Brief Table of Contents -- Table of Contents -- Copyright Page -- Dedication -- Foreword -- List of Contributors -- Part I. Theories And Techniques In The Characterization Of Drug Substances And Excipients -- Chapter 1. Solubility of Pharmaceutical Solids -- 1.1. Introduction -- 1.1.1. Implication of Solubility in Dosage Form Development -- 1.1.2. Basic Concepts of Solubilityand Dissolution -- 1.2. Thermodynamics of solutions -- 1.2.1. Volume of Mixing -- 1.2.2. Enthalpy of Mixing -- 1.2.3. Entropy of Mixing -- 1.2.4. Free Energy of Mixing -- 1.3. Theoretical estimation of solubility -- 1.3.1. Ideal Solutions -- 1.3.2. Effect of Crystallinity -- 1.3.3. Non-ideal Solutions -- 1.3.4. Regular Solution Theory -- 1.3.5. Aqueous Solution Theory -- 1.3.6. The General Solubility Equation (GSE) -- 1.4. Solubilization of drug candidates -- 1.4.1. Solubility Enhancement by pH Control and Salt Formation -- 1.4.2. Solubilization Using Complexation -- 1.4.3. Solubilization by Cosolvents -- 1.4.4. Solubilization by Surfactants (Micellar Solubilization) -- 1.4.5. Solubilization by Combinationof Approaches -- 1.5. Experimental determination of solubility -- 1.5.1. Stability of Solute and Solvent -- 1.5.2. Shakers and Containers -- 1.5.3. Presence of Excess Undissolved Solute -- 1.5.4. Determination of Equilibrium -- 1.5.5. Phase-separation -- 1.5.6. Determination of Solute Content in the Dissolved Phase -- 1.5.7. Experimental Conditions -- Uncited References -- Chapter 2. Crystalline and Amorphous Solids -- 2.1. Introduction -- 2.2. Definitions and Categorization of Solids -- 2.3. Thermodynamics and Phase Diagrams -- 2.3.1. Polymorphs -- 2.3.2. Solvates/Hydrates -- 2.3.3. Cocrystals -- 2.3.4. Amorphous Solids -- 2.4. Pharmaceutical Relevance and Implications -- 2.4.1. Solubility -- 2.4.2. Dissolution Rate and Bioavailability -- 2.4.3. Hygroscopicity.

2.4.4. Reactivity and Chemical Stability -- 2.4.5. Mechanical Properties -- 2.5. Transformations among Solids -- 2.5.1. Induced by Heat -- 2.5.2. Induced by Vapor -- 2.5.3. Induced by Solvents -- 2.5.4. Induced by Mechanical Stresses -- 2.6. Methods of Generating Solids -- 2.6.1. Through Gas -- 2.6.2. Through Liquid -- 2.6.3. Through Solid -- 2.7. Amorphous Drugs and Solid Dispersions -- 2.7.1. Characteristics of Amorphous Phases -- 2.7.2. Characteristics of Amorphous Solid Dispersions -- 2.7.3. Crystallization of Amorphous Drugs and Dispersions -- 2.8. Special Topics -- 2.8.1. Polymorph Screening and Stable Form Screening -- 2.8.2. High Throughput Crystallization -- 2.8.3. Miniaturization in Crystallization -- Uncited Reference -- Chapter 3. Analytical Techniques in Solid-state Characterization -- 3.1. Introduction -- 3.2. Review of Analytical Techniques and Methods -- 3.3. Microscopic Methods -- 3.3.1. Optical Microscopy -- 3.3.2. Electron Microscopy -- 3.4. Thermal Analysis -- 3.4.1. Differential Scanning Calorimetry -- 3.4.2. Thermogravimetric Analysis -- 3.4.3. Microcalorimetry -- 3.5. Diffraction Methods -- 3.5.1. Single-crystal X-ray Diffraction -- 3.5.2. Powder X-ray Diffraction -- 3.6. Vibrational Spectroscopy -- 3.6.1. Infrared Spectroscopy -- 3.6.2. Raman Spectroscopy -- 3.6.3. Near-infrared -- 3.7. Solid-state Nuclear Magnetic Resonance Spectroscopy -- 3.8. Sorption Techniques -- 3.9. Other Techniques -- 3.10. Characterization of Solids Using Complementary Analytical Techniques -- 3.11. Conclusion -- Acknowledgements -- Chapter 4. Salt Screening and Selection -- 4.1. Introduction -- 4.2. Theoretical Considerations -- 4.2.1. pH-Solubility Profiles and the Role of pKa -- 4.2.2. Prediction of Salt Solubility and In Situ Salt Screening -- 4.2.3. Solubility and Dissolution Rate of Salts -- 4.2.4. Dissolution of Salts in GI Fluids.

4.2.5. Impact of Salt Form on Other Solubilization Techniques -- 4.2.6. Effect of Salts on Chemical Stability -- 4.2.7. Potential Disadvantages of Salts -- 4.3. Practical Considerations -- 4.3.1. Drug Substance Considerations -- 4.3.2. Dosage Form Considerations -- 4.3.3. Toxicity Considerations -- 4.3.4. Salt and Form Screening and Selection Strategies -- 4.3.5. The Role of Automation and High Throughput Designs in Salt Screening -- 4.4. Conclusions -- Uncited Reference -- Chapter 5. Drug Stability and Degradation Studies -- 5.1. Introduction -- 5.2. Chemical stability -- 5.2.1. Solution Kinetics -- 5.2.2. Rate Equations -- 5.2.3. Elemental Reactions and Reaction Mechanism -- 5.2.4. Typical Simple Order Kinetics -- 5.2.5. Complex Reactions -- 5.2.6. Arrhenius Equation, Collision Theory, and Transition State Theory -- 5.2.7. Catalysts and Catalysis -- 5.2.8. pH-rate Profiles -- 5.2.9. Solid-state Reaction Kinetics -- 5.2.10. Solid-state Kinetic Models -- 5.2.11. Physical Parameters Affecting Solid-state Kinetics -- 5.2.12. The Role of Moisture -- 5.2.13. Topochemical Reactions -- 5.3. Common pathways of drug degradation -- 5.3.1. Hydrolysis -- 5.3.2. Oxidative Degradation -- 5.3.3. Photochemical Degradation -- 5.3.4. Other Degradation Pathways -- 5.4. Experimental approaches to studying the chemical degradation of drugs -- 5.4.1. Solution Thermal Degradation Studies -- 5.4.2. Solid-state Thermal Degradation Studies -- 5.4.3. Oxidative Degradation Studies -- 5.4.4. Photodegradation Studies -- 5.5. Physical stability and phase transformations[106] -- 5.5.1. Types of Phase Transformations -- 5.5.2. Mechanisms of Phase Transformations -- 5.6. Phase transformations during pharmaceutical processing106 -- 5.6.1. Processes for Preparing Solid Dosage Forms and Associated Potential Phase Transformations.

5.6.2. Anticipating and Preventing Phase Transformations in Process Development -- Chapter 6. Excipient Compatibility -- 6.1. Introduction -- 6.2. Chemistry of Drug-Excipient Interactions -- 6.2.1. Influence of Water and Microenvironmental pH -- 6.2.2. Reactions with Excipients and their Impurities -- 6.2.3. Stabilizing Excipients -- 6.3. Current Practices -- 6.3.1. Experimental Design -- 6.3.2. Sample Preparation and Storage -- 6.3.3. Sample Analysis and Data Interpretation -- 6.4. Conclusions -- Chapter 7. Theory of Diffusion and Pharmaceutical Applications -- 7.1. Introduction -- 7.1.1. Basic Equations of Diffusion -- 7.1.2. Solutions for Diffusion Equations -- 7.2. The diffusion coefficient and its determination -- 7.2.1. Steady State Flux Method -- 7.2.2. Lag Time Method -- 7.2.3. Sorption and Desorption Methods -- 7.3. Pharmaceutical applications -- 7.3.1. Controlled Release -- 7.3.2. Particle Dissolution -- 7.3.3. Packaging Study -- 7.4. Appendix -- 7.4.1. The Error Function and Its Application -- 7.4.2. Derivation of Solution by Separation of Variables -- Chapter 8. Particle, Powder, and Compact Characterization -- 8.1. Introduction -- 8.2. Particle sizecharacterization -- 8.2.1. Light Microscopy -- 8.2.2. Scanning Electron Microscopy -- 8.2.3. Sieving -- 8.2.4. Light Diffraction -- 8.2.5. Importance/Impact of Particle Size Characterization -- 8.3. Powder characterization -- 8.3.1. Density -- 8.3.2. Flow -- 8.4. Compact (mechanical property) characterization -- 8.4.1. Important Mechanical Properties -- 8.4.2. Overview of Methods -- 8.4.3. Quasi-static Testing -- 8.4.4. Dynamic Testing -- 8.5. Conclusions -- Chapter 9. Polymer Properties and Characterization -- 9.1. Introduction -- 9.1.1. Definition, Structure, and Nomenclature -- 9.1.2. Types of Homopolymers and Copolymers -- 9.2. Commonly used cellulose derivatives in solid oral products.

9.3. Basic concepts and characterization of polymeric materials -- 9.3.1. Polymer Composition -- 9.3.2. Molecular Weight -- 9.3.3. Polymers in Solution -- 9.3.4. Structure-Property Relationships -- 9.4. Conclusion -- Uncited References -- Chapter 10. Applied Statistics in Product Development -- 10.1. Introduction -- 10.1.1. Statistics: A Tool for Decision Making and Risk Assessment -- 10.1.2. Sources of Uncertainty -- 10.1.3. Natural (Random) Variation -- 10.1.4. Systematic Error (Bias) and Blunders -- 10.2. Exploring data: types of data -- 10.2.1. Nominal (Categorical) Data -- 10.2.2. Ordinal Data -- 10.2.3. Numerical Data -- 10.2.4. Continuously Variable Data and Digitization Pitfalls -- 10.3. Exploring data: graphical techniques -- 10.3.1. Graphing Nominal Data -- 10.3.2. Bar Charts -- 10.3.3. Pie Charts -- 10.3.4. Graphing Univariate Numerical Data -- 10.3.5. Histograms -- 10.3.6. Quantile Plots -- 10.3.7. Box Plots -- 10.3.8. Graphing Bivariate Data -- 10.3.9. One Variable Nominal: Bar Graphs, Dot Plots, and Line Plots -- 10.3.10. One Variable Nominal: Box Plots -- 10.3.11. Both Variables Numeric and Random: Quantile-Quantile Plots -- 10.3.12. Both Variables Numeric: Scatterplots -- 10.3.13. Multivariate Data -- 10.3.14. Scatterplot Matrices -- 10.4. Data distributions -- 10.4.1. Binomial Distribution -- 10.4.2. Poisson Distribution -- 10.4.3. Normal (Gaussian) Distribution -- 10.4.4. Other Useful Distributions -- 10.5. Location: central tendencies -- 10.5.1. Data for Central Value and Dispersion Examples -- 10.5.2. Arithmetic Mean -- 10.5.3. Median -- 10.6. Dispersion -- 10.6.1. Range -- 10.6.2. Interquartile Range and Median Absolute Deviation from the Median -- 10.6.3. Variance and Standard Deviation -- 10.6.4. Coefficient of Variation -- 10.6.5. Multivariate Covariance and Correlation -- 10.6.6. Correlation and Causality.

10.6.7. Error Propagation.