Solid State Development and Processing of Pharmaceutical Molecules

A guide to the lastest industry principles for optimizing the production of solid state active pharmaceutical ingredients

Solid State Development and Processing of Pharmaceutical Molecules is an authoritative guide that covers the entire pharmaceutical value chain. The authors?noted experts on the topic?examine the importance of the solid state form of chemical and biological drugs and review the development, production, quality control, formulation, and stability of medicines.

The book explores the most recent trends in the digitization and automation of the pharmaceutical production processes that reflect the need for consistent high quality. It also includes information on relevant regulatory and intellectual property considerations. This resource is aimed at professionals in the pharmaceutical industry and offers an in-depth examination of the commercially relevant issues facing developers, producers and distributors of drug substances. This important book:

• Provides a guide for the effective development of solid drug forms
  *' Compares different characterization methods for solid state APIs
• Offers a resource for understanding efficient production methods for solid state forms of chemical and biological drugs
• Includes information on automation, process control, and machine learning as an integral part of the development and production workflows
• Covers in detail the regulatory and quality control aspects of drug development

Written for medicinal chemists, pharmaceutical industry professionals, pharma engineers, solid state chemists, chemical engineers, Solid State Development and Processing of Pharmaceutical Molecules reviews information on the solid state of active pharmaceutical ingredients for their efficient development and production.

Auteur

*Michael Gruss, PhD, is owner and founder of Solid State Concepts. He works as an independent scientific consultant for the pharmaceutical, chemical and nutrition industry. Gruss is author or co-author of more than 15 patent applications in the field of salts, cocrystals and polymorphs.*

Résumé
Solid State Development and Processing of Pharmaceutical Molecules A guide to the lastest industry principles for optimizing the production of solid state active pharmaceutical ingredients Solid State Development and Processing of Pharmaceutical Molecules is an authoritative guide that covers the entire pharmaceutical value chain. The authorsnoted experts on the topicexamine the importance of the solid state form of chemical and biological drugs and review the development, production, quality control, formulation, and stability of medicines. The book explores the most recent trends in the digitization and automation of the pharmaceutical production processes that reflect the need for consistent high quality. It also includes information on relevant regulatory and intellectual property considerations. This resource is aimed at professionals in the pharmaceutical industry and offers an in-depth examination of the commercially relevant issues facing developers, producers and distributors of drug substances. This important book:

• Provides a guide for the effective development of solid drug forms*
• Compares different characterization methods for solid state APIs
• Offers a resource for understanding efficient production methods for solid state forms of chemical and biological drugs
• Includes information on automation, process control, and machine learning as an integral part of the development and production workflows
• Covers in detail the regulatory and quality control aspects of drug development Written for medicinal chemists, pharmaceutical industry professionals, pharma engineers, solid state chemists, chemical engineers, Solid State Development and Processing of Pharmaceutical Molecules reviews information on the solid state of active pharmaceutical ingredients for their efficient development and production.

Contenu
Series Editors Preface xxi

Preface xxiii

1 Aspects for Developing and Processing Solid Forms 1
*Michael Gruss*

1.1 Aspects for Developing and Processing Solid Forms 1

1.1.1 Introduction 1

1.1.2 Education and Personal Background 1

1.1.3 Societal Impact Fishing in ForeignWaters 4

1.1.3.1 Motivation 4

1.1.3.2 The Personal Dimension 5

1.1.3.3 Beyond the Impact on Individuals 6

1.1.3.4 Understanding the Market Not an Easy Task 7

1.1.3.5 Benefits of an Interdisciplinary Mindset 9

1.1.4 The Basis for Mutual Understanding 9

1.1.5 Crystallization is a Separation, Not a Separated Process 11

1.1.6 Some Early Information About Solid-state Properties 13

1.1.7 Digitalization (Not Only) in the Laboratory 13

1.1.7.1 Prerequisites Technology and People 13

1.1.7.2 Connect Data and the Right Information from Synthesis and Analysis 15

1.1.7.3 Contributions and Choices 17

1.1.7.4 Application of Digitalization 18

1.1.7.5 Fully Digitalized Infrastructure 20

1.1.8 Basic Terms and Concepts in theWorld of Solid State 21

1.1.8.1 Crystalline and Amorphous 21

1.1.8.2 Crystallization and Precipitation 23

1.1.8.3 Understanding the Phase Diagram Analytical Characterization of the SolidLiquid and SolidSolid Systems 23

1.1.8.4 Polymorphism 24

1.1.8.5 Multi-component Compounds Salt, Cocrystal, Solvate, and Hydrate 25

1.1.8.6 Solvates, Hydrates, Non-solvated Forms, or Ansolvates 26

1.1.8.7 Dispersed Primary Particles, Aggregates, and Agglomerates 29

1.1.8.8 Particle Size and Particle Size Distribution (PSD) 29

1.1.9 Investigating and Understanding the Polymorphic Landscape 29

1.1.10 Performing the Crystallization 31

1.1.11 Objectives for the Optimization of Crystallization Processes and Solid-State Properties 32

1.1.12 Implementation of In Silico and Simulation Techniques 32

1.1.13 Saving the Investment Addressing Intellectual Property Rights 35

1.1.14 Concluding Remarks 36

List of Abbreviations 37

References 38

2 Determination of Current Knowledge 45
*Andriy Kuzmov and Ronak Savla*

2.1 Why is it Important to Search for Relevant Information Before Starting a Solid-State Project? 45

2.2 Where to Begin a Literature Search for a Solid-State Project? 47

2.2.1 Literature Search 48

2.2.1.1 Focusing Your Literature Search 49

2.2.2 Staying on Top of the Latest Publications 51

2.3 Patent Search 51

2.3.1 Types of Patent Reports 52

2.3.2 Understanding the Elements of Patents 53

2.3.3 Patent Classification 54

2.3.4 Patent Databases 56

2.3.4.1 Free Patent Databases 57

2.4 Other Useful Resources for Solid-State Projects 61

2.4.1 Cambridge Structural Database 61

2.4.2 Crystallography Open Database 62

List of Abbreviations 62

References 63

3 Systematic Screening and Investigation of Solid-State Landscapes 67
*Ulrike Werthmann*

3.1 Introduction 67

3.2 General Aspects of Solid-State Investigations in Early Drug Discovery Phase 68

3.3 Transition Phase from Late Stage Research to Early Stage Development 69

3.4 Solid-State Characteristics in Preclinical Formulations 70

3.5 API-crystallization Strategy in Candidate Profiling Phase 73

3.6 Selection Criteria of a Suitable Solid Form 77

3.7 Knowledge Management 79

3.8 Control of Solid Form Properties in Development 79

3.9 Exploratory Crystallization Experiments 80

List of Abbreviations 87

References 88

4.1 Solid-State Characterization Techniques: Microscopy 91
*Luis Almeida e Sousa and Constança Cacela*

4.1.1 Microscopy 91 4.1.1.1 Optical Microsco...