头孢噻肟钠结晶技术研究
|
摘要
针对我国制药工业头孢噻肟钠生产中存在的产品纯度低,分离困难且结晶过程中易聚结成胶等问题,本工作对其精制结晶技术进行了系统化研究,开发出了新型头孢噻肟钠结晶技术,制备出了符合欧美国际质量水平要求的头孢噻肟钠结晶产品。
头孢噻肟钠为第三代头孢类半合成广谱抗菌素,当前仍有着广泛的国内外市场前景。本研究中,采用显微镜实时观测、X射线粉末衍射(powder-XRD)、扫描电镜(SEM)、红外光谱(FT-IR)等测试手段对头孢噻肟钠结晶过程中出现的成胶现象以及聚结现象进行了分析。并通过调节pH值、设定结晶温度程序以及添加晶种等手段,有效消除了上述现象对结晶过程的影响。
在实验采集头孢噻肟钠晶体X-射线粉末衍射数据的基础上,应用分子模拟软件Cerius2确定了晶胞参数、所属晶系和空间群;基于能量最小化原理确定了空间结构;进而采用BFDH、AE模型预测晶体晶习,并与实验产品进行了对比。
采用动态法考察了头孢噻肟钠在17种纯溶剂中的溶解度,并详细测定了其在5种纯溶剂中的溶解度。根据溶解度特性及产品性能分析,筛选了溶剂系统,建立了纯溶剂中头孢噻肟钠的溶解度模型。动态法测定了不同温度和溶剂配比下,头孢噻肟钠在“水+S溶剂”二元溶剂体系中的溶解度,根据经验方程、λh方程和CNIBS/Redlich-Kister方程建立了二元溶剂体系中的溶解度模型。
测定了头孢噻肟钠溶析结晶的介稳区和诱导期,根据初级成核理论计算了固液表面张力、表面熵因子。结合原子力显微镜(AFM)测定结果,推断晶体表面生长为连续生长机理;借助聚焦光束反射测量仪(FBRM)、颗粒成像测量仪(PVM)、Malvern Mastersizer粒度分析仪、扫描电子显微镜(SEM)及显微镜实时观测等手段对溶析结晶过程中的成核、生长及二次过程进行了分析。
应用间歇动态法测定了头孢噻肟钠溶析结晶过程中的动力学数据。按粒度相关生长模型建立了其结晶动力学方程组,确定了结晶过程中晶体生长速率方程以及二次成核速率方程中的相关参数。
在结晶热力学、结晶动力学以及结晶过程分析的基础上,建立了头孢噻肟钠结晶工艺过程数学模型。实验考察了各种操作参数对产品质量和收率的影响,得到头孢噻肟钠优化结晶工艺操作时间表。
针对头孢噻肟钠结晶产品粒度较小的缺点,开发了球形结晶新工艺。该工艺在保障产品质量的前提下,通过结晶母液中颗粒间的相互作用得到可控粒度的球形聚结产品,可有效改进过滤、运输、贮存,制剂等后续处理工艺。该技术尚可应用于其他药物及生物产品的结晶过程中。
以上有关研究内容尚未见文献报道。
In order to resolve the problems indwelling the industrial crystallization of cefotaxime sodium, such as low purity of the crystal product, difficult separation and the gelation & agglomeration phenomena in the process of crystallization, the investigation on the crystallization of cefotxime sodium has been performed. By means of the new crystallization technology developed in this work, the product, which is up to the standard, has been successfully synthesized.
Cefotaxime sodium, which belonges toβ-lactam antibiotics, is a third generation, semisynthetic, broad-spectrum cephalosporin, and has still a wide market prospect at home and abroad at present. In the current work, by means of real-time observation by microscope, powder-XRD, SEM and FT-IR technology, the gelation and
agglomeration phenomena in the process of crystallization have been investigated, and their effects on the crystallization process have been efficiently avoided by means of regulating the pH value of the mother solution, adjusting the crystallization temperature program and seeding, etc.
By Cerius2, the crystal cell parameters, crystal system and space group of cefotaxime sodium were simulated. At first, possible space groups of cefotaxime sodium can be obtained by indexing its experimental X-ray power diffraction pattern. Subsequently, the crystal structure was determined based on the energy minimization principle; and the crystal habit was predicted by employing BFDH and AE models. The solid-liquid equilibrium behavior of cefotaxime sodium in 17 solvents was investigated, and the solubilities in 5 good solvents were determined by dynamic method. The model equations in pure solvents were established, and then the crystallization solvent system was selected according to solubility and products properties. The solubilities of cefotaxime sodium in water + S binary mixtures were also measured by dynamic method. And different model equations, such as empirical equation,λhequation and CNIBS/Redlich-Kister equation, were employed to correlate the solubility data.
The metastable zone and induction time of crystallization were determined by laser monitoring method and the effects of operation conditions such as temperature, agitation and addition rate of dilute agent were examined. The solid-liquid surface tension and surface entropy factors were estimated based on primary nucleation theory. Combining with the surface morphology acquired by AFM (Atomic Force Microscopy), the growth mechanism of crystal surface was deduced as continuous growth. FBRM (Focused Beam Reflectance Measurement), PVM (Particles Visual Measurement), Malvern Mastersizer and SEM (Scanning Electronic Microscopy) etc were employed to investigate the nucleation, growth and secondary processes in the process of crystallization.
Batch dynamic method was used to research the drowning-out crystallization kinetics behavior of cefotaxime sodium. The crystallization kinetic equations were established with size-dependent growth rate model and the correlation parameters of secondary nucleation and crystal growth rate equations were determined.
Based on the investigation of the crystallization thermodynamics, kinetics and analysis of crystallization technique, the mathematical model of the drowning-out crystallization process was established according to the population balance equations and mass balance equations. The effects of operation conditions on the crystallization process and the quality of product were investigated in detail by both experiments and model simulation, and the optimal operation strategy was established.
The new spherical crystallization technology was developed ascribing to the properties of the small crystal size and morphology of the cefotaxime sodium. On the premise of ensuring the quality of the product, the spherical agglomerated particles can be obtained by this technology, and the post-treatment procedures, such as filtration, transport, storage and granulation etc, can be efficiently improved. This technology can be applied in crystallization procedure of other pharmaceutical and biology products.
No same report to above study results has been published in literature up to date.
头孢噻肟钠为第三代头孢类半合成广谱抗菌素,当前仍有着广泛的国内外市场前景。本研究中,采用显微镜实时观测、X射线粉末衍射(powder-XRD)、扫描电镜(SEM)、红外光谱(FT-IR)等测试手段对头孢噻肟钠结晶过程中出现的成胶现象以及聚结现象进行了分析。并通过调节pH值、设定结晶温度程序以及添加晶种等手段,有效消除了上述现象对结晶过程的影响。
在实验采集头孢噻肟钠晶体X-射线粉末衍射数据的基础上,应用分子模拟软件Cerius2确定了晶胞参数、所属晶系和空间群;基于能量最小化原理确定了空间结构;进而采用BFDH、AE模型预测晶体晶习,并与实验产品进行了对比。
采用动态法考察了头孢噻肟钠在17种纯溶剂中的溶解度,并详细测定了其在5种纯溶剂中的溶解度。根据溶解度特性及产品性能分析,筛选了溶剂系统,建立了纯溶剂中头孢噻肟钠的溶解度模型。动态法测定了不同温度和溶剂配比下,头孢噻肟钠在“水+S溶剂”二元溶剂体系中的溶解度,根据经验方程、λh方程和CNIBS/Redlich-Kister方程建立了二元溶剂体系中的溶解度模型。
测定了头孢噻肟钠溶析结晶的介稳区和诱导期,根据初级成核理论计算了固液表面张力、表面熵因子。结合原子力显微镜(AFM)测定结果,推断晶体表面生长为连续生长机理;借助聚焦光束反射测量仪(FBRM)、颗粒成像测量仪(PVM)、Malvern Mastersizer粒度分析仪、扫描电子显微镜(SEM)及显微镜实时观测等手段对溶析结晶过程中的成核、生长及二次过程进行了分析。
应用间歇动态法测定了头孢噻肟钠溶析结晶过程中的动力学数据。按粒度相关生长模型建立了其结晶动力学方程组,确定了结晶过程中晶体生长速率方程以及二次成核速率方程中的相关参数。
在结晶热力学、结晶动力学以及结晶过程分析的基础上,建立了头孢噻肟钠结晶工艺过程数学模型。实验考察了各种操作参数对产品质量和收率的影响,得到头孢噻肟钠优化结晶工艺操作时间表。
针对头孢噻肟钠结晶产品粒度较小的缺点,开发了球形结晶新工艺。该工艺在保障产品质量的前提下,通过结晶母液中颗粒间的相互作用得到可控粒度的球形聚结产品,可有效改进过滤、运输、贮存,制剂等后续处理工艺。该技术尚可应用于其他药物及生物产品的结晶过程中。
以上有关研究内容尚未见文献报道。
In order to resolve the problems indwelling the industrial crystallization of cefotaxime sodium, such as low purity of the crystal product, difficult separation and the gelation & agglomeration phenomena in the process of crystallization, the investigation on the crystallization of cefotxime sodium has been performed. By means of the new crystallization technology developed in this work, the product, which is up to the standard, has been successfully synthesized.
Cefotaxime sodium, which belonges toβ-lactam antibiotics, is a third generation, semisynthetic, broad-spectrum cephalosporin, and has still a wide market prospect at home and abroad at present. In the current work, by means of real-time observation by microscope, powder-XRD, SEM and FT-IR technology, the gelation and
agglomeration phenomena in the process of crystallization have been investigated, and their effects on the crystallization process have been efficiently avoided by means of regulating the pH value of the mother solution, adjusting the crystallization temperature program and seeding, etc.
By Cerius2, the crystal cell parameters, crystal system and space group of cefotaxime sodium were simulated. At first, possible space groups of cefotaxime sodium can be obtained by indexing its experimental X-ray power diffraction pattern. Subsequently, the crystal structure was determined based on the energy minimization principle; and the crystal habit was predicted by employing BFDH and AE models. The solid-liquid equilibrium behavior of cefotaxime sodium in 17 solvents was investigated, and the solubilities in 5 good solvents were determined by dynamic method. The model equations in pure solvents were established, and then the crystallization solvent system was selected according to solubility and products properties. The solubilities of cefotaxime sodium in water + S binary mixtures were also measured by dynamic method. And different model equations, such as empirical equation,λhequation and CNIBS/Redlich-Kister equation, were employed to correlate the solubility data.
The metastable zone and induction time of crystallization were determined by laser monitoring method and the effects of operation conditions such as temperature, agitation and addition rate of dilute agent were examined. The solid-liquid surface tension and surface entropy factors were estimated based on primary nucleation theory. Combining with the surface morphology acquired by AFM (Atomic Force Microscopy), the growth mechanism of crystal surface was deduced as continuous growth. FBRM (Focused Beam Reflectance Measurement), PVM (Particles Visual Measurement), Malvern Mastersizer and SEM (Scanning Electronic Microscopy) etc were employed to investigate the nucleation, growth and secondary processes in the process of crystallization.
Batch dynamic method was used to research the drowning-out crystallization kinetics behavior of cefotaxime sodium. The crystallization kinetic equations were established with size-dependent growth rate model and the correlation parameters of secondary nucleation and crystal growth rate equations were determined.
Based on the investigation of the crystallization thermodynamics, kinetics and analysis of crystallization technique, the mathematical model of the drowning-out crystallization process was established according to the population balance equations and mass balance equations. The effects of operation conditions on the crystallization process and the quality of product were investigated in detail by both experiments and model simulation, and the optimal operation strategy was established.
The new spherical crystallization technology was developed ascribing to the properties of the small crystal size and morphology of the cefotaxime sodium. On the premise of ensuring the quality of the product, the spherical agglomerated particles can be obtained by this technology, and the post-treatment procedures, such as filtration, transport, storage and granulation etc, can be efficiently improved. This technology can be applied in crystallization procedure of other pharmaceutical and biology products.
No same report to above study results has been published in literature up to date.
引文
[1]王静康,化学工程手册—结晶,北京:化学工业出版社, 1996, 1-3
[2] Moyers C. G., Rousseau R. W., Crystallization operations, in Rousseau R W ed. Handbook of Separation process Technology, New York: John Wiley & sons, 1987, 758
[3]朱洪涛,工业结晶分离技术研究新进展,石油化工, 1999, 28(7): 493- 496
[4] Wey J. S., Karpinski P H, Precipitation process, in Myerson A S, Handbook of industrial crystallization, Boston: Butterworth- Heinemann, 2002. 141
[5] Mullin J. W., Crystallization, 3rd ed., London: Butterworths, 1993
[6]王静康,工业结晶新技术,国际学术动态, 2002, 5: 37-38
[7] http://www.51report.com/free/detail/116024.html
[8] http://www.chemtn.com.cn/Article_Show.asp?ArticleID=3599
[9] http://www.bbmc.edu.cn/jpkc/2006/ylx/jazl/39.doc
[10] http://www.yxbj.com/Article_Print.asp?ArticleID=3589
[11]国家药典委员会,中华人民共和国药典2005年版(二部),北京:化学工业出版社, 2005
[12] M. Zajac, W. Musial, L. Pawlowski, Stability of cefotaxime sodium in solid state, Pharmazie, 2000, 55: 917-918
[13] Gaston Amiard, Dieter Bormann, Walter Duerckheimer, et al., Sodium 3-Acetoxylmethyl-7 -[2-(2–Amino-4-thiazolyl)-2-methoxyimino-acetamido]-ceph-3-eme-4-carboxylate, USP 4224371, 1980
[14] T. Atanassova, Z. Georgieva, V. Lazarova, et al., Synthesis of cefotaxime sodium salt, Pharmazie, 1998, 53: 418
[15] http://www.hnkjcg.com/kjcg2006/a2002000485a.a.htm
[16]张克从,近代晶体学基础,北京:科学出版社, 1987
[17]周公度,晶体结构测定,北京:科学出版社, 1981
[18]韩建成,多晶X射线结构分析,上海:华东师范大学出版社, 1987
[19]陈小明,荣继文,单晶结构分析原理与实践,北京:科学出版社, 2003
[20] Hovmoller S., Zou X. D., Weirich T. E., Crystal structure determination from EM images and electron diffraction patterns, Advances in Imaging and Electron Physics, 2002, 123: 257-289
[21] Zheng J. G., Vincent R,. Steeds J. W., Crystal structure determination of an Al-Fe-Si-Be phase by convergent-beam electron diffraction, Philosophical Magazine A-Physics of CondensedMatter Structure Defects And Mechanical Properties, 1999, 79 (11): 2725-2733
[22] Man L. I., Imamov R. M., Determination of crystal structures by electron diffraction structure analysis, Crystallography Reports, 1998, 43 (6): 940-944
[23] Fossdal A., Brinks H. W., Fichtner M., et al., Determination of the crystal structure of Mg(AlH4)(2)by combined X-ray and neutron diffraction, Journal of Alloys and Compounds, 2005, 387 (1-2): 47-51
[24] Bull C. L., McMillan P. F., Soignard E., et al., Determination of the crystal structure of delta-MoN by neutron diffraction, Journal of Solid State Chemistry, 2004, 177 (4-5): 1488-1492
[25] Rodriguez R., Pacheco S., Vargas S., et al., Crystalline structure determination of anisotropic dimethyl terephthalate crystallites by micro-Raman spectroscopy, Journal of Materials Research, 2000, 15 (6): 1397-1403
[26]郭森立,侯廷军,徐筱杰,等,一个新BEDT-TTF电荷转移盐的晶体结构预测,物理化学学报, 2002, 18 (4): 289-291
[27] Nowell H., Price S. L., Validation of a search technique for crystal structure prediction of flexible molecules by application to piracetam, Acta Crystallographica Section B-Structural Science, 2005, 61: 558-568
[28] Karamertzanis P. G., Price S. L., Challenges of crystal structure prediction of diastereomeric salt pairs, Journal Of Physical Chemistry B, 2005, 109 (36): 17134-17150
[29]方奇,于文涛,晶体学原理,北京:国防工业出版社, 2002, 3
[30]钱易泰,结晶化学导论(第3版),合肥:结晶化学导论, 2005, 3
[31]王英华,晶体学导论,北京:清华大学出版社, 1989
[32]马礼敦, X射线粉末衍射的新起点-Rietveld全谱拟合,物理学进展, 1996, 16 (2): 251- 265.
[33]梁敬魁,粉末衍射法测定晶体结构,北京:科学出版社. 2003: 557
[34] Mighell A. L., Santoro A., Geometrical ambiguities in the indexing of powder patterns. J. Appl. Cryst., 1975, 8: 372-374
[35] Smith G. S., Snyder R. L., FN: a criterion for rating powder diffraction patterns and evaluating the reliability of powder-pattern indexing, J. Appl. Cryst., 1979, 12:60-65
[36] Damodara M. P., Abraham C., Application of X-ray powder diffraction techniques to the solution of unknown crystal structures, Acc. Chem. Res., 1997, 30: 414-422
[37] Kenneth D. M. H., Crystal structure determination from powder diffraction data. Chem. Mater.,1996, 8: 2554-2570
[38]王静康,黄向荣,刘秉文,等,有机分子晶体晶习预测的研究进展,人工晶体学报,2002, 31 (3): 218-223
[39] Bravais A., Etudes Cristallographiques, Paris: Gauthier-Villars, 1866, 1
[40] Hartman P., Perdok W. G., On the Relations Between Structure and Morphology of Crystals III, Acta Cryst., 1955, 8: 525-529
[41] Hartman P., Perdok W. G., On the Relations Between Structure and Morphology of Crystals II, Acta Cryst., 1955, 8: 521-524
[42] Hartman P., Perdok W. G., On the Relations Between Structure and Morphology of Crystals I, Acta Cryst., 1955, 8: 49-52
[43] Hartman P., Bennema P., The attachment energy as a habit controlling factor: I. Theoretical considerations, 1980, 49 (1): 145-156
[44]张缨,有机物系溶液结晶过程中形态学控制研究(博士学位论文),天津大学, 2005.
[45] Inc. A., Cerius2 modeling enviroment, Release 4.0, San Diego: Accelrys Inc., 1999
[46] S. M. Berge, N. L. Henderson, M. J. Frank., Kinetices and mechanism of degradation of cefotaxime sodium in aqueous solution, Journal of pharmaceutical Sciences, 1983, 72(1): 59-63
[47]陈宗淇,王光信,徐桂英,胶体与界面化学,北京:高等教育出版社, 2001, 434
[48]侯万国,孙德军,张春光,应用胶体化学,北京:科学出版社, 1998, 125
[49]沈钟,王果庭,胶体与表面化学,北京:化学工业出版杜, 1997, 111
[50]普劳斯尼茨J. M. (Prausnitz J M ),流体相平衡的分子热力学,北京:化学工业出版社, 1990
[51] Melis S., Verduyn M., Effect of fluid motion on the aggregation of small particles subjectto interaction forces, AIChE J, 1999, 45(7):1383-1393
[52] Shouci Lu, Yuqing Ding, Jinyong Guo, Kinetics of particle aggregation in turbulence, Advance in Colloid and Interface Science, 1998, 78(3): 197-235
[53] Stefano Melis, Marcel Verduyn, Giuseppe Storiti, Effect of fluid motion on theaggregation of small particles subject to interaction forces, AIChE J, 1999,45(7): 1383-1390
[54] Verwey, E. J. W., J. T. G. Overbeek, Theory of the Stability of Lyophobic Colloids, Elsevier, Amsterdam, 1948
[55] Masy J. C., Cournil M., Using a turbinimetric method to study the kinetic of agglomeration of potassium sulfate in liquid medium, Chem Eng Sci, 1991, 46(2): 693-701
[56]瓦拉斯(Walas S M),化工相平衡(韩世钧),北京:中国石化出版社, 1991
[57]普劳斯尼茨J. M. (Prausnitz J M ),流体相平衡的分子热力学,北京:化学工业出版社, 1990
[58]陈慧萍,维生素C冷却结晶过程的研究(博士学位论文),天津:天津大学化工学院, 2000
[59]胡英,流体的分子热力学,北京:高等教育出版社, 1982
[60]金家骏,分子热力学,北京:科学出版社, 1990
[61] Preston G. T., Prausnitz J. M., Thermodynamics of solid solubility in cryogenic solvents, Industrial & Engineering Chemistry Process Design and Development, 1970, 9 (2): 264-271
[62] Myers A. L., Prausnitz J. M., Thermodynamics of solid carbon dioxide solubility in liquid solvents at low temperatures, Industrial & Engineering Chemistry Fundamental, 1965, 4 (2): 209-212
[63]金克新,赵传钧,马沛生,化工热力学,天津:天津大学出版社, 1990, 137-139
[64]陈钟秀,顾飞燕,化工热力学,北京:化学工业出版社, 1993, 151
[65] Preston G. T., Prausnitz J. M., Ind Eng Chem Process Des Dev, 1970, 9: 264
[66] Myers A. L., Prausnitz J. M., Ind Eng Chem Fundam, 1965, 42: 3643
[67]许文,高等化工热力学,天津:天津大学出版社, 2004
[68] Muir R. F., Howart C. S., Predicting solid-liquid equilibrium data from vapor-liquid data, Chem. Eng., 1982, 89(4): 89
[69] Renzo C., Stella D., Gluseppe T., Solubility of Solid acetic acid in acetone-ethanol mixtures, J Chem Eng Data, 1985, 30: 410
[70] Domanska U., Domanski K., Correlation of the solubility of hexacosane in aliphatic alcohols, Fluid phase equilibria, 1991, 68: 103-114
[71] Domanska U., Solubility of n-alkanols (c16, c18, c20) in binary solvent mixtures, Fluid Phase Equilibria, 1989, 46 (2-3): 223-248
[72] Domanska U., Kozlowska M. K., Solubility of imidazoles in ketones, Fluid Phase Equilibria, 2003, 206 (1-2): 253-266
[73] Domanska U., Lachwa J., (solid + liquid) phase equilibria of binary mixtures containing n-methyl-2-pyrrolidinone and long-chain n-alkanols at atmospheric pressure, Fluid Phase Equilibria, 2002, 198 (1): 1-14
[74] Domanska U., Rolinska J., Measurement and correlation of the solubility of n-alkanols (c18, c20) in n-alkanes (c7-c16), Fluid Phase Equilibria, 1993, 86: 233-250
[75] Ferreira L. A., Macedo E. A., Pinho S. P., Pinho solubility of amino acids and diglycine in aqueous alkanol solutions, Chemical Engineering Science, 2004, 59 (15): 3117-3124
[76]朱自强,徐汛,化工热力学(第二版),北京:化学工业出版社, 1991, 161
[77] Domanska U., Domanski K., Correlation of the solubility of hexacosane in aliphatic alcohols, Fluid phase equilibria, 1991, 68: 103-114
[78]刘金晨,陆九芳,氨基酸溶解平衡的热力学研究,清华大学学报:自然科学版, 1997, 37 (12): 32-36
[79]李小森,陆九芳,改进的uniquac模型在非离子表面活性剂溶液中的应用,化工学报,1999, 50 (9): 228-234
[80] Zhu Ziqiang, Yao Shanjing, Jin Zhangli, The Fundamental Theory of Phase Equilibria and Its Applications, Hangzhou: Zhejiang University Press, 1990
[81] Larsan B. L., Rasmussen P., Fredenslund A., A modified UNIFAC group- contribution model for prediction of phase equilibria and heats of mixing, Ind. Eng. Chem. Res., 1987, 26: 2274-2286
[82] Kang J. W., Abildskov J., Gani R., Estimation of mixture properties from first- and second-order group contributions with the UNIFAC model. Ind Eng Chem Res, 2002, 41: 3260-3273
[83] Li Junfa, Prediction of activity coefficient by UNIFAC group contribution method (I), Chemical Engineering, 1991, 19(1): 12-21
[84] Wilson G. M., Deal C. H., Activity coefficient and molecular structure, Ind. Eng. Chem. Fundamen., 1962, 1(13): 292-293
[85]吴献忠,崔晓钰,李美玲, UNIFAC基团贡献法预测混合制冷剂的气液相平衡,化工学报, 2005, 56(10), 1832-1836
[86] Fredenslund A., Gmehling J., Rasmussen P., Vapor-liquid Equilibria Using UNIFAC a Group- contribution Method. New York: Elsevier Scientific Publishing Co., 1997
[87] Gmehling J. G., Anderson T. F., Prausnitz J. M., Solid-liquid equilibrium using UNIFAC,Ind Eng Chem Fundam,1978,17(4): 269
[88]王志容,尹潜,汽液固三相平衡的计算,化学工程, 1986, 14(6): 52
[89] Domanska U, Domanski K, Correlation of the solubility of hexacosane in aliphatic alcohols,Fluid phase equilibria, 1991, 68: 103
[90] Acree W. E. J., Mathematical representation of thermodynamic properties, Part 2. derivation of the (NIBS)/Redlich-Kister mathematical representation from a two-body and three-body interactional mixing model. Thermochim. Acta., 1992, 198: 71-79
[91] Acree W. E. J., Comments concerning“model for solubility estimation in mixed solvent system”, Int. J. Pharm., 1996, 127: 27-30
[92] Jouyban Gharamaleki A., Hanaee J., A novel method for improvement of predictability of the CNIBS/R-K equation, Int. J. Pharm., 1997, 154: 254-247
[93] William E., Acree, J., Thermodynamic properties of ternary non-electrolyte solutions: Part 2. Prediction of infinite dilution activity coefficients and solubilities based on the various nibs and microscopic partition models, Thermochim, Acta., 1990, 158: 11-22
[94] Kristin A. F., Siddharth P., Solubility of benzil in (binary alcohol+1-octanol) solvents, J. Chem. Thermodyna., 1997, 29: 475-481
[95] Carmen E. H., Karen S. C., Lindsay E. R., et al., Solubility of pyrene in binary (alkane + 2-butanol) solvent mixtures, J. Chem. Thermodyna., 1998, 30: 37-42
[96] Buchowski H., Ksiazczak A., Pietrzyk S, Solvent activity along a saturation line and solubility of hydrogen-bonding solids. J Phys Chem, 1980, 84(9): 975-979
[97] Buchowski H., Khiat A., Solubility of solids in liquids: One-parameter solubility equation, Fluid Phase Equilibria, 1986, 25 (3): 273-278
[98] Domanska U., Hofman T., Rolinska J., Solubility and vapour pressures in saturated solutions of high-molecular-weight hydrocarbons, Fluid Phase Equilibria, 1987, 32: 273-293
[99]孔学军,夏清,维生素B6和维生素B6酮的溶解度测定与关联,化学工程, 2000, 28 (6): 38-41
[100]鲍颖,盐酸大观霉素溶析过程研究: [博士学位论文],天津大学, 2003
[101] Wang S., Wang J. K., Yin Q. X., Measurement and correlation of solubility of 7-aminocephalosporanic acid in aqueous acetone mixtures, Ind. Eng. Chem. Res., 2005, 44: 3783-3787
[102] Apelblat A., Manzurola E., Solubilities of o-acetylsalicylic, 4-aminosalicylic, 3, 5-dinitrosalicylic, and p-toluic acid, and magnesium-dl-aspartate in water from T=(278 to 348) K, Journal of Chemical Thermodynamics, 1999, 31: 85-91
[103] Li D. Q., Evans D. G., Duan X., Solid-liquid equilibria of terephthalaldehydic acid in different solvents, Journal of Chemical and Engineering Data, 2002, 47 (5): 1220-1221
[104] Wang S., Wang J., Yin Q., Measurement and correlation of solubility of 7-aminocephalosporanic acid in aqueous acetone mixtures, 2005, 44 (10): 3783-3787
[105]刘江鹤,陈忠民,田洪河,等,苯甲酸溶解度的测定及关联,郑州工业大学学报, 2001, 22 (1): 97-99
[106]任国宾,盐酸帕罗西汀结晶过程研究(博士学位论文),天津大学, 2005 [1074]徐衡,董奕,顺丁烯二酸酐在邻苯二甲酸酯中溶解度的研究,石油化工, 2000, 29 (7): 502-504
[108] Nyvlt J., Solid-liquid equilibria, Amsterdam: Elsevier, 1977
[109] Wise W. S., Nicholson E. B., Solubilities and heats of crystallization of sucrose in aqueous solution, Journal of Chemical Society, 1955, 2714
[110] Mullin J. W., Sipek M, Solubility and density isotherms for potassium aluminium sulphate water-alcohol systems, Journal of Chemical Engineering Data, 1982, 26: 164
[111]丁绪淮,谈遒,工业结晶,北京:化学工业出版社, 1985
[112] Mohan R., Lorenz H., Myerson A. S., Solubility measurement using differential scanning calorimetry, Ind. Eng. Chem. Res., 2002, 41: 4854-4862
[113]王福安,曹庭珠,赵天源,等,喹诺酮类药物的溶解度模型,化工学报, 1996, 47(5): 615-620
[114]王水, 7-氨基头孢烷酸反应结晶过程研究(博士学位论文),天津大学, 2005
[115] S. Wang, J. Wang, Q. Yin, et al., Light Extinction Method for Solubility Measurement, Chinese Optics Letters, 2005, 3(3), 149-151
[116] Atkins P. W., Physical Chemistry[M], Oxford Univ, Press, 1994: 545
[117] Stephen, H.; Stephen, T., Solubility of Inorganic and Organic Compounds, Pergamon Press: Oxford, 1963, 1, 152
[118]程能林,溶剂手册(第二版),北京:化学工业出版社, 2002
[119] Eladio, P. F., Jhoany, A. E., Lauro, N. P., et al., Solubility of Cefotaxime Sodium Salt in Seven Solvents Used in the Pharmaceutical Industry, J. Chem. Eng. Data, 1998, 43, 49-50
[120] M. Barzegar-Jalali, J. Hanaee, Model for solubility estimation in mixed solvent systems, Inter. J. Pharm., 1994, 109, 291-295
[121] Acree W. E. Jr., Zvaigzne A. I., Thermodynamics properties of non-electrolyte solutions, IV, estimation and mathematical representation of solute activity coefficients and solubilities in binary solvents using the CNIBS and modified Wilson equations, Thermochim. Acta., 1991, 178, 151-167
[122] M. Barzegar-Jalali, A. Jouyban-Gharamaleki, A general model from theoretical cosolvency models, Inter. J. Pharm., 1997, 152, 247-250
[123] A. Martin, P. L. Wu, A. Adjei, et al., Extended Hildebrand solubility approach and the log linear solubility equation, J. Pharm. Sci., 1982, 71, 849-856
[124] Ochsner A. B., Belloto R. J., Sokoloski T. D., Prediction of xanthine solubilities using statistical techniques, J. Pharm. Sci., 1985, 74, 132-135
[125] M. Barzegar-Jalali, A. Jouyban-Gharamaleki. Models for calculating solubility in binary solvent systems, Inter. J. Pharm., 1996, 140, 237-246
[126] Dong, Y., Ma, P. S., Xu, W., Study on the solubility of maleic anhydride in 1,2-cyclohexanedicarboxylic acid diisobutyl ester and diethyl ester, J. Chem. Eng. Chin. Univ., 2000, 14, 160-163
[127] Omar W., Ulrich J. Solid liquid equilibrium, metastable zone, and nucleation parameters of the oxalic-water system, Cryst. Growth Des., 2006, 6(8): 1927-1930
[128]龚俊波, 6APA制备及反应结晶过程研究(博士学位论文),天津:天津大学化工学院, 2001
[129] Ulrich J., Strege C. Some aspects of the importance of metastable zone width and nucleation in industrial crystallizers, J. Cryst. Growth, 2002, 237-239: 2130-2135
[130]Е.В.哈姆斯基,著,古涛,叶铁林,译,化学工业中的结晶,北京:化学工业出版社, 1984, 9-12
[131] Mersmann K. Bartosch, How to predict the metastable zone width, J. Crystal Growth,1998, 183(1-2): 240-250
[132] Ting H. H., Mccabe W. L., Supersaturation units and their conversion factor, The Chemical Engineer, 1973, 274: 316
[133] Ulrich J., Strege C., Some aspects of the important of metastable zone width and nucleation in industrial crystallizaters, J. Cryst. Growth, 2002, 237: 2130-2135
[134] Kim K. J., Mersmann A., Estimation of metastable zone width in different nucleation processes, Chem. Eng. Sci., 2001, 56:2315-2324
[135] Gurbuz H., Ozdemir B., Experimental determination of the metastable zone width of borax decahydrate by ultrasonic velocity measurement, J. Cryst. Growth, 2003, 252: 343-349
[136] Titiz-sargut S., Ulrich J., Influence of additives on the width of the metastable zone, Cryst.Growth Des., 2002, 2(5): 371-374
[137] Correia P., Lopes C., Piedade M. E. M., et al., Solubility and metastable zone width of 1-Keto-1,2,3,4-tetrahydro-6-methylcarbazole in acetone, J. Chem. Eng. Data, 2006, 51(4):1306-1309
[138]韩佳宾,王静康,咖啡因在水和乙醇中的介稳区的测定,天津大学学报, 2003,36:765-768
[139] Fawell P. D., Walting H. R., Mutil-angle laser light scattering to measure nucleation induction period, Applied Spectroscopy, 1998, 52(8): 1115
[140] Sohnel O., Mullin J. W., A method for the determination of precipitation induction periods, J Crystal Growth, 1978, 44: 377
[141] Knezic D., Zaccaro J., Myerson A. S., Nucleation induction time in levitated droplets, J. Phys. Chem., B 2004, 108: 672-677
[142] Viedma C., Experimental evidence of chiral symmetry breaking in crystallization from primary nucleation, J. Cryst. Growth, 2006, 261: 118-121
[143] Mersmann A., Calculation of interfacial tensions, J. Cryst. Growth, 1990, 102: 841-847
[144] Sukanya S., Adrian E. F., Edward T. W., The secondary nucleation threshold and crystal growth ofα-glucose monohydrate in aqueous solution, Cryst. Growth. Des., 2006, 3(3):795-801
[145] Botsaris G. D., Qin R. Y., A new mechanism for nuclei formation in suspension crystallizers: the role of interparticle forces, Chem. Eng. Sci., 1997, 52( 2): 3429-3440
[146] Ward M. D., Bulk crystals to surface: combining X-ray diffraction and atomic force microscopy to probe the structure and formation of crystal interfaces, Chem. Rev., 2001, 1697-1725
[147] Bennema P., Theory and experiments for crystal growth from solution: implication for industrial crystallization, Industrial crystallization, New York: Plenum Press, 1976
[148] Barata P. A., Serrano M. L.,“Salting-out precipitation of potassium dihydrogen phosphate(KDP)-Ⅰprecipitation mechanism”, J. Cryst. Growth, 1996, 160: 361-369
[149] Malkin A. J., Kuznetsov Y. G., AFM observation of the surface morphology and impurity effects on orthorhombic hen egg-white lysozyme crystals, J. Cryst. Growth, 2002, 242: 199-208
[150] Geng Y. L., Xu D., Wang X. Q., et al., AFM study of surface morphology of 100 cleavage planes of L-arginine acetate crystals, J. Cryst. Growth, 2005, 282: 208-213
[151] Sours R. E., Zellelow A. Z., Swift J. A., An in situ atomic force microscopy study of uric acid crystal growth, J. Phys. Chem.B, 2005, 109: 9989-9995
[152] Mullin J. W., Garside J., Crystallization of aluminum potassium sulfate: a study in the assessment of crystallizer design data, I: Single crystal growth rates, Trans Int Chem Eng, 1967, 45: 285
[153] David R., Marchal P., Klein J. P., Chem Eng Sci, 1991, 46: 205
[154] Tavare N. S., Garside J., Silica precipitation in a semi-batch crystallizer, Chem Eng Sci, 1993, 48(3): 475
[155] Mahadevan C., Jegatheesan, C. S., Nucleation studies in supersaturated aqueous solutions of chromate doped potassium phosphate, J. India. Chem. Soc., 1999, 76: 47-48
[156] Shiau L. D., Berglund K. A., Model for a cascade crystallizer in the presence of growth rate dispersion, Ind. Eng. Chem. Res., 1987, 26: 2515-2521
[157] Bourne J. R., Davey R. J., McCulloch,J., The growth kinetics of hexamethriene tetramine crystals from a water/acetone solution, Chem. Eng. Sci., 1978, 38: 199
[158] Randolph A. D., Larson M. A., Theory of partifulate process: analysis and techniaues of continuous crystallization (2nd ed), Toronto: Academic Press, 1988, 50-79
[159] Chemaly Z., Muhr H., Fick M., Crystallization kinetics of calcium lactate in amixed-suspension-mixed-product removed crystallizer, Ind. Eng. Chem. Res., 1999, 38: 2803-2808
[160]陈敏恒,丛德滋,方图南,等,化工原理(上册),北京:化学工业出版社, 1999, 146
[161] Heijden A. E., Eerden J. P., Rosmalen G. M., The secondary nucleation rate: a physical model, Chemical Engineering Science, 1994, 49 (18): 3103-3113
[162] Gooch J. R., Hounslow M. J., Monte Carlo Simulation of Size-Enlargement Mechanisms in Crystallization, AIChE Journal, 1996, 42 (7): 1864-1874
[163] Puel F., Fevotte G., Klein J. P., Simulation and analysis of industrial crystallization processes through multidimensional population balance equations, Part 1: a resolution algorithm based on the method of classes, Chem. Eng. Sci., 2003, 58: 3715-3727
[164] Tavare N. S., Chivate M. R., CSD Analysis from a Batch Dilution Crystallizer, Journal of Chemical Engineering of Japan, 1980, 13 (5): 371-379
[165] Tavare N. S., Garside J., Analysis of Batch Crystallizers, Ind. Eng. Chem. Process Des. Dev., 1980, 19: 653-665
[166] Chivate M. R., Palwe B. G., Tavare N. S., Effect of Seed Concentration in a Batch Dilution Crystallizer, Chem.Eng.Commun., 1979, 3: 127-133
[167] Harkins W. D., Gans D. M., Monomolecular films, the solid-liquid interface and the sedimentation and flocculation of powders in liquids, J Phys Chem., 1932, 36(1): 86
[168] Stock D. I., Micro-spherieal aggregation of barium sulphate, Nature, 1952, 170: 423
[169] Smith H. M., Puddington I. E., Spherical agglomeration of barium sulphate, Can. J. Chem., 1960, 38(10): 1911
[170] Yoshiaki Kawashima, Motonari Okumura, Hideo Takenaka, Spherical Crystallization: Direct Spherical Agglomeration of Salicylic Acid crystals During Crystallization, Science, 1982, 216: 1127-1128
[171] Ribardiere, P., Tchoreloff, G., Couarraze, et al, Modification of ketoprofen bead structure produced by the spherical crystallization technique with a two-solvent system, International Journal of Pharmaceutics, 1996, 144: 195-207
[172] Kawashima Y., Aoki S., Takenaka H., Spherical agglomeration of aminophylline crystals during reaction in liquid by the spherical crystallization technique, Chem. Pharm. Bull., 1982, 30(5): 1900
[173] Kawashima Y., Naito M., Lin S. Y., et al., An experimental study of the kinetics of the spherical crystallization of sodium theophylline monohydrate, Powder Technol, 1983, 34(2): 255
[174] Kawashima Y., Lin S. Y., Ogawa M., et al., Preparations of agglomerated crystals of polymorphic mixtures and a new complex of indomethacin-epirizole by the spherical crystallization technique, J. Pharm. Sci., 1985, 74(11): 1152
[175] Kawashima Y., Handa T., Takeuchi H., et al., Crystal modification of phenytoin with polyethylene glycol for improving mechanical strength, dissolution rate and bioavailability by a spherical crystallization technique, Chem. Pharm. Bull., 1986, 34(8): 3376
[176] Kawashima Y., Takeuchi H., Hino T., et a1., Granulation of ascorbic acid by the spherical crystallization method and tablets containing thegranules, JP 1149, 677
[177] Daniel Amaro-Gonzalez, Beatrice Biscans, Spherical agglomeration during crystallization of an active pharmaceutical ingredient, Powder Technology, 2002, 128: 188-194
[178] P. Szabo-Revesz, M. Hasznos-Nezdei, B. Farkas, et al., Crystal growth of drug materials by spherical crystallization, Journal of Crystal Growth, 2002, 237-239: 2240-2245
[179] Woochan Hyung, Yehoon Kim, Seungjoo Haam, et al., Agglomeration behavior of anhydrous L-ornithine-L-aspatate crystals during semi-batch drowning-out crystallization, Korean J. Chem. Eng., 2006, 23: 819-826
[180] Y. Kawashima, F. Cui, H. Takeuchi, et al., Parameters determining the agglomeration behaviour and the micromeritic properties of spherically agglomerated crystals prepared by the spherical crystallization technique with miscible solvent systems, International Journal of Pharmaceutics, 1995, 119: 139-147
[181]杨明世,崔福德,球晶造粒技术在药剂学粒子设计中的应用与进展,中国药学杂志, 2004, 39(2): 85-89
[182] Capes, C. E., Sutherland, J. P., Formation of spheres from finely divided solids in liquid suspension, Ind. Eng. Chem. Proc. Des. Dev., 1967, 6: 146-154
[183] Kawashima, Y., Okumura, M., Takenaka, H., The effect of temperature on the spherical crystallization of salicylic acid, Powder Technology, 1984, 39: 41-47
[2] Moyers C. G., Rousseau R. W., Crystallization operations, in Rousseau R W ed. Handbook of Separation process Technology, New York: John Wiley & sons, 1987, 758
[3]朱洪涛,工业结晶分离技术研究新进展,石油化工, 1999, 28(7): 493- 496
[4] Wey J. S., Karpinski P H, Precipitation process, in Myerson A S, Handbook of industrial crystallization, Boston: Butterworth- Heinemann, 2002. 141
[5] Mullin J. W., Crystallization, 3rd ed., London: Butterworths, 1993
[6]王静康,工业结晶新技术,国际学术动态, 2002, 5: 37-38
[7] http://www.51report.com/free/detail/116024.html
[8] http://www.chemtn.com.cn/Article_Show.asp?ArticleID=3599
[9] http://www.bbmc.edu.cn/jpkc/2006/ylx/jazl/39.doc
[10] http://www.yxbj.com/Article_Print.asp?ArticleID=3589
[11]国家药典委员会,中华人民共和国药典2005年版(二部),北京:化学工业出版社, 2005
[12] M. Zajac, W. Musial, L. Pawlowski, Stability of cefotaxime sodium in solid state, Pharmazie, 2000, 55: 917-918
[13] Gaston Amiard, Dieter Bormann, Walter Duerckheimer, et al., Sodium 3-Acetoxylmethyl-7 -[2-(2–Amino-4-thiazolyl)-2-methoxyimino-acetamido]-ceph-3-eme-4-carboxylate, USP 4224371, 1980
[14] T. Atanassova, Z. Georgieva, V. Lazarova, et al., Synthesis of cefotaxime sodium salt, Pharmazie, 1998, 53: 418
[15] http://www.hnkjcg.com/kjcg2006/a2002000485a.a.htm
[16]张克从,近代晶体学基础,北京:科学出版社, 1987
[17]周公度,晶体结构测定,北京:科学出版社, 1981
[18]韩建成,多晶X射线结构分析,上海:华东师范大学出版社, 1987
[19]陈小明,荣继文,单晶结构分析原理与实践,北京:科学出版社, 2003
[20] Hovmoller S., Zou X. D., Weirich T. E., Crystal structure determination from EM images and electron diffraction patterns, Advances in Imaging and Electron Physics, 2002, 123: 257-289
[21] Zheng J. G., Vincent R,. Steeds J. W., Crystal structure determination of an Al-Fe-Si-Be phase by convergent-beam electron diffraction, Philosophical Magazine A-Physics of CondensedMatter Structure Defects And Mechanical Properties, 1999, 79 (11): 2725-2733
[22] Man L. I., Imamov R. M., Determination of crystal structures by electron diffraction structure analysis, Crystallography Reports, 1998, 43 (6): 940-944
[23] Fossdal A., Brinks H. W., Fichtner M., et al., Determination of the crystal structure of Mg(AlH4)(2)by combined X-ray and neutron diffraction, Journal of Alloys and Compounds, 2005, 387 (1-2): 47-51
[24] Bull C. L., McMillan P. F., Soignard E., et al., Determination of the crystal structure of delta-MoN by neutron diffraction, Journal of Solid State Chemistry, 2004, 177 (4-5): 1488-1492
[25] Rodriguez R., Pacheco S., Vargas S., et al., Crystalline structure determination of anisotropic dimethyl terephthalate crystallites by micro-Raman spectroscopy, Journal of Materials Research, 2000, 15 (6): 1397-1403
[26]郭森立,侯廷军,徐筱杰,等,一个新BEDT-TTF电荷转移盐的晶体结构预测,物理化学学报, 2002, 18 (4): 289-291
[27] Nowell H., Price S. L., Validation of a search technique for crystal structure prediction of flexible molecules by application to piracetam, Acta Crystallographica Section B-Structural Science, 2005, 61: 558-568
[28] Karamertzanis P. G., Price S. L., Challenges of crystal structure prediction of diastereomeric salt pairs, Journal Of Physical Chemistry B, 2005, 109 (36): 17134-17150
[29]方奇,于文涛,晶体学原理,北京:国防工业出版社, 2002, 3
[30]钱易泰,结晶化学导论(第3版),合肥:结晶化学导论, 2005, 3
[31]王英华,晶体学导论,北京:清华大学出版社, 1989
[32]马礼敦, X射线粉末衍射的新起点-Rietveld全谱拟合,物理学进展, 1996, 16 (2): 251- 265.
[33]梁敬魁,粉末衍射法测定晶体结构,北京:科学出版社. 2003: 557
[34] Mighell A. L., Santoro A., Geometrical ambiguities in the indexing of powder patterns. J. Appl. Cryst., 1975, 8: 372-374
[35] Smith G. S., Snyder R. L., FN: a criterion for rating powder diffraction patterns and evaluating the reliability of powder-pattern indexing, J. Appl. Cryst., 1979, 12:60-65
[36] Damodara M. P., Abraham C., Application of X-ray powder diffraction techniques to the solution of unknown crystal structures, Acc. Chem. Res., 1997, 30: 414-422
[37] Kenneth D. M. H., Crystal structure determination from powder diffraction data. Chem. Mater.,1996, 8: 2554-2570
[38]王静康,黄向荣,刘秉文,等,有机分子晶体晶习预测的研究进展,人工晶体学报,2002, 31 (3): 218-223
[39] Bravais A., Etudes Cristallographiques, Paris: Gauthier-Villars, 1866, 1
[40] Hartman P., Perdok W. G., On the Relations Between Structure and Morphology of Crystals III, Acta Cryst., 1955, 8: 525-529
[41] Hartman P., Perdok W. G., On the Relations Between Structure and Morphology of Crystals II, Acta Cryst., 1955, 8: 521-524
[42] Hartman P., Perdok W. G., On the Relations Between Structure and Morphology of Crystals I, Acta Cryst., 1955, 8: 49-52
[43] Hartman P., Bennema P., The attachment energy as a habit controlling factor: I. Theoretical considerations, 1980, 49 (1): 145-156
[44]张缨,有机物系溶液结晶过程中形态学控制研究(博士学位论文),天津大学, 2005.
[45] Inc. A., Cerius2 modeling enviroment, Release 4.0, San Diego: Accelrys Inc., 1999
[46] S. M. Berge, N. L. Henderson, M. J. Frank., Kinetices and mechanism of degradation of cefotaxime sodium in aqueous solution, Journal of pharmaceutical Sciences, 1983, 72(1): 59-63
[47]陈宗淇,王光信,徐桂英,胶体与界面化学,北京:高等教育出版社, 2001, 434
[48]侯万国,孙德军,张春光,应用胶体化学,北京:科学出版社, 1998, 125
[49]沈钟,王果庭,胶体与表面化学,北京:化学工业出版杜, 1997, 111
[50]普劳斯尼茨J. M. (Prausnitz J M ),流体相平衡的分子热力学,北京:化学工业出版社, 1990
[51] Melis S., Verduyn M., Effect of fluid motion on the aggregation of small particles subjectto interaction forces, AIChE J, 1999, 45(7):1383-1393
[52] Shouci Lu, Yuqing Ding, Jinyong Guo, Kinetics of particle aggregation in turbulence, Advance in Colloid and Interface Science, 1998, 78(3): 197-235
[53] Stefano Melis, Marcel Verduyn, Giuseppe Storiti, Effect of fluid motion on theaggregation of small particles subject to interaction forces, AIChE J, 1999,45(7): 1383-1390
[54] Verwey, E. J. W., J. T. G. Overbeek, Theory of the Stability of Lyophobic Colloids, Elsevier, Amsterdam, 1948
[55] Masy J. C., Cournil M., Using a turbinimetric method to study the kinetic of agglomeration of potassium sulfate in liquid medium, Chem Eng Sci, 1991, 46(2): 693-701
[56]瓦拉斯(Walas S M),化工相平衡(韩世钧),北京:中国石化出版社, 1991
[57]普劳斯尼茨J. M. (Prausnitz J M ),流体相平衡的分子热力学,北京:化学工业出版社, 1990
[58]陈慧萍,维生素C冷却结晶过程的研究(博士学位论文),天津:天津大学化工学院, 2000
[59]胡英,流体的分子热力学,北京:高等教育出版社, 1982
[60]金家骏,分子热力学,北京:科学出版社, 1990
[61] Preston G. T., Prausnitz J. M., Thermodynamics of solid solubility in cryogenic solvents, Industrial & Engineering Chemistry Process Design and Development, 1970, 9 (2): 264-271
[62] Myers A. L., Prausnitz J. M., Thermodynamics of solid carbon dioxide solubility in liquid solvents at low temperatures, Industrial & Engineering Chemistry Fundamental, 1965, 4 (2): 209-212
[63]金克新,赵传钧,马沛生,化工热力学,天津:天津大学出版社, 1990, 137-139
[64]陈钟秀,顾飞燕,化工热力学,北京:化学工业出版社, 1993, 151
[65] Preston G. T., Prausnitz J. M., Ind Eng Chem Process Des Dev, 1970, 9: 264
[66] Myers A. L., Prausnitz J. M., Ind Eng Chem Fundam, 1965, 42: 3643
[67]许文,高等化工热力学,天津:天津大学出版社, 2004
[68] Muir R. F., Howart C. S., Predicting solid-liquid equilibrium data from vapor-liquid data, Chem. Eng., 1982, 89(4): 89
[69] Renzo C., Stella D., Gluseppe T., Solubility of Solid acetic acid in acetone-ethanol mixtures, J Chem Eng Data, 1985, 30: 410
[70] Domanska U., Domanski K., Correlation of the solubility of hexacosane in aliphatic alcohols, Fluid phase equilibria, 1991, 68: 103-114
[71] Domanska U., Solubility of n-alkanols (c16, c18, c20) in binary solvent mixtures, Fluid Phase Equilibria, 1989, 46 (2-3): 223-248
[72] Domanska U., Kozlowska M. K., Solubility of imidazoles in ketones, Fluid Phase Equilibria, 2003, 206 (1-2): 253-266
[73] Domanska U., Lachwa J., (solid + liquid) phase equilibria of binary mixtures containing n-methyl-2-pyrrolidinone and long-chain n-alkanols at atmospheric pressure, Fluid Phase Equilibria, 2002, 198 (1): 1-14
[74] Domanska U., Rolinska J., Measurement and correlation of the solubility of n-alkanols (c18, c20) in n-alkanes (c7-c16), Fluid Phase Equilibria, 1993, 86: 233-250
[75] Ferreira L. A., Macedo E. A., Pinho S. P., Pinho solubility of amino acids and diglycine in aqueous alkanol solutions, Chemical Engineering Science, 2004, 59 (15): 3117-3124
[76]朱自强,徐汛,化工热力学(第二版),北京:化学工业出版社, 1991, 161
[77] Domanska U., Domanski K., Correlation of the solubility of hexacosane in aliphatic alcohols, Fluid phase equilibria, 1991, 68: 103-114
[78]刘金晨,陆九芳,氨基酸溶解平衡的热力学研究,清华大学学报:自然科学版, 1997, 37 (12): 32-36
[79]李小森,陆九芳,改进的uniquac模型在非离子表面活性剂溶液中的应用,化工学报,1999, 50 (9): 228-234
[80] Zhu Ziqiang, Yao Shanjing, Jin Zhangli, The Fundamental Theory of Phase Equilibria and Its Applications, Hangzhou: Zhejiang University Press, 1990
[81] Larsan B. L., Rasmussen P., Fredenslund A., A modified UNIFAC group- contribution model for prediction of phase equilibria and heats of mixing, Ind. Eng. Chem. Res., 1987, 26: 2274-2286
[82] Kang J. W., Abildskov J., Gani R., Estimation of mixture properties from first- and second-order group contributions with the UNIFAC model. Ind Eng Chem Res, 2002, 41: 3260-3273
[83] Li Junfa, Prediction of activity coefficient by UNIFAC group contribution method (I), Chemical Engineering, 1991, 19(1): 12-21
[84] Wilson G. M., Deal C. H., Activity coefficient and molecular structure, Ind. Eng. Chem. Fundamen., 1962, 1(13): 292-293
[85]吴献忠,崔晓钰,李美玲, UNIFAC基团贡献法预测混合制冷剂的气液相平衡,化工学报, 2005, 56(10), 1832-1836
[86] Fredenslund A., Gmehling J., Rasmussen P., Vapor-liquid Equilibria Using UNIFAC a Group- contribution Method. New York: Elsevier Scientific Publishing Co., 1997
[87] Gmehling J. G., Anderson T. F., Prausnitz J. M., Solid-liquid equilibrium using UNIFAC,Ind Eng Chem Fundam,1978,17(4): 269
[88]王志容,尹潜,汽液固三相平衡的计算,化学工程, 1986, 14(6): 52
[89] Domanska U, Domanski K, Correlation of the solubility of hexacosane in aliphatic alcohols,Fluid phase equilibria, 1991, 68: 103
[90] Acree W. E. J., Mathematical representation of thermodynamic properties, Part 2. derivation of the (NIBS)/Redlich-Kister mathematical representation from a two-body and three-body interactional mixing model. Thermochim. Acta., 1992, 198: 71-79
[91] Acree W. E. J., Comments concerning“model for solubility estimation in mixed solvent system”, Int. J. Pharm., 1996, 127: 27-30
[92] Jouyban Gharamaleki A., Hanaee J., A novel method for improvement of predictability of the CNIBS/R-K equation, Int. J. Pharm., 1997, 154: 254-247
[93] William E., Acree, J., Thermodynamic properties of ternary non-electrolyte solutions: Part 2. Prediction of infinite dilution activity coefficients and solubilities based on the various nibs and microscopic partition models, Thermochim, Acta., 1990, 158: 11-22
[94] Kristin A. F., Siddharth P., Solubility of benzil in (binary alcohol+1-octanol) solvents, J. Chem. Thermodyna., 1997, 29: 475-481
[95] Carmen E. H., Karen S. C., Lindsay E. R., et al., Solubility of pyrene in binary (alkane + 2-butanol) solvent mixtures, J. Chem. Thermodyna., 1998, 30: 37-42
[96] Buchowski H., Ksiazczak A., Pietrzyk S, Solvent activity along a saturation line and solubility of hydrogen-bonding solids. J Phys Chem, 1980, 84(9): 975-979
[97] Buchowski H., Khiat A., Solubility of solids in liquids: One-parameter solubility equation, Fluid Phase Equilibria, 1986, 25 (3): 273-278
[98] Domanska U., Hofman T., Rolinska J., Solubility and vapour pressures in saturated solutions of high-molecular-weight hydrocarbons, Fluid Phase Equilibria, 1987, 32: 273-293
[99]孔学军,夏清,维生素B6和维生素B6酮的溶解度测定与关联,化学工程, 2000, 28 (6): 38-41
[100]鲍颖,盐酸大观霉素溶析过程研究: [博士学位论文],天津大学, 2003
[101] Wang S., Wang J. K., Yin Q. X., Measurement and correlation of solubility of 7-aminocephalosporanic acid in aqueous acetone mixtures, Ind. Eng. Chem. Res., 2005, 44: 3783-3787
[102] Apelblat A., Manzurola E., Solubilities of o-acetylsalicylic, 4-aminosalicylic, 3, 5-dinitrosalicylic, and p-toluic acid, and magnesium-dl-aspartate in water from T=(278 to 348) K, Journal of Chemical Thermodynamics, 1999, 31: 85-91
[103] Li D. Q., Evans D. G., Duan X., Solid-liquid equilibria of terephthalaldehydic acid in different solvents, Journal of Chemical and Engineering Data, 2002, 47 (5): 1220-1221
[104] Wang S., Wang J., Yin Q., Measurement and correlation of solubility of 7-aminocephalosporanic acid in aqueous acetone mixtures, 2005, 44 (10): 3783-3787
[105]刘江鹤,陈忠民,田洪河,等,苯甲酸溶解度的测定及关联,郑州工业大学学报, 2001, 22 (1): 97-99
[106]任国宾,盐酸帕罗西汀结晶过程研究(博士学位论文),天津大学, 2005 [1074]徐衡,董奕,顺丁烯二酸酐在邻苯二甲酸酯中溶解度的研究,石油化工, 2000, 29 (7): 502-504
[108] Nyvlt J., Solid-liquid equilibria, Amsterdam: Elsevier, 1977
[109] Wise W. S., Nicholson E. B., Solubilities and heats of crystallization of sucrose in aqueous solution, Journal of Chemical Society, 1955, 2714
[110] Mullin J. W., Sipek M, Solubility and density isotherms for potassium aluminium sulphate water-alcohol systems, Journal of Chemical Engineering Data, 1982, 26: 164
[111]丁绪淮,谈遒,工业结晶,北京:化学工业出版社, 1985
[112] Mohan R., Lorenz H., Myerson A. S., Solubility measurement using differential scanning calorimetry, Ind. Eng. Chem. Res., 2002, 41: 4854-4862
[113]王福安,曹庭珠,赵天源,等,喹诺酮类药物的溶解度模型,化工学报, 1996, 47(5): 615-620
[114]王水, 7-氨基头孢烷酸反应结晶过程研究(博士学位论文),天津大学, 2005
[115] S. Wang, J. Wang, Q. Yin, et al., Light Extinction Method for Solubility Measurement, Chinese Optics Letters, 2005, 3(3), 149-151
[116] Atkins P. W., Physical Chemistry[M], Oxford Univ, Press, 1994: 545
[117] Stephen, H.; Stephen, T., Solubility of Inorganic and Organic Compounds, Pergamon Press: Oxford, 1963, 1, 152
[118]程能林,溶剂手册(第二版),北京:化学工业出版社, 2002
[119] Eladio, P. F., Jhoany, A. E., Lauro, N. P., et al., Solubility of Cefotaxime Sodium Salt in Seven Solvents Used in the Pharmaceutical Industry, J. Chem. Eng. Data, 1998, 43, 49-50
[120] M. Barzegar-Jalali, J. Hanaee, Model for solubility estimation in mixed solvent systems, Inter. J. Pharm., 1994, 109, 291-295
[121] Acree W. E. Jr., Zvaigzne A. I., Thermodynamics properties of non-electrolyte solutions, IV, estimation and mathematical representation of solute activity coefficients and solubilities in binary solvents using the CNIBS and modified Wilson equations, Thermochim. Acta., 1991, 178, 151-167
[122] M. Barzegar-Jalali, A. Jouyban-Gharamaleki, A general model from theoretical cosolvency models, Inter. J. Pharm., 1997, 152, 247-250
[123] A. Martin, P. L. Wu, A. Adjei, et al., Extended Hildebrand solubility approach and the log linear solubility equation, J. Pharm. Sci., 1982, 71, 849-856
[124] Ochsner A. B., Belloto R. J., Sokoloski T. D., Prediction of xanthine solubilities using statistical techniques, J. Pharm. Sci., 1985, 74, 132-135
[125] M. Barzegar-Jalali, A. Jouyban-Gharamaleki. Models for calculating solubility in binary solvent systems, Inter. J. Pharm., 1996, 140, 237-246
[126] Dong, Y., Ma, P. S., Xu, W., Study on the solubility of maleic anhydride in 1,2-cyclohexanedicarboxylic acid diisobutyl ester and diethyl ester, J. Chem. Eng. Chin. Univ., 2000, 14, 160-163
[127] Omar W., Ulrich J. Solid liquid equilibrium, metastable zone, and nucleation parameters of the oxalic-water system, Cryst. Growth Des., 2006, 6(8): 1927-1930
[128]龚俊波, 6APA制备及反应结晶过程研究(博士学位论文),天津:天津大学化工学院, 2001
[129] Ulrich J., Strege C. Some aspects of the importance of metastable zone width and nucleation in industrial crystallizers, J. Cryst. Growth, 2002, 237-239: 2130-2135
[130]Е.В.哈姆斯基,著,古涛,叶铁林,译,化学工业中的结晶,北京:化学工业出版社, 1984, 9-12
[131] Mersmann K. Bartosch, How to predict the metastable zone width, J. Crystal Growth,1998, 183(1-2): 240-250
[132] Ting H. H., Mccabe W. L., Supersaturation units and their conversion factor, The Chemical Engineer, 1973, 274: 316
[133] Ulrich J., Strege C., Some aspects of the important of metastable zone width and nucleation in industrial crystallizaters, J. Cryst. Growth, 2002, 237: 2130-2135
[134] Kim K. J., Mersmann A., Estimation of metastable zone width in different nucleation processes, Chem. Eng. Sci., 2001, 56:2315-2324
[135] Gurbuz H., Ozdemir B., Experimental determination of the metastable zone width of borax decahydrate by ultrasonic velocity measurement, J. Cryst. Growth, 2003, 252: 343-349
[136] Titiz-sargut S., Ulrich J., Influence of additives on the width of the metastable zone, Cryst.Growth Des., 2002, 2(5): 371-374
[137] Correia P., Lopes C., Piedade M. E. M., et al., Solubility and metastable zone width of 1-Keto-1,2,3,4-tetrahydro-6-methylcarbazole in acetone, J. Chem. Eng. Data, 2006, 51(4):1306-1309
[138]韩佳宾,王静康,咖啡因在水和乙醇中的介稳区的测定,天津大学学报, 2003,36:765-768
[139] Fawell P. D., Walting H. R., Mutil-angle laser light scattering to measure nucleation induction period, Applied Spectroscopy, 1998, 52(8): 1115
[140] Sohnel O., Mullin J. W., A method for the determination of precipitation induction periods, J Crystal Growth, 1978, 44: 377
[141] Knezic D., Zaccaro J., Myerson A. S., Nucleation induction time in levitated droplets, J. Phys. Chem., B 2004, 108: 672-677
[142] Viedma C., Experimental evidence of chiral symmetry breaking in crystallization from primary nucleation, J. Cryst. Growth, 2006, 261: 118-121
[143] Mersmann A., Calculation of interfacial tensions, J. Cryst. Growth, 1990, 102: 841-847
[144] Sukanya S., Adrian E. F., Edward T. W., The secondary nucleation threshold and crystal growth ofα-glucose monohydrate in aqueous solution, Cryst. Growth. Des., 2006, 3(3):795-801
[145] Botsaris G. D., Qin R. Y., A new mechanism for nuclei formation in suspension crystallizers: the role of interparticle forces, Chem. Eng. Sci., 1997, 52( 2): 3429-3440
[146] Ward M. D., Bulk crystals to surface: combining X-ray diffraction and atomic force microscopy to probe the structure and formation of crystal interfaces, Chem. Rev., 2001, 1697-1725
[147] Bennema P., Theory and experiments for crystal growth from solution: implication for industrial crystallization, Industrial crystallization, New York: Plenum Press, 1976
[148] Barata P. A., Serrano M. L.,“Salting-out precipitation of potassium dihydrogen phosphate(KDP)-Ⅰprecipitation mechanism”, J. Cryst. Growth, 1996, 160: 361-369
[149] Malkin A. J., Kuznetsov Y. G., AFM observation of the surface morphology and impurity effects on orthorhombic hen egg-white lysozyme crystals, J. Cryst. Growth, 2002, 242: 199-208
[150] Geng Y. L., Xu D., Wang X. Q., et al., AFM study of surface morphology of 100 cleavage planes of L-arginine acetate crystals, J. Cryst. Growth, 2005, 282: 208-213
[151] Sours R. E., Zellelow A. Z., Swift J. A., An in situ atomic force microscopy study of uric acid crystal growth, J. Phys. Chem.B, 2005, 109: 9989-9995
[152] Mullin J. W., Garside J., Crystallization of aluminum potassium sulfate: a study in the assessment of crystallizer design data, I: Single crystal growth rates, Trans Int Chem Eng, 1967, 45: 285
[153] David R., Marchal P., Klein J. P., Chem Eng Sci, 1991, 46: 205
[154] Tavare N. S., Garside J., Silica precipitation in a semi-batch crystallizer, Chem Eng Sci, 1993, 48(3): 475
[155] Mahadevan C., Jegatheesan, C. S., Nucleation studies in supersaturated aqueous solutions of chromate doped potassium phosphate, J. India. Chem. Soc., 1999, 76: 47-48
[156] Shiau L. D., Berglund K. A., Model for a cascade crystallizer in the presence of growth rate dispersion, Ind. Eng. Chem. Res., 1987, 26: 2515-2521
[157] Bourne J. R., Davey R. J., McCulloch,J., The growth kinetics of hexamethriene tetramine crystals from a water/acetone solution, Chem. Eng. Sci., 1978, 38: 199
[158] Randolph A. D., Larson M. A., Theory of partifulate process: analysis and techniaues of continuous crystallization (2nd ed), Toronto: Academic Press, 1988, 50-79
[159] Chemaly Z., Muhr H., Fick M., Crystallization kinetics of calcium lactate in amixed-suspension-mixed-product removed crystallizer, Ind. Eng. Chem. Res., 1999, 38: 2803-2808
[160]陈敏恒,丛德滋,方图南,等,化工原理(上册),北京:化学工业出版社, 1999, 146
[161] Heijden A. E., Eerden J. P., Rosmalen G. M., The secondary nucleation rate: a physical model, Chemical Engineering Science, 1994, 49 (18): 3103-3113
[162] Gooch J. R., Hounslow M. J., Monte Carlo Simulation of Size-Enlargement Mechanisms in Crystallization, AIChE Journal, 1996, 42 (7): 1864-1874
[163] Puel F., Fevotte G., Klein J. P., Simulation and analysis of industrial crystallization processes through multidimensional population balance equations, Part 1: a resolution algorithm based on the method of classes, Chem. Eng. Sci., 2003, 58: 3715-3727
[164] Tavare N. S., Chivate M. R., CSD Analysis from a Batch Dilution Crystallizer, Journal of Chemical Engineering of Japan, 1980, 13 (5): 371-379
[165] Tavare N. S., Garside J., Analysis of Batch Crystallizers, Ind. Eng. Chem. Process Des. Dev., 1980, 19: 653-665
[166] Chivate M. R., Palwe B. G., Tavare N. S., Effect of Seed Concentration in a Batch Dilution Crystallizer, Chem.Eng.Commun., 1979, 3: 127-133
[167] Harkins W. D., Gans D. M., Monomolecular films, the solid-liquid interface and the sedimentation and flocculation of powders in liquids, J Phys Chem., 1932, 36(1): 86
[168] Stock D. I., Micro-spherieal aggregation of barium sulphate, Nature, 1952, 170: 423
[169] Smith H. M., Puddington I. E., Spherical agglomeration of barium sulphate, Can. J. Chem., 1960, 38(10): 1911
[170] Yoshiaki Kawashima, Motonari Okumura, Hideo Takenaka, Spherical Crystallization: Direct Spherical Agglomeration of Salicylic Acid crystals During Crystallization, Science, 1982, 216: 1127-1128
[171] Ribardiere, P., Tchoreloff, G., Couarraze, et al, Modification of ketoprofen bead structure produced by the spherical crystallization technique with a two-solvent system, International Journal of Pharmaceutics, 1996, 144: 195-207
[172] Kawashima Y., Aoki S., Takenaka H., Spherical agglomeration of aminophylline crystals during reaction in liquid by the spherical crystallization technique, Chem. Pharm. Bull., 1982, 30(5): 1900
[173] Kawashima Y., Naito M., Lin S. Y., et al., An experimental study of the kinetics of the spherical crystallization of sodium theophylline monohydrate, Powder Technol, 1983, 34(2): 255
[174] Kawashima Y., Lin S. Y., Ogawa M., et al., Preparations of agglomerated crystals of polymorphic mixtures and a new complex of indomethacin-epirizole by the spherical crystallization technique, J. Pharm. Sci., 1985, 74(11): 1152
[175] Kawashima Y., Handa T., Takeuchi H., et al., Crystal modification of phenytoin with polyethylene glycol for improving mechanical strength, dissolution rate and bioavailability by a spherical crystallization technique, Chem. Pharm. Bull., 1986, 34(8): 3376
[176] Kawashima Y., Takeuchi H., Hino T., et a1., Granulation of ascorbic acid by the spherical crystallization method and tablets containing thegranules, JP 1149, 677
[177] Daniel Amaro-Gonzalez, Beatrice Biscans, Spherical agglomeration during crystallization of an active pharmaceutical ingredient, Powder Technology, 2002, 128: 188-194
[178] P. Szabo-Revesz, M. Hasznos-Nezdei, B. Farkas, et al., Crystal growth of drug materials by spherical crystallization, Journal of Crystal Growth, 2002, 237-239: 2240-2245
[179] Woochan Hyung, Yehoon Kim, Seungjoo Haam, et al., Agglomeration behavior of anhydrous L-ornithine-L-aspatate crystals during semi-batch drowning-out crystallization, Korean J. Chem. Eng., 2006, 23: 819-826
[180] Y. Kawashima, F. Cui, H. Takeuchi, et al., Parameters determining the agglomeration behaviour and the micromeritic properties of spherically agglomerated crystals prepared by the spherical crystallization technique with miscible solvent systems, International Journal of Pharmaceutics, 1995, 119: 139-147
[181]杨明世,崔福德,球晶造粒技术在药剂学粒子设计中的应用与进展,中国药学杂志, 2004, 39(2): 85-89
[182] Capes, C. E., Sutherland, J. P., Formation of spheres from finely divided solids in liquid suspension, Ind. Eng. Chem. Proc. Des. Dev., 1967, 6: 146-154
[183] Kawashima, Y., Okumura, M., Takenaka, H., The effect of temperature on the spherical crystallization of salicylic acid, Powder Technology, 1984, 39: 41-47