Crystallization of Organic Compounds - An Industrial Perspective

Crystallization of Organic Compounds
 
Practical resource covering applications of crystallization principles with methodologies, case studies, and numerous industrial examples for emphasis
 
Based on the authors' hands-on experiences as process engineers, through the use of case studies and examples of crystallization processes, ranging from laboratory development through manufacturing scale-up, Crystallization of Organic Compounds guides readers through the practical applications of crystallization and emphasizes strategies that have proven to be successful, enabling readers to avoid common pitfalls that can render standard procedures unsuccessful.
 
Most chapters feature multiple examples that guide readers, step by step, through the crystallization of active pharmaceutical ingredients (APIs), including an analysis of the major methods of carrying out crystallization operations, their strengths and potential issues, as well as numerous examples of crystallization processes from development through manufacturing scale.
 
Advancements in the field of crystallization have been integrated throughout the book in the newly revised Second Edition to ensure the content adequately reflects current state-of-the-art industrial know-hows and practice. The new edition also adds chapters addressing downstream operations after the crystallization, including filtration/washing and drying, together with industrial use cases.
 
Crystallization of Organic Compounds includes detailed information on:
* Solubility and solid behavior, covering phase rule, polymorph, salt/co-crystal, chiral resolution and in-silico solubility prediction; and kinetics, covering seed, supersaturation, nucleation, crystal growth and model-based experimental design
* Critical issues in the crystallization practice, covering oiling out, seeding/wet-milling, agglomeration/aggregation, mixing scale-up and quality-by-design principles
* Cooling, anti-solvent, evaporation and reactive crystallization process design, covering batch and continuous operations with industrial examples
* Special applications, covering crystallization with ultrasound, reaction selectivity enhancement, and computation fluid dynamics, and solid dispersion
 
With highly practical coverage of the subject, Crystallization of Organic Compounds is an essential resource for engineers and chemists involved with the development, scaling, or operation of crystallization process in the pharmaceutical and fine chemical industries, particularly those with degrees in chemical engineering and chemistry.

List of contents

Preface ix
 
1. Introduction to Crystallization 1
 
1.1 Crystal Properties and Polymorphs (Chapters 2 and 3) 3
 
1.2 Nucleation and Growth Kinetics (chapter 4) 4
 
1.3 Mixing and Scale- Up (Chapter 5) 4
 
1.4 Critical Issues and Quality by Design (Chapter 6) 5
 
1.5 Crystallization Process Options (Chapters 7-10) 6
 
1.6 Downstream Operations (Chapters 11 And 12) 12
 
1.7 Special Applications (chapter 13) 13
 
2. Properties 15
 
2.1 Solubility 15
 
2.2 Supersaturation, Metastable Zone, and Induction Time 26
 
2.3 Oil, Amorphous, and Crystalline States 30
 
2.4 Polymorphism 36
 
2.5 Solvate 40
 
2.6 Solid Compound, Solid Solution, and Solid Mixture 42
 
2.7 Inclusion and Occlusion 45
 
2.8 Adsorption, Hygroscopicity, and Deliquesce 47
 
2.9 Crystal Morphology 50
 
2.10 Partical Size Distribution and Surface Area 53
 
3. Polymorphism 57
 
3.1 Phase Rule 57
 
3.2 Phase Transition 58
 
3.3 Prediction of Crystal Structure and its Formation 60
 
3.4 Selection and Screening of Crystal Forms 66
 
3.5 Examples 75
 
Example 3.1 Indomethacin 76
 
Example 3.2 Sulindac 77
 
Example 3.3 Losartan 79
 
Example 3.4 Finasteride 81
 
Example 3.5 Ibuprofen Lysinate 83
 
Example 3.6 HCl Salt of a Drug Candidate 84
 
Example 3.7 Second HCl Salt of a Drug Candidate 87
 
Example 3.8 Prednisolone t- Butylacetate 91
 
Example 3.9 Phthalylsulfathiazole 93
 
4. Kinetics 95
 
4.1 Supersaturation and Rate Processes 96
 
4.2 Nucleation 97
 
4.3 Crystal Growth and Agglomeration 105
 
4.4 Nucleate/Seed Aging and Ostwald Ripening 116
 
4.5 Delivered Product: Purity, Cystal Form, Size and Morphology, and Chemical and Physical Stability 119
 
4.6 Design of Experiment (DOE)-- Model- Based Approach 119
 
4.7 Model- Free Feedback Control 123
 
5. Mixing and Crystallization 125
 
5.1 Introduction 125
 
5.2 Mixing Considerations and Factors 126
 
5.3 Mixing Effects on Nucleation 130
 
5.4 Mixing Effects on Crystal Growth 135
 
5.5 Mixing Distribution and Scale- Up 139
 
5.6 Crystallization Equipment 141
 
5.7 Process Design and Examples 150
 
Example 5.1 Mixing Impact on Crystallization Kinetics 150
 
Example 5.2 Mixing Scale- Up Impact on Particle Size 151
 
6. Critical Issues and Quality by Design 155
 
6.1 Quality By Design 155
 
6.2 Basic Properties 156
 
6.3 Seed 158
 
6.4 Supersaturation 162
 
6.5 Mixing and Scale-- Selection of Equipment and Operating Procedures 172
 
6.6 Strategic Considerations for Crystallization Process Development 174
 
6.7 Summary of Critical Issues 176
 
7. Cooling Crystallization 177
 
7.1 Batch Operation 177
 
7.2 Continuous Operations 183
 
7.3 Process Design-- Examples 187
 
Example 7.1 Intermediate in a Multistep Synthesis 187
 
Example 7.2 Pure Crystallization of an API 191
 
Example 7.3 Crystallization Using the Heel from the Previous Batch as Seed 194
 
Example 7.4 Resolution of Ibuprofen Via Stereospecific Crystallization 195
 
Example 7.5 Crystallization of Pure Bulk with Polymorphism 199
 
Example 7.6 Continuous Separation of Stereoisomers 201
 
8. Evaporative Crystallization 207
 
8.1 Introduction 207
 
8.2 Solubility Diagrams 207
 
8.3 Factors Affecting Nucleation and Growth 210
 
8.4 Scale- Up 211
 
8.5

About the author

Hsien-Hsin Tung, PhD, is the co-founder of AcrysPharm, LLC. He founded the crystallization lab. at Merck and center of excellence of particle engineering at AbbVie. Edward L. Paul, PhD, (deceased) was retired Director of Chemical Engineering R & D at Merck Research Laboratories. Michael Midler, PhD, (deceased) was retired Senior Investigator, Chemical Engineering R&D at Merck. James A. McCauley, PhD, was a senior investigator in the Analytical R & D at Merck until his retirement, after which he became an adjunct professor in the Department of Chemical and Biochemical Engineering at Rutgers University.

Summary

Crystallization of Organic Compounds

Practical resource covering applications of crystallization principles with methodologies, case studies, and numerous industrial examples for emphasis

Based on the authors' hands-on experiences as process engineers, through the use of case studies and examples of crystallization processes, ranging from laboratory development through manufacturing scale-up, Crystallization of Organic Compounds guides readers through the practical applications of crystallization and emphasizes strategies that have proven to be successful, enabling readers to avoid common pitfalls that can render standard procedures unsuccessful.

Most chapters feature multiple examples that guide readers, step by step, through the crystallization of active pharmaceutical ingredients (APIs), including an analysis of the major methods of carrying out crystallization operations, their strengths and potential issues, as well as numerous examples of crystallization processes from development through manufacturing scale.

Advancements in the field of crystallization have been integrated throughout the book in the newly revised Second Edition to ensure the content adequately reflects current state-of-the-art industrial know-hows and practice. The new edition also adds chapters addressing downstream operations after the crystallization, including filtration/washing and drying, together with industrial use cases.

Crystallization of Organic Compounds includes detailed information on:
* Solubility and solid behavior, covering phase rule, polymorph, salt/co-crystal, chiral resolution and in-silico solubility prediction; and kinetics, covering seed, supersaturation, nucleation, crystal growth and model-based experimental design
* Critical issues in the crystallization practice, covering oiling out, seeding/wet-milling, agglomeration/aggregation, mixing scale-up and quality-by-design principles
* Cooling, anti-solvent, evaporation and reactive crystallization process design, covering batch and continuous operations with industrial examples
* Special applications, covering crystallization with ultrasound, reaction selectivity enhancement, and computation fluid dynamics, and solid dispersion

With highly practical coverage of the subject, Crystallization of Organic Compounds is an essential resource for engineers and chemists involved with the development, scaling, or operation of crystallization process in the pharmaceutical and fine chemical industries, particularly those with degrees in chemical engineering and chemistry.

Product details

• Authors: James A. McCauley, McCauley James A., Michael Midler, Michael et Midler, Midler Michael, Edward L Paul, Edward L. Paul, Edward L. (Merck & Co. Paul, Paul Edward L., Tung, Hsien-Hsin Tung, Hsien-Hsin (Acryspharm Tung, Hsien-Hsin Paul Tung
• Publisher: Wiley, John and Sons Ltd
• Languages: English
• Product format: Hardback
• Released: 01.10.2023
• EAN: 9781119879466
• ISBN: 978-1-119-87946-6
• No. of pages: 384
• Subjects: Natural sciences, medicine, IT, technology > Technology > Chemical engineering; Chemie, Prozesssteuerung, chemistry, Chemical Engineering, Industrial Chemistry, chemische Verfahrenstechnik, Technische u. Industrielle Chemie, Process Engineering