Cover -- Title Page -- Copyright -- Contents -- Series Editors Preface -- Preface -- Chapter 1 Aspects for Developing and Processing Solid Forms -- 1.1 Aspects for Developing and Processing Solid Forms -- 1.1.1 Introduction -- 1.1.2 Education and Personal Background -- 1.1.3 Societal Impact - Fishing in Foreign Waters -- 1.1.3.1 Motivation -- 1.1.3.2 The Personal Dimension -- 1.1.3.3 Beyond the Impact on Individuals -- 1.1.3.4 Understanding the Market - Not an Easy Task -- 1.1.3.5 Benefits of an Interdisciplinary Mindset -- 1.1.4 The Basis for Mutual Understanding -- 1.1.5 Crystallization is a Separation, Not a Separated Process -- 1.1.6 Some Early Information About Solid-state Properties -- 1.1.7 Digitalization (Not Only) in the Laboratory -- 1.1.7.1 Prerequisites - Technology and People -- 1.1.7.2 Connect Data and the Right Information from Synthesis and Analysis -- 1.1.7.3 Contributions and Choices -- 1.1.7.4 Application of Digitalization -- 1.1.7.5 Fully Digitalized Infrastructure -- 1.1.8 Basic Terms and Concepts in the World of Solid State -- 1.1.8.1 Crystalline and Amorphous -- 1.1.8.2 Crystallization and Precipitation -- 1.1.8.3 Understanding the Phase Diagram - Analytical Characterization of the Solid-Liquid and Solid-Solid Systems -- 1.1.8.4 Polymorphism -- 1.1.8.5 Multi-component Compounds - Salt, Cocrystal, Solvate, and Hydrate -- 1.1.8.6 Solvates, Hydrates, Non-solvated Forms, or Ansolvates -- 1.1.8.7 Dispersed Primary Particles, Aggregates, and Agglomerates -- 1.1.8.8 Particle Size and Particle Size Distribution (PSD) -- 1.1.9 Investigating and Understanding the Polymorphic Landscape -- 1.1.10 Performing the Crystallization -- 1.1.11 Objectives for the Optimization of Crystallization Processes and Solid-State Properties -- 1.1.12 Implementation of In Silico and Simulation Techniques.

1.1.13 Saving the Investment - Addressing Intellectual Property Rights -- 1.1.14 Concluding Remarks -- List of Abbreviations -- References -- Chapter 2 Determination of Current Knowledge -- 2.1 Why Is it Important to Search for Relevant Information Before Starting a Solid-State Project? -- 2.2 Where to Begin a Literature Search for a Solid-State Project? -- 2.2.1 Literature Search -- 2.2.1.1 Focusing Your Literature Search -- 2.2.2 Staying on Top of the Latest Publications -- 2.3 Patent Search -- 2.3.1 Types of Patent Reports -- 2.3.2 Understanding the Elements of Patents -- 2.3.3 Patent Classification -- 2.3.4 Patent Databases -- 2.3.4.1 Free Patent Databases -- 2.4 Other Useful Resources for Solid-State Projects -- 2.4.1 Cambridge Structural Database -- 2.4.2 Crystallography Open Database -- List of Abbreviations -- References -- Chapter 3 Systematic Screening and Investigation of Solid-State Landscapes -- 3.1 Introduction -- 3.2 General Aspects of Solid-State Investigations in Early Drug Discovery Phase -- 3.3 Transition Phase from Late Stage Research to Early Stage Development -- 3.4 Solid-State Characteristics in Preclinical Formulations -- 3.5 API-crystallization Strategy in Candidate Profiling Phase -- 3.6 Selection Criteria of a Suitable Solid Form -- 3.7 Knowledge Management -- 3.8 Control of Solid Form Properties in Development -- 3.9 Exploratory Crystallization Experiments -- List of Abbreviations -- References -- Chapter 4.1 Solid-State Characterization Techniques: Microscopy -- 4.1.1 Microscopy -- 4.1.1.1 Optical Microscopy -- 4.1.1.1.1 Bright-Field Microscopy -- 4.1.1.1.2 Dark-Field Microscopy -- 4.1.1.1.3 Polarized Light Microscopy -- 4.1.1.1.4 Other Optical Microscopy Variants -- 4.1.1.2 Electron Microscopy -- 4.1.1.2.1 Scanning Electron Microscopy -- 4.1.1.2.2 Transmission Electron Microscopy -- 4.1.1.3 Atomic Force Microscopy.

4.1.1.4 Microscopy in Regulatory Documents -- List of Abbreviations -- References -- Chapter 4.2 Standards and Trends in Analytical Characterization - X-ray Diffraction (XRD) -- 4.2.1 X-ray Diffraction -- 4.2.1.1 Introduction -- 4.2.1.2 Measurement Principles -- 4.2.1.2.1 The Crystal Lattice -- 4.2.1.2.2 The Space Group Symmetry -- 4.2.1.2.3 What Determines a Diffraction Peak -- 4.2.1.2.4 X-ray Scattering Technics -- 4.2.2 Technics -- 4.2.2.1 Single Crystal X-ray Diffraction -- 4.2.2.2 Powder X-ray Diffraction -- 4.2.2.2.1 Alternative Methods for Structure Determination -- 4.2.3 Instrumentation -- 4.2.3.1 X-ray Sources -- 4.2.3.2 Diffractometer Geometries -- 4.2.3.2.1 Reflection Geometry -- 4.2.3.2.2 Transmission Geometry -- 4.2.3.2.3 Benchtop Diffractometers -- 4.2.3.3 Detectors -- 4.2.3.4 Peak Asymmetry -- 4.2.3.5 Reproducibility of Diffraction Patterns: The Texture Effect (Preferred Orientation) -- 4.2.3.6 Databases of Known Diffraction Patterns -- 4.2.4 Measurement -- 4.2.4.1 Instrument Calibration -- 4.2.4.2 Sample Preparation -- 4.2.5 Data Evaluation -- 4.2.5.1 Qualitative Phase Analysis -- 4.2.5.1.1 Phase Identification or Identity Check -- 4.2.5.1.2 Amorphous Content -- 4.2.5.2 Quantification -- 4.2.5.2.1 Based on Calibration Curve -- 4.2.5.2.2 Based on Internal Standard Addition -- 4.2.5.2.3 Based on Rietveld Refinement -- 4.2.5.3 Advanced Phase Analysis -- List of Abbreviations -- References -- Further Reading -- Chapter 4.3 Standards and Trends in Solid-State Characterization Techniques - Thermal Analysis -- 4.3.1 Introduction -- 4.3.2 Thermal Analysis in Drug Development -- 4.3.2.1 Solid form Landscape -- 4.3.2.2 Compatibility Studies -- 4.3.2.3 Other Applications -- 4.3.3 Methods -- 4.3.3.1 Differential Scanning Calorimetry -- 4.3.3.1.1 Techniques -- 4.3.3.1.2 Sample Preparation and Measuring Parameters -- 4.3.3.1.3 Evaluation.

4.3.3.1.4 Special Applications -- 4.3.3.1.5 Detection Limits -- 4.3.3.2 Thermogravimetric Analysis -- 4.3.3.2.1 Technique -- 4.3.3.2.2 Sample Preparation and Measuring Parameters -- 4.3.3.2.3 Evaluation -- 4.3.3.2.4 Special Applications -- 4.3.4 Case Studies -- 4.3.4.1 Understanding Polymorphic Transitions -- 4.3.4.2 The Power of Ultra-fast Heating Rates -- 4.3.4.3 Understanding Amorphous Phases -- 4.3.4.4 Identification of Solvate Structures -- 4.3.5 Quality and Regulatory Aspects -- 4.3.6 Outlook -- Acknowledgments -- List of Abbreviations -- Notes -- References -- Chapter 4.4 Standards and Trends in Solid-State Characterization Techniques: Infrared (IR) Spectroscopy -- 4.4.1 Infrared (IR) Spectroscopy -- 4.4.1.1 Introduction -- 4.4.1.2 IR Spectroscopy as Identity Method for Drug Substances -- 4.4.1.2.1 Transmission Mode -- 4.4.1.2.2 Attenuated Total Reflectance (ATR) -- 4.4.1.2.3 Sample preparation -- 4.4.1.2.4 Analysis and Reporting -- 4.4.1.2.5 Examples and Limitations -- 4.4.1.2.6 Method Validation of IR Spectroscopy Identification and Quantification Methods -- 4.4.1.3 Application of IR Microscopy-Imaging Methods in Drug Development -- 4.4.1.3.1 Spatial Resolution -- 4.4.1.3.2 Measurement Setups -- 4.4.1.3.3 Case Studies -- 4.4.1.4 Conclusion -- List of Abbreviations -- References -- Chapter 4.5 Transmission Raman Spectroscopy - Implementation in Pharmaceutical Quality Control -- 4.5.1 Raman Spectroscopy - From Research to Broad Applications in Industry -- 4.5.1.1 Objective -- 4.5.1.1.1 History -- 4.5.1.1.2 Introduction -- 4.5.1.1.3 The Raman Effect -- 4.5.2 Analytical use of Raman Spectroscopy for Pharmaceutical Purposes -- 4.5.2.1 Transmission Raman Spectroscopy (TRS) -- 4.5.2.1.1 Principles of Transmission Raman Spectroscopy -- 4.5.2.1.2 A Practical Guide to a Successful Business Case.