Title Page -- Copyright Page -- Contents -- Contributor List -- Preface -- Part I Fundamentals of Mixing -- Chapter 1 Mixing Theory -- 1.1 Introduction -- 1.2 Describing Mixtures -- 1.3 Scale of Scrutiny -- 1.4 Quantifying Mixedness for Coarse and Fine-Grained Mixtures -- 1.4.1 Coarse and Fine-Grained Mixtures -- 1.4.2 Scale and Intensity of Segregation -- 1.5 Determining the End-Point of Mixing: Comparison of Mixing Indices -- 1.6 Continuous Flow Mixers -- 1.6.1 Idealized Mixing Patterns -- 1.6.2 Residence Time Distributions -- 1.6.3 Back-Mixing and Filtering of Disturbances Using a CSTR -- References -- Chapter 2 Turbulent Mixing Fundamentals -- 2.1 Introduction -- 2.2 The Velocity Field and Turbulence -- 2.3 Circulation and Macro-Mixing -- 2.4 Fully Turbulent Limits and the Scaling of Turbulence -- 2.5 The Spectrum of Turbulent Length Scales, Injection of a Scalar (Either Reagent or Additive) and the Macro-, Meso- and Micro-Scales of Mixing -- 2.6 Turbulence and Mixing of Solids, Liquids, and Gases -- 2.7 Specifying Mixing Requirements for a Process -- 2.8 Conclusions -- Notation -- Roman Characters -- Greek Characters -- References -- Chapter 3 Laminar Mixing Fundamentals -- 3.1 Laminar Flows -- 3.2 Mixing in Laminar Flows -- 3.2.1 Chaos and Laminar Chaotic Mixing -- 3.2.2 Granular Chaotic Mixing -- 3.3 Recent Advances -- References -- Chapter 4 Sampling and Determination of Adequacy of Mixing -- 4.1 Introduction, Process Understanding, and Regulations -- 4.2 Theory of Sampling -- 4.3 Sampling of Pharmaceutical Powder Blends -- 4.4 Stratified Sampling Approach -- 4.5 Testing -- 4.6 Process Knowledge/Process Analytical Technology -- 4.7 Real Time Spectroscopic Monitoring of Powder Blending -- 4.8 Looking Forward, Recommendations -- 4.9 Conclusion -- 4.10 Acknowledgments -- References -- Part II Applications -- Chapter 5 Particles and Blending.

5.1 Introduction -- 5.2 Particle Geometry -- 5.2.1 Particle Size and Size Distribution -- 5.2.2 Particle Shape and Shape Distribution -- 5.3 Particle Interactions -- 5.3.1 van der Waals Forces -- 5.3.2 Electrostatic Forces -- 5.3.3 Adsorbed Liquid Layers and Liquid Bridges -- 5.3.4 Solid Bridges -- 5.3.5 Use of AFM to Measure Interparticle Forces -- 5.3.6 Interparticle Friction -- 5.4 Empirical Investigations of Particles and Blending -- 5.4.1 Blending of Powders -- 5.4.2 Impact of Particle Geometry on Blending -- 5.4.3 Impact of Interparticle Forces on Blending -- 5.4.4 Impact of Blender Conditions on Blending -- 5.5 Simulation Techniques -- 5.5.1 Full Physics Models Using Discrete Element Modeling -- 5.5.2 Continuum Models -- 5.5.3 Cellular Automata -- References -- Chapter 6 Continuous Powder Mixing -- 6.1 Introduction -- 6.2 Overview -- 6.3 Theoretical Characterization -- 6.3.1 Residence Time Distribution (RTD) Modeling -- 6.3.2 Variance Reduction Ratio -- 6.4 Experimental Characterization -- 6.4.1 Hold-Up -- 6.4.2 Residence Time Distribution (RTD) Measurements -- 6.4.3 Mean Strain -- 6.5 Continuous Mixing Efficiency -- 6.5.1 Variance Reduction Ratio -- 6.5.2 Blend Homogeneity -- 6.6 Effects of Process Parameters on Mixing Behavior and Performance -- 6.6.1 Hold-Up -- 6.6.2 RTD Measurements -- 6.7 Mixing Performance -- 6.7.1 Modeling -- 6.7.2 PAT, QbD, and Control -- 6.8 Conclusions and Continuing Efforts -- References -- Chapter 7 Dispersion of Fine Powders in Liquids: Particle Incorporation and Size Reduction -- 7.1 Particle Incorporation into Liquids -- 7.1.1 Wetting -- 7.1.2 Stirred Tanks for Particle Incorporation -- 7.1.3 In-Line Devices Used for Particle Incorporation -- 7.2 Break Up of Fine Powder Clusters in Liquids -- 7.2.1 Mechanisms of Break Up -- 7.2.2 Process Devices for Deagglomeration\Size Reduction of Agglomerates -- References.

Chapter 8 Wet Granulation and Mixing -- 8.1 Introduction -- 8.2 Nucleation -- 8.2.1 Drop Penetration Time -- 8.2.2 Dimensionless Spray Flux -- 8.2.3 Nucleation Regime Map -- 8.3 Consolidation and Growth -- 8.3.1 Granule Consolidation -- 8.3.2 Granule Growth Behaviour -- 8.3.3 Granule Growth Regime Map -- 8.4 Breakage -- 8.4.1 Single Granule Strength and Deformation -- 8.4.2 In-Granulator Breakage Studies -- 8.4.3 Aiding Controlled Granulation via Breakage -- 8.5 Endpoint Control -- 8.5.1 Granulation Time -- 8.5.2 Impeller Power Consumption -- 8.5.3 Online Measurement of Granule Size -- 8.5.4 NIR and Other Spectral Methods -- References -- Chapter 9 Emulsions -- 9.1 Introduction -- 9.2 Properties of Emulsions -- 9.2.1 Morphology -- 9.2.2 Volumetric Composition -- 9.2.3 Drop Size Distributions and Average Drop Sizes -- 9.2.4 Rheology -- 9.3 Emulsion Stability and Surface Forces -- 9.3.1 Surface Forces -- 9.3.2 Emulsion Stability -- 9.4 Principles of Emulsion Formation -- 9.4.1 Low Energy Emulsification -- 9.4.2 High Energy Emulsification -- 9.5 Emulsification Equipment -- 9.5.1 Stirred Vessels -- 9.5.2 Static Mixers -- 9.5.3 High Shear Mixers -- 9.5.4 High-Pressure Homogenizers -- 9.5.5 Ultrasonic Homogenizers -- 9.6 Concluding Remarks -- Nomenclature -- Greek symbols -- References -- Chapter 10 Mixing of Pharmaceutical Solid-Liquid Suspensions -- 10.1 Introduction -- 10.1.1 Linking Solid-Liquid Processing to Critical Quality Attributes -- 10.1.2 Material Properties and Composition -- 10.1.3 Impact of Blending and Homogenization -- 10.1.4 Impact of Turbulence -- 10.1.5 Impact of Heat Transfer -- 10.2 Scale-Up of Operations Involving Solid Suspensions -- 10.2.1 The Nature of Suspensions -- 10.2.2 Scale-Up and Scale-Down Rules -- 10.2.3 Identification of Agitator Duties -- 10.2.4 Solid-Liquid Unit Operations.

10.3 General Principles of Solid-Liquid Suspensions -- 10.3.1 Rheological Behaviour of the Continuous Phase -- 10.3.2 Rheology of Suspensions -- 10.3.3 Terminal Velocity of Particles -- 10.3.4 Turbulence -- 10.4 Solids Charging -- 10.4.1 Charging to Batch Vessels -- 10.4.2 Charging Difficult Powders -- 10.5 Solid Suspension -- 10.5.1 States of Solid Suspension -- 10.5.2 Prediction of Minimum Speed for Complete Suspension -- 10.6 Solid Distribution -- 10.6.1 Agitator Speed -- 10.6.2 Homogeneity -- 10.6.3 Geometry -- 10.6.4 Practical Guidelines -- 10.7 Blending in Solid-Liquid Systems -- 10.7.1 Mixing Time -- 10.7.2 Viscoplastic Slurries Yield Stress and Cavern Formation -- 10.8 Mass Transfer -- 10.9 Size Reduction, Deagglomeration and Attrition -- 10.9.1 Breaking Particles through Turbulent Forces -- 10.9.2 Breaking Particles through Impact -- Nomenclature -- Greek symbols -- Abbreviations -- References -- Part III Equipment -- Chapter 11 Powder Blending Equipment -- 11.1 Introduction -- 11.2 Blending Mechanisms -- 11.3 Blend Time -- 11.4 Fill Level -- 11.5 Segregation -- 11.6 Powder Processing Difficulties -- 11.7 Blender Classification -- 11.7.1 Tumble Blenders -- 11.7.2 Rotating Element Blenders -- 11.7.3 Granulators -- 11.7.4 Other Blenders - Mullers and Custom Blenders -- 11.8 Continuous Blenders -- 11.9 Blender Selection -- 11.10 Equipment Specifications -- 11.10.1 Materials of Construction -- 11.10.2 Electrical Classification -- 11.10.3 Drives and Seals -- References -- Chapter 12 Fluid Mixing Equipment Design -- 12.1 Introduction -- 12.2 Equipment Description -- 12.2.1 Laboratory Mixers -- 12.2.2 Development Mixers -- 12.2.3 Portable Mixers -- 12.2.4 Top-Entering Mixers -- 12.2.5 High-Shear Dispersers -- 12.2.6 High Viscosity Mixers -- 12.2.7 Multi-Shaft Mixers -- 12.2.8 Bottom-Entering Mixers -- 12.2.9 Glass-Lined Mixers and Vessels.

12.2.10 Side-Entering Mixers -- 12.2.11 Vessel Geometry -- 12.2.12 Baffles -- 12.3 Measurements -- 12.3.1 Power -- 12.3.2 Torque -- 12.3.3 Tip Speed -- 12.3.4 Blend Time -- 12.4 Mixing Classifications -- 12.4.1 Liquid Mixing -- 12.4.2 Solids Suspension -- 12.4.3 Gas Dispersion -- 12.4.4 Viscous Mixing -- 12.5 Mechanical Design -- 12.5.1 Shaft Design -- 12.5.2 Shaft Seals -- 12.5.3 Materials of Construction -- 12.5.4 Surface Finish -- 12.5.5 Motors -- 12.5.6 Drives -- 12.6 Static Mixers -- 12.6.1 Twisted Element -- 12.6.2 Structured Element -- 12.6.3 Basic Design -- 12.7 Challenges and Troubleshooting -- 12.7.1 Careful Observations -- 12.7.2 Process Problems -- Nomenclature -- Greek -- References -- Chapter 13 Scale-Up -- 13.1 Introduction -- 13.2 Similarity and Scale-Up Concepts -- 13.2.1 Dimensional Analysis -- 13.2.2 Similarity -- 13.2.3 Applied Scale-Up -- 13.3 Testing Methods -- 13.4 Observation and Measurement -- 13.5 Scale-Up Methods -- 13.5.1 Scale-Up with Geometric Similarity -- 13.5.2 Example of Geometric Similarity Scale-Up -- 13.5.3 Scale-Up Without Geometric Similarity -- 13.5.4 Example of Non-Geometric Scale-Up -- 13.5.5 Scale-Up for Powder Mixing -- 13.6 Summary -- Nomenclature -- Greek -- References -- Chapter 14 Equipment Qualification, Process and Cleaning Validation -- 14.1 Introduction -- 14.2 Blending Equipment Commissioning and Qualification -- 14.2.1 Outline of the Verification Approach -- 14.2.2 Requirements Phase -- 14.2.3 Specifications and Design Review Phase -- 14.2.4 Verification Phase -- 14.3 Blending and Mixing Validation -- 14.3.1 Why do You Need to Validate Pharmaceutical Blends/Mixes? -- 14.3.2 When do You Need to Validate Blending/Mixing? -- 14.3.3 Components of Blending/Mixing Validation -- 14.3.4 What to Validate -- 14.4 Blending Cleaning Validation -- 14.4.1 Cleaning Development Studies.

14.4.2 Cleaning Validation.