Pharmaceutical Blending and Mixing

Herausgegeben von Cullen, P. J.; Romañach, Rodolfo J.; Abatzaglou, Nicolas; Rielly, Chris D.

• Gebundenes Buch

Produktbeschreibung

Written in four parts, this book provides a dedicated and in-depth reference for blending within the pharmaceutical manufacturing industry. It links the science of blending with regulatory requirements associated with pharmaceutical manufacture. The contributors are a combination of leading academic and industrial experts, who provide an informed and industrially relevant perspective of the topic. This is an essential book for the pharmaceutical manufacturing industry, and related academic researchers in pharmaceutical science and chemical and mechanical engineering.

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Produktdetails

• Verlag: Wiley & Sons
• 1. Auflage
• Seitenzahl: 512
• Erscheinungstermin: Juli 2015
• Englisch
• Abmessung: 250mm x 175mm x 32mm
• Gewicht: 1056g
• ISBN-13: 9780470710555
• ISBN-10: 0470710551
• Artikelnr.: 35676968

Autorenporträt

Dr PJ Cullen is a lecturer in?the Faculty of Engineering at the University of New South Wales. His current research interests include rheology, mixing, chemical imaging and non-thermal plasmas for biological applications in food. He has published over 35 journal papers, 15 book chapters and edited 1 book on food mixing. Professor Rodolfo J. Romañach is Professor of Chemistry at the University of Puerto Rico. He has over 20 years of experience in vibrational spectroscopy, and worked in Puerto Rico's pharmaceutical industry for 12 years prior to joining the UPR-Mayagüez faculty. In the pharmaceutical industry he worked extensively in assay and cleaning validation, and in providing analytical support for API and pharmaceutical process related problems. Professor Nicolas Abatzaglou is Director of the?Chemical Engineering and Biotechnological Engineering Department and Holder of the Pfizer Chair: PAT in Pharmaceutical Engineering at the Universite de Sherbrooke, Canada. He is the current recipient of Quebec's Minister of Education (MELS Chantier II) Fellowship award for his excellence in research and teaching. Professor Chris Rielly is Head of the Department of Chemical Engineering at Loughborough University. He has taught chemical engineering for over 20 years at Cambridge and Loughborough Universities and is a Fellow of the Institution of Chemical Engineers with more than 20 years of experience working in experimental and computational fluid mechanics. His interests include multi-phase flow, mass transfer and turbulent mixing in chemical processing equipment. He has served on the Scientific Committees of the European Conference on Mixing, the International Conference on Gas-Liquid-Solid Reaction Engineering and the Process Innovation and Intensification Conference. He is an academic consultant to BHR Group's Fluid Mixing Processes Industrial Consortium and Chairman of the IChemE's Fluid Mixing Subject Group. He has previously edited books.

Inhaltsangabe

Contributor List xv Preface xvii Part I Fundamentals of Mixing 1 1 Mixing Theory 3 Chris D. Rielly 1.1 Introduction 3 1.2 Describing Mixtures 5 1.3 Scale of Scrutiny 6 1.4 Quantifying Mixedness for Coarse and Fine
Grained Mixtures 8 1.4.1 Coarse and Fine
Grained Mixtures 8 1.4.2 Scale and Intensity of Segregation 9 1.5 Determining the End
Point of Mixing: Comparison of Mixing Indices 15 1.6 Continuous Flow Mixers 19 1.6.1 Idealized Mixing Patterns 19 1.6.2 Residence Time Distributions 21 1.6.3 Back
Mixing and Filtering of Disturbances Using a CSTR 23 References 24 2 Turbulent Mixing Fundamentals 27 Suzanne M. Kresta 2.1 Introduction 27 2.2 The Velocity Field and Turbulence 28 2.3 Circulation and MacröMixing 29 2.4 Fully Turbulent Limits and the Scaling of Turbulence 32 2.5 The Spectrum of Turbulent Length Scales, Injection of a Scalar (Either Reagent or Additive) and the Macrö, Mesö and MicröScales of Mixing 34 2.6 Turbulence and Mixing of Solids, Liquids, and Gases 37 2.7 Specifying Mixing Requirements for a Process 38 2.8 Conclusions 39 Notation 39 Roman Characters 39 Greek Characters 40 References 40 3 Laminar Mixing Fundamentals 43 P.J. Cullen and N.N. Misra 3.1 Laminar Flows 43 3.2 Mixing in Laminar Flows 44 3.2.1 Chaos and Laminar Chaotic Mixing 45 3.2.2 Granular Chaotic Mixing 50 3.3 Recent Advances 53 References 54 4 Sampling and Determination of Adequacy of Mixing 57 Rodolfo J. Romañach 4.1 Introduction, Process Understanding, and Regulations 57 4.2 Theory of Sampling 59 4.3 Sampling of Pharmaceutical Powder Blends 63 4.4 Stratified Sampling Approach 65 4.5 Testing 67 4.6 Process Knowledge/Process Analytical Technology 68 4.7 Real Time Spectroscopic Monitoring of Powder Blending 70 4.8 Looking Forward, Recommendations 73 4.9 Conclusion 74 4.10 Acknowledgments 75 References 75 Part II Applications 79 5 Particles and Blending 81 Reuben D. Domike and Charles L. Cooney 5.1 Introduction 81 5.2 Particle Geometry 82 5.2.1 Particle Size and Size Distribution 82 5.2.2 Particle Shape and Shape Distribution 83 5.3 Particle Interactions 84 5.3.1 van der Waals Forces 84 5.3.2 Electrostatic Forces 85 5.3.3 Adsorbed Liquid Layers and Liquid Bridges 85 5.3.4 Solid Bridges 86 5.3.5 Use of AFM to Measure Interparticle Forces 87 5.3.6 Interparticle Friction 89 5.4 Empirical Investigations of Particles and Blending 90 5.4.1 Blending of Powders 90 5.4.2 Impact of Particle Geometry on Blending 92 5.4.3 Impact of Interparticle Forces on Blending 93 5.4.4 Impact of Blender Conditions on Blending 95 5.5 Simulation Techniques 95 5.5.1 Full Physics Models Using Discrete Element Modeling 96 5.5.2 Continuum Models 97 5.5.3 Cellular Automata 98 References 98 6 Continuous Powder Mixing 101 Juan G. Osorio, Aditya U. Vanarase, Rodolfo J. Romañach, and Fernando J. Muzzio 6.1 Introduction 101 6.2 Overview 102 6.3 Theoretical Characterization 107 6.3.1 Residence Time Distribution (RTD) Modeling 107 6.3.2 Variance Reduction Ratio 108 6.4 Experimental Characterization 108 6.4.1 Hold
Up 109 6.4.2 Residence Time Distribution (RTD) Measurements 109 6.4.3 Mean Strain 110 6.5 Continuous Mixing Efficiency 110 6.5.1 Variance Reduction Ratio 110 6.5.2 Blend Homogeneity 111 6.6 Effects of Process Parameters on Mixing Behavior and Performance 112 6.6.1 Hold
Up 113 6.6.2 RTD Measurements 113 6.7 Mixing Performance 118 6.7.1 Modeling 120 6.7.2 PAT, QbD, and Control 122 6.8 Conclusions and Continuing Efforts 124 References 125 7 Dispersion of Fine Powders in Liquids: Particle Incorporation and Size Reduction 129 Gül N. Özcan-Tas
k
n 7.1 Particle Incorporation into Liquids 129 7.1.1 Wetting 130 7.1.2 Stirred Tanks for Particle Incorporation 132 7.1.3 In
Line Devices Used for Particle Incorporation 140 7.2 Break Up of Fine Powder Clusters in Liquids 143 7.2.1 Mechanisms of Break Up 146 7.2.2 Process Devices for Deagglomeration\Size Reduction of Agglomerates 147 References 150 8 Wet Granulation and Mixing 153 Karen P. Hapgood and Rachel M. Smith 8.1 Introduction 153 8.2 Nucleation 154 8.2.1 Drop Penetration Time 156 8.2.2 Dimensionless Spray Flux 158 8.2.3 Nucleation Regime Map 160 8.3 Consolidation and Growth 162 8.3.1 Granule Consolidation 162 8.3.2 Granule Growth Behaviour 164 8.3.3 Granule Growth Regime Map 165 8.4 Breakage 167 8.4.1 Single Granule Strength and Deformation 167 8.4.2 In
Granulator Breakage Studies 170 8.4.3 Aiding Controlled Granulation via Breakage 172 8.5 Endpoint Control 174 8.5.1 Granulation Time 175 8.5.2 Impeller Power Consumption 176 8.5.3 Online Measurement of Granule Size 176 8.5.4 NIR and Other Spectral Methods 177 References 178 9 Emulsions 183 Andrzej W. Pacek 9.1 Introduction 183 9.2 Properties of Emulsions 185 9.2.1 Morphology 185 9.2.2 Volumetric Composition 185 9.2.3 Drop Size Distributions and Average Drop Sizes 186 9.2.4 Rheology 191 9.3 Emulsion Stability and Surface Forces 195 9.3.1 Surface Forces 195 9.3.2 Emulsion Stability 199 9.4 Principles of Emulsion Formation 203 9.4.1 Low Energy Emulsification 204 9.4.2 High Energy Emulsification 205 9.5 Emulsification Equipment 216 9.5.1 Stirred Vessels 216 9.5.2 Static Mixers 218 9.5.3 High Shear Mixers 219 9.5.4 High
Pressure Homogenizers 223 9.5.5 Ultrasonic Homogenizers 225 9.6 Concluding Remarks 226 Nomenclature 226 Greek symbols 228 References 228 10 Mixing of Pharmaceutical Solid
Liquid Suspensions 233 Mostafa Barigou and Frans L. Muller 10.1 Introduction 233 10.1.1 Linking Solid
Liquid Processing to Critical Quality Attributes 233 10.1.2 Material Properties and Composition 234 10.1.3 Impact of Blending and Homogenization 234 10.1.4 Impact of Turbulence 237 10.1.5 Impact of Heat Transfer 237 10.2 Scale
Up of Operations Involving Solid Suspensions 237 10.2.1 The Nature of Suspensions 237 10.2.2 Scale
Up and Scale
Down Rules 239 10.2.3 Identification of Agitator Duties 240 10.2.4 Solid
Liquid Unit Operations 242 10.3 General Principles of Solid
Liquid Suspensions 243 10.3.1 Rheological Behaviour of the Continuous Phase 243 10.3.2 Rheology of Suspensions 246 10.3.3 Terminal Velocity of Particles 249 10.3.4 Turbulence 254 10.4 Solids Charging 257 10.4.1 Charging to Batch Vessels 257 10.4.2 Charging Difficult Powders 261 10.5 Solid Suspension 261 10.5.1 States of Solid Suspension 261 10.5.2 Prediction of Minimum Speed for Complete Suspension 262 10.6 Solid Distribution 269 10.6.1 Agitator Speed 269 10.6.2 Homogeneity 270 10.6.3 Geometry 271 10.6.4 Practical Guidelines 272 10.7 Blending in Solid
Liquid Systems 272 10.7.1 Mixing Time 272 10.7.2 Viscoplastic Slurries Yield Stress and Cavern Formation 272 10.8 Mass Transfer 275 10.9 Size Reduction, Deagglomeration and Attrition 277 10.9.1 Breaking Particles through Turbulent Forces 277 10.9.2 Breaking Particles through Impact 278 Nomenclature 281 Greek symbols 281 Abbreviations 282 References 282 Part III Equipment 287 11 Powder Blending Equipment 289 David S. Dickey 11.1 Introduction 289 11.2 Blending Mechanisms 290 11.3 Blend Time 290 11.4 Fill Level 291 11.5 Segregation 291 11.6 Powder Processing Difficulties 292 11.7 Blender Classification 292 11.7.1 Tumble Blenders 293 11.7.2 Rotating Element Blenders 298 11.7.3 Granulators 303 11.7.4 Other Blenders - Mullers and Custom Blenders 304 11.8 Continuous Blenders 305 11.9 Blender Selection 306 11.10 Equipment Specifications 307 11.10.1 Materials of Construction 309 11.10.2 Electrical Classification 309 11.10.3 Drives and Seals 309 References 310 12 Fluid Mixing Equipment Design 311 David S. Dickey 12.1 Introduction 311 12.2 Equipment Description 312 12.2.1 Laboratory Mixers 312 12.2.2 Development Mixers 313 12.2.3 Portable Mixers 313 12.2.4 Top-Entering Mixers 315 12.2.5 High-Shear Dispersers 318 12.2.6 High Viscosity Mixers 319 12.2.7 Multi-Shaft Mixers 319 12.2.8 Bottom-Entering Mixers 320 12.2.9 Glass-Lined Mixers and Vessels 321 12.2.10 Side-Entering Mixers 322 12.2.11 Vessel Geometry 322 12.2.12 Baffles 323 12.3 Measurements 323 12.3.1 Power 324 12.3.2 Torque 326 12.3.3 Tip Speed 327 12.3.4 Blend Time 327 12.4 Mixing Classifications 328 12.4.1 Liquid Mixing 328 12.4.2 Solids Suspension 330 12.4.3 Gas Dispersion 332 12.4.4 Viscous Mixing 333 12.5 Mechanical Design 334 12.5.1 Shaft Design 334 12.5.2 Shaft Seals 335 12.5.3 Materials of Construction 336 12.5.4 Surface Finish 337 12.5.5 Motors 338 12.5.6 Drives 339 12.6 Static Mixers 339 12.6.1 Twisted Element 339 12.6.2 Structured Element 339 12.6.3 Basic Design 340 12.7 Challenges and Troubleshooting 341 12.7.1 Careful Observations 341 12.7.2 Process Problems 341 Nomenclature 342 Greek 343 References 343 13 Scale
Up 345 David S. Dickey 13.1 Introduction 345 13.2 Similarity and Scale
Up Concepts 346 13.2.1 Dimensional Analysis 346 13.2.2 Similarity 347 13.2.3 Applied Scale
Up 349 13.3 Testing Methods 350 13.4 Observation and Measurement 352 13.5 Scale
Up Methods 354 13.5.1 Scale
Up with Geometric Similarity 354 13.5.2 Example of Geometric Similarity Scale
Up 358 13.5.3 Scale
Up Without Geometric Similarity 359 13.5.4 Example of Non
Geometric Scale
Up 361 13.5.5 Scale
Up for Powder Mixing 364 13.6 Summary 367 Nomenclature 367 Greek 368 References 368 14 Equipment Qualification, Process and Cleaning Validation 369 Ian Jones and Chris Smalley 14.1 Introduction 369 14.2 Blending Equipment Commissioning and Qualification 370 14.2.1 Outline of the Verification Approach 370 14.2.2 Requirements Phase 371 14.2.3 Specifications and Design Review Phase 373 14.2.4 Verification Phase 375 14.3 Blending and Mixing Validation 380 14.3.1 Why do You Need to Validate Pharmaceutical Blends/Mixes? 382 14.3.2 When do You Need to Validate Blending/Mixing? 384 14.3.3 Components of Blending/Mixing Validation 385 14.3.4 What to Validate 386 14.4 Blending Cleaning Validation 389 14.4.1 Cleaning Development Studies 389 14.4.2 Cleaning Validation 395 14.5 Conclusion 398 14.6 Acknowledgements 399 References 399 Part IV Optimization and Control 401 15 Process Analytical Technology for Blending 403 Nicolas Abatzoglou 15.1 Introduction 403 15.1.1 The Role of PAT in Pharmaceutical Manufacturing: Is PAT Really New? 404 15.1.2 Why PAT is Feasible 405 15.1.3 Where PAT can be Applied in Pharmaceutical Manufacturing 406 15.1.4 The Regulatory Framework 406 15.2 Chemometrics and Data Management 408 15.2.1 PAT Data Management and Interpretation 409 15.3 Near
Infrared Spectroscopy (NIRS) 412 15.4 Raman Spectroscopy (RS) 419 15.5 Image Analysis 422 15.6 LIF Spectroscopy 424 15.7 Effusivity 426 15.8 Other Potential Sensor Technologies 426 15.9 Comments on PAT in Liquid Formulation Mixing 427 References 427 16 Imaging Fluid Mixing 431 Mi Wang 16.1 Introduction 431 16.2 Point Measurement Techniques 433 16.3 Photographic Imaging 435 16.4 Digital Particle Image Velocimetry 439 16.5 Magnetic Resonance Imaging 443 16.6 Positron Emission Particle Tracking Imaging 444 16.7 Electrical Process Tomography 446 References 452 17 Discrete Element Method (DEM) Simulation of Powder Mixing Process 459 Ali Hassanpour and Mojtaba Ghadiri 17.1 Introduction to DEM and its Application in Pharmaceutical Powder Processing 459 17.2 DEM Simulation of Powder Mixing 461 17.3 Validation and Comparison with the Experiments 468 17.4 Concluding Remarks 474 References 475 Index 479