. Finally, the theoretical metastable zone widths based on arbitrary induction periods are obtained. Meanwhile, the induction periods are measured at various levels of reagent concentration and solution pH by applying the conductivity method. Accordingly, the metastable zone widths are determined experimentally and compared with the theoretical results. It is concluded that the present method is an useful tool for determining the metastable zone width of aqueous supersaturated CaC₂—Na₂C0₃—HCl solution.     

Determination of Metastable Zone Width and Nucleation Induction Period of Palm Oil and its Olein/Stearin in Melting Layer Crystallization

Measurement methods of metastable zone width (MZW) and nucleation induction time for melting layer crystallization of palm oil (PO) and its olein/stearin (POL/PST) were established, and the effects of cooling rate (corresponding to various supercoolings) on MZWs and induction time for melting layer crystallization of PO, POL, and PST were determined. The results indicated that the MZW coherently rose with increasing cooling rates with respect to PO and POL, while it declined with higher cooling rates for PST. The induction period results demonstrated that the nucleation induction periods of PO, PST, and POL decreased with increasing supercoolings, and the lag time for nucleation negatively correlated to the melting point of oils at the same supercooling. These data could offer significant instruction in designing and controlling the melting layer crystallization process for palm oil.     

Solvated behavior and crystal growth mechanism of erythromycin in aqueous acetone solution

The solubility of erythromycin acetone solvate and dihydrate was experimentally determined in aqueous acetone mixtures at different temperature. It has been demonstrated that solubility curves of the two solvates intersected at given solvent composition at various temperature, suggesting a transition behavior between two solvates. The induction period of acetone solvate at different supersaturation was measured by the laser monitoring observation technique. Based on classical homogeneous nucleation theory, the solid-liquid interfacial tension and surface entropy factor were calculated from the induction period data. From the surface entropy factor values calculated, together with surface morphology observation by the atomic force microscopy (AFM), the growth mechanism of erythromycin acetone solvate is consistent with continuous growth mode.