Note: Intro -- 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 Introduction -- 2.2 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 Prediction -- References -- 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 Salts -- 4.7 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 Mobility -- 6.6.1 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 -- 7.4 Conformationally Disordered (CONDIS) Crystals -- 7.5 Plastic Crystals -- 7.6 Nanocrystals -- REFERENCES -- 8 X-Ray Crystallography and Crystal Packing Analysis -- 8.1 Introduction -- 8.2 Crystals -- 8.3 Miller Indices and Crystal Faces -- 8.4 Determination of the Miller Indices of the Faces of a Crystal -- 8.5 Determination of Crystal Structure -- 8.5.1 Diffraction of X-Rays -- 8.5.2 Experimental Measurements -- 8.5.3 Determination of Space Group Symmetry -- 8.5.4 Calculation of the Density of the Crystal -- 8.5.5 Structure Determination. , 8.5.6 Crystal Packing Drawings -- 8.5.7 Atomic Displacement Parameters and Molecular Mobility -- 8.5.8 Variable Temperature X-Ray Studies -- References -- 9 X-ray Powder Diffraction -- 9.1 Introduction -- 9.2 X-Ray Powder Diffraction of Crystalline Materials -- 9.3 Qualitative Analysis of Crystalline Materials -- 9.4 Phase Transformations -- 9.5 Quantitative Phase Analysis Using XRPD -- 9.6 Solving Crystal Structures using Powder X-ray Diffraction -- 9.7 X-ray Diffraction of Amorphous and Crystal Mesophase Forms -- 9.8 Pair Distribution Function -- 9.9 X-ray Diffractometers -- 9.10 Variable Temperature XRPD -- References -- 10 Differential Scanning Calorimetry and Thermogravimetric Analysis -- 10.1 Introduction -- 10.2 The Basics of Differential Scanning Calorimetry -- 10.3 Thermal Transitions of Pharmaceutical Materials -- 10.3.1 Melting -- 10.3.2 Glass Transition in Amorphous Solids -- 10.3.3 Enthalpy Relaxation for Amorphous Solids -- 10.3.4 Crystallization -- 10.3.5 Crystal Form Transitions -- 10.3.6 Desolvation/Dehydration -- 10.3.7 Chemical Degradation -- 10.4 DSC Instrumentation -- 10.4.1 Heat Flux DSC -- 10.4.2 Power-Compensated DSC -- 10.4.3 Modulated DSC -- 10.4.4 Fast Scan DSC -- 10.4.5 Operation of DSC Instrumentation -- 10.5 Thermogravimetric Analysis -- 10.6 Operating a TGA Instrument -- 10.7 Evolved Gas Analysis -- 10.8 Applications of DSC and TGA -- 10.8.1 The Study of Polymorphs, Solvates, and Hydrates -- 10.8.2 Polymer Characterization -- 10.8.3 Characterization of Amorphous Forms and Amorphous Solid Dispersions -- 10.8.4 Dehydration and Desolvation Kinetics -- 10.8.5 Optimization of the Freezing-Drying Cycle in Lyophilization -- 10.8.6 Determination of Chemical Purity of Organic Compounds -- 10.8.7 Study of Solid-State Reactions -- 10.8.8 Characterization of Macromolecules and Their Interactions -- 10.9 Summary of Using DSC and TGA. , References -- 11 Microscopy -- 11.1 Introduction -- 11.2 Light Microscopy -- 11.3 Polarized Light Microscopy -- 11.4 Thermal Microscopy -- 11.5 Functionality of the Light Microscope -- 11.6 Digital Microscope -- 11.7 Application of Light Microscopy to Pharmaceutical Materials -- 11.7.1 Amorphous and Crystalline Materials -- 11.7.2 Characterization of Polymorphs, Hydrates, and Solvates -- 11.7.3 Polymorph Conversion -- 11.7.4 Control of Crystallization -- 11.7.5 Screening for Cocrystals -- 11.7.6 Analysis of Particle Size -- 11.7.7 Contaminant Analysis -- 11.8 Scanning Electron Microscope -- 11.9 Environmental Scanning Electron Microscopy -- 11.10 Atomic Force Microscopy -- References -- 12 Vibrational Spectroscopy -- 12.1 Introduction -- 12.2 The Nature of Molecular Vibrations -- 12.3 Fourier Transformed Infrared Spectroscopy -- 12.4 Material Characterization by FT-IR Spectroscopy -- 12.5 FT-IR Instrumentation -- 12.6 Diffuse Reflectance FT-IR -- 12.7 Attenuated Total Reflectance FT-IR -- 12.8 FT-IR Microscopy -- 12.9 Near Infrared Spectroscopy -- 12.10 Raman Spectroscopy -- 12.11 Raman Instrumentation and Sampling -- 12.12 Raman Microscope -- 12.13 Terahertz Spectroscopy -- 12.14 Comparison of FT-IR, NIR, Raman, and Terahertz Spectroscopy -- 12.14.1 Spectral Information -- 12.14.2 Spectral Resolution -- 12.14.3 Sampling -- 12.14.4 Environmental Control -- 12.14.5 Microscopy -- 12.14.6 Florescence and Photodamage -- References -- 13 Solid-State NMR Spectroscopy -- 13.1 Introduction -- 13.2 An Overview of Solid-State 13C CP/MAS NMR Spectroscopy -- 13.3 Solid-State NMR Studies of Pharmaceuticals -- 13.4 Phase Identification in Dosage Forms -- 13.5 Other Basic Solid-State NMR Experiments Useful for Pharmaceutical Analysis -- 13.5.1 Interrupted Decoupling for Protonated CarbonAtoms -- 13.5.2 Bloch-Decay Experiments for Screening Submolecular Mobility. , 13.6 Determination of the Domain Structure of Amorphous Dispersions Using Solid-State NMR -- References -- 14 Particle and Powder Analysis -- 14.1 Introduction -- 14.2 Particles in Pharmaceutical Systems -- 14.2.1 Micelles -- 14.2.2 Protein Aggregates -- 14.2.3 Liposomes -- 14.2.4 Microemulsions -- 14.2.5 Nanoemulsions -- 14.2.6 Nanosuspensions -- 14.2.7 Nanoparticles -- 14.2.8 Aerosols -- 14.2.9 Emulsions -- 14.2.10 Suspensions -- 14.2.11 Powders -- 14.2.12 Granules -- 14.2.13 Pellets -- 14.3 Particle Size and Shape -- 14.4 Particle Size Distribution -- 14.5 Dynamic Light Scattering -- 14.6 Zeta Potential -- 14.7 Laser Diffraction -- 14.8 Dynamic Image Analysis -- 14.9 Sieve Analysis -- 14.10 Bulk Properties of Pharmaceutical Particulates and Powders -- 14.11 Surface Area Measurement -- References -- 15 Hygroscopic Properties of Solids -- 15.1 Introduction -- 15.2 Water Vapor Sorption-Desorption -- 15.3 Water Vapor Sorption Isotherms, Relative Humidity, and Water Activity -- 15.4 Measurement of Water Content and Water Vapor Sorption/Desorption Isotherms -- 15.4.1 Measurement of Water Content -- 15.4.2 Measurement of Water Vapor SorptionDesorption Isotherms -- 15.5 Modes of Water Vapor Sorption -- 15.5.1 Introduction -- 15.5.2 Adsorption -- 15.5.3 Deliquescence -- 15.5.4 Capillary Condensation -- 15.5.5 Absorption by Amorphous Solids -- References -- 16 Mechanical Properties of Pharmaceutical Materials -- 16.1 Introduction -- 16.2 Stress and Strain -- 16.3 Elasticity -- 16.4 Plasticity -- 16.5 Viscoelasticity -- 16.6 Brittleness -- 16.7 Hardness -- 16.8 Powder Compression -- 16.9 Powder Compression Models and Compressibility -- 16.10 Compactibility and Tensile Strength -- 16.11 Effect of Solid Form on Mechanical Properties -- 16.12 Effect of Moisture on Mechanical Properties -- 16.13 Methods for Testing Mechanical Properties: Beam Bending. , 16.13.1 Thermomechanical Analyzer.