地塞米松磷酸钠结晶新工艺的研究
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摘要
地塞米松磷酸钠是一种重要的肾上腺糖皮质激素类药物，在临床上有十分广泛的应用。目前，国内生产的地塞米松磷酸钠与国外同类产品相比，在粒度、纯度及结晶过程的收率等方面都存在着一定的差距。本论文对地塞米松磷酸钠晶体结构与晶习、结晶热力学和动力学及生产规模的反应－溶析藕合结晶工艺进行了研究与分析，并在此基础上完成了年产60吨地塞米松磷酸钠的藕合结晶过程的设计与生产实施。
利用X-射线粉末衍射仪搜集了地塞米松磷酸钠晶体的衍射数据，用TREOR90指标化程序计算得到了地塞米松磷酸钠晶体的晶胞参数及其所属晶系；应用扫描电子显微镜(SEM)观察的方法分析考察了结晶方法、溶剂类型及温度对地塞米松磷酸钠产品晶习的影响。
采用激光法测定了地塞米松磷酸钠在各种溶剂中的溶解度并考察了温度和溶剂配比对溶解度的影响情况；测定了地塞米松磷酸钠在甲醇－丙酮－水体系中的结晶介稳区；运用最小二乘法回归得到了溶解度与介稳区的经验数学模型；对地塞米松磷酸钠反应及溶析结晶动力学进行了分析。
结合晶体生产习性、热力学和动力学特性以及对实验室研究结果的分析，建立了地塞米松磷酸钠耦合结晶过程优化操作时间表，并成功完成了生产过程的设计放大与实施，产品的各项指标均达到国际水平。本论文所做的有关地塞米松磷酸钠晶体结构、结晶生产新工艺的研究与应用在国内外的文献中尚未见到过任何报道。
Dexamethasone sodium phosphate is one kind of important drugs of ardrenal cortex hormone, and it is widely used in clinical application. Up to now, home-made dexamethasone sodium phosphate is not as good as those overseas products in terms of its purity and size etc. In this paper, the crystal structure, crystal habit, crystallization thermodynamics, crystallization kinetics and the plant-scale reaction-dilution coupled crystallization technics of dexamethasone sodium phosphate was studied. The manufacturing process with output of 60 ton/year for dexamethasone sodium phosphate was designed and set up.
The diffraction data for dexamethasone sodium phosphate crystal was collected by X-ray diffraction technique. Using the indexing program named TREOR90, the unit cell parameters and space group for dexamethasone sodium phosphate were obtained by the indexing of its diffraction data. The effect of crystallization method, solvent and temperature on crystal habit of dexamethasone sodium phosphate were investigated by SEM(scanning electronics microscope) analysis.
The solubility of dexamethasone sodium phosphate in different solvents was determined by laser monitor method. The effect of temperature and solvent on solubility was discussed. Crystallization metastable zone of dexamethasone sodium phosphate in methanol-acetone-water system was determined. The empirical model for solubility and metastabel zone of dexamethasone sodium phosphate was gotten by the least square method. The reaction and dilution crystallization kinetics for dexmethasone sodium phosphate were analyzed.
The empirical optimum operation schedule for dexamethasone sodium phosphate coupled crystallization process was established by synthetically considering property of crystal production, thermodynamics, kinetics and experimental study results. The manufacturing process for dexamethasone sodium phosphate was successfully designed and industrialized. The quality of the crystal product is as good as overseas product or better. The work about crystal structure and the crystallization new technics for dexamethasone sodium phosphate, which was done in this paper, has not been reported in any literatures.
利用X-射线粉末衍射仪搜集了地塞米松磷酸钠晶体的衍射数据，用TREOR90指标化程序计算得到了地塞米松磷酸钠晶体的晶胞参数及其所属晶系；应用扫描电子显微镜(SEM)观察的方法分析考察了结晶方法、溶剂类型及温度对地塞米松磷酸钠产品晶习的影响。
采用激光法测定了地塞米松磷酸钠在各种溶剂中的溶解度并考察了温度和溶剂配比对溶解度的影响情况；测定了地塞米松磷酸钠在甲醇－丙酮－水体系中的结晶介稳区；运用最小二乘法回归得到了溶解度与介稳区的经验数学模型；对地塞米松磷酸钠反应及溶析结晶动力学进行了分析。
结合晶体生产习性、热力学和动力学特性以及对实验室研究结果的分析，建立了地塞米松磷酸钠耦合结晶过程优化操作时间表，并成功完成了生产过程的设计放大与实施，产品的各项指标均达到国际水平。本论文所做的有关地塞米松磷酸钠晶体结构、结晶生产新工艺的研究与应用在国内外的文献中尚未见到过任何报道。
Dexamethasone sodium phosphate is one kind of important drugs of ardrenal cortex hormone, and it is widely used in clinical application. Up to now, home-made dexamethasone sodium phosphate is not as good as those overseas products in terms of its purity and size etc. In this paper, the crystal structure, crystal habit, crystallization thermodynamics, crystallization kinetics and the plant-scale reaction-dilution coupled crystallization technics of dexamethasone sodium phosphate was studied. The manufacturing process with output of 60 ton/year for dexamethasone sodium phosphate was designed and set up.
The diffraction data for dexamethasone sodium phosphate crystal was collected by X-ray diffraction technique. Using the indexing program named TREOR90, the unit cell parameters and space group for dexamethasone sodium phosphate were obtained by the indexing of its diffraction data. The effect of crystallization method, solvent and temperature on crystal habit of dexamethasone sodium phosphate were investigated by SEM(scanning electronics microscope) analysis.
The solubility of dexamethasone sodium phosphate in different solvents was determined by laser monitor method. The effect of temperature and solvent on solubility was discussed. Crystallization metastable zone of dexamethasone sodium phosphate in methanol-acetone-water system was determined. The empirical model for solubility and metastabel zone of dexamethasone sodium phosphate was gotten by the least square method. The reaction and dilution crystallization kinetics for dexmethasone sodium phosphate were analyzed.
The empirical optimum operation schedule for dexamethasone sodium phosphate coupled crystallization process was established by synthetically considering property of crystal production, thermodynamics, kinetics and experimental study results. The manufacturing process for dexamethasone sodium phosphate was successfully designed and industrialized. The quality of the crystal product is as good as overseas product or better. The work about crystal structure and the crystallization new technics for dexamethasone sodium phosphate, which was done in this paper, has not been reported in any literatures.
引文
[1] 中华人民共和国卫生部药典委员会，《中华人民共和国药典》，北京：化学工业出版社，2000
[2] 周公度，结构化学基础，北京：北京大学出版社，1989
[3] Strom C S, Leusen F J J, Geertman R M, Morphology of the diasteremeric salt of the alkaloid ephedrine and a chlorine substituted cyclic phosphoric acid, J Crystal Growth, 1997, 171: 236
[4] Aquilano D, Rubbo M, Catti M, etc, Theoretical equilibrium and growth morphology of CaCO3 polymorphs, J Crystal Growth, 1997, 182: 168
[5] Wang Jingkang, Xue Luzhong, Zhang Meijing, Advanced method to development for pharmaceutical crystallization processes,15th ISIC, Sorrento: 2002, 551
[6] Meiyulee Oliver Monier, The control of crystal morphorlogy of pharmaceutical
products,14th ISIC, 1999: 2110
[7] Wolfgang Beckrnann, Pharmaceutical crystallization polymorphs, pseudo-polymorphs and particle formation, 15th ISIC，Sorrento: 2002, 1
[8] Farkas B, Horvath K, Szent-Kirrallyi Z, Elaboration of a test method for examination of polymorphism of active pharmaceutical ingredients(API), 15th ISIC, Sorrento: 2002, 587
[9] Haselhuhn F, Kind M, Pseudo-polymorphic behavior of precipitated calcium-oxalate, 15th ISIC, Sorrento: 2002, 47
[10] Prywer J, Theoretical analysis of changes in habit of growing crystals in response to variable growth rates of individual faces, J Cryst growth, 1999, 197: 271
[11] Liu X Y, Principles for predicting the morphology of crystals and application ton-paraffin crystals, J Cryst Growth, 1999, 199(Part 2): 1281
[12] Davey R J, Solvent effects in crystallization process, Current Topics in Materials Science, Vol 8
[13] Grimbergen R F P, Meekes H, Bennema P, et al, Explanation for the supersaturation dependence of the morphology of lysozyme crystals, J Cryst Growth, 1999, 207(1-2): 112
[14] Kitamura M, Ishizu T, Growth kinetics and morphological change of polymorphs of L-glutamic acid, J Cryst Growth, 2000,209: 138
[15] Lee M Y, Rohl A L, Gale J D, et al, The influence of metal ion inclusion on the morphology of gibbsite，Trans IchemE, 1996, 74(A): 739-743.
[16] 庄莆, 韩萍扬, 陈萍, 宝红BK的晶相研究, 华东化工学院学报, 1990, 16(4): 439
[17] 韩建成，多晶X射线结构分析，上海：华东师范大学出版社，1987
[18] 黄胜涛, 固体X射线学, 北京：高等教育出版社, 1983
[19] 王仁卉，郭可信，晶体学的对称群，北京：科学出版社，1990
[20] Finnie S D, Ristic R I, Sherwood J N, etc, Morphological and growth rate distributions of small self-nucleated paracetamol crystals grown from aqueous solutions, Journal of Crystal Growth, 1999, 207: 308
[21] Hartman P, Perdok W G, On the relations between structure and morphology of crystals(II),
Acta Cryst, 1955, 8: 521
[22] 王静康, 黄向荣, 张缨等, 晶习预测研究进展, 人工晶体学报, 2002, 31: 218
[23] Hartman P, Bennema P, The attachment energy as a habit controlling factor(I), J Crystal Growth, 1980, 49: 145
[24] Hartman P, The attachment energy as a habit controlling factor(II), J Crystal Growth, 1980, 49: 157
[25] Hartman P, The attachment energy as a habit controlling factor(III), J Crystal Growth, 1980, 49: 166
[26] Burgess C, Rapid reversed-phase high-performance liquid chromatographic analysis of steroid products, Journal of Chromatography, 1978,149:233
[27] 姚兴田，乔志毅，地塞米松磷酸钠注射液的反相高效液相色谱测定法，医药工业， 1988，19（4）：172
[28] 姜雄平，于文胜，复方脑栓通注射液中地塞米松磷酸钠的HPLC测定， 中国医药工业杂志，1996，27（4）：173
[29] Dijkstra J, Dekker D, High-performance liquid chromatographic determination of
phosphate esters of dexamethasone and prednisolone and their sulphate adducts, Journal of Chromatography,1982,238:247
[30] Denise G, Bruce A L, Analysis of Dexamethasone sodium phosphate formulations by high-performance liquid chromatography, Journal of chromatography, 1980, 193:160
[31] Bandita D, Sanat K C, Saroj K D, Thin layer chromatographic method for rapid
identification and quantification of corticosteroid sodium phosphates in pharmaceutical preparations, Journal of Liquid Chromatography,1986,9(16):3461
[32] 顾秀秋，薄层层析法检查地塞米松磷酸钠中的其他辎体，药物分析杂志，1985，5（2）：113
[33] Mullin J W, Sipek M, Solubility and density isotherms for potassium aluminium sulphate water-alcohol systems, Journal of Chemical Engineering Data,1982,26:164
[34] Miers H A, Isaac F, The spontaneous crystallization of binary mixtures, Proceedings of the Royal Scoiety,1907,A79:322
[35] Ting H H, Mccabe W L, Supersaturation units and their conversion factor, The Chemical Engineer,1973,274:316
[36] Mullin J W, Jancic S J, Interpretation of metastable zone widths, Trans Inst Chem Eng,1979,57(3):188
[37] 冯仁君，有机物系结晶介稳区的研究（学位论文），天津：天津大学化学工程系，1989
[38] 谈遒，冯仁君，张敏华，中国化工学会首届工业结晶学术报告会，天津，1990
[39] 丁绪淮，谈遒, 工业结晶,北京：化学工业出版社，1985
[40] Mullin J W, Crystallization, 3rd ed., London: Butterworths, 1993
[41] Botsaris G D, Secondary nucleation-a review, Industrial crystallization, New York:
Plenum Press,1976
[42] Powers H E C, Nucleation and early crystal growth, The Industrial Chemist,1963,39:351
[43] Garside J, Davey R J, Secondary contact nucleation: kinetics, growth and scale-up, Chemical Engineering Communications,1980,4:392
[44] Kuboi R, Nienow A W, Conti R, Mechanical attrition of crystals in stirred vessels, Industrial crystallization 84, Amsterdam: North Holland Pub Co, 1984
[45] Ru—Ying Qin，Botsaris G D, A new mechanism for nuclei formation in suspension crystallizers: the role of interparticle forces, Chem Eng Sci, 1997, 52( 2): 3429
[46] Botsaris G D, Denk E G ，Chua J, Nucleation in an impurity concentration gradient, AIChE Symp Ser, 1972, 68( 12): 21
[47] Lewis B, Nucleation and growth theory, Crystal Growth, Oxford: Pergamon Press,1980
[48] Chernov A A, Formation of crystal in solution, Contemporary Physics,1989,30:251
[49] Bennema P, Theory and experiments for crystal growth from solution: implication for industrial crystallization, Industrial crystallization, New York: Plenum Press,1976
[50] Berthoud A, Theorie de la formation des faces d’un crystal, Journal de Chimique Physique,1912,10:624
[51] Larson M A, Garside J, Crystallizer design techniques using the population balance. The Chemical Engineer, 1973,318
[52] Bransom S H, Factors in the design of Continuous crystallizer, Br Chem Eng , 1960,5:838
[53] Canning T F, Randolph A D, Some aspects of crystallization theory: system that violate McCabe’s △L laws, AIChE J, 1967,13:5
[54] Mydlarz J, Jones A G, On modelling the size-dependent growth rate of potassium sulphate in an MSMPR crystallizer, Chem Eng Commun , 1989,90:47
[55] Abegg C F, Stevens J D, Larson M A , Crystal size distribution in continuous crystallizer when growth rate is size-dependent, AIChE J, 1968,14: 188
[56] Rojkowski Z, A new empirical kinetics equation of size-dependent crystal growth and its use, Krist Tech, 1977,12:1121
[57] Rojkowski Z, Two parameter kinetic equation of size dependent crystal growth, Krist Tech, 1978,13:1277
[58] Mydlarz J, Jones A G, On the estimation of size-dependent crystal growth rate functions in MSMPR crystallizers, Chem Eng J, 1993,53:125
[59] Mydlarz J, Kinetyka wzrostu krysztalow w krystalizatorze MSMPR, Sci Pap Inst Chem Eng Heating Equip, Wroclaw Tech Univ, Monograph(1991)
[60] Janse A H, DeJong E J, The occurrence of growth dispersion and its consequences, Industrial Crystallization, New York: Plenum Press,1976
[61] Berglund K A, Larson M A, Modeling of growth rate dispersion of citric acid monohydrate in continuous crystallizer, AIChE J,1984,30(2):280
[62] Larson M A, White E T, Ramanarayanan K A, Growth rate dispersion in MSMPR crystallizers, AIChE J,1985,31(1):90
[63] Berglund K A, Kaufman E L, Larson M A, Growth of contact nuclei of potassium nitrate, AIChE J,1983,29(5):867
[64] Janse A H, Proceeding of 11th Symposium on Industrial Crystallization, Munich:Garmisch Partenkirchen, 1990
[65] Larson M A, Advance in industrial crystallization，全国医药结晶及粒子过程技术学术会议，天津，1996
[66] Nielsen A E, Kinetics of Precipitation,Oxford:Pergamon,1964
[67] 陆杰，反应结晶（沉淀）研究（博士学位论文），天津：天津大学化工学院，1997
[68] 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
[69] Kofler, Proceeding of 11th symposium on Industrial crystallization, Munich:Garmisch Partenkirchen, 1990
[70] Mydlarz J, Jones A G, Crystallization and agglomeration kinetics during the batch drowning-out precipitation of potash alum with aqueous acetone, Power Technology,1991,65:187
[71] Sowul L, Epstein M A F, Crystallization kinetics of sucrose in a CMSMPR evaporative crystallizer, Ind Eng Chem Proc Des Dev,1981,20(2):197
[72] Wey J S, Analysis of batch crystallization process, Chem Eng Commun,1985, 35(1-6):231
[73] Tavare N S, Batch crystallizers: a review, Chem Eng Commun,1987,61(1-6):259
[74] Tavare N S, Garside J, Analysis of Batch crystallizers, Ind Eng Chem Process Des Dev,1980,19:653
[75] Tavare N S, Garside J, Simultaneous estimation of crystal nucleation and growth kinetics from batch experiments, Chem Eng Res Des,1986,64:109
[76] 郝红勋，地塞米松磷酸钠耦合结晶过程研究（博士论文），天津：天津大学化工学院，2003
[2] 周公度，结构化学基础，北京：北京大学出版社，1989
[3] Strom C S, Leusen F J J, Geertman R M, Morphology of the diasteremeric salt of the alkaloid ephedrine and a chlorine substituted cyclic phosphoric acid, J Crystal Growth, 1997, 171: 236
[4] Aquilano D, Rubbo M, Catti M, etc, Theoretical equilibrium and growth morphology of CaCO3 polymorphs, J Crystal Growth, 1997, 182: 168
[5] Wang Jingkang, Xue Luzhong, Zhang Meijing, Advanced method to development for pharmaceutical crystallization processes,15th ISIC, Sorrento: 2002, 551
[6] Meiyulee Oliver Monier, The control of crystal morphorlogy of pharmaceutical
products,14th ISIC, 1999: 2110
[7] Wolfgang Beckrnann, Pharmaceutical crystallization polymorphs, pseudo-polymorphs and particle formation, 15th ISIC，Sorrento: 2002, 1
[8] Farkas B, Horvath K, Szent-Kirrallyi Z, Elaboration of a test method for examination of polymorphism of active pharmaceutical ingredients(API), 15th ISIC, Sorrento: 2002, 587
[9] Haselhuhn F, Kind M, Pseudo-polymorphic behavior of precipitated calcium-oxalate, 15th ISIC, Sorrento: 2002, 47
[10] Prywer J, Theoretical analysis of changes in habit of growing crystals in response to variable growth rates of individual faces, J Cryst growth, 1999, 197: 271
[11] Liu X Y, Principles for predicting the morphology of crystals and application ton-paraffin crystals, J Cryst Growth, 1999, 199(Part 2): 1281
[12] Davey R J, Solvent effects in crystallization process, Current Topics in Materials Science, Vol 8
[13] Grimbergen R F P, Meekes H, Bennema P, et al, Explanation for the supersaturation dependence of the morphology of lysozyme crystals, J Cryst Growth, 1999, 207(1-2): 112
[14] Kitamura M, Ishizu T, Growth kinetics and morphological change of polymorphs of L-glutamic acid, J Cryst Growth, 2000,209: 138
[15] Lee M Y, Rohl A L, Gale J D, et al, The influence of metal ion inclusion on the morphology of gibbsite，Trans IchemE, 1996, 74(A): 739-743.
[16] 庄莆, 韩萍扬, 陈萍, 宝红BK的晶相研究, 华东化工学院学报, 1990, 16(4): 439
[17] 韩建成，多晶X射线结构分析，上海：华东师范大学出版社，1987
[18] 黄胜涛, 固体X射线学, 北京：高等教育出版社, 1983
[19] 王仁卉，郭可信，晶体学的对称群，北京：科学出版社，1990
[20] Finnie S D, Ristic R I, Sherwood J N, etc, Morphological and growth rate distributions of small self-nucleated paracetamol crystals grown from aqueous solutions, Journal of Crystal Growth, 1999, 207: 308
[21] Hartman P, Perdok W G, On the relations between structure and morphology of crystals(II),
Acta Cryst, 1955, 8: 521
[22] 王静康, 黄向荣, 张缨等, 晶习预测研究进展, 人工晶体学报, 2002, 31: 218
[23] Hartman P, Bennema P, The attachment energy as a habit controlling factor(I), J Crystal Growth, 1980, 49: 145
[24] Hartman P, The attachment energy as a habit controlling factor(II), J Crystal Growth, 1980, 49: 157
[25] Hartman P, The attachment energy as a habit controlling factor(III), J Crystal Growth, 1980, 49: 166
[26] Burgess C, Rapid reversed-phase high-performance liquid chromatographic analysis of steroid products, Journal of Chromatography, 1978,149:233
[27] 姚兴田，乔志毅，地塞米松磷酸钠注射液的反相高效液相色谱测定法，医药工业， 1988，19（4）：172
[28] 姜雄平，于文胜，复方脑栓通注射液中地塞米松磷酸钠的HPLC测定， 中国医药工业杂志，1996，27（4）：173
[29] Dijkstra J, Dekker D, High-performance liquid chromatographic determination of
phosphate esters of dexamethasone and prednisolone and their sulphate adducts, Journal of Chromatography,1982,238:247
[30] Denise G, Bruce A L, Analysis of Dexamethasone sodium phosphate formulations by high-performance liquid chromatography, Journal of chromatography, 1980, 193:160
[31] Bandita D, Sanat K C, Saroj K D, Thin layer chromatographic method for rapid
identification and quantification of corticosteroid sodium phosphates in pharmaceutical preparations, Journal of Liquid Chromatography,1986,9(16):3461
[32] 顾秀秋，薄层层析法检查地塞米松磷酸钠中的其他辎体，药物分析杂志，1985，5（2）：113
[33] Mullin J W, Sipek M, Solubility and density isotherms for potassium aluminium sulphate water-alcohol systems, Journal of Chemical Engineering Data,1982,26:164
[34] Miers H A, Isaac F, The spontaneous crystallization of binary mixtures, Proceedings of the Royal Scoiety,1907,A79:322
[35] Ting H H, Mccabe W L, Supersaturation units and their conversion factor, The Chemical Engineer,1973,274:316
[36] Mullin J W, Jancic S J, Interpretation of metastable zone widths, Trans Inst Chem Eng,1979,57(3):188
[37] 冯仁君，有机物系结晶介稳区的研究（学位论文），天津：天津大学化学工程系，1989
[38] 谈遒，冯仁君，张敏华，中国化工学会首届工业结晶学术报告会，天津，1990
[39] 丁绪淮，谈遒, 工业结晶,北京：化学工业出版社，1985
[40] Mullin J W, Crystallization, 3rd ed., London: Butterworths, 1993
[41] Botsaris G D, Secondary nucleation-a review, Industrial crystallization, New York:
Plenum Press,1976
[42] Powers H E C, Nucleation and early crystal growth, The Industrial Chemist,1963,39:351
[43] Garside J, Davey R J, Secondary contact nucleation: kinetics, growth and scale-up, Chemical Engineering Communications,1980,4:392
[44] Kuboi R, Nienow A W, Conti R, Mechanical attrition of crystals in stirred vessels, Industrial crystallization 84, Amsterdam: North Holland Pub Co, 1984
[45] Ru—Ying Qin，Botsaris G D, A new mechanism for nuclei formation in suspension crystallizers: the role of interparticle forces, Chem Eng Sci, 1997, 52( 2): 3429
[46] Botsaris G D, Denk E G ，Chua J, Nucleation in an impurity concentration gradient, AIChE Symp Ser, 1972, 68( 12): 21
[47] Lewis B, Nucleation and growth theory, Crystal Growth, Oxford: Pergamon Press,1980
[48] Chernov A A, Formation of crystal in solution, Contemporary Physics,1989,30:251
[49] Bennema P, Theory and experiments for crystal growth from solution: implication for industrial crystallization, Industrial crystallization, New York: Plenum Press,1976
[50] Berthoud A, Theorie de la formation des faces d’un crystal, Journal de Chimique Physique,1912,10:624
[51] Larson M A, Garside J, Crystallizer design techniques using the population balance. The Chemical Engineer, 1973,318
[52] Bransom S H, Factors in the design of Continuous crystallizer, Br Chem Eng , 1960,5:838
[53] Canning T F, Randolph A D, Some aspects of crystallization theory: system that violate McCabe’s △L laws, AIChE J, 1967,13:5
[54] Mydlarz J, Jones A G, On modelling the size-dependent growth rate of potassium sulphate in an MSMPR crystallizer, Chem Eng Commun , 1989,90:47
[55] Abegg C F, Stevens J D, Larson M A , Crystal size distribution in continuous crystallizer when growth rate is size-dependent, AIChE J, 1968,14: 188
[56] Rojkowski Z, A new empirical kinetics equation of size-dependent crystal growth and its use, Krist Tech, 1977,12:1121
[57] Rojkowski Z, Two parameter kinetic equation of size dependent crystal growth, Krist Tech, 1978,13:1277
[58] Mydlarz J, Jones A G, On the estimation of size-dependent crystal growth rate functions in MSMPR crystallizers, Chem Eng J, 1993,53:125
[59] Mydlarz J, Kinetyka wzrostu krysztalow w krystalizatorze MSMPR, Sci Pap Inst Chem Eng Heating Equip, Wroclaw Tech Univ, Monograph(1991)
[60] Janse A H, DeJong E J, The occurrence of growth dispersion and its consequences, Industrial Crystallization, New York: Plenum Press,1976
[61] Berglund K A, Larson M A, Modeling of growth rate dispersion of citric acid monohydrate in continuous crystallizer, AIChE J,1984,30(2):280
[62] Larson M A, White E T, Ramanarayanan K A, Growth rate dispersion in MSMPR crystallizers, AIChE J,1985,31(1):90
[63] Berglund K A, Kaufman E L, Larson M A, Growth of contact nuclei of potassium nitrate, AIChE J,1983,29(5):867
[64] Janse A H, Proceeding of 11th Symposium on Industrial Crystallization, Munich:Garmisch Partenkirchen, 1990
[65] Larson M A, Advance in industrial crystallization，全国医药结晶及粒子过程技术学术会议，天津，1996
[66] Nielsen A E, Kinetics of Precipitation,Oxford:Pergamon,1964
[67] 陆杰，反应结晶（沉淀）研究（博士学位论文），天津：天津大学化工学院，1997
[68] 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
[69] Kofler, Proceeding of 11th symposium on Industrial crystallization, Munich:Garmisch Partenkirchen, 1990
[70] Mydlarz J, Jones A G, Crystallization and agglomeration kinetics during the batch drowning-out precipitation of potash alum with aqueous acetone, Power Technology,1991,65:187
[71] Sowul L, Epstein M A F, Crystallization kinetics of sucrose in a CMSMPR evaporative crystallizer, Ind Eng Chem Proc Des Dev,1981,20(2):197
[72] Wey J S, Analysis of batch crystallization process, Chem Eng Commun,1985, 35(1-6):231
[73] Tavare N S, Batch crystallizers: a review, Chem Eng Commun,1987,61(1-6):259
[74] Tavare N S, Garside J, Analysis of Batch crystallizers, Ind Eng Chem Process Des Dev,1980,19:653
[75] Tavare N S, Garside J, Simultaneous estimation of crystal nucleation and growth kinetics from batch experiments, Chem Eng Res Des,1986,64:109
[76] 郝红勋，地塞米松磷酸钠耦合结晶过程研究（博士论文），天津：天津大学化工学院，2003
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