Crystallization is an important technique for separation and purification of substances as well as for product design in chemical, pharmaceutical and biotechnological process industries.

This ready reference and handbook draws on research work and industrial practice of a large group of experts in the various areas of industrial crystallization processes, capturing the essence of current trends, the markets, design tools and technologies in this key field. Along the way, it outlines trouble free production, provides laboratory controls, analyses case studies and discusses new challenges.

First the instrumentation and techniques used to measure the crystal size distribution, the nucleation and solubility points, and the chemical composition of the solid and liquid phase are outlined. Then the main techniques adopted to control industrial crystallizers, starting from fundamental approaches to the most advanced ones, including the multivariable predictive control are described. An overview of the main crystallizer types is given with details of the main control schemes adopted in industry as well as the more suitable sensors and actuators.

Angelo Chianese is full Professor of Chemical Plant Design at the University of Rome La Sapienza. He worked as a process engineer for the first 10 years of his working life, before joining academia. Prof. Chianese has more than 30 years in the field of industrial crystallization.
In this respect, he collaborated with the major academic laboratories all over the world and major industrial companies. Between 1998 and 2001 he was the coordinator of the European Thematic Network on Industrial Crystallization (acronym. CRYSOPT) and since 1990 was partner in many European projects. He is one of the two Italian delegates at the European Working Party on Crystallization.

Herman J. M. Kramer is associate professor at the Delft University of Technology, The Netherlands, working on the design, monitoring and control of crystallization and precipitation processes. He headed a large number of international multi client, multidisciplinary, research projects on design, monitoring and control of industrial crystallization. He was president of the Dutch Association of Crystal growth and is nowadays member of the European Working Party of Industrial Crystallization.

PREFACE

CHARACTERIZATION OF CRYSTAL SIZE DISTRIBUTION
Introduction
Particle Size Distribution
Particle Size Distribution Moments
Particle Size Distribution Characterization on the Basis of Mass Distribution

FORWARD LIGHT SCATTERING
Introduction
Principles of Laser Diffraction
Scatter Theory
Deconvolution
The Effects of Shape
Multiple Scattering
Application of Laser Diffraction for Monitoring and Control of Industrial Crystallization Processes
Conclusions

FOCUSED BEAM REFLECTANCE MEASUREMENT
Measurement Principle
Application Examples
Advantages and Limitations

TURBIDIMETRY FOR THE ESTIMATION OF CRYSTAL AVERAGE SIZE
Introduction
Determination of Average Particle Size from Specific Turbidity
Procedure to Evaluate Average Crystal Size by Turbidimetry for a High Solid Slurry Concentration
Conclusion

IMAGING
Introduction
Literature Overview
The Sensor Design
Application of In Situ Imaging for Monitoring Crystallization Processes
Conclusions

TURBIDIMETRY AND NEPHELOMETRY
Introduction
Measurement of Nucleation and Solubility Points
The Developed Turbidimetric and Nephelometric Instruments
The Examined Systems
Obtained Results

SPEED OF SOUND
Introduction
In-Process Ultrasound Measurement
Determining Solubility and Metastable Zone Width
Measuring Crystal Growth Rates
Detecting Phase Transitions with Ultrasound

IN-LINE PROCESS REFRACTOMETER FOR CONCENTRATION MEASUREMENT IN SUGAR CRYSTALLIZERS
Introduction
Measurement Principle
In-Line Instrument Features and Benefits
Features and Benefits
Example of Application in the Crystallization
Conclusion

ATR-FTIR SPECTROSCOPY
Introduction
Calibration
Speciation Monitoring
Co-Crystal Formation
Solubility Measurement
Crystal Growth Rates
Polymorph Transformation
Crystallization Monitoring and Control
Impurity Monitoring
Conclusions

RAMAN SPECTROSCOPY
Introduction
Factors Influencing the Raman Spectrum
Calibration
Applications
Conclusions

BASIC RECIPE CONTROL
Introduction
Incentives for Basic Recipe Control
Main Mechanisms, Sensors, and Actuators
Basic Recipe Control Strategy
Seeding as a Process Actuator
Rate of Supersaturation Generation
Mixing and Suspension of Solids
Fines Removal and Dissolution
Implementation of Basic Recipe Control
Conclusions

SEEDING TECHNIQUE IN BATCH CRYSTALLIZATION
Introduction
Seeding Operation: Main Principles and Phenomena
Use of Seeding for Batch Crystallization: Main Process Parameters
Control of Batch Crystallization by Seeding: Empirical Rules for Design

ADVANCED RECIPE CONTROL
Introduction
Incentives and Strategy of the Advanced Recipe Control
Modeling for Optimization, Prediction, and Control
Model Validation
Rate of Supersaturation Generation
Mixing Conditions
Implementation
Example of Modeling, Optimization, and Open-Loop Control of a 75-l Draft-Tube Crystallizer
Conclusions

ADVANCED MODEL-BASED RECIPE CONTROL
Introduction
Online Dynamic Optimization
MPC for Batch Crystallization
Conclusions and Perspectives

FINES REMOVAL
Introduction
Fines Removal by Heat Dissolution
Modeling of an MSMPR Continuous Crystallizer with Fines Removal
Fines Destruction in the Industrial Practice
CSD Control by Fines Removal for Pilot Scale Crystallizers
The Cycling Phenomenon as Undesired Effect of Fines Destruction in Industrial Crystallizers

MODEL PREDICTIVE CONTROL
Introduction
Approach for Designing and Implementing an MPC Control System
Process Modeling
The Performance Index
Constraints
The MPC Optimization
Tuning
State Estimation
Implementation
MPC of Crystallization Processes
Delta-Mode MPC
Conclusions and Perspectives

INDUSTRIAL CRYSTALLIZERS DESIGN AND CONTROL
Introduction
Forced Circulation Crystallizer
Draft-Tube-Baffle Crystallizer
Process Variables in Crystallizer Operation
Sensors
Control Devices