Solid-State Properties of Pharmaceutical Materials

 
 
Standards Information Network (Verlag)
  • erschienen am 12. Juli 2017
  • |
  • 432 Seiten
 
E-Book | PDF mit Adobe-DRM | Systemvoraussetzungen
978-1-119-26444-6 (ISBN)
 
Presents a detailed discussion of important solid-state properties, methods, and applications of solid-state analysis
* Illustrates the various phases or forms that solids can assume and discussesvarious issues related to the relative stability of solid forms and tendencies to undergo transformation
* Covers key methods of solid state analysis including X-ray powder diffraction, thermal analysis, microscopy, spectroscopy, and solid state NMR
* Reviews critical physical attributes of pharmaceutical materials, mainly related to drug substances, including particle size/surface area, hygroscopicity, mechanical properties, solubility, and physical and chemical stability
* Showcases the application of solid state material science in rational selection of drug solid forms, analysis of various solid forms within drug substance and the drug product, and pharmaceutical product development
* Introduces appropriate manufacturing and control procedures using Quality by Design, and other strategies that lead to safe and effective products with a minimum of resources and time
1. Auflage
  • Englisch
  • New York
  • |
  • USA
John Wiley & Sons Inc
  • Für Beruf und Forschung
  • 27,82 MB
978-1-119-26444-6 (9781119264446)
weitere Ausgaben werden ermittelt
Stephen R. Byrn, PhD is Charles B. Jordan Professor of Medicinal Chemistry in the School of Pharmacy, Purdue University. Dr. Byrn has founded and directed several programs at Purdue University including CAMP, the Center for AIDS Research, the Molecules to Market program, and Purdue's graduate programs in regulatory and quality compliance. Dr. Byrn has served as chair of the Pharmaceutical Sciences Advisory Committee to the FDA and Chair of the Drug Substances Technical Committee, Product Quality Research Initiative. Dr. Byrn is co-founder of SSCI, Inc. a cGMP research and information Company.
George Zografi, PhD is the Edward Kremers Professor Emeritus of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison. He was the recipient of the APhA Ebert Prize in 1984 and 2001, the AAPS Dale E. Wurster Award for Pharmaceutics in 1990 and its Distinguished Scientist Award in 1995, as well as the Volwiler Research Achievement Award of the American Association of Colleges of Pharmacy.
Xiaoming (Sean) Chen, PhD is currently the Director of Formulation Development in Antares Pharma Inc. Prior to that, he held various positions in pharmaceutical product development at Schering-Plough, OSI Pharmaceuticals, Astellas Pharma, and Shionogi Inc. He has published over a dozen of papers in peer-reviewed journals and is a co-inventor of four US patents.
  • 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
  • 16.13.2 Dynamic Mechanical Analyzer
  • 16.14 Nanoindentation
  • References
  • 17 Solubility and Dissolution
  • 17.1 Introduction
  • 17.2 Principle Concepts Associated with Solubility
  • 17.3 Prediction of Aqueous Drug Solubility
  • 17.4 Solubility of Pharmaceutical Solid Forms
  • 17.5 Solubility Determination Using the Shake Flask Method
  • 17.6 High Throughput Screening of Solubility
  • 17.7 Solubility Measurement of Metastable Forms
  • 17.8 Kinetic Solubility Measurement
  • 17.9 Solubility Determination of Drugs in Polymer Matrices
  • 17.10 Dissolution Testing
  • 17.11 Nonsink Dissolution Test
  • 17.12 Intrinsic Dissolution Studies
  • References
  • 18 Physical Stability of Solids
  • 18.1 Introduction
  • 18.2 Underlying Basis for Physical Instability in Pharmaceutical Systems
  • 18.3 Disorder in Crystals
  • 18.3.1 Quantitative Determination of Partially Amorphous Material in Crystals
  • 18.3.2 Solvent-Mediated Phase Transformations
  • 18.4 Examples of the Role of Process-Induced Disorder in Solid-State Physical Instability in Pharmaceutical Systems
  • 18.5 Considerations in Evaluating Solid-State Physical Stability
  • References
  • 19 Chemical Stability of Solids
  • 19.1 Introduction
  • 19.2 Examples of Chemical Reactivity in the Solid State
  • 19.3 Some General Principles that Establish the Rate of Chemical Reactions in Solution
  • 19.3.1 Some General Principles Governing the Rates of Solid-State Reactions
  • 19.4 The Role of Crystal Defects in Solid-State Reactions
  • 19.5 Chemical Reactivity in the Amorphous Solid State
  • 19.6 Chemical Reactivity and Processed-Induced Disorder
  • 19.7 The Effects of Residual Water on Solid-State Chemical Reactivity
  • 19.8 Drug-Excipient Interactions
  • 19.9 Summary
  • References
  • 20 Solid-State Properties of Proteins
  • 20.1 Introduction
  • 20.2 Solution Properties of Proteins
  • 20.3 Amorphous Properties of Proteins
  • 20.4 Crystalline Properties of Proteins
  • 20.5 Local Molecular Motions and the Dynamical Transitional Temperature,Td
  • 20.6 Solid-State Physical and Chemical Stability of Proteins
  • 20.7 Cryoprotection and Lyoprotection
  • References
  • 21 Form Selection of Active Pharmaceutical Ingredients
  • 21.1 Introduction
  • 21.2 Form Selection
  • 21.3 Amorphous Form Screening
  • 21.4 Salt Selection
  • 21.5 Cocrystal Screening
  • 21.6 Polymorph Screening
  • 21.7 Slurrying
  • 21.8 High Throughput Screening
  • 21.9 Crystallization in Confined Space
  • 21.10 Nonsolvent-Based Polymorph Screening
  • 21.11 Polymer-Induced Heteronucleation
  • 21.12 Physical Characterization
  • 21.13 Thermodynamic Stability and form Selection
  • References
  • 22 Mixture Analysis
  • 22.1 Introduction
  • 22.2 Limitations of Wet Chemistry
  • 22.3 Pharmaceutical Analysis in the Solid State
  • 22.3.1 Sample Preparation
  • 22.3.2 Data Collection
  • 22.3.3 Data Transformation
  • 22.3.4 Development and Validation of a Calibration Model
  • 22.4 Measurement of Amorphous Content
  • 22.5 Detection of the Degree of Crystallinity
  • 22.6 Quantification of Mixtures of Polymorphs
  • 22.7 Salt and Free Form Composition
  • 22.8 Process Analytical Technology
  • 22.8.1 Physical and Chemical Attributes of a Process
  • 22.8.2 Selection of Process Analyzers
  • 22.8.3 Location of the Process Analyzer
  • 22.8.4 Development of Analytical Models for Process Monitoring
  • 22.8.5 Validation
  • References
  • 23 Product Development
  • 23.1 Chemistry, Manufacture, and Control
  • 23.2 Preformulation
  • 23.3 Drug Excipient Compatibility
  • 23.4 Solid Dispersions
  • 23.5 Abuse-Deterrent Dosage Forms
  • 23.6 Drug-Eluting Stents
  • 23.7 Dry Powder Inhalers (DPI)
  • 23.8 Lyophilization and Biopharmaceutical Products
  • References
  • 24 Quality by Design
  • 24.1 Introduction
  • 24.2 Quality by Design Wheel
  • 24.3 Learning Before Doing
  • 24.4 Risk-Based Orientation
  • 24.5 API Attributes and Process Design
  • 24.6 Development and Design Space
  • 24.7 Process Design: Crystallization
  • 24.8 Phase Transformations During Wet Granulation
  • 24.9 Dissolution Tests with an IVIVC for Quality by Design
  • 24.10 Conclusion
  • References
  • Index
  • EULA

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