{"product_id":"process-analytical-technology-9780470722077","title":"Process Analytical Technology","description":"\u003cb\u003eBook Synopsis\u003c\/b\u003e\u003cbr\u003eProcess Analytical Technology explores the concepts of this technology and its application in the chemical and pharmaceutical industry from the point of view of the analytical chemist.\u003cbr\u003e\u003cbr\u003e\u003cb\u003eTrade Review\u003c\/b\u003e\u003cbr\u003e\"Overall, this excellent compilation is highly recommended.\" \u003cb\u003e\u003ci\u003e(\u003c\/i\u003e\u003c\/b\u003e\u003ci\u003eOrganic Process Research and Development,\u003c\/i\u003e January 2011)\u003cbr\u003e \u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cb\u003eTable of Contents\u003c\/b\u003e\u003cbr\u003e\u003cp\u003ePreface to the Second Edition xvii\u003c\/p\u003e \u003cp\u003eList of Contributors xix\u003c\/p\u003e \u003cp\u003eList of Abbreviations xxi\u003c\/p\u003e \u003cp\u003e\u003cb\u003e1 Overview of Process Analysis and PAT 1\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eJason E. Dickens\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e1.1 Introduction 1\u003c\/p\u003e \u003cp\u003e1.1.1 Historical perspective 3\u003c\/p\u003e \u003cp\u003e1.1.2 Business drivers 4\u003c\/p\u003e \u003cp\u003e1.2 Execution of Process Analysis Projects 5\u003c\/p\u003e \u003cp\u003e1.2.1 Wisdoms 5\u003c\/p\u003e \u003cp\u003e1.2.2 Team structure 6\u003c\/p\u003e \u003cp\u003e1.2.3 Project life cycle 6\u003c\/p\u003e \u003cp\u003e1.2.4 Project scoping 9\u003c\/p\u003e \u003cp\u003e1.2.5 Common challenges and pitfalls 10\u003c\/p\u003e \u003cp\u003e1.3 Process Instrumentation 12\u003c\/p\u003e \u003cp\u003e1.3.1 Process instrumentation types 12\u003c\/p\u003e \u003cp\u003e1.3.2 Novel process instrumentation 12\u003c\/p\u003e \u003cp\u003e1.4 Conclusions 13\u003c\/p\u003e \u003cp\u003e1.5 Glossary of Acronyms and Terms 14\u003c\/p\u003e \u003cp\u003eReferences 14\u003c\/p\u003e \u003cp\u003e\u003cb\u003e2 Implementation of Process Analytical Technologies 17\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eRobert Guenard and Gert Thurau\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e2.1 Introduction to Implementation of Process Analytical Technologies (PAT) in the Industrial Setting 17\u003c\/p\u003e \u003cp\u003e2.1.1 Definition of process analytics 18\u003c\/p\u003e \u003cp\u003e2.1.2 Differences between process analyzers and laboratory analysis 19\u003c\/p\u003e \u003cp\u003e2.1.3 General industrial drivers for PA 19\u003c\/p\u003e \u003cp\u003e2.1.4 Types of applications (R\u0026amp;D versus manufacturing) 20\u003c\/p\u003e \u003cp\u003e2.1.5 Organizational considerations 20\u003c\/p\u003e \u003cp\u003e2.2 Generalized Process Analytics Work Process 23\u003c\/p\u003e \u003cp\u003e2.2.1 Project identification and definition 24\u003c\/p\u003e \u003cp\u003e2.2.2 Analytical application development 26\u003c\/p\u003e \u003cp\u003e2.2.3 Design, specify and procure 26\u003c\/p\u003e \u003cp\u003e2.2.4 Implementation in production 28\u003c\/p\u003e \u003cp\u003e2.2.5 Routine operation 29\u003c\/p\u003e \u003cp\u003e2.2.6 Continuous improvement 30\u003c\/p\u003e \u003cp\u003e2.3 Considerations for PAT Implementation in the Pharmaceutical Industry 30\u003c\/p\u003e \u003cp\u003e2.3.1 Introduction 30\u003c\/p\u003e \u003cp\u003e2.3.2 Business model 30\u003c\/p\u003e \u003cp\u003e2.3.3 Technical differences 31\u003c\/p\u003e \u003cp\u003e2.3.4 Regulatory Aspects of Process Analytics in the Pharmaceutical Industry –the Concept of Quality by Design 33\u003c\/p\u003e \u003cp\u003e2.4 Conclusions 36\u003c\/p\u003e \u003cp\u003eReferences 36\u003c\/p\u003e \u003cp\u003e\u003cb\u003e3 Process Sampling: Theory of Sampling – the Missing Link in Process Analytical Technologies (PAT) 37\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eKim H. Esbensen and Peter Paasch-Mortensen\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e3.1 Introduction 37\u003c\/p\u003e \u003cp\u003e3.2 Theory of Sampling – Introduction 39\u003c\/p\u003e \u003cp\u003e3.2.1 Heterogeneity 41\u003c\/p\u003e \u003cp\u003e3.2.2 Constitutional heterogeneity 41\u003c\/p\u003e \u003cp\u003e3.2.3 Distributional heterogeneity 42\u003c\/p\u003e \u003cp\u003e3.2.4 Structurally correct sampling 45\u003c\/p\u003e \u003cp\u003e3.2.5 Incorrect sampling error 45\u003c\/p\u003e \u003cp\u003e3.2.6 Increment delimitation error 45\u003c\/p\u003e \u003cp\u003e3.2.7 Increment extraction error 46\u003c\/p\u003e \u003cp\u003e3.2.8 Increment preparation error 46\u003c\/p\u003e \u003cp\u003e3.2.9 Increment weighing error 47\u003c\/p\u003e \u003cp\u003e3.2.10 Total sampling error 48\u003c\/p\u003e \u003cp\u003e3.2.11 Global estimation error 48\u003c\/p\u003e \u003cp\u003e3.3 Mass Reduction as a Specific Sampling Procedure 48\u003c\/p\u003e \u003cp\u003e3.4 Fundamental Sampling Principle 51\u003c\/p\u003e \u003cp\u003e3.5 Sampling – a Very Practical Issue 51\u003c\/p\u003e \u003cp\u003e3.5.1 Sampling unit operations 52\u003c\/p\u003e \u003cp\u003e3.5.2 Understanding process sampling: 0-D versus 1-D LOTS 52\u003c\/p\u003e \u003cp\u003e3.5.3 Grab sampling – 0-D and 1-D 54\u003c\/p\u003e \u003cp\u003e3.5.4 Correct process sampling: increment delimitation\/extraction 56\u003c\/p\u003e \u003cp\u003e3.5.5 PAT versus correct process sampling – what is required? 58\u003c\/p\u003e \u003cp\u003e3.6 Reactors and Vessels – Identical Process Sampling Issues 60\u003c\/p\u003e \u003cp\u003e3.6.1 Correct process sampling with existing process technology 62\u003c\/p\u003e \u003cp\u003e3.6.2 Upward flux – representative colocated PAT sampling 62\u003c\/p\u003e \u003cp\u003e3.6.3 Upstream colocated PAT sampler 64\u003c\/p\u003e \u003cp\u003e3.7 Heterogeneity Characterization of 1-D lots: Variography 66\u003c\/p\u003e \u003cp\u003e3.7.1 Process sampling modes 67\u003c\/p\u003e \u003cp\u003e3.7.2 The experimental variogram 67\u003c\/p\u003e \u003cp\u003e3.7.3 Sampling plan simulation and estimation of TSE 71\u003c\/p\u003e \u003cp\u003e3.7.4 TSE estimation for 0-D lots – batch sampling 72\u003c\/p\u003e \u003cp\u003e3.7.5 Corporate QC benefits of variographic analysis 73\u003c\/p\u003e \u003cp\u003e3.8 Data Quality – New Insight from the TOS 75\u003c\/p\u003e \u003cp\u003e3.9 Validation in Chemometrics and PAT 76\u003c\/p\u003e \u003cp\u003e3.10 Summary 78\u003c\/p\u003e \u003cp\u003eReferences 79\u003c\/p\u003e \u003cp\u003e\u003cb\u003e4 UV-visible Spectroscopy for On-line Analysis 81\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eMarcel A. Liauw, Lewis C. Baylor and Patrick E. O’Rourke\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e4.1 Introduction 81\u003c\/p\u003e \u003cp\u003e4.2 Theory 82\u003c\/p\u003e \u003cp\u003e4.2.1 Chemical concentration 82\u003c\/p\u003e \u003cp\u003e4.2.2 Color 84\u003c\/p\u003e \u003cp\u003e4.2.3 Film thickness 85\u003c\/p\u003e \u003cp\u003e4.2.4 Turbidity 85\u003c\/p\u003e \u003cp\u003e4.2.5 Plasmons\/nanoparticles 85\u003c\/p\u003e \u003cp\u003e4.3 Instrumentation 85\u003c\/p\u003e \u003cp\u003e4.4 Sample Interface 86\u003c\/p\u003e \u003cp\u003e4.4.1 Cuvette\/vial 87\u003c\/p\u003e \u003cp\u003e4.4.2 Flow cells 87\u003c\/p\u003e \u003cp\u003e4.4.3 Insertion probe 87\u003c\/p\u003e \u003cp\u003e4.4.4 Reflectance probe 89\u003c\/p\u003e \u003cp\u003e4.5 Implementation 89\u003c\/p\u003e \u003cp\u003e4.5.1 A complete process analyzer 89\u003c\/p\u003e \u003cp\u003e4.5.2 Troubleshooting 89\u003c\/p\u003e \u003cp\u003e4.6 Applications 91\u003c\/p\u003e \u003cp\u003e4.6.1 Gas and vapor analysis 92\u003c\/p\u003e \u003cp\u003e4.6.2 Liquid analysis 92\u003c\/p\u003e \u003cp\u003e4.6.3 Solid analysis 96\u003c\/p\u003e \u003cp\u003e4.6.4 Other applications 99\u003c\/p\u003e \u003cp\u003e4.7 Detailed Application Notes 100\u003c\/p\u003e \u003cp\u003e4.7.1 Gas and vapor analysis: toluene 100\u003c\/p\u003e \u003cp\u003e4.7.2 Liquid analysis: breakthrough curves 101\u003c\/p\u003e \u003cp\u003e4.7.3 Solids analysis: extruded plastic color 101\u003c\/p\u003e \u003cp\u003e4.7.4 Film thickness determination: polymer 103\u003c\/p\u003e \u003cp\u003e4.8 Conclusion 104\u003c\/p\u003e \u003cp\u003eReferences 104\u003c\/p\u003e \u003cp\u003e\u003cb\u003e5 Near-infrared Spectroscopy for Process Analytical Technology: Theory, Technology and Implementation 107\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eMichael B. Simpson\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e5.1 Introduction 107\u003c\/p\u003e \u003cp\u003e5.2 Theory of Near-infrared Spectroscopy 112\u003c\/p\u003e \u003cp\u003e5.3 Analyser Technologies in the Near-infrared 114\u003c\/p\u003e \u003cp\u003e5.3.1 Light sources and detectors for near-infrared analyzers 114\u003c\/p\u003e \u003cp\u003e5.3.2 The scanning grating monochromator and polychromator diode-array 119\u003c\/p\u003e \u003cp\u003e5.3.3 The acousto-optic tunable filter (AOTF) analyzer 123\u003c\/p\u003e \u003cp\u003e5.3.4 Fourier transform near-infrared analyzers 127\u003c\/p\u003e \u003cp\u003e5.3.5 Emerging technologies in process NIR analyzers 134\u003c\/p\u003e \u003cp\u003e5.4 The Sampling Interface 136\u003c\/p\u003e \u003cp\u003e5.4.1 Introduction 136\u003c\/p\u003e \u003cp\u003e5.4.2 Problem samples: liquids, slurries and solids 142\u003c\/p\u003e \u003cp\u003e5.4.3 The use of fiber optics 145\u003c\/p\u003e \u003cp\u003e5.5 Practical Examples of Near-infrared Analytical Applications 147\u003c\/p\u003e \u003cp\u003e5.5.1 Refinery hydrocarbon streams 148\u003c\/p\u003e \u003cp\u003e5.5.2 Polyols, ethoxylated derivatives, ethylene oxide\/propylene oxide polyether polyols 149\u003c\/p\u003e \u003cp\u003e5.5.3 Oleochemicals, fatty acids, fatty amines and biodiesel 151\u003c\/p\u003e \u003cp\u003e5.6 Conclusion 152\u003c\/p\u003e \u003cp\u003eReferences 153\u003c\/p\u003e \u003cp\u003e\u003cb\u003e6 Infrared Spectroscopy for Process Analytical Applications 157\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eJohn P. Coates\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e6.1 Introduction 157\u003c\/p\u003e \u003cp\u003e6.2 Practical Aspects of IR Spectroscopy 161\u003c\/p\u003e \u003cp\u003e6.3 Instrumentation Design and Technology 163\u003c\/p\u003e \u003cp\u003e6.4 Process IR Instrumentation 166\u003c\/p\u003e \u003cp\u003e6.4.1 Commercially available IR instruments 167\u003c\/p\u003e \u003cp\u003e6.4.2 Important IR component technologies 172\u003c\/p\u003e \u003cp\u003e6.4.3 New technologies for IR components and instruments 176\u003c\/p\u003e \u003cp\u003e6.4.4 Requirements for process infrared analyzers 178\u003c\/p\u003e \u003cp\u003e6.4.5 Sample handling for IR process analyzers 185\u003c\/p\u003e \u003cp\u003e6.4.6 Issues for consideration in the implementation of process IR 187\u003c\/p\u003e \u003cp\u003e6.5 Applications of Process IR Analyzers 189\u003c\/p\u003e \u003cp\u003e6.6 Process IR Analyzers: a Review 191\u003c\/p\u003e \u003cp\u003e6.7 Trends and Directions 192\u003c\/p\u003e \u003cp\u003eReferences 193\u003c\/p\u003e \u003cp\u003e\u003cb\u003e7 Raman Spectroscopy 195\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eNancy L. Jestel\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e7.1 Attractive Features of Raman Spectroscopy 195\u003c\/p\u003e \u003cp\u003e7.1.1 Quantitative information 195\u003c\/p\u003e \u003cp\u003e7.1.2 Flexible sample forms and sizes used as accessed without damage 196\u003c\/p\u003e \u003cp\u003e7.1.3 Flexible sample interfaces 196\u003c\/p\u003e \u003cp\u003e7.1.4 Attractive spectral properties and advantageous selection rules 197\u003c\/p\u003e \u003cp\u003e7.1.5 High sampling rate 197\u003c\/p\u003e \u003cp\u003e7.1.6 Stable and robust equipment 198\u003c\/p\u003e \u003cp\u003e7.2 Potential Issues with Raman Spectroscopy 198\u003c\/p\u003e \u003cp\u003e7.2.1 High background signals 198\u003c\/p\u003e \u003cp\u003e7.2.2 Stability 198\u003c\/p\u003e \u003cp\u003e7.2.3 Too much and still too little sensitivity 199\u003c\/p\u003e \u003cp\u003e7.2.4 Personnel experience 199\u003c\/p\u003e \u003cp\u003e7.2.5 Cost 200\u003c\/p\u003e \u003cp\u003e7.3 Fundamentals of Raman Spectroscopy 200\u003c\/p\u003e \u003cp\u003e7.4 Raman Instrumentation 203\u003c\/p\u003e \u003cp\u003e7.4.1 Safety 203\u003c\/p\u003e \u003cp\u003e7.4.2 Laser wavelength selection 204\u003c\/p\u003e \u003cp\u003e7.4.3 Laser power and stability 204\u003c\/p\u003e \u003cp\u003e7.4.4 Spectrometer 205\u003c\/p\u003e \u003cp\u003e7.4.5 Sample interface (probes) 206\u003c\/p\u003e \u003cp\u003e7.4.6 Communications 208\u003c\/p\u003e \u003cp\u003e7.4.7 Maintenance 209\u003c\/p\u003e \u003cp\u003e7.5 Quantitative Raman 209\u003c\/p\u003e \u003cp\u003e7.6 Applications 212\u003c\/p\u003e \u003cp\u003e7.6.1 Acylation, alkylation, catalytic cracking, and transesterification 213\u003c\/p\u003e \u003cp\u003e7.6.2 Bioreactors 213\u003c\/p\u003e \u003cp\u003e7.6.3 Blending 214\u003c\/p\u003e \u003cp\u003e7.6.4 Calcination 214\u003c\/p\u003e \u003cp\u003e7.6.5 Catalysis 215\u003c\/p\u003e \u003cp\u003e7.6.6 Chlorination 216\u003c\/p\u003e \u003cp\u003e7.6.7 Counterfeit pharmaceuticals 217\u003c\/p\u003e \u003cp\u003e7.6.8 Extrusion 218\u003c\/p\u003e \u003cp\u003e7.6.9 Forensics 218\u003c\/p\u003e \u003cp\u003e7.6.10 Hydrogenation 218\u003c\/p\u003e \u003cp\u003e7.6.11 Hydrolysis 219\u003c\/p\u003e \u003cp\u003e7.6.12 Medical diagnostics 219\u003c\/p\u003e \u003cp\u003e7.6.13 Microwave-assisted organic synthesis 219\u003c\/p\u003e \u003cp\u003e7.6.14 Mobile or field uses 220\u003c\/p\u003e \u003cp\u003e7.6.15 Natural products 220\u003c\/p\u003e \u003cp\u003e7.6.16 Orientation, stress, or strain 221\u003c\/p\u003e \u003cp\u003e7.6.17 Ozonolysis 222\u003c\/p\u003e \u003cp\u003e7.6.18 Polymerization 222\u003c\/p\u003e \u003cp\u003e7.6.19 Polymer curing 224\u003c\/p\u003e \u003cp\u003e7.6.20 Polymorphs (crystal forms) 225\u003c\/p\u003e \u003cp\u003e7.6.21 Product properties 228\u003c\/p\u003e \u003cp\u003e7.6.22 Purification: distillation, filtration, drying 229\u003c\/p\u003e \u003cp\u003e7.6.23 Thin films or coatings 229\u003c\/p\u003e \u003cp\u003e7.7 Current State of Process Raman Spectroscopy 230\u003c\/p\u003e \u003cp\u003eReferences 231\u003c\/p\u003e \u003cp\u003e\u003cb\u003e8 Near-infrared Chemical Imaging for Product and Process Understanding 245\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eE. Neil Lewis, Joseph W. Schoppelrei, Lisa Makein, Linda H. Kidder and Eunah Lee\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e8.1 The PAT Initiative 245\u003c\/p\u003e \u003cp\u003e8.2 The Role of Near-infrared Chemical Imaging (NIR-CI) in the Pharmaceutical Industry 246\u003c\/p\u003e \u003cp\u003e8.2.1 Characterization of solid dosage forms 246\u003c\/p\u003e \u003cp\u003e8.2.2 ‘A picture is worth a thousand words’ 247\u003c\/p\u003e \u003cp\u003e8.3 Evolution of NIR Imaging Instrumentation 247\u003c\/p\u003e \u003cp\u003e8.3.1 Spatially resolved spectroscopy – mapping 247\u003c\/p\u003e \u003cp\u003e8.3.2 The infrared focal-plane array 247\u003c\/p\u003e \u003cp\u003e8.3.3 Wavelength selection 248\u003c\/p\u003e \u003cp\u003e8.3.4 The benefits of NIR spectroscopy 248\u003c\/p\u003e \u003cp\u003e8.3.5 NIR imaging instrumentation 249\u003c\/p\u003e \u003cp\u003e8.4 Chemical Imaging Principles 251\u003c\/p\u003e \u003cp\u003e8.4.1 The hypercube 251\u003c\/p\u003e \u003cp\u003e8.4.2 Data analysis 251\u003c\/p\u003e \u003cp\u003e8.4.3 Spectral correction 252\u003c\/p\u003e \u003cp\u003e8.4.4 Spectral preprocessing 253\u003c\/p\u003e \u003cp\u003e8.4.5 Classification 253\u003c\/p\u003e \u003cp\u003e8.4.6 Image processing – statistical 255\u003c\/p\u003e \u003cp\u003e8.4.7 Image processing – morphology 257\u003c\/p\u003e \u003cp\u003e8.5 PAT Applications 257\u003c\/p\u003e \u003cp\u003e8.5.1 Content uniformity measurements – ‘self calibrating’ 258\u003c\/p\u003e \u003cp\u003e8.5.2 Quality assurance – imaging an intact blister pack 260\u003c\/p\u003e \u003cp\u003e8.5.3 Contaminant detection 261\u003c\/p\u003e \u003cp\u003e8.5.4 Imaging of coatings – advanced design delivery systems 263\u003c\/p\u003e \u003cp\u003e8.6 Processing Case Study: Estimating ‘Abundance’ of Sample Components 267\u003c\/p\u003e \u003cp\u003e8.6.1 Experimental 268\u003c\/p\u003e \u003cp\u003e8.6.2 Spectral correction and preprocessing 268\u003c\/p\u003e \u003cp\u003e8.6.3 Analysis 268\u003c\/p\u003e \u003cp\u003e8.6.4 Conclusions 273\u003c\/p\u003e \u003cp\u003e8.7 Processing Case Study: Determining Blend Homogeneity Through Statistical Analysis 273\u003c\/p\u003e \u003cp\u003e8.7.1 Experimental 273\u003c\/p\u003e \u003cp\u003e8.7.2 Observing visual contrast in the image 274\u003c\/p\u003e \u003cp\u003e8.7.3 Statistical analysis of the image 274\u003c\/p\u003e \u003cp\u003e8.7.4 Blend uniformity measurement 276\u003c\/p\u003e \u003cp\u003e8.7.5 Conclusions 276\u003c\/p\u003e \u003cp\u003e8.8 Final Thoughts 277\u003c\/p\u003e \u003cp\u003eAcknowledgements 278\u003c\/p\u003e \u003cp\u003eReferences 278\u003c\/p\u003e \u003cp\u003e\u003cb\u003e9 Acoustic Chemometric Monitoring of Industrial Production Processes 281\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eMaths Halstensen and Kim H. Esbensen\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e9.1 What is Acoustic Chemometrics? 281\u003c\/p\u003e \u003cp\u003e9.2 How Acoustic Chemometrics Works 282\u003c\/p\u003e \u003cp\u003e9.2.1 Acoustic sensors 282\u003c\/p\u003e \u003cp\u003e9.2.2 Mounting acoustic sensors (accelerometers) 283\u003c\/p\u003e \u003cp\u003e9.2.3 Signal processing 284\u003c\/p\u003e \u003cp\u003e9.2.4 Chemometric data analysis 284\u003c\/p\u003e \u003cp\u003e9.2.5 Acoustic chemometrics as a PAT tool 284\u003c\/p\u003e \u003cp\u003e9.3 Industrial Production Process Monitoring 285\u003c\/p\u003e \u003cp\u003e9.3.1 Fluidized bed granulation monitoring 285\u003c\/p\u003e \u003cp\u003e9.3.2 Pilot scale studies 286\u003c\/p\u003e \u003cp\u003e9.3.3 Monitoring of a start-up sequence of a continuous fluidized bed granulator 291\u003c\/p\u003e \u003cp\u003e9.3.4 Process monitoring as an early warning of critical shutdown situations 295\u003c\/p\u003e \u003cp\u003e9.3.5 Acoustic chemometrics for fluid flow quantification 296\u003c\/p\u003e \u003cp\u003e9.4 Available On-line Acoustic Chemometric Equipment 299\u003c\/p\u003e \u003cp\u003e9.5 Discussion 301\u003c\/p\u003e \u003cp\u003e9.5.1 Granulator monitoring 301\u003c\/p\u003e \u003cp\u003e9.5.2 Process state monitoring 301\u003c\/p\u003e \u003cp\u003e9.5.3 Ammonia concentration monitoring 301\u003c\/p\u003e \u003cp\u003e9.6 Conclusions 302\u003c\/p\u003e \u003cp\u003eReferences 302\u003c\/p\u003e \u003cp\u003e\u003cb\u003e10 Process NMR Spectroscopy: Technology and On-line Applications 303\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eJohn C. Edwards and Paul J. Giammatteo\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e\u003ci\u003e10.1 Introduction 303\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e10.2 NMR Spectroscopy Overview 305\u003c\/p\u003e \u003cp\u003e10.2.1 The NMR phenomenon 305\u003c\/p\u003e \u003cp\u003e10.2.2 Time–domain-NMR: utilization of the FID and spin relaxation 309\u003c\/p\u003e \u003cp\u003e10.2.3 High-resolution NMR: obtaining a spectrum with resolved chemical shift information 312\u003c\/p\u003e \u003cp\u003e10.3 Process NMR Instrumentation 313\u003c\/p\u003e \u003cp\u003e10.3.1 Spectrometer and magnet design 313\u003c\/p\u003e \u003cp\u003e10.3.2 Sampling and experimental design 316\u003c\/p\u003e \u003cp\u003e10.4 Postprocessing Methodologies for NMR Data 317\u003c\/p\u003e \u003cp\u003e10.5 Advantages and Limitations of NMR as a Process Analytical Technology 320\u003c\/p\u003e \u003cp\u003e10.5.1 Advantages 320\u003c\/p\u003e \u003cp\u003e10.5.2 Limitations 321\u003c\/p\u003e \u003cp\u003e10.6 On-line and At-line Applications 321\u003c\/p\u003e \u003cp\u003e10.6.1 Time–domain NMR 322\u003c\/p\u003e \u003cp\u003e10.6.2 High-resolution NMR: chemometric applications 323\u003c\/p\u003e \u003cp\u003e10.7 Current Development and Applications 330\u003c\/p\u003e \u003cp\u003e10.8 Conclusions 331\u003c\/p\u003e \u003cp\u003eReferences 332\u003c\/p\u003e \u003cp\u003e\u003cb\u003e11 Fluorescent Sensing and Process Analytical Applications 337\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eJason E. Dickens\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e11.1 Introduction 337\u003c\/p\u003e \u003cp\u003e11.2 Luminescence Fundamentals 338\u003c\/p\u003e \u003cp\u003e11.2.1 Luminescence nomenclature 338\u003c\/p\u003e \u003cp\u003e11.2.2 Luminescence processes 338\u003c\/p\u003e \u003cp\u003e11.2.3 Fluorophore classification 338\u003c\/p\u003e \u003cp\u003e11.3 LIF Sensing Fundamentals 341\u003c\/p\u003e \u003cp\u003e11.3.1 LIF sensing classification 341\u003c\/p\u003e \u003cp\u003e11.3.2 Luminescence spectroscopy 342\u003c\/p\u003e \u003cp\u003e11.3.3 LIF signal response function 343\u003c\/p\u003e \u003cp\u003e11.4 LIF Sensing Instrumentation 343\u003c\/p\u003e \u003cp\u003e11.4.1 LIF photometric instrument specification 345\u003c\/p\u003e \u003cp\u003e11.4.2 LIF Instrument selection 347\u003c\/p\u003e \u003cp\u003e11.5 Luminescent Detection Risks 347\u003c\/p\u003e \u003cp\u003e11.6 Process Analytical Technology Applications 348\u003c\/p\u003e \u003cp\u003e11.6.1 Petrochemical, chemical and nuclear field applications 349\u003c\/p\u003e \u003cp\u003e11.6.2 Pharmaceutical PAT applications 349\u003c\/p\u003e \u003cp\u003e11.7 Conclusions 350\u003c\/p\u003e \u003cp\u003eReferences 351\u003c\/p\u003e \u003cp\u003e\u003cb\u003e12 Chemometrics in Process Analytical Technology (PAT) 353\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003ci\u003eCharles E. Miller\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e12.1 Introduction 353\u003c\/p\u003e \u003cp\u003e12.1.1 What is chemometrics? 353\u003c\/p\u003e \u003cp\u003e12.1.2 Some history 354\u003c\/p\u003e \u003cp\u003e12.1.3 Some philosophy 355\u003c\/p\u003e \u003cp\u003e12.1.4 Chemometrics in analytical chemistry? 355\u003c\/p\u003e \u003cp\u003e12.1.5 Chemometrics in process analytical chemistry? 356\u003c\/p\u003e \u003cp\u003e12.2 Foundations of Chemometrics 356\u003c\/p\u003e \u003cp\u003e12.2.1 Notation 356\u003c\/p\u003e \u003cp\u003e12.2.2 Some basic statistics 358\u003c\/p\u003e \u003cp\u003e12.2.3 Linear regression 359\u003c\/p\u003e \u003cp\u003e12.2.4 Multiple linear regression 361\u003c\/p\u003e \u003cp\u003e12.2.5 Principal components analysis (PCA) 362\u003c\/p\u003e \u003cp\u003e12.2.6 Design of experiments (DOE) 366\u003c\/p\u003e \u003cp\u003e12.3 Chemometric Methods in PAT 368\u003c\/p\u003e \u003cp\u003e12.3.1 Data preprocessing 369\u003c\/p\u003e \u003cp\u003e12.3.2 Quantitative model building 377\u003c\/p\u003e \u003cp\u003e12.3.3 Qualitative model building 389\u003c\/p\u003e \u003cp\u003e12.3.4 Exploratory analysis 397\u003c\/p\u003e \u003cp\u003e12.4 Overfitting and Model Validation 407\u003c\/p\u003e \u003cp\u003e12.4.1 Overfitting and underfitting 407\u003c\/p\u003e \u003cp\u003e12.4.2 Test set validation 408\u003c\/p\u003e \u003cp\u003e12.4.3 Cross validation 410\u003c\/p\u003e \u003cp\u003e12.5 Outliers 413\u003c\/p\u003e \u003cp\u003e12.5.1 Introduction to outliers 413\u003c\/p\u003e \u003cp\u003e12.5.2 Outlier detection and remediation 413\u003c\/p\u003e \u003cp\u003e12.6 Calibration Strategies in PAT 416\u003c\/p\u003e \u003cp\u003e12.6.1 The ‘calibration strategy space’ 417\u003c\/p\u003e \u003cp\u003e12.6.2 Strategies for direct versus inverse modeling methods 418\u003c\/p\u003e \u003cp\u003e12.6.3 Hybrid strategies 419\u003c\/p\u003e \u003cp\u003e12.7 Sample and Variable Selection in Chemometrics 420\u003c\/p\u003e \u003cp\u003e12.7.1 Sample selection 420\u003c\/p\u003e \u003cp\u003e12.7.2 Variable selection 421\u003c\/p\u003e \u003cp\u003e12.8 Troubleshooting\/Improving an Existing Method 425\u003c\/p\u003e \u003cp\u003e12.8.1 Method assessment 425\u003c\/p\u003e \u003cp\u003e12.8.2 Model improvement strategies 425\u003c\/p\u003e \u003cp\u003e12.9 Calibration Transfer and Instrument Standardization 426\u003c\/p\u003e \u003cp\u003e12.9.1 Slope\/intercept adjustment 428\u003c\/p\u003e \u003cp\u003e12.9.2 Piecewise direct standardization (PDS) 428\u003c\/p\u003e \u003cp\u003e12.9.3 Generalized least squares (GLS) weighting 429\u003c\/p\u003e \u003cp\u003e12.9.4 Shenk–Westerhaus method 429\u003c\/p\u003e \u003cp\u003e12.9.5 Other transfer\/standardization methods 429\u003c\/p\u003e \u003cp\u003e12.10 Chemometric Model Deployment Issues in PAT 430\u003c\/p\u003e \u003cp\u003e12.10.1 Outliers in prediction 430\u003c\/p\u003e \u003cp\u003e12.10.2 Deployment software 432\u003c\/p\u003e \u003cp\u003e12.10.3 Data systems, and control system integration 432\u003c\/p\u003e \u003cp\u003e12.10.4 Method updating 433\u003c\/p\u003e \u003cp\u003e12.11 People Issues 433\u003c\/p\u003e \u003cp\u003e12.12 The Final Word 434\u003c\/p\u003e \u003cp\u003eReferences 434\u003c\/p\u003e \u003cp\u003e\u003cb\u003e13 On-line PAT Applications of Spectroscopy in the Pharmaceutical Industry 439\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eBrandye Smith-Goettler\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e13.1 Background 439\u003c\/p\u003e \u003cp\u003e13.2 Reaction Monitoring 441\u003c\/p\u003e \u003cp\u003e13.3 Crystallization 442\u003c\/p\u003e \u003cp\u003e13.4 API Drying 443\u003c\/p\u003e \u003cp\u003e13.5 Nanomilling 444\u003c\/p\u003e \u003cp\u003e13.6 Hot-melt Extrusion 445\u003c\/p\u003e \u003cp\u003e13.7 Granulation 446\u003c\/p\u003e \u003cp\u003e13.7.1 Wet granulation 446\u003c\/p\u003e \u003cp\u003e13.7.2 Roller compaction 449\u003c\/p\u003e \u003cp\u003e13.8 Powder Blending 450\u003c\/p\u003e \u003cp\u003e13.8.1 Lubrication 451\u003c\/p\u003e \u003cp\u003e13.8.2 Powder flow 451\u003c\/p\u003e \u003cp\u003e13.9 Compression 452\u003c\/p\u003e \u003cp\u003e13.10 Coating 452\u003c\/p\u003e \u003cp\u003e13.11 Biologics 453\u003c\/p\u003e \u003cp\u003e13.11.1 Fermentation 453\u003c\/p\u003e \u003cp\u003e13.11.2 Freeze-drying 454\u003c\/p\u003e \u003cp\u003e13.12 Cleaning Validation 454\u003c\/p\u003e \u003cp\u003e13.13 Conclusions 455\u003c\/p\u003e \u003cp\u003eReferences 455\u003c\/p\u003e \u003cp\u003e\u003cb\u003e14 NIR spectroscopy in Pharmaceutical Analysis: Off-line and At-line PAT Applications 463\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eMarcelo Blanco Romía and Manel Alcalá Bernárdez\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e14.1 Introduction 463\u003c\/p\u003e \u003cp\u003e14.1.1 Operational procedures 464\u003c\/p\u003e \u003cp\u003e14.1.2 Instrument qualification 466\u003c\/p\u003e \u003cp\u003e14.2 Foundation of Qualitative Method Development 466\u003c\/p\u003e \u003cp\u003e14.2.1 Pattern recognition methods 467\u003c\/p\u003e \u003cp\u003e14.2.2 Construction of spectral libraries 468\u003c\/p\u003e \u003cp\u003e14.2.3 Identification and qualification 470\u003c\/p\u003e \u003cp\u003e14.3 Foundation of Quantitative Method Development 471\u003c\/p\u003e \u003cp\u003e14.3.1 Selection and preparation of samples 472\u003c\/p\u003e \u003cp\u003e14.3.2 Preparation and selection of samples 473\u003c\/p\u003e \u003cp\u003e14.3.3 Determination of reference values 474\u003c\/p\u003e \u003cp\u003e14.3.4 Acquisition of spectra 474\u003c\/p\u003e \u003cp\u003e14.3.5 Construction of the calibration model 475\u003c\/p\u003e \u003cp\u003e14.3.6 Model validation 476\u003c\/p\u003e \u003cp\u003e14.3.7 Prediction of new samples 476\u003c\/p\u003e \u003cp\u003e14.4 Method Validation 476\u003c\/p\u003e \u003cp\u003e14.5 Calibration Transfer 476\u003c\/p\u003e \u003cp\u003e14.6 Pharmaceutical Applications 478\u003c\/p\u003e \u003cp\u003e14.6.1 Identification of raw materials 478\u003c\/p\u003e \u003cp\u003e14.6.2 Homogeneity 478\u003c\/p\u003e \u003cp\u003e14.6.3 Moisture 480\u003c\/p\u003e \u003cp\u003e14.6.4 Determination of physical parameters 481\u003c\/p\u003e \u003cp\u003e14.6.5 Determination of chemical composition 483\u003c\/p\u003e \u003cp\u003e14.7 Conclusions 485\u003c\/p\u003e \u003cp\u003eReferences 486\u003c\/p\u003e \u003cp\u003e\u003cb\u003e15 Near-infrared Spectroscopy (NIR) as a PAT Tool in the Chemical Industry: Added Value and Implementation Challenges 493\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eAnn M. Brearley and Susan J. Foulk\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e15.1 Introduction 493\u003c\/p\u003e \u003cp\u003e15.2 Successful Process Analyzer Implementation 494\u003c\/p\u003e \u003cp\u003e15.2.1 A process for successful process analyzer implementation 494\u003c\/p\u003e \u003cp\u003e15.2.2 How NIR process analyzers contribute to business value 497\u003c\/p\u003e \u003cp\u003e15.2.3 Issues to consider in setting technical requirements for a process analyzer 498\u003c\/p\u003e \u003cp\u003e15.2.4 Capabilities and limitations of NIR 499\u003c\/p\u003e \u003cp\u003e15.2.5 General challenges in process analyzer implementation 500\u003c\/p\u003e \u003cp\u003e15.2.6 Approaches to calibrating an NIR analyzer on-line 502\u003c\/p\u003e \u003cp\u003e15.2.7 Special challenges in NIR monitoring of polymer melts 505\u003c\/p\u003e \u003cp\u003e15.3 Example Applications 506\u003c\/p\u003e \u003cp\u003e15.3.1 Monitoring monomer conversion during emulsion polymerization 506\u003c\/p\u003e \u003cp\u003e15.3.2 Monitoring a diethylbenzene isomer separation process 508\u003c\/p\u003e \u003cp\u003e15.3.3 Monitoring the composition of copolymers and polymer blends in an extruder 509\u003c\/p\u003e \u003cp\u003e15.3.4 Rapid identification of carpet face fiber 512\u003c\/p\u003e \u003cp\u003e15.3.5 Monitoring the composition of spinning solution 514\u003c\/p\u003e \u003cp\u003e15.3.6 Monitoring end groups and viscosity in polyester melts 516\u003c\/p\u003e \u003cp\u003e15.3.7 In-line monitoring of a copolymerization reaction 518\u003c\/p\u003e \u003cp\u003eReferences 520\u003c\/p\u003e \u003cp\u003e\u003cb\u003e16 Future Trends for PAT for Increased Process Understanding and Growing Applications in Biomanufacturing 521\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eKatherine A. Bakeev and Jose C. Menezes\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e16.1 Introduction 521\u003c\/p\u003e \u003cp\u003e16.2 Regulatory Guidance and its Impact on PAT 522\u003c\/p\u003e \u003cp\u003e16.3 Going Beyond Process Analyzers Towards Solutions 524\u003c\/p\u003e \u003cp\u003e16.3.1 Design of experiments for risk-based analysis 526\u003c\/p\u003e \u003cp\u003e16.3.2 Sample and process fingerprinting with PAT tools 527\u003c\/p\u003e \u003cp\u003e16.3.3 Design and Control Spaces 528\u003c\/p\u003e \u003cp\u003e16.3.4 Chemometrics and process analysis 528\u003c\/p\u003e \u003cp\u003e16.4 Emerging Application Areas of PAT 529\u003c\/p\u003e \u003cp\u003e16.4.1 Biofuels 529\u003c\/p\u003e \u003cp\u003e16.4.2 Biomanufacturing 530\u003c\/p\u003e \u003cp\u003e16.5 New and Emerging Sensor and Control Technologies 531\u003c\/p\u003e \u003cp\u003e16.5.1 Terahertz spectroscopy 531\u003c\/p\u003e \u003cp\u003e16.5.2 Integrated sensing and processing 532\u003c\/p\u003e \u003cp\u003e16.5.3 Dielectric spectroscopy 533\u003c\/p\u003e \u003cp\u003e16.5.4 Process chromatography 533\u003c\/p\u003e \u003cp\u003e16.5.5 Mass spectrometry 534\u003c\/p\u003e \u003cp\u003e16.5.6 Microwave resonance 534\u003c\/p\u003e \u003cp\u003e16.5.7 Novel sensors 535\u003c\/p\u003e \u003cp\u003e16.5.8 Inferential sensors 536\u003c\/p\u003e \u003cp\u003e16.6 Advances in Sampling: NeSSI 537\u003c\/p\u003e \u003cp\u003e16.7 Challenges Ahead 537\u003c\/p\u003e \u003cp\u003e16.7.1 Continuous process validation 538\u003c\/p\u003e \u003cp\u003e16.7.2 Data challenges: data handling and fusion 539\u003c\/p\u003e \u003cp\u003e16.7.3 Regulatory challenges 539\u003c\/p\u003e \u003cp\u003e16.7.4 Enterprise systems for managing data 539\u003c\/p\u003e \u003cp\u003e16.8 Conclusion 540\u003c\/p\u003e \u003cp\u003eReferences 540\u003c\/p\u003e \u003cp\u003eIndex 545\u003c\/p\u003e","brand":"John Wiley \u0026 Sons Inc","offers":[{"title":"Default Title","offer_id":49402418659671,"sku":"9780470722077","price":141.26,"currency_code":"GBP","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0817\/1739\/5799\/files\/9780470722077.jpg?v=1730480341","url":"https:\/\/bookcurl.com\/products\/process-analytical-technology-9780470722077","provider":"Book Curl","version":"1.0","type":"link"}