Content: Solid-State Properties of Pharmaceutical Materials
Contents
Preface
Acknowledgments
1 Solid-State Properties and Pharmaceutical Development
1.1 Introduction
1.2 Solid-State Forms
1.3 ICH Q6A Decision Trees
1.4 "Big Questions" for Drug Development
1.5 Accelerating Drug Development
1.6 Solid-State Chemistry in Preformulation and Formulation
1.7 Learning Before Doing and Quality by Design
1.8 Performance and Stability in Pharmaceutical Development
1.9 Moisture Uptake
1.10 Solid-State Reactions
1.11 Noninteracting Formulations: Physical Characterizations
References
2 Polymorphs 2.1 Introduction2.2 How Are Polymorphs Formed?
2.3 Structural Aspect of Polymorphs
2.3.1 Configurational Polymorphs
2.3.2 Conformational Polymorphs
2.4 Physical, Chemical, and Mechanical Properties
2.4.1 Solubility
2.4.2 Chemical Stability
2.4.3 Mechanical Properties
2.5 Thermodynamic Stability of Polymorphs
2.5.1 Monotropy and Enantiotropy
2.5.2 Burger and Rambergers Rules
2.5.3 vant Hoff Plot
2.5.4 DG/Temperature Diagram
2.6 Polymorph Conversion
2.6.1 Solution-Mediated Transformation
2.6.2 Solid-State Conversion
2.7 Control of Polymorphs
2.8 Polymorph Screening 2.9 Polymorph PredictionReferences
3 Solvates and Hydrates
3.1 Introduction
3.2 Pharmaceutical Importance of Hydrates
3.3 Classification of Pharmaceutical Hydrates
3.4 Water Activity
3.5 Stoichiometric Hydrates
3.6 Nonstoichiometric Hydrates
3.7 Hydration/Dehydration
3.8 Preparation and Characterization of Hydrates and Solvates
References
4 Pharmaceutical Salts
4.1 Introduction
4.2 Importance of Pharmaceutical Salts
4.3 Weak Acid, Weak Base, and Salt
4.4 pH-Solubility Profiles of Ionizable Compounds
4.5 Solubility, Dissolution, and Bioavailability of Pharmaceutical Salts 4.6 Physical Stability of Pharmaceutical Salts4.7 Strategies for Salt Selection
References
5 Pharmaceutical Cocrystals
5.1 Introduction
5.2 Cocrystals and Crystal Engineering
5.3 Solubility Phase Diagrams For Cocrystals
5.4 Preparation of Cocrystals
5.5 Dissolution and Bioavailability of Cocrystals
5.6 Comparison of Pharmaceutical Salts and Cocrystals
References
6 Amorphous Solids
6.1 Introduction
6.2 The Formation of Amorphous Solids
6.3 Methods of Preparing Amorphous Solids
6.4 The Glass Transition Temperature
6.5 Structural Features of Amorphous Solids 6.6 Molecular Mobility6.6.1 Overview of Molecular Mobility
6.6.2 Viscosity and Molecular Mobility
6.6.3 Relaxation Time
6.6.4 Fragility in Supercooled Liquids
6.6.5 Diffusive Relaxation Time in the Glassy State
6.6.6 Secondary Relaxations in Amorphous Solids
6.7 Mixtures of Amorphous Solids
6.7.1 Overview
6.7.2 Thermodynamics of Molecular Mixing in Amorphous Solids
6.7.3 The Glass Transition Temperature and Molecular Mobility of Miscible Amorphous Mixtures
References
7 Crystal Mesophases and Nanocrystals
7.1 Introduction
7.2 Overview of Crystal Mesophases
7.3 Liquid Crystals