Solid-State Chemistry of Drugs – Table of Contents

PART 1: INTRODUCTION TO THE SOLID-STATE CHEMISTRY OF DRUGS

Chapter 1: Drugs as Molecular Solids
Role of solid-state technology in the pharmaceutical industry –The crystalline state: basic concepts — A given substance can crystallize in different ways concept — Properties that affect pharmaceutical behavior — How crystals form — Properties of amorphous solids — Moisture uptake by solids — Lyophilized powders — Patents on various crystal forms — Solid-state reactions of drugs — Stability testing — Summary — References

PART 2: METHODS OF ANALYSIS

Chapter 2: X-Ray Crystallography
Introduction to x-ray crystallography — Crystals — Determination of the crystal structure — Crystal-packing drawings — Thermal parameters and molecular mobility — References

Chapter 3: The X-Ray Powder Diffraction Method
Instruments for powder diffraction measurements — Powder diffraction using synchrotron radiation — The Hanawalt system — Comparing x-ray powder data — variable temperature and atmosphere studies — Quantitative analysis of mixtures — References

Chapter 4: Microscopy
Birefringence — Interfacial angles — Particle size measurements by microscopy — Thermal microscopy — Microscopy in freeze drying — Scanning electron microscopy, tunneling microscopy, and atomic force microscopy — References

Chapter 5: Thermal Methods of Analysis
Thermogravimetric Analysis (TGA) — Differential Scanning Calorimetry (DSC) — Calorimetry — References

Chapter 6: Dissolution Testing
Testing — Mechanism — Dissolution apparatus — Intrinsic dissolution testing — Accuracy and interpretation — Conclusions — References

Chapter 7: Particle-Size Analysis
Methods for particle-size analysis — Surface-area analysis — Analysis of particles in metered dose inhalers — Particle-size eduction — References

Chapter 8: Infrared Spectroscopy of Solids
Infrared spectra of polymorphs — Infrared spectra of solvates — Analysis of mixtures by infrared spectroscopy — References

Chapter 9: Solid-State NMR Spectroscopy
An overview of solid-state 13C CP/MAS NMR spectroscopy — Solid-state NMR studies of pharmaceuticals — Phase identification in dosage forms — Other basic solid-state NMR experiments useful for pharmaceutical analysis — Summary — References

PART 3: POLYMORPHS, SOLVATES, AND AMORPHOUS FORMS

Chapter 10: Polymorphs
Classic examples of polymorphism — Conformational and configurational polymorphism — Sulfonamides — Steroids — Barbiturates — Other drugs — Carbohydrates — Polymorphs of antibiotics — Polymorphism and chemical stability — Polymorphism and bioavailability — Polymorphism and its pharmaceutical application — References

Chapter 11: Hydrates and Solvates
Hydrates — Conditions under which hydrates may form — Formation of hydrates in air: stability of hydrates at different relative humidities — Deliquescence and efflorescence — Factors governing the formation of solvates in mixed solvents — Stability of organic solvates in air — Summary — References

Chapter 12: Amorphous Solids
Properties of amorphous forms — References

PART 4: PHYSICAL TRANSFORMATIONS OF CRYSTALLINE MATERIAL

Chapter 13: Polymorphic Interconversions
Interconversion of polymorphs in the solid state — The induction of phase transformations by stresses — Polymorphic transformations of pharmaceuticals — Solution-mediated phase transformations of drugs — References

Chapter 14: Loss of Solvent of Crystallization
Review of desolvation reactions — The mechanism of desolvation reactions — Desolvated solvates — Summary — References

PART 5: CHEMICAL TRANSFORMATION IN THE SOLID STATE

Chapter 15: Theoretical Analysis of Solid-State Chemical Reactions
Criteria for solid-state reactions — Steps in a solid-state reaction — Molecular mobility — The topochemical postulate — References

Chapter 16: Oxidation Reactions
Oxidations of rubrene and tetramethylrubrene — Ozonolysis of stilbenes — Reactions of free radicals with oxygen — Oxidation of Vitamin A — Oxidation of Vitamin C (ascorbic acid) in tablets — Oxidation of Vitamin D2 — Oxidation of reserpine — Oxidation of polyene antibiotics — Photooxidation of dyes used in coating tablets — Oxidation reactions preceded by loss of solvent — Oxidation of dialuric acid monohydrate: the importance of moisture in accelerating solid-state reactions — Study of the solid-state oxidation of pharmaceuticals containing olefinic functionalities using microcalorimetry — Summary — References

Chapter 17: Additions of Gases: Solid-State Hydrolyses
Reactions of crystals with ammonia gas — Rates of reaction of crystalline carboxylic acids with ammonia gas — Reactions of solids with Cl 2 or Br 2– Solid-state hydrolyses — Summary — References

Chapter 18: Gas-Producing Decomposition Reactions
Solid-state dehydration of hydroxyl compounds — Solid-state decarboxylation reactions — Decomposition of explosives — Summary — References

Chapter 19: Photochemical Reactions
Cinnamic acids, styrylthiophenes, and dienes: the topochemical postulate — Anthracenes, pyrones, and oxazindones: exceptions to the topochemical postulate — Quinones — Indigo: the role of molecular conformation — Polymerizations — Dimerizations of pyrones — Nucleic acids — Photochemistry and mobility in amorphous solids — Effect of ionizing radiation on crystals of biologically important compounds — Drugs and natural products — Summary — References

Chapter 20: Thermal Reactions
Rearrangement reactions –Thermal retro-cycloaddition reactions — Drugs and other compounds of biological interest — Studies using calorimetry — Summary — References

Chapter 21: Reaction Kinetics
Equations for kinetic analysis of solid state reactions — Examples of solid-state kinetic studies — Summary — References

Chapter 22: Miscellaneous Topics
Role of defects in solid-state reactions — Solid-state reactions — Cystallization — Atomic Force Microscopy (AFM) — Prediction of crystal structures and polymorphs — Particle design and the physics of tablet compaction — Solid-state stability of protein pharmaceuticals — Mobility of solids — Mobility and reactivity of solids — Regulatory aspects of the solid-state chemistry of drugs — Conclusion — References