Crystallization of Organic Compounds : An Industrial Perspective

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Format: eBook
Pub. Date: 2009-06-01
Publisher(s): Wiley-AIChE
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Summary

Filled with industrial examples emphasizing the practical applications of crystallization methodologiesBased on the authors' hands-on experiences as process engineers at Merck, Crystallization of Organic Compounds guides readers through the practical aspects of crystallization. It uses plenty of case studies and examples of crystallization processes, ranging from development through manufacturing scale-up. The book not only emphasizes strategies that have been proven successful, it also helps readers avoid common pitfalls that can render standard procedures unsuccessful.The goal of this text is twofold:Build a deeper understanding of the fundamental properties of crystallization as well as the impact of these properties on crystallization process development.Improve readers' problem-solving abilities by using actual industrial examples with real process constraints.Crystallization of Organic Compounds begins with detailed discussions of fundamental thermodynamic properties, nucleation and crystal growth kinetics, process dynamics, and scale-up considerations. Next, it investigates modes of operation, including cooling, evaporation, anti-solvent, and reactive crystallization. The authors conclude with special applications such as ultrasound in crystallization and computational fluid dynamics in crystallization. Most chapters feature multiple examples that guide readers step by step through the crystallization of active pharmaceutical ingredients (APIs).With its focus on industrial applications, this book is recommended for chemical engineers and chemists who are involved with the development, scale-up, or operation of crystallization processes in the pharmaceutical and fine chemical industries.

Table of Contents

Preface
Introduction to Crystallization Issues
Crystal Properties and Polymorphism (Chapters 2 and 3)
Nucleation and Growth Kinetics (Chapter 4)
Critical Issues (Chapter 5)
Mixing and Crystallization (Chapter 6)
Crystallization Process Options (Chapters 7-10)
Special Applications (Chapter 11)
Regulatory Issues
Properties
Solubility
Supersaturation, Metastable Zone, and Induction Time
Oil, Amorphous, and Crystalline States
Polymorphism
Solvate
Solid Compound, Solid Solution, and Solid Mixture
Inclusion and Occlusion
Adsorption, Hygroscopicity, and Deliquescence
Crystal Morphology
Particle Size Distribution and Surface Area
Polymorphism
Phase Rule
Phase Transition
Examples
Indomethacin
Sulindac
Losartan
Finasteride
Ibuprofen Lysinate
HCl Salt of a Drug Candidate
Second HCl Salt of a Drug Candidate
Prednisolone t-Butylacetate
Phthalylsulfathiazole
Future Direction
Kinetics
Supersaturation and Rate Processes
Nucleation
Crystal Growth
Nucleate/Seed Aging and Ostwald Ripening
Delivered Product: Size Distribution and Morphology
Critical Issues in Crystallization Practice
Introduction
Nucleation
Growth
Oiling Out, Agglomeration/Aggregation
Seeding
Rate of Generation of Supersaturation
Summary of Critical Issues
Mixing and Crystallization
Introduction
Mixing Considerations
Mixing Effects on Nucleation
Mixing Effects on Crystal Growth
Mixing Scale-up
Crystallization Equipment
Cooling Crystallization
Batch Operation
Continuous Operations
Process Design-Examples
Intermediate in a Multistep Synthesis
Pure Crystallization of an API
Crystallization Using the Heel from the Previous Batch as Seed
Resolution of Ibuprofen Via Stereospecific Crystallization
Crystallization of Pure Bulk with Polymorphism
Continuous Separation of Stereoisomers
Evaporative Crystallization
Introduction
Solubility Diagrams
Factors Affecting Nucleation and Growth
Scale-up 171
Equipment
Crystallization of a Pharmaceutical Intermediate Salt
Crystallization of the Sodium Salt of a Drug Candidate
Antisolvent Crystallization
Semibatch Operation
Crystallization of an Intermediate
Rejection of Isomeric Impurities of Final Bulk Active Product
Crystallization of a Pharmaceutical Product with Poor Nucleation and Growth Characteristics
Impact of Solvent and Supersaturation on Particle Size and Crystal Form
In-Line Mixing Crystallization
Crystallization of an API Using Impinging Jets
Crystallization of a Pharmaceutical Product Candidate Using an Impinging Jet with Recycle
Reactive Crystallization
Introduction
Control of Particle Size
Key Issues in Organic Reactive Crystallization
Scale-up
Reactive Crystallization of an API
Reactive Crystallization of an Intermediate
Reactive Crystallization of a Sodium Salt of an API
Reactive Crystallization of an API
Creation of Fine Particles-In-Line Reactive Crystallization
Special Applications
Introduction
Crystallization with Supercritical Fluids
Ultrasound in Crystallization
Computational Fluid Dynamics in Crystallization
Sterile Crystallization of Imipenem
Enhanced Selectivity of a Consecutive-Competitive Reaction by Crystallization of the Desired Product During the Reaction
Applying Solubility to Improve Reaction Selectivity
Melt Crystallization of Dimethyl Sulfoxide
Freeze Crystallization of Imipenem
Continuous Separation of Stereoisomers
Strategic Considerations for Development of a New Crystallization Process
References
Index
Table of Contents provided by Publisher. All Rights Reserved.

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