{"product_id":"process-analytical-technology-isbn-9780470722077","title":"Process Analytical Technology","description":"\u003ci\u003eProcess Analytical Technology\u003c\/i\u003e explores the concepts of PAT and its application in the chemical and pharmaceutical industry from the point of view of the analytical chemist. In this new edition all of the original chapters have been updated and revised, and new chapters covering the important topics of sampling, NMR, fluorescence, and acoustic chemometrics have been added.  \u003cp\u003eCoverage includes:\u003c\/p\u003e \u003cul\u003e \u003cli\u003eImplementation of Process Analytical Technologies\u003c\/li\u003e \u003cli\u003eUV-Visible Spectroscopy for On-line Analysis\u003c\/li\u003e \u003cli\u003eInfrared Spectroscopy for Process Analytical Applications\u003c\/li\u003e \u003cli\u003eProcess Raman Spectroscopy\u003c\/li\u003e \u003cli\u003eProcess NMR Spectrscopy: Technology and On-line Applications\u003c\/li\u003e \u003cli\u003eFluorescent Sensing and Process Analytical Applications\u003c\/li\u003e \u003cli\u003eChemometrics in Process Analytical Technology (PAT)\u003c\/li\u003e \u003cli\u003eOn-Line PAT Applications of Spectroscopy in the Pharmaceutical Industry\u003c\/li\u003e \u003cli\u003eFuture Trends for PAT for Increased Process Understanding and Growing Applications in Biomanufacturing\u003c\/li\u003e \u003cli\u003eNIR Chemical Imaging\u003c\/li\u003e \u003c\/ul\u003e \u003cp\u003eThis volume is an important starting point for anyone wanting to implement PAT and is intended not only to assist a newcomer to the field but also to provide up-to-date information for those who practice process analytical chemistry and PAT.\u003c\/p\u003e \u003cp\u003eIt is relevant for chemists, chemical and process engineers, and analytical chemists working on process development, scale-up and production in the pharmaceutical, fine and specialty chemicals industries, as well as for academic chemistry, chemical engineering, chemometrics and pharmaceutical science research groups focussing on PAT.\u003c\/p\u003e \u003cp\u003e\u003cb\u003eReview from the First Edition\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e“The book provides an excellent first port of call for anyone seeking material and discussions to understand the area better. It deserves to be found in every library that serves those who are active in the field of Process Analytical Technology.”—\u003ci\u003eCurrent Engineering Practice\u003c\/i\u003e\u003c\/p\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  \"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  \u003cp\u003e\u003cstrong\u003eKatherine A. Bakeev\u003c\/strong\u003e is Principal Scientist with GlaxoSmithKline in King of Prussia, PA where she works in the Process Analytics and Chemometrics group supporting chemical development. She has twelve years of industrial experience including work in process analytical chemistry with ISP, and as a product specialist for Foss NIRSystems. She holds a PhD in Polymer Science and Engineering from the University of Massachusetts in Amherst, and a Masters in Technology Management from Stevens Institute of Technology. She has given numerous presentations on the use of near-infrared spectroscopy (NIR), and in 2007 received the Coblentz Society Craver Award for her work in NIR and chemometrics.   \u003ci\u003eProcess Analytical Technology\u003c\/i\u003e explores the concepts of PAT and its application in the chemical and pharmaceutical industry from the point of view of the analytical chemist. In this new edition all of the original chapters have been updated and revised, and new chapters covering the important topics of sampling, NMR, fluorescence, and acoustic chemometrics have been added.  \u003c\/p\u003e\u003cp\u003eCoverage includes:\u003c\/p\u003e \u003cul\u003e \u003cli\u003eImplementation of Process Analytical Technologies\u003c\/li\u003e \u003cli\u003eUV-Visible Spectroscopy for On-line Analysis\u003c\/li\u003e \u003cli\u003eInfrared Spectroscopy for Process Analytical Applications\u003c\/li\u003e \u003cli\u003eProcess Raman Spectroscopy\u003c\/li\u003e \u003cli\u003eProcess NMR Spectrscopy: Technology and On-line Applications\u003c\/li\u003e \u003cli\u003eFluorescent Sensing and Process Analytical Applications\u003c\/li\u003e \u003cli\u003eChemometrics in Process Analytical Technology (PAT)\u003c\/li\u003e \u003cli\u003eOn-Line PAT Applications of Spectroscopy in the Pharmaceutical Industry\u003c\/li\u003e \u003cli\u003eFuture Trends for PAT for Increased Process Understanding and Growing Applications in Biomanufacturing\u003c\/li\u003e \u003cli\u003eNIR Chemical Imaging\u003c\/li\u003e \u003c\/ul\u003e \u003cp\u003eThis volume is an important starting point for anyone wanting to implement PAT and is intended not only to assist a newcomer to the field but also to provide up-to-date information for those who practice process analytical chemistry and PAT.\u003c\/p\u003e \u003cp\u003eIt is relevant for chemists, chemical and process engineers, and analytical chemists working on process development, scale-up and production in the pharmaceutical, fine and specialty chemicals industries, as well as for academic chemistry, chemical engineering, chemometrics and pharmaceutical science research groups focussing on PAT.\u003c\/p\u003e \u003cp\u003e\u003cb\u003eReview from the First Edition\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e“The book provides an excellent first port of call for anyone seeking material and discussions to understand the area better. It deserves to be found in every library that serves those who are active in the field of Process Analytical Technology.”—\u003ci\u003eCurrent Engineering Practice\u003c\/i\u003e\u003c\/p\u003e","brand":"Wiley","offers":[{"title":"Default Title","offer_id":47989860237541,"sku":"NP9780470722077","price":209.95,"currency_code":"USD","in_stock":false}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/1842\/7735\/files\/9780470722077.jpg?v=1761785707","url":"https:\/\/k12savings.com\/es\/products\/process-analytical-technology-isbn-9780470722077","provider":"K12savings","version":"1.0","type":"link"}