Kooperativer Bibliotheksverbund

UID:

Format: 1 online resource (816 pages).

ISBN: 9780128144220 , 9780128144213

Series Statement: Advances in pharmaceutical product development and research series

Note: Front Cover -- Dosage Form Design Parameters -- Copyright Page -- Dedication -- Contents -- List of Contributors -- About the Editor -- 1 Levels of Solid State Properties: Role of Different Levels During Pharmaceutical Product Development -- 1.1 Introduction -- 1.2 Solids and its Forms -- 1.2.1 Amorphous -- 1.2.2 Polymorphs -- 1.2.2.1 Solvates/Hydrates -- 1.2.2.2 Salts/Cocrystals -- 1.3 Levels of SSP -- 1.3.1 Molecular Level -- 1.3.2 Particle Level -- 1.3.3 Bulk Level -- 1.4 Solid State Thermodynamics -- 1.5 Bioavailability of Solids -- 1.6 Polymorphism and its Types -- 1.6.1 Enantiotropy and Monotropy -- 1.6.1.1 Density Rule -- 1.6.1.2 Infrared Rule -- 1.7 Formulation Methods of Polymorphs -- 1.7.1 Solvent Evaporation Method -- 1.7.2 Slow Cooling Approach -- 1.7.3 Solvent Diffusion Technique -- 1.7.4 Vapor Diffusion Method -- 1.7.5 Sublimation -- 1.8 Characterization of Polymorphs -- 1.9 Evaluation Technique -- 1.9.1 Dissolution -- 1.9.2 The Temperature-Dependent Solubility of Polymorphs: van't Hoff Plot -- 1.9.3 Biological Studies -- 1.10 Importance of SSP in Pharmaceutical Product Development -- 1.10.1 Importance of Particle Size -- 1.10.1.1 Biopharmaceutical Aspect of Particle Size -- 1.11 Conclusion -- Acknowledgments -- References -- Further Reading -- 2 Polymorphism and its Implications in Pharmaceutical Product Development -- 2.1 Introduction -- 2.1.1 Solids -- 2.1.2 Industrial Perspectives -- 2.2 Potential Solid Polymorphic Forms -- 2.2.1 Crystal -- 2.2.2 Crystal Solvates or Hydrates -- 2.2.3 Crystal Desolvated Solvates (Dehydrated Hydrates) -- 2.2.4 Amorphous -- 2.3 Formation of Polymorphs: Theoretical Considerations -- 2.3.1 Ostwald's Rule of Stages -- 2.3.2 Cross-Nucleation -- 2.3.3 Heterogeneous Two-Dimensional Nucleation: Chemotaxy, Ledge-Directed Epitaxial Growth, and Two-Dimensional Lattice Mat... , 2.3.4 Additive-Induced Polymorph Selection -- 2.4 Effect of Polymorphism on Different Drug Properties -- 2.4.1 Physical and Thermodynamic Properties -- 2.4.1.1 Morphology -- 2.4.1.2 Density and Refractive Index -- 2.4.1.3 Wettability -- 2.4.1.4 Melting Point -- 2.4.1.5 Solubility -- 2.4.1.6 Thermal Stability -- 2.4.2 Kinetic Properties -- 2.4.2.1 Dissolution -- 2.4.2.2 Kinetics of Solid-State Reaction -- 2.4.2.3 Stability -- 2.4.3 Surface Properties -- 2.4.3.1 Surface Free Energy -- 2.4.3.2 Crystal Habit -- 2.4.3.3 Surface Area -- 2.4.3.4 Particle Size Distribution -- 2.4.4 Mechanical Properties -- 2.4.4.1 Compressibility and Hardness -- 2.4.5 Chemical Properties -- 2.4.5.1 Reactivity -- 2.5 Techniques of Polymorph Preparation -- 2.5.1 Solvent Evaporation Technique -- 2.5.2 Slow Cooling Technique -- 2.5.3 Solvent Diffusion Technique -- 2.5.4 Vapor Diffusion Technique -- 2.5.5 Vacuum Sublimation Technique -- 2.5.6 Crystallization in the Presence of Tailor-Made Additives -- 2.6 Characterization Techniques of Polymorphs -- 2.6.1 Differential Scanning Calorimetry -- 2.6.2 Thermogravimetric Analysis -- 2.6.3 Infrared (FT-IR) Spectroscopy -- 2.6.4 Raman Spectroscopy -- 2.6.5 Powder X-Ray Diffraction -- 2.6.6 Single-Crystal XRD -- 2.6.7 Solid-State NMR (SSNMR) -- 2.6.8 Terahertz Spectroscopy -- 2.6.9 Optical and Electron Microscopy -- 2.6.10 Incoherent Inelastic Neutron Scattering -- 2.7 Evaluation of Polymorphs -- 2.7.1 Solubility of Polymorphs: Van't Hoff Plot -- 2.7.2 Dissolution Study -- 2.8 Polymorphism in Drug Products: Challenges for the Pharmaceutical Industry -- 2.9 Regulatory Considerations -- 2.10 Conclusion -- Acknowledgments -- Abbreviations -- References -- 3 Basics of Crystallization Process Applied in Drug Exploration -- 3.1 Introduction -- 3.2 Crystallization: Basic Concepts and Mechanisms in Crystallization. , 3.2.1 Crystal Lattice-Building Block Arrangements and Symmetries -- 3.2.2 Crystal Habit, Morphology, and Generation of Different Crystal Habits -- 3.2.3 Primary Mechanism and Types of Nucleation -- 3.2.4 Crystallization Process and Mier's Supersaturation Theory -- 3.2.4.1 Mier's Supersaturation Process -- 3.2.5 Metastable Zone and Induction of Nucleation -- 3.2.6 Ostwald Law of Stages in Crystal Formation -- 3.2.7 Ideal and Real Crystals Growth -- 3.2.7.1 Birth and Spread Model of Crystal Growth via 2D Nucleation -- 3.2.7.2 Real Crystals Growth -- 3.3 Energetics of Crystallization -- 3.4 Experimental Protocols for Polymorph Screening -- 3.5 Crystallization Techniques -- 3.5.1 Sublimation -- 3.5.2 Precipitation -- 3.5.3 Crystallization from a Single Solvent -- 3.5.4 Evaporation Technique (From a Binary Mixture of Solvents) -- 3.5.5 Vapor Diffusion -- 3.5.6 Thermal Treatment -- 3.5.7 Melt Crystallization -- 3.5.8 Crystalline Solvates-Thermal Desolvation -- 3.5.9 Growth in the Presence of Additives -- 3.5.10 Grinding -- 3.5.11 Lyophilization -- 3.5.12 Laser-Induced Crystallization -- 3.5.13 Capillary Crystallization -- 3.5.14 Sonocrystallization -- 3.5.15 Crystallization by Ionic Liquids -- 3.5.16 Crystallization in Supercritical Liquids -- 3.6 Crystallization-Agglomeration Control -- 3.7 Crystallization-Application in Drug Research -- 3.7.1 Preparation of API-Control of Crystal Properties -- 3.7.1.1 Selection of Process Variables -- 3.7.1.2 Cocrystal Formation -- 3.7.1.3 Process Analytical Technology and Process Control -- 3.7.2 Novel Crystalline Pharmaceuticals for Pulmonic Target-Chiral Isomers Separation by Crystallization -- 3.7.3 Crystallization of Chiral Isomers Separation -- 3.8 Conclusions -- Acknowledgments -- Abbreviations -- References -- 4 Role of Amorphous State in Drug Delivery. , 4.1 Introduction: Basic Concepts of Amorphous State of Solid -- 4.1.1 Properties of Amorphous Solids -- 4.1.2 Concept of Glass Transition Temperature (Tg) -- 4.1.2.1 Thermodynamic Necessity for Tg -- 4.1.2.2 The Kinetic Point of View of Tg -- 4.1.2.3 Factors Affecting Tg Value -- 4.1.3 Molecular Mobility -- 4.1.3.1 Global Mobility -- 4.1.3.2 Local Mobility -- 4.1.4 Fragility of Amorphous Materials -- 4.1.4.1 Strong Glass Formers -- 4.1.4.2 Fragile Glass Formers -- 4.1.4.3 Prediction of Fragility -- 4.1.5 Physical and Chemical Stability of the Amorphous Forms -- 4.1.5.1 Physical Stability -- 4.1.5.1.1 The Relationship Between the Physical Stability and Tg -- 4.1.5.2 Chemical Stability -- 4.1.5.2.1 Enhanced Rate of Degradation -- 4.1.5.2.2 Changes in Mechanism and Kinetics of Degradation Reaction -- 4.1.5.3 Shelf Life Prediction of Amorphous Pharmaceutical Preparations -- 4.1.6 Glass Forming Ability of Pharmaceutical Substances -- 4.2 Significance of Amorphous State in Pharmaceutical Formulation -- 4.2.1 Solubility Enhancement of Active Pharmaceutical Ingredients -- 4.2.1.1 Spring Parachute Effect During Solubility Studies -- 4.2.2 Functionality Enhancement of Pharmaceutical Excipients -- 4.2.2.1 Tablet Compression -- 4.2.2.2 Polymeric Tablet Coating -- 4.3 Techniques for Stabilization of Amorphous Forms in Pharmaceutical Formulation -- 4.3.1 Storage at Temperatures Lower Than Tg -- 4.3.2 Vitrification-Based Stabilization: Antiplasticization Approach -- 4.3.2.1 Application of Gordon-Taylor Equation to Binary Amorphous Mixtures -- 4.3.2.1.1 Indication of the Ideality of Mixing of Two Components -- 4.3.2.1.2 Assessment of the Effect of Different Levels of a Second Material on Tg of Another -- 4.3.2.1.3 Evaluation of the Degree of Intermolecular Interaction of Individual Components and Between the Drug and the Poly... , 4.3.3 Drug-Carrier/Polymer Interaction -- 4.3.4 Nano-Confinement in the Nanopores of Mesoporous Inorganic Silicates -- 4.4 Amorphous Solid Dispersions -- 4.4.1 Mechanisms of Dissolution Enhancement -- 4.4.2 Carriers used in Amorphous Solid Dispersions -- 4.4.2.1 Polymeric Carriers -- 4.4.2.2 Inorganic Mesoporous Carriers -- 4.4.3 Preparation of Amorphous Solid Dispersions -- 4.4.3.1 Solvent-Based Methods -- 4.4.3.1.1 Vacuum Solvent Evaporation -- 4.4.3.1.2 Spray Drying and Spray Drying-Related Methods -- 4.4.3.1.3 Freeze Drying and Freeze Drying-Related Methods -- 4.4.3.1.4 Addition of Antisolvent -- 4.4.3.1.5 Electrospray Technique -- 4.4.3.1.6 Supercritical Fluid-Based Methods -- 4.4.3.2 Solvent Free Methods -- 4.4.3.2.1 Vapor Condensation -- 4.4.3.2.2 Mechanical Destruction of a Crystalline Mass -- 4.4.3.2.3 Rapid Cooling (Quenching) of a Melt -- 4.4.3.2.3.1 Fusion Method -- 4.4.3.2.3.2 Hot Melt Extrusion -- 4.4.3.3 Innovative Methods: Combined Solvent Evaporation/Spray Drying-Melt Extrusion -- 4.5 Structure Characterization and Quantification of the Amorphous Content in Pharmaceutical Systems -- 4.5.1 Thermal Analysis -- 4.5.1.1 Differential Scanning Calorimetry and Related Techniques -- 4.5.1.2 Isothermal Microcalorimetry -- 4.5.2 Spectroscopic Techniques -- 4.5.2.1 X-Ray Powder Diffraction and Related Techniques -- 4.5.2.2 Vibrational Spectroscopy Techniques -- 4.5.2.3 Solid State Nuclear Magnetic Resonance (NMR) -- 4.5.3 Microscopic Techniques -- 4.5.3.1 Microthermal Analysis -- 4.5.4 Vapor Sorption -- 4.5.5 Gas/Liquid Displacement Pycnometry -- 4.5.6 Viscosity/Viscoelastic Characterization -- 4.5.7 Phosphorescent/Fluorescent Molecular Probes -- 4.6 Case Studies -- 4.6.1 The Classic Case of Novobiocin -- 4.6.2 The Novel Case of Kaletra -- 4.6.3 Insulin Preparations -- 4.7 Conclusion and Future Perspective -- Abbreviations -- References. , 5 Particulate Level Properties and its Implications on Product Performance and Processing.

Language: English

UID:

Format: 1 online resource (816 pages).

ISBN: 9780128144220 , 9780128144213

Series Statement: Advances in pharmaceutical product development and research series

Note: Front Cover -- Dosage Form Design Parameters -- Copyright Page -- Dedication -- Contents -- List of Contributors -- About the Editor -- 1 Levels of Solid State Properties: Role of Different Levels During Pharmaceutical Product Development -- 1.1 Introduction -- 1.2 Solids and its Forms -- 1.2.1 Amorphous -- 1.2.2 Polymorphs -- 1.2.2.1 Solvates/Hydrates -- 1.2.2.2 Salts/Cocrystals -- 1.3 Levels of SSP -- 1.3.1 Molecular Level -- 1.3.2 Particle Level -- 1.3.3 Bulk Level -- 1.4 Solid State Thermodynamics -- 1.5 Bioavailability of Solids -- 1.6 Polymorphism and its Types -- 1.6.1 Enantiotropy and Monotropy -- 1.6.1.1 Density Rule -- 1.6.1.2 Infrared Rule -- 1.7 Formulation Methods of Polymorphs -- 1.7.1 Solvent Evaporation Method -- 1.7.2 Slow Cooling Approach -- 1.7.3 Solvent Diffusion Technique -- 1.7.4 Vapor Diffusion Method -- 1.7.5 Sublimation -- 1.8 Characterization of Polymorphs -- 1.9 Evaluation Technique -- 1.9.1 Dissolution -- 1.9.2 The Temperature-Dependent Solubility of Polymorphs: van't Hoff Plot -- 1.9.3 Biological Studies -- 1.10 Importance of SSP in Pharmaceutical Product Development -- 1.10.1 Importance of Particle Size -- 1.10.1.1 Biopharmaceutical Aspect of Particle Size -- 1.11 Conclusion -- Acknowledgments -- References -- Further Reading -- 2 Polymorphism and its Implications in Pharmaceutical Product Development -- 2.1 Introduction -- 2.1.1 Solids -- 2.1.2 Industrial Perspectives -- 2.2 Potential Solid Polymorphic Forms -- 2.2.1 Crystal -- 2.2.2 Crystal Solvates or Hydrates -- 2.2.3 Crystal Desolvated Solvates (Dehydrated Hydrates) -- 2.2.4 Amorphous -- 2.3 Formation of Polymorphs: Theoretical Considerations -- 2.3.1 Ostwald's Rule of Stages -- 2.3.2 Cross-Nucleation -- 2.3.3 Heterogeneous Two-Dimensional Nucleation: Chemotaxy, Ledge-Directed Epitaxial Growth, and Two-Dimensional Lattice Mat... , 2.3.4 Additive-Induced Polymorph Selection -- 2.4 Effect of Polymorphism on Different Drug Properties -- 2.4.1 Physical and Thermodynamic Properties -- 2.4.1.1 Morphology -- 2.4.1.2 Density and Refractive Index -- 2.4.1.3 Wettability -- 2.4.1.4 Melting Point -- 2.4.1.5 Solubility -- 2.4.1.6 Thermal Stability -- 2.4.2 Kinetic Properties -- 2.4.2.1 Dissolution -- 2.4.2.2 Kinetics of Solid-State Reaction -- 2.4.2.3 Stability -- 2.4.3 Surface Properties -- 2.4.3.1 Surface Free Energy -- 2.4.3.2 Crystal Habit -- 2.4.3.3 Surface Area -- 2.4.3.4 Particle Size Distribution -- 2.4.4 Mechanical Properties -- 2.4.4.1 Compressibility and Hardness -- 2.4.5 Chemical Properties -- 2.4.5.1 Reactivity -- 2.5 Techniques of Polymorph Preparation -- 2.5.1 Solvent Evaporation Technique -- 2.5.2 Slow Cooling Technique -- 2.5.3 Solvent Diffusion Technique -- 2.5.4 Vapor Diffusion Technique -- 2.5.5 Vacuum Sublimation Technique -- 2.5.6 Crystallization in the Presence of Tailor-Made Additives -- 2.6 Characterization Techniques of Polymorphs -- 2.6.1 Differential Scanning Calorimetry -- 2.6.2 Thermogravimetric Analysis -- 2.6.3 Infrared (FT-IR) Spectroscopy -- 2.6.4 Raman Spectroscopy -- 2.6.5 Powder X-Ray Diffraction -- 2.6.6 Single-Crystal XRD -- 2.6.7 Solid-State NMR (SSNMR) -- 2.6.8 Terahertz Spectroscopy -- 2.6.9 Optical and Electron Microscopy -- 2.6.10 Incoherent Inelastic Neutron Scattering -- 2.7 Evaluation of Polymorphs -- 2.7.1 Solubility of Polymorphs: Van't Hoff Plot -- 2.7.2 Dissolution Study -- 2.8 Polymorphism in Drug Products: Challenges for the Pharmaceutical Industry -- 2.9 Regulatory Considerations -- 2.10 Conclusion -- Acknowledgments -- Abbreviations -- References -- 3 Basics of Crystallization Process Applied in Drug Exploration -- 3.1 Introduction -- 3.2 Crystallization: Basic Concepts and Mechanisms in Crystallization. , 3.2.1 Crystal Lattice-Building Block Arrangements and Symmetries -- 3.2.2 Crystal Habit, Morphology, and Generation of Different Crystal Habits -- 3.2.3 Primary Mechanism and Types of Nucleation -- 3.2.4 Crystallization Process and Mier's Supersaturation Theory -- 3.2.4.1 Mier's Supersaturation Process -- 3.2.5 Metastable Zone and Induction of Nucleation -- 3.2.6 Ostwald Law of Stages in Crystal Formation -- 3.2.7 Ideal and Real Crystals Growth -- 3.2.7.1 Birth and Spread Model of Crystal Growth via 2D Nucleation -- 3.2.7.2 Real Crystals Growth -- 3.3 Energetics of Crystallization -- 3.4 Experimental Protocols for Polymorph Screening -- 3.5 Crystallization Techniques -- 3.5.1 Sublimation -- 3.5.2 Precipitation -- 3.5.3 Crystallization from a Single Solvent -- 3.5.4 Evaporation Technique (From a Binary Mixture of Solvents) -- 3.5.5 Vapor Diffusion -- 3.5.6 Thermal Treatment -- 3.5.7 Melt Crystallization -- 3.5.8 Crystalline Solvates-Thermal Desolvation -- 3.5.9 Growth in the Presence of Additives -- 3.5.10 Grinding -- 3.5.11 Lyophilization -- 3.5.12 Laser-Induced Crystallization -- 3.5.13 Capillary Crystallization -- 3.5.14 Sonocrystallization -- 3.5.15 Crystallization by Ionic Liquids -- 3.5.16 Crystallization in Supercritical Liquids -- 3.6 Crystallization-Agglomeration Control -- 3.7 Crystallization-Application in Drug Research -- 3.7.1 Preparation of API-Control of Crystal Properties -- 3.7.1.1 Selection of Process Variables -- 3.7.1.2 Cocrystal Formation -- 3.7.1.3 Process Analytical Technology and Process Control -- 3.7.2 Novel Crystalline Pharmaceuticals for Pulmonic Target-Chiral Isomers Separation by Crystallization -- 3.7.3 Crystallization of Chiral Isomers Separation -- 3.8 Conclusions -- Acknowledgments -- Abbreviations -- References -- 4 Role of Amorphous State in Drug Delivery. , 4.1 Introduction: Basic Concepts of Amorphous State of Solid -- 4.1.1 Properties of Amorphous Solids -- 4.1.2 Concept of Glass Transition Temperature (Tg) -- 4.1.2.1 Thermodynamic Necessity for Tg -- 4.1.2.2 The Kinetic Point of View of Tg -- 4.1.2.3 Factors Affecting Tg Value -- 4.1.3 Molecular Mobility -- 4.1.3.1 Global Mobility -- 4.1.3.2 Local Mobility -- 4.1.4 Fragility of Amorphous Materials -- 4.1.4.1 Strong Glass Formers -- 4.1.4.2 Fragile Glass Formers -- 4.1.4.3 Prediction of Fragility -- 4.1.5 Physical and Chemical Stability of the Amorphous Forms -- 4.1.5.1 Physical Stability -- 4.1.5.1.1 The Relationship Between the Physical Stability and Tg -- 4.1.5.2 Chemical Stability -- 4.1.5.2.1 Enhanced Rate of Degradation -- 4.1.5.2.2 Changes in Mechanism and Kinetics of Degradation Reaction -- 4.1.5.3 Shelf Life Prediction of Amorphous Pharmaceutical Preparations -- 4.1.6 Glass Forming Ability of Pharmaceutical Substances -- 4.2 Significance of Amorphous State in Pharmaceutical Formulation -- 4.2.1 Solubility Enhancement of Active Pharmaceutical Ingredients -- 4.2.1.1 Spring Parachute Effect During Solubility Studies -- 4.2.2 Functionality Enhancement of Pharmaceutical Excipients -- 4.2.2.1 Tablet Compression -- 4.2.2.2 Polymeric Tablet Coating -- 4.3 Techniques for Stabilization of Amorphous Forms in Pharmaceutical Formulation -- 4.3.1 Storage at Temperatures Lower Than Tg -- 4.3.2 Vitrification-Based Stabilization: Antiplasticization Approach -- 4.3.2.1 Application of Gordon-Taylor Equation to Binary Amorphous Mixtures -- 4.3.2.1.1 Indication of the Ideality of Mixing of Two Components -- 4.3.2.1.2 Assessment of the Effect of Different Levels of a Second Material on Tg of Another -- 4.3.2.1.3 Evaluation of the Degree of Intermolecular Interaction of Individual Components and Between the Drug and the Poly... , 4.3.3 Drug-Carrier/Polymer Interaction -- 4.3.4 Nano-Confinement in the Nanopores of Mesoporous Inorganic Silicates -- 4.4 Amorphous Solid Dispersions -- 4.4.1 Mechanisms of Dissolution Enhancement -- 4.4.2 Carriers used in Amorphous Solid Dispersions -- 4.4.2.1 Polymeric Carriers -- 4.4.2.2 Inorganic Mesoporous Carriers -- 4.4.3 Preparation of Amorphous Solid Dispersions -- 4.4.3.1 Solvent-Based Methods -- 4.4.3.1.1 Vacuum Solvent Evaporation -- 4.4.3.1.2 Spray Drying and Spray Drying-Related Methods -- 4.4.3.1.3 Freeze Drying and Freeze Drying-Related Methods -- 4.4.3.1.4 Addition of Antisolvent -- 4.4.3.1.5 Electrospray Technique -- 4.4.3.1.6 Supercritical Fluid-Based Methods -- 4.4.3.2 Solvent Free Methods -- 4.4.3.2.1 Vapor Condensation -- 4.4.3.2.2 Mechanical Destruction of a Crystalline Mass -- 4.4.3.2.3 Rapid Cooling (Quenching) of a Melt -- 4.4.3.2.3.1 Fusion Method -- 4.4.3.2.3.2 Hot Melt Extrusion -- 4.4.3.3 Innovative Methods: Combined Solvent Evaporation/Spray Drying-Melt Extrusion -- 4.5 Structure Characterization and Quantification of the Amorphous Content in Pharmaceutical Systems -- 4.5.1 Thermal Analysis -- 4.5.1.1 Differential Scanning Calorimetry and Related Techniques -- 4.5.1.2 Isothermal Microcalorimetry -- 4.5.2 Spectroscopic Techniques -- 4.5.2.1 X-Ray Powder Diffraction and Related Techniques -- 4.5.2.2 Vibrational Spectroscopy Techniques -- 4.5.2.3 Solid State Nuclear Magnetic Resonance (NMR) -- 4.5.3 Microscopic Techniques -- 4.5.3.1 Microthermal Analysis -- 4.5.4 Vapor Sorption -- 4.5.5 Gas/Liquid Displacement Pycnometry -- 4.5.6 Viscosity/Viscoelastic Characterization -- 4.5.7 Phosphorescent/Fluorescent Molecular Probes -- 4.6 Case Studies -- 4.6.1 The Classic Case of Novobiocin -- 4.6.2 The Novel Case of Kaletra -- 4.6.3 Insulin Preparations -- 4.7 Conclusion and Future Perspective -- Abbreviations -- References. , 5 Particulate Level Properties and its Implications on Product Performance and Processing.

Language: English

UID:

Format: 1 online resource (816 pages).

ISBN: 9780128144220 , 9780128144213

Series Statement: Advances in pharmaceutical product development and research series

Note: Front Cover -- Dosage Form Design Parameters -- Copyright Page -- Dedication -- Contents -- List of Contributors -- About the Editor -- 1 Levels of Solid State Properties: Role of Different Levels During Pharmaceutical Product Development -- 1.1 Introduction -- 1.2 Solids and its Forms -- 1.2.1 Amorphous -- 1.2.2 Polymorphs -- 1.2.2.1 Solvates/Hydrates -- 1.2.2.2 Salts/Cocrystals -- 1.3 Levels of SSP -- 1.3.1 Molecular Level -- 1.3.2 Particle Level -- 1.3.3 Bulk Level -- 1.4 Solid State Thermodynamics -- 1.5 Bioavailability of Solids -- 1.6 Polymorphism and its Types -- 1.6.1 Enantiotropy and Monotropy -- 1.6.1.1 Density Rule -- 1.6.1.2 Infrared Rule -- 1.7 Formulation Methods of Polymorphs -- 1.7.1 Solvent Evaporation Method -- 1.7.2 Slow Cooling Approach -- 1.7.3 Solvent Diffusion Technique -- 1.7.4 Vapor Diffusion Method -- 1.7.5 Sublimation -- 1.8 Characterization of Polymorphs -- 1.9 Evaluation Technique -- 1.9.1 Dissolution -- 1.9.2 The Temperature-Dependent Solubility of Polymorphs: van't Hoff Plot -- 1.9.3 Biological Studies -- 1.10 Importance of SSP in Pharmaceutical Product Development -- 1.10.1 Importance of Particle Size -- 1.10.1.1 Biopharmaceutical Aspect of Particle Size -- 1.11 Conclusion -- Acknowledgments -- References -- Further Reading -- 2 Polymorphism and its Implications in Pharmaceutical Product Development -- 2.1 Introduction -- 2.1.1 Solids -- 2.1.2 Industrial Perspectives -- 2.2 Potential Solid Polymorphic Forms -- 2.2.1 Crystal -- 2.2.2 Crystal Solvates or Hydrates -- 2.2.3 Crystal Desolvated Solvates (Dehydrated Hydrates) -- 2.2.4 Amorphous -- 2.3 Formation of Polymorphs: Theoretical Considerations -- 2.3.1 Ostwald's Rule of Stages -- 2.3.2 Cross-Nucleation -- 2.3.3 Heterogeneous Two-Dimensional Nucleation: Chemotaxy, Ledge-Directed Epitaxial Growth, and Two-Dimensional Lattice Mat... , 2.3.4 Additive-Induced Polymorph Selection -- 2.4 Effect of Polymorphism on Different Drug Properties -- 2.4.1 Physical and Thermodynamic Properties -- 2.4.1.1 Morphology -- 2.4.1.2 Density and Refractive Index -- 2.4.1.3 Wettability -- 2.4.1.4 Melting Point -- 2.4.1.5 Solubility -- 2.4.1.6 Thermal Stability -- 2.4.2 Kinetic Properties -- 2.4.2.1 Dissolution -- 2.4.2.2 Kinetics of Solid-State Reaction -- 2.4.2.3 Stability -- 2.4.3 Surface Properties -- 2.4.3.1 Surface Free Energy -- 2.4.3.2 Crystal Habit -- 2.4.3.3 Surface Area -- 2.4.3.4 Particle Size Distribution -- 2.4.4 Mechanical Properties -- 2.4.4.1 Compressibility and Hardness -- 2.4.5 Chemical Properties -- 2.4.5.1 Reactivity -- 2.5 Techniques of Polymorph Preparation -- 2.5.1 Solvent Evaporation Technique -- 2.5.2 Slow Cooling Technique -- 2.5.3 Solvent Diffusion Technique -- 2.5.4 Vapor Diffusion Technique -- 2.5.5 Vacuum Sublimation Technique -- 2.5.6 Crystallization in the Presence of Tailor-Made Additives -- 2.6 Characterization Techniques of Polymorphs -- 2.6.1 Differential Scanning Calorimetry -- 2.6.2 Thermogravimetric Analysis -- 2.6.3 Infrared (FT-IR) Spectroscopy -- 2.6.4 Raman Spectroscopy -- 2.6.5 Powder X-Ray Diffraction -- 2.6.6 Single-Crystal XRD -- 2.6.7 Solid-State NMR (SSNMR) -- 2.6.8 Terahertz Spectroscopy -- 2.6.9 Optical and Electron Microscopy -- 2.6.10 Incoherent Inelastic Neutron Scattering -- 2.7 Evaluation of Polymorphs -- 2.7.1 Solubility of Polymorphs: Van't Hoff Plot -- 2.7.2 Dissolution Study -- 2.8 Polymorphism in Drug Products: Challenges for the Pharmaceutical Industry -- 2.9 Regulatory Considerations -- 2.10 Conclusion -- Acknowledgments -- Abbreviations -- References -- 3 Basics of Crystallization Process Applied in Drug Exploration -- 3.1 Introduction -- 3.2 Crystallization: Basic Concepts and Mechanisms in Crystallization. , 3.2.1 Crystal Lattice-Building Block Arrangements and Symmetries -- 3.2.2 Crystal Habit, Morphology, and Generation of Different Crystal Habits -- 3.2.3 Primary Mechanism and Types of Nucleation -- 3.2.4 Crystallization Process and Mier's Supersaturation Theory -- 3.2.4.1 Mier's Supersaturation Process -- 3.2.5 Metastable Zone and Induction of Nucleation -- 3.2.6 Ostwald Law of Stages in Crystal Formation -- 3.2.7 Ideal and Real Crystals Growth -- 3.2.7.1 Birth and Spread Model of Crystal Growth via 2D Nucleation -- 3.2.7.2 Real Crystals Growth -- 3.3 Energetics of Crystallization -- 3.4 Experimental Protocols for Polymorph Screening -- 3.5 Crystallization Techniques -- 3.5.1 Sublimation -- 3.5.2 Precipitation -- 3.5.3 Crystallization from a Single Solvent -- 3.5.4 Evaporation Technique (From a Binary Mixture of Solvents) -- 3.5.5 Vapor Diffusion -- 3.5.6 Thermal Treatment -- 3.5.7 Melt Crystallization -- 3.5.8 Crystalline Solvates-Thermal Desolvation -- 3.5.9 Growth in the Presence of Additives -- 3.5.10 Grinding -- 3.5.11 Lyophilization -- 3.5.12 Laser-Induced Crystallization -- 3.5.13 Capillary Crystallization -- 3.5.14 Sonocrystallization -- 3.5.15 Crystallization by Ionic Liquids -- 3.5.16 Crystallization in Supercritical Liquids -- 3.6 Crystallization-Agglomeration Control -- 3.7 Crystallization-Application in Drug Research -- 3.7.1 Preparation of API-Control of Crystal Properties -- 3.7.1.1 Selection of Process Variables -- 3.7.1.2 Cocrystal Formation -- 3.7.1.3 Process Analytical Technology and Process Control -- 3.7.2 Novel Crystalline Pharmaceuticals for Pulmonic Target-Chiral Isomers Separation by Crystallization -- 3.7.3 Crystallization of Chiral Isomers Separation -- 3.8 Conclusions -- Acknowledgments -- Abbreviations -- References -- 4 Role of Amorphous State in Drug Delivery. , 4.1 Introduction: Basic Concepts of Amorphous State of Solid -- 4.1.1 Properties of Amorphous Solids -- 4.1.2 Concept of Glass Transition Temperature (Tg) -- 4.1.2.1 Thermodynamic Necessity for Tg -- 4.1.2.2 The Kinetic Point of View of Tg -- 4.1.2.3 Factors Affecting Tg Value -- 4.1.3 Molecular Mobility -- 4.1.3.1 Global Mobility -- 4.1.3.2 Local Mobility -- 4.1.4 Fragility of Amorphous Materials -- 4.1.4.1 Strong Glass Formers -- 4.1.4.2 Fragile Glass Formers -- 4.1.4.3 Prediction of Fragility -- 4.1.5 Physical and Chemical Stability of the Amorphous Forms -- 4.1.5.1 Physical Stability -- 4.1.5.1.1 The Relationship Between the Physical Stability and Tg -- 4.1.5.2 Chemical Stability -- 4.1.5.2.1 Enhanced Rate of Degradation -- 4.1.5.2.2 Changes in Mechanism and Kinetics of Degradation Reaction -- 4.1.5.3 Shelf Life Prediction of Amorphous Pharmaceutical Preparations -- 4.1.6 Glass Forming Ability of Pharmaceutical Substances -- 4.2 Significance of Amorphous State in Pharmaceutical Formulation -- 4.2.1 Solubility Enhancement of Active Pharmaceutical Ingredients -- 4.2.1.1 Spring Parachute Effect During Solubility Studies -- 4.2.2 Functionality Enhancement of Pharmaceutical Excipients -- 4.2.2.1 Tablet Compression -- 4.2.2.2 Polymeric Tablet Coating -- 4.3 Techniques for Stabilization of Amorphous Forms in Pharmaceutical Formulation -- 4.3.1 Storage at Temperatures Lower Than Tg -- 4.3.2 Vitrification-Based Stabilization: Antiplasticization Approach -- 4.3.2.1 Application of Gordon-Taylor Equation to Binary Amorphous Mixtures -- 4.3.2.1.1 Indication of the Ideality of Mixing of Two Components -- 4.3.2.1.2 Assessment of the Effect of Different Levels of a Second Material on Tg of Another -- 4.3.2.1.3 Evaluation of the Degree of Intermolecular Interaction of Individual Components and Between the Drug and the Poly... , 4.3.3 Drug-Carrier/Polymer Interaction -- 4.3.4 Nano-Confinement in the Nanopores of Mesoporous Inorganic Silicates -- 4.4 Amorphous Solid Dispersions -- 4.4.1 Mechanisms of Dissolution Enhancement -- 4.4.2 Carriers used in Amorphous Solid Dispersions -- 4.4.2.1 Polymeric Carriers -- 4.4.2.2 Inorganic Mesoporous Carriers -- 4.4.3 Preparation of Amorphous Solid Dispersions -- 4.4.3.1 Solvent-Based Methods -- 4.4.3.1.1 Vacuum Solvent Evaporation -- 4.4.3.1.2 Spray Drying and Spray Drying-Related Methods -- 4.4.3.1.3 Freeze Drying and Freeze Drying-Related Methods -- 4.4.3.1.4 Addition of Antisolvent -- 4.4.3.1.5 Electrospray Technique -- 4.4.3.1.6 Supercritical Fluid-Based Methods -- 4.4.3.2 Solvent Free Methods -- 4.4.3.2.1 Vapor Condensation -- 4.4.3.2.2 Mechanical Destruction of a Crystalline Mass -- 4.4.3.2.3 Rapid Cooling (Quenching) of a Melt -- 4.4.3.2.3.1 Fusion Method -- 4.4.3.2.3.2 Hot Melt Extrusion -- 4.4.3.3 Innovative Methods: Combined Solvent Evaporation/Spray Drying-Melt Extrusion -- 4.5 Structure Characterization and Quantification of the Amorphous Content in Pharmaceutical Systems -- 4.5.1 Thermal Analysis -- 4.5.1.1 Differential Scanning Calorimetry and Related Techniques -- 4.5.1.2 Isothermal Microcalorimetry -- 4.5.2 Spectroscopic Techniques -- 4.5.2.1 X-Ray Powder Diffraction and Related Techniques -- 4.5.2.2 Vibrational Spectroscopy Techniques -- 4.5.2.3 Solid State Nuclear Magnetic Resonance (NMR) -- 4.5.3 Microscopic Techniques -- 4.5.3.1 Microthermal Analysis -- 4.5.4 Vapor Sorption -- 4.5.5 Gas/Liquid Displacement Pycnometry -- 4.5.6 Viscosity/Viscoelastic Characterization -- 4.5.7 Phosphorescent/Fluorescent Molecular Probes -- 4.6 Case Studies -- 4.6.1 The Classic Case of Novobiocin -- 4.6.2 The Novel Case of Kaletra -- 4.6.3 Insulin Preparations -- 4.7 Conclusion and Future Perspective -- Abbreviations -- References. , 5 Particulate Level Properties and its Implications on Product Performance and Processing.

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