Table of Contents
About the Authors VII
Preface IX
List of Symbols XV
1 Introduction 1
1.1 Crystallization in the Chemical Processing Industries 1
1.2 Crystallization as a Multiscale Design Problem 3
1.3 An Integrative Approach to Crystallization Process Design 4
1.4 Organization of the Book 6
2 Basics of Solid-Liquid Equilibrium Phase Behavior 9
2.1 Solid-Liquid Equilibrium 9
2.1.1 Melting point and solubility 9
2.1.2 Phase diagram and Gibbs phase rule 10
2.2 Molecular Systems 11
2.2.1 Single component systems 11
2.2.2 Binary systems 12
2.2.3 Ternary systems 19
2.2.4 Quaternary systems 24
2.2.5 Multicomponent systems 28
2.2.6 Reactive systems 35
2.3 Electrolyte Systems 39
2.3.1 Acid-base systems 42
2.3.2 Conjugate salt systems 44
2.3.3 Multicomponent salt system 48
2.4 Summary 51
3 Thermodynamic-Based Conceptual Design of Crystallization Processes 57
3.1 Movements in Composition Space 57
3.1.1 Lever rule 58
3.1.2 Representation of basic operations on SLE phase diagram 60
3.2 Maximum Recovery of a Pure Solid 62
3.3 Crystallization of Desirable Product 73
3.4 Complete Dissolution 79
3.5 Summary 83
4 Synthesis of Crystallization-Based Separation Processes 89
4.1 Crystallization as a Separation Process 89
4.2 Bypassing the Thermodynamic Boundary 89
4.2.1 Ternary system 89
4.2.2 Quaternary system 97
4.2.3 Multicomponent system 100
4.2.4 Conjugate salt system 102
4.3 Effect of Solvent 109
4.3.1 Solvent selection 109
4.3.2 Solvent switching 111
4.4 Hybrid Separation Process 113
4.5 Summary 120
5 Crystallization Processes Involving More Complex Phase Behaviors 126
5.1 Adductive Crystallization 126
5.1.1 SLE phase behavior involving adduct 126
5.1.2 Process synthesis 127
5.2 Chiral Resolution by Crystallization 131
5.2.1 SLE phase behavior of chiral systems 132
5.2.2 Process synthesis 134
5.2.3 Hybrid process for chiral resolution 138
5.3 Solid Solution Crystallization 141
5.3.1 SLE phase behavior of solid solution systems 141
5.3.2 Process synthesis 142
5.4 Amino Acid and Protein Crystallization 149
5.4.1 SLE phase behavior of amino acid systems 149
5.4.2 Process synthesis 151
5.5 Antisolvent Crystallization 156
5.5.1 Solid-liquid-liquid equilibrium phase behavior 156
5.5.2 Process synthesis 159
5.6 Supercritical Fluid Crystallization 162
5.6.1 Solid-fluid equilibrium phase behavior 162
5.6.2 Process synthesis 166
5.7 Summary 170
6 Impact of Kinetics and Mass Transfer on Crystallization 176
6.1 Kinetic Effects in Crystallization Process 176
6.1.1 Supersaturation 176
6.1.2 Nucleation and growth models 177
6.2 Actual Process Path 179
6.3 Preferential Crystallization 181
6.4 Kinetically Controlled Reactive Crystallization 184
6.5 Polymorphic Crystallization 190
6.5.1 SLE phase behavior of polymorphic systems 191
6.5.2 Process synthesis 193
6.6 Summary 202
7 Management of Particle Size Distribution and Impurities in Crystallization Processes 207
7.1 Crystallizer Model 207
7.1.1 Population balance 207
7.1.2 Solutions of population balance equations 210
7.2 Particle Size Distribution Management 211
7.2.1 PSD manipulation in batch crystallization 211
7.2.2 PSD targeting in continuous crystallization 220
7.2.3 Scale-up consideration in PSD management 225
7.3 Impurity Management 227
7.3.1 Control of inclusion impurities 228
7.3.2 Removal of inclusion impurities by melt crystallization 233
7.3.3 Crystallization downstream processing system 238
7.3.4 Simultaneous washing and melt crystallization 244
7.4 Summary 247
8 Determination of Solid-Liquid Equilibrium Phase Behavior and Crystallization Kinetics 253
8.1 Strategy for SLE Phase Behavior Determination 253
8.2 Modeling of SLE Phase Behavior 254
8.2.1 Solubility equation and solubility product equation 255
8.2.2 Activity coefficient models 260
8.2.3 Equation of!state models 260
8.3 Prediction of Solid-Liquid Equilibrium Phase Behavior 264
8.3.1 Group contribution methods 264
8.3.2 Quantum chemistry methods 270
8.4 Experimental Determination of SLE Phase Behavior 270
8.4.1 Thermal method for obtaining SLE data 271
8.4.2 Synthetic method for obtaining SLE data 276
8.4.3 Analytical method for obtaining SLE data 279
8.4.4 Fitting of model parameters 280
8.4.5 Boundary verification 287
8.5 Experimental Determination of Crystallization Kinetics 292
8.6 Summary 294
9 Concluding Remarks 300
9.1 A Hierarchical, Multiscale, Integrative Approach 300
9.2 Outlook 303
Appendix: Solutions to Selected Exercise Problems 307
References 331
Index 347
