Introduction to Crystallization Process Development

Abstract

This course provides an introduction to a systematic method for developing crystallization processes – starting with the analysis of the solid-liquid equilibrium (SLE) behavior of the system, then systematically synthesizing a crystallization process based on the SLE behavior. Fundamental issues such as solubility and physical properties will be discussed,along with relevant theories, methods, and models that have been used in many industrial applications for developing an optimum crystallization process. Various examples will be provided to illustrate this approach.

What can youlearn?

　　How to analyze solubility and SLE phase behavior for the purpose of conceptual design of crystallization processes.

　　How to use the knowledge of SLE phase behavior in synthesizing crystallization processes and defining the optimum processing conditions.

　　How to integrate synthesis, analysis, and experimental effort in developing crystallization processes.

　　How to solve basic crystallization process design problems, as illustrated using application examples.

Course content

　　1. Crystallization process development – an overview

　　　　。Motivational examples

　　　　。Issues in crystallization process development

　　2. Basics of solid-liquid equilibrium (SLE) phase behavior

　　　　。Solubility and SLE phase diagrams

　　　　。Multicomponent SLE phase behavior

　　3. Thermodynamic-based conceptual design of crystallization processes

　　　　。Thermodynamic boundaries and movements in composition space

　　　　。Using SLE phase diagrams in crystallization process design

　　　　。Application examples: maximizing yield, preventing crystallization of impurities

　　4. Design of crystallization-based separation and purification processes

　　　　。Synthesis of crystallization-based separation processes

　　　　。Application examples: separation of inorganic salts

　　5. 　Modeling of SLE phase behavior

　　　　。Thermodynamics of phase equilibrium

　　　　。Modeling of SLE phase diagrams

　　6. Integrative crystallization process development

　　　　。Role of experimental data in crystallization process development

　　　　。Design of experiments and analysis of experimental data

Advanced Crystallization Process Development

Abstract

This course focuses on advanced topics not covered in the elementary level course, such as systems involving chiral enantiomers, polymorphs, and solid solutions. The discussion also goes beyond thermodynamics/solid-liquid equilibrium considerations to include kinetics and mass transfer issues which are responsible in controlling particle size distribution and impurity incorporation into the solid products.

What can you expect to learn?

　　。How to design crystallization processes and defining the optimum processing conditions for systems involving complex SLE behavior.

　　。How to account for mass kinetics and mass transfer issues in obtaining a product with the desired purity.

　　。How to control the particle size distribution (PSD) in crystallization operation.

　　。How to consider crystallizer design and scale-up issues in developing the crystallization process.

Course content

　　1. Crystallization-based separation processes involving complex SLE behavior

　　　　。Resolution of chiral enantiomers

　　　　。Polymorphic crystallization

　　　　。Systems with solid solutions

　　2. Impurity management in crystallization processes

　　　　。Mechanisms and prevention of impurity incorporation

　　　　。Design of downstream processing systems

　　3. Particle size distribution targeting

　　　　。Crystallization kinetics and PSD

　　　　。Targeting PSD in crystallization operations

　　4. Crystallizer design and scale-up issues

　　　　。Design of industrial crystallizers

　　　　。Scale-up rules and mixing considerations