Pharmaceutical chemistry and technology Books

Book SynopsisAn authoritative reference that contains the most up-to-date information knowledge, approaches, and applications of lipid crystals Crystallization of Lipids is a comprehensive resource that offers the most current and emerging knowledge, techniques and applications of lipid crystals. With contributions from noted experts in the field, the text covers the basic research of polymorphic structures, molecular interactions, nucleation and crystal growth and crystal network formation of lipid crystals which comprise main functional materials employed in food, cosmetic and pharmaceutical industry. The authors highlight trans-fat alternative and saturated-fat reduction technology to lipid crystallization. These two issues are the most significant challenges in the edible-application technology of lipids, and a key solution is lipid crystallization. The text focuses on the crystallization processes of lipids under various external influences of thermal flucTable of ContentsPreface xiii List of Contributors xv 1 Introduction: Relationships of Structures, Properties, and Functionality 1 Kiyotaka Sato 1.1 Introduction 1 1.2 Lipid Species 1 1.2.1 Hydrocarbons 1 1.2.2 Fatty Acids 2 1.2.3 Alcohols and Waxes 4 1.2.4 Acylglycerols 4 1.3 Physical States and the Functionality of Lipid Products 5 1.4 Formation Processes of Lipid Crystals 7 1.5 Polymorphism 9 1.6 Aging and Deterioration 11 1.7 Trans‐Fat Alternative and Saturated‐Fat Reduction Technology 13 References 15 2 Polymorphism of Lipid Crystals 17 Kiyotaka Sato 2.1 Introduction 17 2.2 Thermal Behavior of Polymorphic Transformations 17 2.3 Molecular Properties 20 2.3.1 Subcell and Chain‐Length Structures 20 2.3.2 Conformation of Hydrocarbon Chains 24 2.3.3 Glycerol Conformations 25 2.3.4 Polytypism 26 2.4 Fatty Acids 27 2.4.1 Saturated Fatty Acids 27 2.4.2 Unsaturated Fatty Acids 32 2.5 Monoacylglycerols and Diacylglycerols 37 2.5.1 Crystal/Molecular Structures 37 2.5.2 Polymorphic Behavior 39 2.6 Triacylglycerols (TAGs) 41 2.6.1 Crystal/Molecular Structures 42 2.6.2 Polymorphic Behavior 46 2.7 Conclusions 54 References 54 3 Molecular Interactions and Mixing Phase Behavior of Lipid Crystals 61 Eckhard Floeter, Michaela Haeupler, and Kiyotaka Sato 3.1 Introduction 61 3.2 Thermodynamic Considerations 63 3.2.1 Framework for Engineering Calculations 63 3.2.2 Phase Behavior of Co‐Crystallizing Components 66 3.2.3 Governing Principles for Phase Boundaries 70 3.3 Effects of Molecular Structures on the Phase Behavior 70 3.3.1 Aliphatic Chain‐Chain Interactions: n‐Alkanes 71 3.3.2 Mixtures of Fatty Acids 72 3.3.3 Mixtures of Partial Glyceride Fatty‐Acid Esters 81 3.3.4 Mixtures of TAGs 82 3.4 Mixing Behavior of TAGs in Natural and Interesterified Fats 92 3.4.1 Cocoa Butter 93 3.4.2 Palm Oil 94 3.4.3 Coconut Oil 95 3.4.4 Milk Fat 95 3.4.5 Interesterified Fats 96 3.5 Crystallization Properties 97 3.6 Conclusions 98 References 100 4 Fundamental Aspects of Crystallization of Lipids 105 Hironori Hondoh, Satoru Ueno, and Kiyotaka Sato 4.1 Introduction 105 4.2 Physical and Structural Properties of Lipid Liquids 105 4.2.1 Preheating Effects 106 4.2.2 Liquid Phases of Triacylglycerols 109 4.3 Driving Forces for Crystallization 112 4.4 Nucleation 114 4.4.1 Homogeneous versus Heterogeneous 114 4.4.2 Polymorph‐Dependent Nucleation Kinetics 118 4.4.3 Secondary Nucleation 121 4.4.4 Crystal Seeding 122 4.5 Kinetics of Crystal Growth 125 4.5.1 Mechanism of Crystal Growth 125 4.5.2 Crystal Growth Rate 127 4.5.3 Polymorph‐Dependent Growth Rate 129 4.5.4 Spherulite 130 4.5.5 Epitaxial Growth 132 4.5.6 Morphology of Crystals 133 4.6 Conclusions 135 Acknowledgment 136 References 136 5 Supramolecular Assembly of Fat Crystal Networks from the Nanoscale to the Mesoscale 143 Fernanda Peyronel, Nuria C. Acevedo, David A. Pink, and Alejandro G. Marangoni 5.1 Introduction 143 5.2 Cryo‐TEM 144 5.2.1 Challenges Associated with the Microscopic Observation of Fat Microstructure 144 5.2.2 Sample Preparation for Cryo‐TEM 145 5.2.3 Nanoscale Structure Characterization 146 5.2.4 Effects of External Fields on Fat Nanostructure 148 5.3 Physical Interactions, Models, and Mathematical Methods 154 5.3.1 Models in General 155 5.3.2 Coarse‐Grained Interactions: Nano‐ to Mesoscale 156 5.3.3 Models Using Spheres 157 5.3.4 Introduction to Modeling the Statics and Dynamics of Aggregates 157 5.3.5 Static Structure Functions 158 5.3.6 Application 1: CNP Aggregation. Tristearin Solids in Triolein Oil 158 5.3.7 Application 2: Complex Oils. Tristearin Solids in Complex Oils 161 5.3.8 Application 3: Nanoscale Phase Separation in Edible Oils 162 5.4 Ultra Small Angle X‐Ray Scattering (USAXS) 164 5.4.1 Principles of X‐Ray Scattering 164 5.4.2 USAXS Instrumentation at the APS 167 5.4.3 Sample Preparation 168 5.4.4 Unified Fit and Guinier‐Porod Models 168 5.4.5 Experimental Results 170 5.5 Concluding Remarks 174 Acknowledgments 175 References 175 6 Effects of Dynamic Temperature Variations on Microstructure and Polymorphic Behavior of Lipid Systems 183 Laura Bayés‐García, Teresa Calvet, and Miquel À. Cuevas‐Diarte 6.1 Introduction 183 6.2 Influence on the Polymorphic Behavior in Bulk State 183 6.2.1 Single Tag Components 183 6.2.2 Binary Mixtures of TAGs 189 6.3 Colloidal Dispersion States 193 6.3.1 Emulsions 193 6.3.2 Organogels 196 6.4 Role of Thermal Treatments on End Food Products Properties 198 6.4.1 Milk Fats 198 6.4.2 Other Dairy Products 199 6.4.3 Cocoa Butter 200 6.4.4 Vegetable Fats 204 6.5 Conclusions 206 References 207 7 Lipid Crystal Networks Structured under Shear Flow 211 Farnaz Maleky and Gianfranco Mazzanti 7.1 Introduction 211 7.2 Overview of the Formation of Fat Crystals 212 7.3 Temperature Gradients and Optimal Supercooling 213 7.4 Basic Concepts on Shear Flow 214 7.5 Fat Crystallization under Shear 216 7.5.1 Shear Affects Polymorphic Transformations 216 7.5.2 Crystalline Orientation Induced by Shear Flow 219 7.5.3 Shear Affects Fat Structural Properties at the Micro‐ and Nano‐Length Scales 224 7.5.4 Physicochemical Properties of Sheared Fat Matrices 227 7.5.5 Effects of Shear Flow on Mass Transfer Dynamics of Crystallizing and Crystallized Materials 231 7.6 Concluding Remarks 233 References 234 8 Tailoring Lipid Crystal Networks with High‐Intensity Ultrasound 241 Yubin Ye, Peter R. Birkin, and Silvana Martini 8.1 Introduction 241 8.2 Fundamentals of Sonication 242 8.2.1 Acoustic Driving Force 242 8.2.2 Acoustic Cell Characteristics 243 8.2.3 Cavitation 244 8.2.4 Experimental Conditions 245 8.3 Tailoring Lipid Crystal Networks 246 8.3.1 Crystallization Kinetics 246 8.3.2 Inferential Mechanism 249 8.3.3 Postsonication Changes 250 8.4 Practical Considerations 255 8.4.1 Oxidation 255 8.4.2 Scale Up 257 8.4.3 Combination with Other Processing Methods 258 8.5 Conclusions and Future Research 258 References 259 9 Effects of Foreign and Indigenous Minor Components 263 Kevin W. Smith and Kiyotaka Sato 9.1 Introduction 263 9.2 Basic Understanding 264 9.3 Effects of Foreign Components 265 9.3.1 Emulsifiers 265 9.3.2 Indigenous Minor Components 276 9.4 Other Additives 276 9.5 Conclusions 278 References 279 10 Crystallization Properties of Milk Fats 283 Christelle Lopez 10.1 Introduction 283 10.2 Milk Fat: A Wide Diversity of Fatty Acids and Triacylglycerols (TAGs) 284 10.3 Crystallization Properties of Bovine Anhydrous Milk Fat (AMF) 285 10.3.1 Thermal Properties 285 10.3.2 Effect of Cooling Rate on AMF Crystals 286 10.3.3 Effect of Shear on AMF Crystals 295 10.3.4 Effect of Minor Lipid Compounds 295 10.4 Crystallization of TAGs in Bovine Milk Fat Globules and Emulsion Droplets 296 10.4.1 Effect of Cooling Rate and Tempering 298 10.4.2 Effect of the Size of Milk Fat Globules and Lipid Droplets 304 10.5 Crystallization Properties of Milk Fat in Dairy Products 306 10.6 Tag Compositions Affecting Crystallization Properties of Milk Fat 308 10.6.1 Technological Process: Dry Fractionation 308 10.6.2 Dietary Manipulations 312 10.6.3 Milk Fat from Various Mammal Species 315 10.7 Liquid Tag Phase 316 10.8 Conclusions 317 References 318 11 Crystallization Behavior of Sunflower Oil–Based Fats for Edible Applications 323 Maria L. Herrera and Silvana Martini 11.1 Introduction 323 11.2 High Stearic High Oleic Sunflower Oil 324 11.2.1 Fractionation of HSHO‐SFO 324 11.2.2 Crystallization Behavior 326 11.2.3 Polymorphic Behavior 329 11.3 Blends of Sunflower Oil and Milk Fat 337 11.3.1 Chemical Composition 340 11.3.2 Physical Properties 340 11.3.3 Addition of Palmitic Sucrose Ester 344 11.4 HSHO‐Based CBE 347 11.5 Conclusions 348 References 348 12 Physical Properties of Organogels Developed with Selected Low‐Molecular‐Weight Gelators 353 Jorge F. Toro‐Vazquez, Flor Alvarez‐Mitre, and Miriam Charó‐Alonso 12.1 Introduction 353 12.2 Basic Aspects of LMOGs: From Molecular Architecture to Functional Assemblies 355 12.3 Why Developing Organogels with Vegetable Oils? 356 12.3.1 Vegetable Oils as Solvent in the Development of Organogels with LMOGs 357 12.3.2 Relationship between Molecular Structure of LMOGs and Physical Properties of Organogels 367 12.4 Organogels of Candelilla Wax 373 12.4.1 Rheological Properties of Candelilla Wax Organogels Developed Applying Shear Rate 373 12.4.2 Applications of Candelilla Wax Organogels 377 12.5 Conclusions 377 References 379 13 Formation and Properties of Biopolymer‐Based Oleogels 385 Ashok R. Patel 13.1 Introduction 385 13.2 Formation of Polymer‐Based Oleogels 386 13.2.1 Polymer Oleogelation through Direct Methods 387 13.2.2 Polymer Oleogelation through Indirect Methods 389 13.3 Properties of Polymer‐Based Oleogels 393 13.3.1 Mechanical Properties 393 13.3.2 Temperature Sensitivity 394 13.3.3 Stability in Presence of Water 397 13.4 Potential Applications of Polymer‐Based Oleogels 397 13.4.1 Replacement of Beef Fat in Frankfurters 397 13.4.2 Heat‐Resistant Chocolates 397 13.4.3 Polymer Oleogels as Alternative to Full‐Fat Shortenings 397 13.4.4 Bakery Applications of Ethyl Cellulose Oleogels 398 13.5 Conclusions: Opportunities and Challenges 398 Acknowledgments 401 References 402 14 Lipid Crystallization in Water‐in‐Oil Emulsions 405 Nicole L. Green and Dérick Rousseau 14.1 Introduction 405 14.2 Basics of Emulsion Properties 406 14.3 Emulsifier Effects on W/O Emulsions 408 14.3.1 Mono‐ and Diacylglycerols (E471) 409 14.3.2 Sucrose Fatty‐Acid Esters (E473) 411 14.3.3 Lecithins (E322) 412 14.3.4 Sorbitan Esters and Polyesters (E491‐E496) 413 14.3.5 Polyglycerol Esters (E475 – E476) 415 14.4 Stabilization Modes of W/O Emulsions 415 14.4.1 Pickering Stabilization 416 14.4.2 Network Stabilization 420 14.4.3 Combined Pickering and Network Stabilization 421 14.5 Conclusions 423 References 424 15 Crystallization of Lipids in Oil‐in‐Water Emulsion States 431 John N. Coupland 15.1 The Basic Concepts 431 15.2 Surface Nucleation 432 15.3 Polymorphic Transitions in Droplets 436 15.4 Morphology of Crystalline Droplets 437 15.5 Colloidal Stability of Crystalline Droplets 439 15.6 Conclusions 442 References 443 16 Lipid Crystals and Microstructures in Animal Meat Tissues 447 Michiyo Motoyama, Genya Watanabe, and Keisuke Sasaki 16.1 Introduction 447 16.2 Depot Fat and Crystalline State 448 16.2.1 Adipose Tissue 448 16.2.2 Triacylglycerol (TAG) Compositions of Animal Fats 449 16.3 Fat Crystals and Quality of Porcine Adipose Tissue 450 16.3.1 Polymorphism of Extracted Porcine Fat Crystals 450 16.3.2 Fat Crystals and Macroscopic Meat Quality 454 16.3.3 Application to Actual Meat and Meat Products 455 16.4 Crystal Microstructures in Adipose Tissues 460 16.5 Concluding Remarks 462 Acknowledgments 462 References 462 17 Conventional and New Techniques to Monitor Lipid Crystallization 465 Annelien Rigolle, Koen Van Den Abeele, and Imogen Foubert 17.1 Introduction: What Would Be a Perfect Technique? 465 17.2 Conventional Techniques (and Advances Made) 466 17.2.1 Pulsed Nuclear Magnetic Resonance 466 17.2.2 Differential Scanning Calorimetry 469 17.2.3 X‐Ray Diffraction 472 17.2.4 Rheology 474 17.2.5 Microscopy 476 17.3 “New” Techniques with Potential for Online Monitoring 478 17.3.1 Ultrasonic Techniques 478 17.3.2 Laser Backscattering 484 17.3.3 Near‐Infrared and Raman Spectroscopy 485 17.4 Conclusions 485 Acknowledgments 486 References 487 Index 493

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Book SynopsisPhysiologically Based Pharmacokinetic (PBPK) Modeling and Simulations The first book dedicated to the emerging field of physiologically based pharmacokinetic modeling (PBPK) Now in its second edition, Physiologically Based Pharmacokinetic (PBPK) Modelling and Simulations: Principles, Methods, and Applications in the Pharma Industry remains the premier reference book throughout the rapidly growing PBPK user community. Using clear and concise language, author Sheila Annie Peters connects theory with practice as she explores the vast potential of PBPK modeling for improving drug discovery and development. This fully updated new edition covers key developments in the field of PBPK modelling and simulations that have emerged in recent years. A brand-new section provides case studies in different application areas of PBPK modelling, including drug-drug interaction, genetic polymorphism, renal impairment, and pediatric extrapolation. Additional chapters address Table of ContentsPreface xix Acknowledgements xxi About the companion xxiii Section I. Principles, Methods, andBackground Information 1 1 A Review of Pharmacokinetic and Pharmacodynamic Principles 3 1.1 Introduction 4 1.2 Pharmacokinetic Principles 4 1.2.1 Routes of Drug Administration 4 1.2.2 Intravenous Bolus 4 1.2.3 Plasma Protein Binding and Blood–Plasma Ratio 9 1.2.4 Hepatic, Renal, and Biliary Clearances 12 1.2.5 Extravascular (Subcutaneous, Intramuscular, and Per Oral) Absorption 16 1.2.6 Absorption from Solid Dosage Forms 20 1.2.7 Role of Transporters in ADME 22 1.2.8 Linear and Non-Linear Pharmacokinetics 24 1.2.9 Intravenous Infusion, Repeated Dosing, Steady State Kinetics, and Accumulation 25 1.2.10 Active Metabolite and Prodrug Kinetics 28 1.3 Pharmacokinetic Variability 32 1.4 Pharmacokinetics Optimization in Drug Discovery 34 1.5 Pharmacodynamic Principles 34 1.5.1 Pharmacological Targets and Drug Action 35 1.5.2 Functional Adaptation Processes 39 1.5.3 Biomarkers, Surrogate Endpoints, and Clinical Endpoints 41 Keywords 47 References 48 2 A Review of Drug–Drug Interactions 51 2.1 Introduction 51 2.2 Drug Interactions Mediated by Enzymes and Transporters at Various Sites 54 2.3 Factors Affecting DDI 54 2.4 In Vitro Methods to Evaluate Drug–Drug Interactions 56 2.4.1 Candidate Drug as a Potential Perpetrator 57 2.4.2 Candidate Drug as a Potential Victim of Inhibition 58 2.5 Sources of Uncertainty 59 2.6 Therapeutic Protein–Drug Interaction 59 References 61 3 Modeling Pharmacokinetics, Pharmacodynamics, And Drug Interactions 65 3.1 Introduction 66 3.2 Modeling Pharmacokinetics 66 3.2.1 Compartmental Modeling of Linear and Nonlinear Pharmacokinetics (Enzyme and/or Transporter Capacity Limitation as Well as Target-Mediated Drug Disposition) 67 3.2.2 Population Pharmacokinetics 76 3.3 Pharmacokinetics/Pharmacodynamics and PK/Efficacy (Exposure/ Response) Modeling 80 3.3.1 PK/PD Models for Direct Effect: Sigmoid Emax Model 84 3.3.2 PK/PD Models for Direct Effect: Classical Receptor Theory 86 3.3.3 PK/PD Models Accommodating Delayed Pharmacological Response 89 3.3.4 PK/PD Models Accommodating Functional Adaptation Leading to Nonlinearity in Pharmacological Response with Respect to Time 96 3.3.5 PK/Efficacy Modeling 97 3.3.6 Translation of PK/PD and PK/Efficacy Modeling to Human 100 3.3.7 Average, Minimum, and Maximum Steady-State Concentrations 104 3.3.8 Estimation of Biologically Effective Dose in Human 107 3.3.9 Therapeutic Window 109 3.3.10 Static Models for Drug Interactions 109 3.4 Physiologically Based Pharmacokinetic (PBPK) Modeling and Its Integration with Pharmacodynamics and Efficacy Models 112 3.4.1 PK Modeling Compartmental vs PBPK 112 3.4.2 PK Variability: Population PK (popPK) Modeling vs PBPK 114 3.4.3 Integration of PBPK with PD, Quantitative Systems Pharmacology (QSP) Models or Quantitative Systems Toxicologyand Safety (QSTS) 114 3.4.4 PBPK Models to Evaluate Drug–Drug Interactions 115 3.4.5 DDI Risk Assessment with PBPK vs Static Models 118 Keywords 123 References 125 4 Physiological Model For Absorption 129 4.1 Introduction 130 4.2 Drug Absorption and Gut Bioavailability 130 4.2.1 Solubility and Dissolution Rate 130 4.2.2 Permeability: Transcellular, Paracellular, and Carrier-Mediated Pathways 136 4.2.3 Barriers to Membrane Transport – Luminal Degradation, Efflux, and Gut Metabolism 138 4.3 Factors Affecting Drug Absorption and Gut Bioavailability 140 4.3.1 Physiological Factors Affecting Oral Drug Absorption and Species Differences in Physiology 140 4.3.2 Compound-Dependent Factors 144 4.3.3 Formulation-Dependent Factors 144 4.4 In Silico Predictions of Passive Permeability and Solubility 147 4.4.1 In Silico Models for Permeability 147 4.4.2 In Silico Models for Solubility 147 4.5 Measurement of Permeability, Solubility, Luminal Stability, Efflux, Intestinal Metabolism 148 4.5.1 In Vitro, In Situ, and In Vivo Models for Effective Permeability 148 4.5.2 Measurement of Thermodynamic or Equilibrium Solubility 153 4.5.3 Luminal Stability 154 4.5.4 Efflux 154 4.5.5 In Vitro Models for Gut Metabolism and Estimation of Fraction Escaping Gut Metabolism 155 4.6 Absorption Modeling 156 Keywords 162 References 163 5 Physiological Model For Distribution 169 5.1 Introduction 170 5.2 Factors Affecting Tissue Distribution of Xenobiotics 170 5.2.1 Physiological Factors and Species Differences in Physiology 171 5.2.2 Compound-Dependent Factors 176 5.3 In Silico Models of Tissue Partition Coefficients 176 5.4 Measurement of Parameters Representing the Rate and Extent of Tissue Distribution 181 5.4.1 Assessment of Rate and Extent of Brain Penetration 181 5.5 Physiological Model for Drug Distribution 186 5.6 Drug Concentrations at the Site of Action 187 Keywords 189 References 189 6 Physiological Models For Drug Metabolism And Excretion 193 6.1 Introduction 193 6.2 Factors Affecting Drug Metabolism and Excretion of Xenobiotics 194 6.3 Models for Hepatobiliary and Renal Excretion 197 6.3.1 In Silico Models 197 6.3.2 In Vitro Models for Hepatic Metabolism 197 6.3.3 In Vitro Models for Transporters 200 6.4 Physiological Models 203 6.4.1 Hepato-Biliary Elimination of Parent Drug and Metabolites 205 6.4.2 Renal Excretion 208 References 211 7 Generic Whole-Body Physiologically Based Pharmacokinetic Modeling 217 7.1 Introduction 217 7.2 Structure of a Generic Physiologically-Based Pharmacokinetic (PBPK) Model 218 7.3 Somatic Compartments 220 7.3.1 Lungs (LU) 220 7.3.2 Arterial Blood (ART) 220 7.3.3 Venous Blood (VEN) 220 7.3.4 Stomach (ST) 220 7.3.5 Gut (GU) 220 7.4 Model Assumptions 221 7.5 PBPK Software 221 References 223 8 Pbpk Modeling Of Biotherapeutics 225 8.1 Introduction 226 8.2 Therapeutic Proteins 226 8.2.1 Peptides and Proteins 226 8.2.2 Antibodies and Antibody-Based Therapies 227 8.3 Pharmacokinetics of Therapeutic Proteins 234 8.3.1 Absorption 234 8.3.2 Renal Elimination 235 8.3.3 Immunogenicity 235 8.3.4 PEGylation 239 8.3.5 Transport by Convective and Transcytotic Extravasation 239 8.3.6 Catabolic Elimination (Proteolysis) 239 8.3.7 FcRn-Mediated Protection of IgGs Against Catabolism in FcRn-Rich Cells 241 8.3.8 Distribution and lymphatic elimination 242 8.3.9 Target-Mediated Drug Disposition and Receptor-Mediated Endocytosis 243 8.4 PBPK Modeling of Monoclonal Antibodies 244 8.4.1 Full PBPK Model for Monoclonal Antibodies 244 8.4.2 Minimal PBPK Model for Monoclonal Antibodies 253 8.5 Applications of PBPK Modeling of Monoclonal Antibodies 253 8.5.1 Pharmacokinetic Scaling 253 8.5.2 PBPK Integration with Pharmacodynamics of Monoclonal Antibodies 255 Keywords 156 References 258 9 Uncertainty And Population Variability 263 9.1 Introduction 264 9.2 Distinguishing Uncertainty and Variability 264 9.3 Sources of Uncertainty in Drug-related Parameters 264 9.4 Sources of Variability in System Parameters 266 9.5 Handling Population Variability 269 9.5.1 A POSTERIORI and A PRIORI Approaches to Handling Population Variability 269 9.5.2 Correlations Between Parameters 271 9.6 Uncertainty and Sensitivity Analysis 272 9.6.1 Local Sensitivity Analysis (One-at-a-time (OAT) and Derivative-based Methods) 272 9.6.2 Parameter Interactions and Global Sensitivity Analysis (GSA) 275 9.6.3 Global Sensitivity Analysis for Correlated Parameters (cGSA) 278 9.6.4 Applications of Sensitivity Analysis for PBPK Models 280 9.6.5 Limitations of Global Sensitivity Analysis 281 9.7 Uncertainty and Population Variability in Clinical Efficacy and Safety 282 Keywords 285 References 285 10 Nonclinical, Clinical, and Model-Informed Drug Development 293 10.1 Introduction: An Overview of Different Phases of Drug Development 294 10.2 Nonclinical Development 295 10.2.1 Preclinical Pharmacology, PK/PD Modeling, and Human Dose Prediction 297 10.2.2 Safety and Toxicology Studies 297 10.2.3 Studies with Radiolabeled Compound 298 10.3 Clinical Pharmacology Studies 302 10.3.1 First-in-Human, Single, and Multiple Ascending Dose Studies 302 10.3.2 Biopharmaceutics – Absolute Oral Bioavailability and Bioequivalence Study 304 10.3.3 Food Effect Study 304 10.3.4 Organ (Hepatic and Renal) Impairment Study 305 10.3.5 Pediatric Assessment 306 10.3.6 Mass Balance Study 307 10.3.7 Drug Interaction Study 307 10.3.8 Pharmacogenomics Study 308 10.3.9 Thorough QT (TQT) and Concentration QT (C-QT) Study 308 10.3.10 Immunogenicity Assays and Comparability Study for Biologics 309 10.3.11 Drug Labelling 309 10.4 Clinical Development in Oncology 310 10.5 Fast Track Routes to Address Unmet Medical Need in the Treatment of Serious Conditions 311 10.6 Model-Informed Drug Development 312 10.7 Physiologically Based Pharmacokinetic Models Complementing Clinical Pharmacology Studies 314 10.8 PBPK in Oncology 315 Regulatory Guidelines 316 References 319 Section II. Applications In The Pharmaceutical Industry 323 11 Overview Of Pbpk Applications 325 11.1 Introduction 325 11.2 PBPK Applications for Internal Decisions 326 11.3 PBPK Applications for Regulatory Filing 328 11.4 PBPK Modeling and Simulations Along the Value Chain 332 References 335 12 Applications Of Hypothesis Generation And Testing With Pbpk Models 337 12.1 Introduction 338 12.2 Hypothesis Generation and Testing with PBPK Models 338 12.2.1 Parameter Estimation from Intravenous Pharmacokinetic Profiles 338 12.2.2 Simulation of Oral PK Profile 341 12.2.3 Sensitivity Analysis 342 12.2.4 Verification of Hypotheses 346 12.2.5 Auto-inhibition of Drug-Metabolizing Enzymes, Uptake and Efflux Transporters 347 12.3 Hypothesis Generation and Testing Along the Value Chain 348 12.4 Conclusions 351 References 351 13 Applications of Physiologically Based Pharmacokinetic Models Integrated With Drug Effect Models (Pbpk/Pd) 353 13.1 Introduction: Integration of PBPK with Drug Effect Models 354 13.2 Dosing in Specific Populations 355 13.3 PBPK/PD for Bottom-Up Prediction of Inter-Patient Variability in Drug Response 357 13.4 PBPK/PD for Predicting the Inter-Patient Variability in Response to Prodrugs and Active Metabolites 358 13.5 PBPK/PD When Systemic Concentrations are not the Driver forDrug Response 359 13.5.1 Pre-Systemic Drug Target 359 13.5.2 Effect-Site Drug Concentration Different from Systemic Concentration 360 13.6 PBPK/PD for Monoclonal Antibodies 362 13.7 PBPK Models Linked to Quantitative Systems Pharmacology and Toxicology Models 363 13.7.1 PBPK–QST Models to Predict Drug-Induced Liver Injury 363 13.7.2 PBPK–QST Models to Predict Drug-Induced Cardiotoxicity 367 13.8 Conclusions 371 References 371 14 Pbpk Modeling and Simulations to Evaluate Clinical Drug-Drug Interactions 375 14.1 Introduction 376 14.2 Clinical DDI Studies and Modeling Approaches to Address Key Questions Related to Drug–Drug Interactions 376 14.2.1 Dedicated Clinical DDI Studies 378 14.2.2 Investigation of Phenotypic Effects for NMEs Predominantly Cleared by Polymorphic Enzyme or Transporter 379 14.2.3 Prospective Nested DDI Study 380 14.2.4 Cocktail DDI Study 381 14.2.5 PBPK Modeling and Simulations 381 14.2.6 Claims Relating to Results of DDI Studies 381 14.2.7 Impact on Label 382 14.3 PBPK Modeling of Different Types of Drug Interactions 382 14.3.1 PBPK Modeling Strategy: New Molecular Entity as Victim of CYP-Based Drug Interactions 382 14.3.2 PBPK Modeling Strategy: New Molecular Entity as Perpetrator of CYP-Based Drug Interactions 383 14.3.3 Non-CYP Based Drug Interactions 384 14.3.4 Transporter-Mediated Drug Interactions 385 14.4 DDI Predictions with PBPK Modeling and Simulations in Clinical Drug Development and Regulatory Submissions 387 14.4.1 DDI Predictions Along the Value Chain (Figure 14.5) 387 14.4.2 Possible Regulatory Outcomes, Based on the Predictions from a Verified and Validated PBPK Model 389 14.4.3 Regulatory Acceptance of PBPK Analyses Included in Regulatory Submissions 390 14.4.4 Predictive Performance of PBPK Models 391 14.5 Comparison of DDI Prediction Using Static and Dynamic Models 392 14.6 Conclusions 393 References 394 15 Dose Extrapolation Across Populations (Healthy Adult Caucasian To Pediatric, Pregnant Women, Different Ethnicities, Geriatric, Smokers And Obese Populations) 397 15.1 Introduction 398 15.2 PBPK Modeling Strategy for Dose Extrapolation to Specific Populations 398 15.3 Potential Benefits of PBPK Modeling for Dose Extrapolations to Specific Populations 399 15.4 Dose Extrapolations to Specific populations 404 15.4.1 Pediatric Starting Dose Selection 404 15.4.2 Pregnancy 406 15.4.3 Ethnicity – Japanese Population 407 15.4.4 Geriatric Population 408 15.4.5 Obese 409 15.4.6 Smokers 410 15.5 Conclusions 410 References 411 16 Dose Extrapolation Across Populations: Healthy Adult To Hepatic And Renal Impairment Populations 417 16.1 Introduction 418 16.2 Pathophysiological Changes in Organ Impairment 419 16.2.1 Hepatic Impairment 419 16.2.2 Renal Impairment 420 16.3 PBPK Modeling Strategy: Model Development, Verification, Validation, and Application 420 16.4 Benefits of Applying Validated PBPK Models to Organ-Impaired Populations 421 16.4.1 Enhancing Regulatory Confidence in the Application of PBPK Modeling for the Prediction of Exposure in the Organ-Impaired Population 421 16.4.2 Contribution of PBPK to the Totality of Evidence in Evaluating the Effect of Renal Impairment on Drug Exposure to Inform Labelling 424 16.5 Conclusions 425 References 426 17 Absorption-Related Applications Of Pbpk Modeling 429 17.1 Introduction 429 17.2 In Vitro – In Vivo Disconnect, Parameter Non-Identifiability and the Importance of Identifying Factors Limiting Absorption Through a Deconvolution of the Mechanisms Contributing to Gut Bioavailability 431 17.3 Non-Regulatory Internal Applications of PBPK Modeling and Simulations 433 17.3.1 Prediction of Fraction Absorbed 433 17.3.2 Oral Formulation Development 433 17.4 Regulatory Applications of PBPK Modeling and Simulations 438 17.4.1 Food–Drug Interactions 438 17.4.2 Interactions of a Poorly Soluble Weak Base with Acid Reducing Agents (ARAs) 444 17.4.3 In Vitro – In Vivo Correlations (IVIVCs) to Serve as Surrogate for Bioequivalence Testing (Case Study 12) 445 17.4.4 Biowaivers Based on Virtual Bioequivalence 449 17.4.5 Virtual Bioequivalence of Locally Acting Products (LAPs) 450 17.5 Conclusions 450 References 452 18 Regulatory Guidelines On The Reporting Of Physiologically Based Pharmacokinetic (Pbpk) Modeling Analysis 457 18.1 Introduction 457 18.2 Food and Drug Administration (FDA) Guidelines 458 18.3 European Medicines Agency (EMA) Guidelines 459 18.4 Comparison of FDA and EMA Guidelines 461 18.5 Risk-Informed Evidentiary Framework to Assess PBPK Model Credibility 463 18.6 Drug Model Verification of Locally Acting Products (LAPs) 464 References 466 19 Resolving The Challenges To Establishing Confidence In Pbpk Models 469 19.1 Introduction 470 19.2 Requirements for Developing Mechanistically Credible PBPK Models for the Three Broad Categories of Applications 470 19.3 Challenges to Developing Mechanistically Credible PBPK Models and Consequences 473 19.3.1 Model Building 473 19.3.2 Model Verification of Predicted Exposure and Validation of Predictive Performance 476 19.4 Resolving the Challenges to Developing Mechanistically Credible PBPK Models 476 19.5 Totality of Evidence 478 19.6 Conclusions 480 References 481 20 Epilogue 483 20.1 PBPK Modeling Successes 483 20.2 Challenges 484 20.2.1 Drug Model Parameterization 484 20.2.2 Knowledge Gaps in Physiological Parameters 485 20.2.3 Prospective Validation of Prediction Performance 485 20.3 Meeting the Challenges 485 20.4 Future Directions for PBPK Modeling 486 References 488 Section III. Case Studies Of Pbpk Applications In The Pharmaceutical Industry 491 Case Study 1 Hypothesis Testing (Solubility) 493 Case Study 2 Hypothesis Testing (Gastric Emptying) 499 Case Study 3 Hypothesis Testing (Intestinal Loss) 505 Case Study 4 Pbpk/Pd 509 Case Study 5 Drug–Drug Interaction (Inhibition) 515 Case Study 6 Drug–Drug Interaction (Induction) 521 Case Study 7 Genetic Polymorphism 527 Case Study 8 Pediatric Extrapolation 535 Case Study 9 Pregnancy 541 Case Study 10 Hepatic Impairment 547 Case Study 11 Renal Impairment 555 Case Study 12 Absorption – Ivivc 561 Appendices 567 Index 579

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Book SynopsisBioanalytical Aspects in Biological Therapeutics Deepen your understanding of how critical data are generated from bioanalysis In Bioanalytical Aspects in Biological Therapeutics, a team of renowned chemists, immunologists, and biologists delivers a timely and practical exploration of the diverse scientific and technical literature on the bioanalytical investigation of current biotherapeutics under development. The book discusses the challenges and considerations for bioanalytical support, covering a wide range of central topics in the field, including overview and basic immunology for testing of biological therapeutics, pharmacokinetic aspects, clinical immunogenicity prediction and testing, biomarker testing, biotransformation assessment for biologics, statistical aspects of bioanalytical testing, regulatory expectations, and more. Drug development and analysis professionals will learn how critical data are generated from bioanalysis and how proven tools and methods are applied to thTable of ContentsPreface viiXiaohui Xu and Weifeng Xu Foreword ixBinodh DeSilva Acknowledgments xiii About the Editors xv List of Contributors xvii 1 Overview of the Development of Biotherapeutics and the Role of Bioanalytical Sciences 1Robert Dodge 2 Basic Immunology for Bioanalytical Testing of Biotherapeutics 23Kang Chen and Weifeng Xu 3 Platform and Instrument Considerations in Bioanalytical Testing 51Dominic Warrino and Franklin Spriggs 4 Pharmacokinetic Assays 67Tong-Yuan Yang and Eric Wakshull 5 Recent Progress in Biomarker Bioanalysis and Target Engagement Assessment 87Yan G. Ni, Lindsay E. King and Carmen Fernández-Metzler 6 Immunogenicity Risk Assessment for Biotherapeutics 141Jochem Gokemeijer 7 Bioanalytical Strategy to Support Clinical Immunogenicity Assessment: Anti-drug Antibodies 159Ying Wang and Michael Luong 8 Bioanalytical Scheme for Antidrug Neutralizing Antibody Assays 185Weifeng Xu, Bonnie Wu and Jim McNally 9 Critical Reagents in Bioanalysis 209Yang Xu, Agostinho Gomes Rocha, Shannon Chilewski, Krisna C. Duong-Ly, Kun Yang and Jonathan Haulenbeek 10 Statistical Aspects of Bioanalytical Testing 239Arkady M. Gershteyn and Mark Ma 11 Bioanalytical Aspects in Biological Therapeutics: Biotransformation 277Wenying Jian, Cong Wei and Jinping Gan 12 New Modalities: Multidomain Therapeutics and Gene Therapy Programs 309Kelly Colletti and Mark Ma 13 Regulatory Aspects for Assay Development, Validation, and Sample Analysis 327Amy Lavelle and Megan Wiberg Index 355

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Book SynopsisMarket access is the fourth hurdle in the drug development process and the primary driver for global income of any new drug. Without a strategy in place for pricing, showing value for effectiveness and an understanding of the target purchasers' needs, the drug will fail to reach its intended market value. Introduction to Market Access for Pharmaceuticals is based on an accredited course in this area, taken from the European Market Access University Diploma (EMAUD), and is affiliated with Aix Marseille University.Key Features:The first guide to market access for pharmaceuticals based on tested teaching materialsAddresses both pharmaceutical and vaccine productsIncludes case studies and scenariosCovers market access consdierations for Western Europe, the USA, Japan and ChinaExplains the impact the changing healthcare market will have on your productTable of ContentsChapter 1: Health as a GoodChapter 2: Decision-Making in Public HealthChapter 3: Definition and ConceptsChapter 4: HTA Decision Analysis frameworkChapter 5: Early HTA AdviceChapter 6: Overview of Market Access AgreementsChapter 7: External Reference PricingChapter 8: Gap between Payers and RegulatorsChapter 9: Early Access ProgramsChapter 10: Market Access of Orphan DrugsChapter 11: Market Access of Vaccines in Developed CountriesChapter 12: FranceChapter 13: GermanyChapter 14: ItalyChapter 15: SpainChapter 16: SwedenChapter 17: United KingdomChapter 18: The United StatesChapter 19: JapanChapter 20: China

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Book SynopsisA Practical Guide to Managing Clinical Trials is a basic, comprehensive guide to conducting clinical trials. Designed for individuals working in research site operations, this user-friendly reference guides the reader through each step of the clinical trial process from site selection, to site set-up, subject recruitment, study visits, and to study close-out. Topics include staff roles/responsibilities/training, budget and contract review and management, subject study visits, data and document management, event reporting, research ethics, audits and inspections, consent processes, IRB, FDA regulations, and good clinical practices. Each chapter concludes with a review of key points and knowledge application.Unique to this book is A View from India, a chapter-by-chapter comparison of clinical trial practices in India versus the U.S. Throughout the book and in Chapter 10, readers will glimpse some of the challenges and opportunities in the emerging and Trade Review'"A Practical Guide to Managing Clinical Trials" provides a good introduction to the basics of clinical research for investigators, study coordinators, and other site personnel. The clear writing makes the book a quick read.' – Norman M. Goldfarb for Journal of Clinical Research Best Practices, Vol. 13, No. 12, December 2017.'"A Practical Guide to Managing Clinical Trials" provides a good introduction to the basics of clinical research for investigators, study coordinators, and other site personnel. The clear writing makes the book a quick read.' – Norman M. Goldfarb for Journal of Clinical Research Best Practices, Vol. 13, No. 12, December 2017.Table of ContentsChapter 1: Rules, Roles and ResponsibilitiesChapter 2: Products, Protocols, and Pre-trial PreparationChapter 3: Sponsor, Site and Study Start-upChapter 4: Enticement, Enrollment, and Engagement: The Informed Consent ProcessChapter 5: From Enrollment to Final VisitChapter 6: Collaborating for Compliance and Quality Data – Monitoring and AuditsChapter 7: Building BudgetsChapter 8: Contracts, Clauses and Closing the DealChapter 9: US Clinical Trials – Additional TopicsChapter 10: Clinical Research and India

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Book SynopsisOligonucleotides represent one of the most significant pharmaceutical breakthroughs in recent years, showing great promise as diagnostic and therapeutic agents for malignant tumors, cardiovascular disease, diabetes, viral infections, and many other degenerative disorders. The Handbook of Analysis of Oligonucleotides and Related Products is an essential reference manual on the practical application of modern and emerging analytical techniques for the analysis of this unique class of compounds. A strong collaboration among thirty leading analytical scientists from around the world, the book provides readers with a comprehensive overview of the most commonly used analytical techniques and their advantages and limitations in assuring the identity, purity, quality, and strength of an oligonucleotide intended for therapeutic use.Topics discussed include: Strategies for enzymatic or chemical degradation of chemically modified oligonucleotides toTrade ReviewThis is a unique resource for guiding the analysis of oligonucleotide-based drug products. No other single source provides such a comprehensive overview of the necessary analytical techniques that assess the qualitative characteristics of oligonucleotides intended for pharmaceutical use.—Rachel R Chennault, Ph.D.(American College of Clinical Pharmacy), in Doody's Notes Table of ContentsPurity Analysis and Impurities Determination by Reversed-Phase High- Performance Liquid Chromatography. Purity Analysis and Impurities Determination by AEX-HPLC. Purity Analysis and Molecular Weight Determination by Size Exclusion HPLC Analysis. Analysis of Oligonucleotides by Liquid Chromatography—Mass Spectrometry. Sequence Determination and Confirmation by MS/M S and MALDI-TOF. Tm Analysis of Oligonucleotides. Purity and Content Analysis of Oligonucleotides by Capillary Gel Electrophoresis. Bioanalysis of Therapeutic Oligonucleotides Using Hybridization-Based Immunoassay Techniques. Oligonucleotide Assay and Potency. Microbial Analysis: Endotoxin Testing. Analysis of Residual Solvents by Head Space Gas Chromatography. Determination of Extinction Coefficient. Structural Determination by NMR. Infrared Analysis of Oligonucleotides. Stability Indicating Methods for Oligonucleotide Products. Analysis by Hydrophilic Interaction Chromatography. Determination of Base Composition. Analysis of Metals in Oligonucleotides. Regulatory Considerations for the Development of Oligonucleotide Therapeutics.

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Book SynopsisUsing time-to-event analysis methodology requires careful definition of the event, censored observation, provision of adequate follow-up, number of events, and independence or noninformativeness of the censoring mechanisms relative to the event. Design and Analysis of Clinical Trials with Time-to-Event Endpoints provides a thorough presentation of the design, monitoring, analysis, and interpretation of clinical trials in which time-to-event is of critical interest.After reviewing time-to-event endpoint methodology, clinical trial issues, and the design and monitoring of clinical trials, the book focuses on inferential analysis methods, including parametric, semiparametric, categorical, and Bayesian methods; an alternative to the Cox model for small samples; and estimation and testing for change in hazard. It then presents descriptive and graphical methods useful in the analysis of time-to-event endpoints. The next several chapters explore a variety of Trade Review… One of the strengths of the book is the collection, discussion and illustration of the many diverse time-to-event problems that may occur in practice. … this publication provides a comprehensive overview of classical and emerging ideas in the analysis of time-to-event problems. Written by experts in their area, the book has a wealth of references in each topic should the reader wish to learn about or extend their understanding of individual concepts or analysis methods. It is a worthwhile book to have in the library for anyone working in designing, conducting, analysing or interpreting studies with time-to-event outcomes.—Australian & New Zealand Journal of Statistics, 2011Table of ContentsOverview of Time-to-Event Endpoint Methodology. Design (and Monitoring) of Clinical Trials with Time-to-Event Endpoints. Overview of Time-to-Event Parametric Methods. Overview of Semiparametric Inferential Methods for Time-to-Event Endpoints. Overview of Inferential Methods for Categorical Time-to-Event Data. Overview of Bayesian Inferential Methods Including Time-to-Event Endpoints. An Efficient Alternative to the Cox Model for Small Time-to-Event Trials. Estimation and Testing for Change in Hazard for Time-to-Event Endpoints. Overview of Descriptive and Graphical Methods for Time-to-Event Data. Design and Analysis of Analgesic Trials. Design and Analysis of Analgesic Trials with Paired Time-to-Event Endpoints. Time-to-Event Endpoint Methods in Antibiotic Trials. Design and Analysis of Cardiovascular Prevention Trials. Design and Analysis of Antiviral Trials. Cure Rate Models with Applications to Melanoma and Prostate Cancer Data. Parametric Likelihoods for Multiple Nonfatal Competing Risks and Death, with Application to Cancer Data. Design, Summarization, Analysis, and Interpretation of Cancer Prevention Trials. LASSO Method in Variable Selection for Right-Censored Time-to-Event Data with Application to Astrocytoma Brain Tumor and Chronic Myelogenous Leukemia. Selecting Optimal Treatments Based on Predictive Factors. Application of Time-to-Event Methods in the Assessment of Safety in Clinical Trials. Design and Analysis of Chronic Carcinogenicity Studies of Pharmaceuticals in Rodents. Design and Analysis of Time-to-Tumor Response in Animal Studies: A Bayesian Perspective. Index.

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Book SynopsisThis book covers the essentials of drug delivery research and provides a unique forum for scientific experimental methods that are exclusively focused by the in-vitro, ex-vivo, and in-vivo methodologies of drug delivery research and felicitates translational research. The book includes recent and novel approaches in evaluation methods of transdermal, nasal, ocular, oral and intraoral, gastro-retentive, colon-targeted, and brain-targeted drug delivery systems. Providing up to date and comprehensive information, this text is invaluable to students, teachers, scientists, and others employed in the field of drug delivery. Table of Contents1. In-Vitro and In-Vivo Tools in Emerging Drug Delivery Scenario: Challenges and Updates 2. Intraoral and Peroral Drug Delivery Systems 3. Transdermal Drug Delivery Systems 4. Nasal and Pulmonary Drug Delivery Systems 5. Ocular Drug Delivery Systems 6. Gastroretentive Drug Delivery Systems 7. Colon Targeted Drug Delivery Systems 8. Brain Targeted Drug Delivery Systems 9. Parenteral Drug Delivery Systems Appendix: Characterization Parameter and Common Characterization Tools

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Book SynopsisWhat's the Deal with Biosimilars?Biosimilars are gaining momentum as new protein therapeutic candidates that can help fill a vital need in the healthcare industry. The biological drugs are produced by recombinant DNA technology that allows for large-scale production and an overall reduction time in costs and development. Part of a two-volume set that covers varying aspects of biosimilars, Biosimilars and Interchangeable Biologics: Strategic Elements explores the strategic planning side of biosimilar drugs and targets issues surrounding biosimilars that are linked to legal matters. This includes principal patents and intellectual property, regulatory pathways, and concerns about affordability on a global scale. It addresses the complexity of biosimilar products, and it discusses the utilization of biosimilars and related biological drugs in expanding world markets.Of specific interest to practitioners, researchers, and scientists Table of ContentsIntroduction to Biosimilar and Interchangeable Products. Intellectual Property Issues for Biosimilars. European Regulatory Guidance. EMA-Approved Biosimilars. FDA Regulatory Guidance. ROW Regulatory Guidance. US Commercialization. Global Commercialization. Quality and Lifecycle Management.

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Book SynopsisCompletely revised text that reflects to emergent trends and cutting-edge advances in pharmaceutical biotechnology, this Third Edition provides a well-balanced framework for understanding every major aspect of pharmaceutical biotechnology, including drug development, production, dosage forms, administration, and therapeutic developments. New chapters cover evolving areas regarding biopharmaceuticals, including oligonucleotides, siRNA and various monoclonal antibodies, immunogenicity, gene therapy, and the regulatory issues factoring into the biopharmaceutical approval processTable of ContentsMolecular Biotechnology. Biophysical and Biochemical Analysis of Recombinant Protein Structure and Analysis of Proteins. Production and Downstream Processing of Biotech Products. Formulation of Biotech Products, Including Biopharmaceutical Considerations. Pharmacokinetics and Pharmacodynamics of Peptide and Protein Drugs. Immunogenicity. Genomics, Proteomics and Additional Biotechnology-related Techniques. Gene Therapy. Oligonucleotides and siRNA. Hematopoetic Growth Factors. Interferons and Interleukins. Insulins. Growth Hormones. Recombinant Thrombolytics and Coagulation Factors. General Considerations of Monoclonal Antibodies. Monoclonal Antibodies in Oncology. Monoclonal Antibodies in Transplantation. Monoclonal Antibodies in Anti-inflammatory Therapy. Recombinant Human Deoxyribonuclease. Follicle-stimulating Hormone. Vaccines. Dispensing Biotechnology Products. Economic Considerations in Medical Biotechnology. Regulatory Issues and Drug Product Approval for Biopharmaceuticals

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Book SynopsisNovel drug delivery technologies strive to bypass challenging biological layers to elicit desired pharmacological activity. The skin, one of our key defensive barriers, allows certain topically applied substances and toxins to pass. The dermatokinetics of a drug determines the efficacy of treatment of skin disorders.Presenting the first comprehensive reference on this important area of research, Dermatokinetics of Therapeutic Agents includes a general overview of the theoretical as well as practical aspects of dermatokinetics and addresses the impact of a drug delivery system on the dermatokinetics of drugs. Chapters and illustrations cover introductory aspects and the significance, methods, and models used in dermatokinetic studies of therapeutic agents.Topics include: Theoretical Models for Dermatokinetics of Therapeutic Agents Drug Delivery Approaches to Modulate Dermatokinetics of DrugsTable of ContentsIntroduction to Dermatokinetics. Theoretical Models for Dermatokinetics of Therapeutic Agents. Drug Delivery Approaches to Modulate Dermatokinetics of Drugs. Conventional Methods of Cutaneous Drug Sampling. Cutaneous Microdialysis. Sampling Substrates by Skin Permeablization. Spectroscopic Techniques in Dermatokinetics Studies. Dermatokinetics of Gene Therapeutics. Regulatory Perspective of Dermatokinetic Studies.

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Book SynopsisThe nutritional and medicinal value of metals, such as zinc, calcium, and iron, has been known in traditional medicine for a long time. Other metals, such as silver and gold, may also have therapeutic and health benefits. Ancient medicines have long incorporated their use in the treatment of diseases, and they have also more recently been explored for treatment in allopathic medicine, birthing the concept of metallonutraceuticals. The challenge of using metals in the human body is to find forms that are safe and effective.Handbook of Metallonutraceuticals presents basic concepts related to the nutritional and therapeutic use of metals, product development strategies, and some ideas ready to be applied for condition-specific metallonutraceuticals. The book begins with an overview of the nutraceuticals field and the need for metallonutraceuticals. It considers the roles of various metals in metabolism, reviews the ethnopharmacology and ethnomedicine of metals, and coverTable of ContentsConcept, Definition, and Need for Metallonutraceuticals. Roles of Metals in Metabolism. Ethnopharmacology and Ethnomedicine of Metals. Characterization of Metallonutraceuticals. Characterization Bioavailability and Drug Interactions of Metallonutraceuticals. Therapeutic Applications of Nanometals. Metallonanotherapeutics for Neurodegenerative Diseases. Nanometals and Complexes in Cancer Diagnosis and Therapy. Application of Metals in Traditional Chinese Medicine. Metalloenzymes: Relevance in Biological Systems and Potential Applications. Application of Nanosilver in Nutraceuticals. Regulatory Pathways and Intellectual Property Rights for Metallonutraceuticals. Gold Nanoparticles: A Promising Nanometallic Drug Delivery System with Many Therapeutic Applications. Index.

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Book SynopsisMaintaining a practical perspective, Bioequivalence and Statistics in Clinical Pharmacology, Second Edition explores statistics used in day-to-day clinical pharmacology work. The book is a starting point for those involved in such research and covers the methods needed to design, analyze, and interpret bioequivalence trials; explores when, how, and why these studies are performed as part of drug development; and demonstrates the methods using real world examples. Drawing on knowledge gained directly from working in the pharmaceutical industry, the authors set the stage by describing the general role of statistics. Once the foundation of clinical pharmacology drug development, regulatory applications, and the design and analysis of bioequivalence trials are established, including recent regulatory changes in design and analysis and in particular sample-size adaptation, they move on to related topics in clinical pharmacology involving the use of cross-over Trade Review"The two authors are well-respected statisticians with numerous publications in BE and broad pharmaceutical industry experience. … The book is written in plain language and statistics is presented with minimum mathematical proof, which makes it a great introduction and reference for statisticians and clinical pharmacologists. With case studies and associated SAS and R codes included in the book and website, both statisticians and clinical pharmacologists will find this book helpful in understanding the context to use a method and implementing the ready-to-use codes. Particularly, each chapter begins with an interesting real-life story of the authors working as statisticians in the pharmaceutical industry, which makes the reading delightful. …In summary, Bioequivalence and Statistics in Clinical Pharmacology, Second Edition, provides an update on regulatory recommendations, statistical methods, and applications in clinical pharmacology and BE studies to support drug product development. With its inclusion of SAS and R codes, this book will be a valuable reference for pharmaceutical scientists, statisticians, and regulators working in these areas."—Wangjie Sun and Wenlei Jiang, US Food and Drug Administration, in Journal of the American Statistical Association, January 2018"This book is a second edition of the authors’ take on the concepts and methods in the analysis and design of bioequivalence studies, supported by references to regulation authorities’ guidelines ... The authors are working in the pharmaceutical industry and therefore bring a view from the inside compared to the other reference work in the field by academics … Throughout the book, different examples with data and codes are provided both showing and not showing bioequivalence to facilitate the learning process. … To conclude, this book covers efficiently the statistical methods of bioequivalence testing and their many applications in clinical pharmacology. Furthermore, the dense reference list provides a helpful guide for the reader to go in deeper details on topics of interest."—Julie Bertrand, Faculté de Médecine Bichat, IAME, in Journal of Biopharmaceutical Statistics, May 2017"The first edition of Bioequivalence and Statistics in Clinical Pharmacology was a classic text book for researchers and statisticians in the field of clinical pharmacology and pharmaceutical industry. This new second edition is a timely update with the inclusion of new areas such as adaptive bioequivalence trials, scaled average bioequivalence testing, and vaccine trials. This is one of few books in the literature with the focus on statistical issues in clinical pharmacology and bioequivalence. The topics it covers are critical for understanding the pharmacology of an investigational drug, and are becoming increasingly important in the era of precision medicine. The book is just as well structured as the first edition, in an accessible, thorough, and clear manner. Case studies and associated SAS code included in the book are extremely helpful. In summary, the book is a most welcome addition to the collection of pharmaceutic statisticians and researchers in clinical pharmacology." —Liang Fang, Director of Biostatistics, Gilead Sciences Inc."Bioequivalence and Statistics in Clinical Pharmacology, Second Edition, provides readers with a statistical background of bioequivalence and presents several special topics in clinical pharmacology. This second edition contains updated and extended discussions of these topics and includes new chapters on adaptive bioequivalence studies, scaled average bioequivalence, and vaccine trials. The book’s presentation is comprehensive and clear, and is complimented by numerous illustrations, examples, and computer programs with data analyses. Scientists and practitioners working in industry, regulatory authorities, and academia will find this book useful, interesting, and enjoyable due to the delightful and instructive stories featured in the introductions of each chapter, the various important and relevant topics covered by these chapters, and the informative and practical technical appendices."—Laszlo Endrenyi, Professor Emeritus, University of TorontoPraise for the First Edition:"… the book provides a good introduction to common uses of statistics in early phases of the drug development process by using a good mix of technical detail, intuitive understanding and factual knowledge. … personal accounts together with the numerous real data examples which are accompanied by SAS code for analysis and the opportunity to download the data to gain first-hand experience are the best features of the book. … the authors did a fine job in providing an introduction to statistics in the early stages of the drug development process. The availability of real example data allows the reader to engage himself easily in the topic and the long experience of the authors ensures that many different aspects of pharmacological studies are discussed."—Thomas Jaki, Lancaster University, Journal of the Royal Statistical Society, Series A, 2010"I really enjoyed reading this book. Each chapter includes an excellent introduction based on Scott Patterson's experience working as a biometrician. This will especially be of interest to young statisticians starting their career in the pharmaceutical industry. Therefore, I strongly recommend this book to all pharmaceutical statisticians to learn more of the challenging statistical problems being generated in drug development. In addition, the presented material provides a springboard for all scientists from academia who are looking to do research in this area of medical applications."—Dieter Haushcke, Biometrics, September, 2006"The authors formulate bioequivalence exhaustively and clearly. … Given the background of the authors, they constitute a key piece of social information in understanding the context in which clinical pharmacology research develops within the pharmaceutical industry."—Journal of Biopharmaceutical Statistics"The two authors are well-respected statisticians with numerous publications in BE and broad pharmaceutical industry experience. … The book is written in plain language and statistics is presented with minimum mathematical proof, which makes it a great introduction and reference for statisticians and clinical pharmacologists. With case studies and associated SAS and R codes included in the book and website, both statisticians and clinical pharmacologists will find this book helpful in understanding the context to use a method and implementing the ready-to-use codes. Particularly, each chapter begins with an interesting real-life story of the authors working as statisticians in the pharmaceutical industry, which makes the reading delightful. …In summary, Bioequivalence and Statistics in Clinical Pharmacology, Second Edition, provides an update on regulatory recommendations, statistical methods, and applications in clinical pharmacology and BE studies to support drug product development. With its inclusion of SAS and R codes, this book will be a valuable reference for pharmaceutical scientists, statisticians, and regulators working in these areas."—Wangjie Sun and Wenlei Jiang, US Food and Drug Administration, in Journal of the American Statistical Association, January 2018"This book is a second edition of the authors’ take on the concepts and methods in the analysis and design of bioequivalence studies, supported by references to regulation authorities’ guidelines ... The authors are working in the pharmaceutical industry and therefore bring a view from the inside compared to the other reference work in the field by academics … Throughout the book, different examples with data and codes are provided both showing and not showing bioequivalence to facilitate the learning process. … To conclude, this book covers efficiently the statistical methods of bioequivalence testing and their many applications in clinical pharmacology. Furthermore, the dense reference list provides a helpful guide for the reader to go in deeper details on topics of interest."—Julie Bertrand, Faculté de Médecine Bichat, IAME, in Journal of Biopharmaceutical Statistics, May 2017"The first edition of Bioequivalence and Statistics in Clinical Pharmacology was a classic text book for researchers and statisticians in the field of clinical pharmacology and pharmaceutical industry. This new second edition is a timely update with the inclusion of new areas such as adaptive bioequivalence trials, scaled average bioequivalence testing, and vaccine trials. This is one of few books in the literature with the focus on statistical issues in clinical pharmacology and bioequivalence. The topics it covers are critical for understanding the pharmacology of an investigational drug, and are becoming increasingly important in the era of precision medicine. The book is just as well structured as the first edition, in an accessible, thorough, and clear manner. Case studies and associated SAS code included in the book are extremely helpful. In summary, the book is a most welcome addition to the collection of pharmaceutic statisticians and researchers in clinical pharmacology." —Liang Fang, Director of Biostatistics, Gilead Sciences Inc."Bioequivalence and Statistics in Clinical Pharmacology, Second Edition, provides readers with a statistical background of bioequivalence and presents several special topics in clinical pharmacology. This second edition contains updated and extended discussions of these topics and includes new chapters on adaptive bioequivalence studies, scaled average bioequivalence, and vaccine trials. The book’s presentation is comprehensive and clear, and is complimented by numerous illustrations, examples, and computer programs with data analyses. Scientists and practitioners working in industry, regulatory authorities, and academia will find this book useful, interesting, and enjoyable due to the delightful and instructive stories featured in the introductions of each chapter, the various important and relevant topics covered by these chapters, and the informative and practical technical appendices."—Laszlo Endrenyi, Professor Emeritus, University of TorontoPraise for the First Edition:"… the book provides a good introduction to common uses of statistics in early phases of the drug development process by using a good mix of technical detail, intuitive understanding and factual knowledge. … personal accounts together with the numerous real data examples which are accompanied by SAS code for analysis and the opportunity to download the data to gain first-hand experience are the best features of the book. … the authors did a fine job in providing an introduction to statistics in the early stages of the drug development process. The availability of real example data allows the reader to engage himself easily in the topic and the long experience of the authors ensures that many different aspects of pharmacological studies are discussed."—Thomas Jaki, Lancaster University, Journal of the Royal Statistical Society, Series A, 2010"I really enjoyed reading this book. Each chapter includes an excellent introduction based on Scott Patterson's experience working as a biometrician. This will especially be of interest to young statisticians starting their career in the pharmaceutical industry. Therefore, I strongly recommend this book to all pharmaceutical statisticians to learn more of the challenging statistical problems being generated in drug development. In addition, the presented material provides a springboard for all scientists from academia who are looking to do research in this area of medical applications."—Dieter Haushcke, Biometrics, September, 2006"The authors formulate bioequivalence exhaustively and clearly. … Given the background of the authors, they constitute a key piece of social information in understanding the context in which clinical pharmacology research develops within the pharmaceutical industry."—Journal of Biopharmaceutical StatisticsTable of ContentsBioequivalence & Biopharmaceutical DevelopmentDrug Development and Clinical PharmacologyAims of This BookBiopharmaceutical DevelopmentClinical PharmacologyStatistics in Clinical PharmacologyStructure of the BookHistory and Regulation of BioequivalenceWhen and How BE Studies Are PerformedWhy Are BE Studies Performed?Deciding When Formulations Are BioequivalentPotential Issues with TOST BioequivalentCurrent International RegulationSome Practical NotesTesting for Average BioequivalenceBackgroundLinear Model for 2 x 2 DataApplying the TOST ProcedureCarry-over, Sequence, and Interaction EffectsChecking Assumptions Made about the Linear ModelPower and Sample Size for ABE in the 2 x 2 DesignExample Where Test and Reference Are Not ABENonparametric AnalysisBE Studies with More Than Two PeriodsBackgroundThree-period DesignsWithin-subject VariabilityRobust Analyses for Three Period DesignsFour-period DesignsDesignes with More Than Two TreatmentsAdjusting for Multiple TestingNonparametric Analyses of TmaxTechnical appendix: EfficiencyTables of DataSpecial Topics in BioequivalenceDealing with Special BE ChallengesRestricted Maximum Likelihood ModellingFailing BE and the DER AssessmentSimulationData-based SimulationCarry-overOptimal DesignsDetermining Trial SizeWhat Outliers Are and How to Handle Their DataBayesian BE AssessmentAdaptive Bioequivalence TrialsBackgroundTwo-stage design for testing for ABETOST using the standard combination testExample of using the standard combination testThe maximum combination testExample of using the maximum combination testConditional errors and conditional powerAlgorithm for sample size re-estimationOperating characteristicsConclusionsTechniccal Appendix: R codeScaled Average Bioequivalence TestingBackgroundScaled Average Bioequivalence in EuropeScaled Average Bioequivalence in USADiscussion and CautionsClinical PharmacologyClinical Pharmacology Safety StudiesBackgroundFirst-time-in-humansSub-chronic Dosing StudiesFood-Effect Assessment and DDIsDose-ProportionalityTechnical AppendixQTcBackgroundModelling of QTc DataInterpreting the QTc Modelling FindingsDesign of a Thorough QTc Study in the FutureClinical Pharmacology Efficacy StudiesBackgroundSub-chronic DosingPhase IIa and the Proof of ConceptPopulation PharmacokineticsPopulation and PharmacokineticsAbsolute and Relative BioavailabilityAge and Gender Pharmacokinetic StudiesEthnicityLiver DiseaseKidney DiseaseTechnical Appendix Vaccines & Epilogue Vaccine TrialsBrief Introduction to Vaccine Research and DevelopmentPhase I Vaccine StudiesProof of Concept and Phase IILot ConsistencyConcomitant VaccinationCross-over Trials in VaccinesEpilogue BibliographyIndex

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Book SynopsisSince 1945, The Annual Deming Conference on Applied Statistics has been an important event in the statistics profession. In Clinical Trial Biostatistics and Biopharmaceutical Applications, prominent speakers from past Deming conferences present novel biostatistical methodologies in clinical trials as well as up-to-date biostatistical applications from the pharmaceutical industry.Divided into five sections, the book begins with emerging issues in clinical trial design and analysis, including the roles of modeling and simulation, the pros and cons of randomization procedures, the design of Phase II dose-ranging trials, thorough QT/QTc clinical trials, and assay sensitivity and the constancy assumption in noninferiority trials. The second section examines adaptive designs in drug development, discusses the consequences of group-sequential and adaptive designs, and illustrates group sequential design in R. The third section focuses on oncology clinical triTrade Review"This book of timely, self-contained chapters covers a wide range of current methods and unresolved challenges in clinical trial statistical methods and will prove to be an essential guide for biostatisticians who work in this field."—Dirk F. Moore, Journal of Biopharmaceutical Statistics". . . the contributed chapters in this collection are clearly written, easily digestible, and well-referenced. The book is a useful resource for the clinical trialist interested in obtaining a quick overview of standard practices and current methodological development for a specific biostatistical application, or a worthwhile read for the researcher seeking to familiarize him or herself with a diversity of emerging topics in clinical trials.—Megan T. Smith, University of California, IrvineTable of ContentsEmerging Issues in Clinical Trial Design and Analysis. Adaptive Clinical Trials. Clinical Trials in Oncology. Multiple Comparisons in Clinical Trials. Clinical Trials in the Genomic Era. Index.

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Book SynopsisAs the generic pharmaceutical industry continues to grow and thrive, so does the need to conduct adequate, efficient bioequivalence studies. In recent years, there have been significant changes to the statistical models for evaluating bioequivalence. In addition, advances in the analytical technology used to detect drug and metabolite levels have made bioequivalence testing more complex. The second edition of Handbook of Bioequivalence Testing has been completely updated to include the most current information available, including new findings in drug delivery and dosage form design and revised worldwide regulatory requirements.New topics include: A historical perspective on generic pharmaceuticals New guidelines governing submissions related to bioequivalency studies, along with therapeutic code classifications Models of noninferiority Biosimilarity of large molecule drugs Bioequivalence of complementary andTrade Review"This handbook offers a complete description of every aspect of bioequivalence testing … [It] is an essential, one-of-a-kind resource for anyone interested in bioequivalence. There are no other books that compile so many aspects in one place."—Jennifer L. Colon, PharmD, Temple University School of Pharmacy, in Doody’s Review Service Table of ContentsHistorical Perspective on Generic Pharmaceuticals. Physicochemical Basis of Bioequivalence Testing. Drug Delivery Factors. Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling. Bioequivalence Testing Rationale and Principles. Bioequivalence Waivers. Statistical Evaluation of Bioequivalence Data. Regulatory Inspection Process. Fed Bioequivalence Studies. Topical Drugs. Bioequivalence of Nasal Products. Bioequivalence of Complementary and Alternate Medicines. Bioequivalence of Biosimilar Products. Bioequivalence Testing: The US Perspective. Bioequivalence Testing: European Perspective. Bioequivalence Testing: The ROW Perspective. Bioequivalence Testing Protocols. Bioequivalence Documentation. Good Laboratory Practices. Bioanalytical Method Validation. Good Clinical Practice. Computer and Software Validation. Outsourcing and Monitoring of Bioequivalence Studies. Epilogue: Future of Bioequivalence Testing. Appendix A: Glossary of Terms. Appendix B: Dissolution Testing Requirements for US FDA Submission. Bibliography. Index.

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Book SynopsisAdverse Drug Interactions: A Handbook for Prescribers assists clinicians by providing key information on potential adverse effects that can result from prescribing two or more drugs for simultaneous use. Interactions that are likely to give rise to life-threatening conditions, and which must therefore be completely avoided, are clearly highlighted. Less threatening but nonetheless important interactions necessitating practical measures, such as frequent monitoring and advice to patients, are also discussed.Presented in a user-friendly format, the book is organised by drug class and provides a brief summary of the mechanism underlying a particular interaction, alternative drugs lacking the same reactions that may be considered, and instructions for monitoring patients when adverse effects occur. All interactions listed in the previous edition have been reviewed and updated using the latest information available. The clinical reality of tTrade Review“There is much to commend. There are useful preliminary sections on the complexity of drug–drug interactions and the emerging role of electronic decision support systems… I was particularly pleased to see the inclusion of interactions with herbal and common over-the-counter medications, alcohol, ‘classic’ recreational drugs, vitamins and minerals, and key food groups.”—Daniel Marks, University College London Hospital, London, British Journal of Hospital MedicineTable of ContentsDrugs Acting on the Cardiovascular System. Drugs Acting on the Central Nervous System. Anticancer and Immunomodulating Drugs. Anticoagulants. Antidiabetic Drugs. Other Endocrine Drugs. Analgesics. Musculoskeletal Drugs. Anesthetic Drugs: General. Drugs to Treat Infections. Drugs Acting on the Gastrointestinal Tract. Respiratory Drugs. Metabolic Drugs. Obstetrics and Gynecology. Drugs Used to Treat the Urinary System. Drugs of Abuse. Miscellaneous. Over-the-Counter/Online Drugs, Traditional and Herbal Remedies. Appendices.

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Book SynopsisGood Manufacturing Practice (GMP) ensures medicinal products are produced consistently and controlled to the quality standards appropriate for their intended use and as required by product specifications or marketing authorization. Annex 11 details the European Medicines Agency (EMA) GMP requirements for computer systems.The purpose of Annex 11 is to provide the EMA healthcare industry with consistent criteria for effective implementation, control, and use of computer systems. EU Annex 11 Guide to Computer Validation Compliance for the Worldwide Health Agency GMP supplies practical information to facilitate compliance with computer system GMP requirements, while highlighting and integrating the Annex 11 guidelines into the computer compliance program.The ideas presented in this book are based on the author's 25 years of experience with computer validation in the healthcare industry with various computer systems development, maintenance, and quality functiTable of ContentsIntroduction. SLC, Computer Validation, and Annex 11. Annex 11 Principles. Risk Management. Personnel. Suppliers and Service Providers. Validation. Data. Accuracy Checks. Data Storage. Printouts. Audit Trails—Ensuring Data Integrity. Change and Configuration Management. Periodic Evaluation: Independent Review to Ensure Continued Validation of Computerized Systems. Security. Incident Management. Electronic Signatures: Electronic Signing Requirements. Batch Certification and Release. Business Continuity. Archiving. SLC Documentation. Relevant Procedural Controls. Maintaining the Validated State in Computer Systems. Annex 11 and the Cloud. EU GMP Chapter 4–Documentation and Annex 11. Annex 11 and Electronic Records Integrity. Annex 11 and 21 CFR Part 11: Comparisons for International Compliance.

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Book SynopsisThe recent introduction of nanomedicines in the drug therapy arena is revolutionizing the management of severe diseases. The key advance in the field is the optimization of the biological fate of drug molecules, thus improving the therapeutic effect while keeping to a very minimum the associated toxicity. Volume one of this book series, Nanoplatforms in Drug Delivery, established the basic aspects in the development of drug-loaded nanoplatforms, the so-called nanomedicines or nanodrugs, focusing on representative materials and strategies used in their formulation. Taking advantage of the advanced conceptualizations on nanomedicine engineering that were described in volume one, volume two, Nano-Engineering Strategies and Nanomedicines against Severe Diseases, analyzes in depth special features related to the formulation of nanoplatforms for oral, dental, topical and transdermal, pulmonary and nasal, ocular and otic, vaginal, and brain drug delivery Table of ContentsPreface to the Book Series. Preface to Volume 2. Emerging Technologies of Polymers for Nanomedicine Applications. Nanotechnology for Oral Drug Delivery and Targeting. Nanoparticulate Systems for Dental Drug Delivery. Nanotechnology for Topical and Transdermal Drug Delivery and Targeting. Nanotechnology for Pulmonary and Nasal Drug Delivery. Lipid Nanoplatforms for Pulmonary Drug Delivery. Nanotechnology for Ocular and Otic Drug Delivery and Targeting. Nanotechnology for Vaginal Drug Delivery and Targeting. Potential Nanocarriers for Brain Drug Delivery. Nanomaterials and Cancer Therapy. Nanomedicine in Cardiovascular Disease. Nano(Neuro)Medicinal Interventions for Neurodegenerative Disorders: a Meta-Analysis of Concurrent Challenges and Strategic Solutions. Nanomedicines against Infectious Diseases. Nanomedicines against Chronic Inflammatory Diseases. Nanomedicine Biopharmaceuticals for Metabolic Diseases. Nanotechnology in Gene Knockdown and miRNA Replacement in Vivo. Nanotheranostics.

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Book SynopsisThe premise of Quality by Design (QbD) is that the quality of the pharmaceutical product should be based upon a thorough understanding of both the product and the manufacturing process. This state-of-the-art book provides a single source of information on emerging statistical approaches to QbD and risk-based pharmaceutical development. A comprehensive resource, it combines in-depth explanations of advanced statistical methods with real-life case studies that illustrate practical applications of these methods in QbD implementation. Table of ContentsBACKGROUND. Introduction. ANALYTICAL METHOD. Statistical Methods for Analytical Procedure Development, Validation and Transfer. Parallelism Testing of Bioassay. Validation of Assay Linearity. ROCESS DEVELOPMENT. Residual Host Cell DNA Risk Assessment. Statistical Evaluations of Viral Clearance. Pre-filtration Bio-burden Testing. Process Validation and Verification. MANUFACTURING. Specifications.

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Book SynopsisThe emergence of nanotherapeutics is attributable to the integration of nanotechnology, recombinant DNA technology, and synthetic organic chemistry with medicine for treating critical human diseases in a more efficient and specific molecular approach than therapy with conventionally-designed and formulated drugs. Nanotherapeutics: From Laboratory to Clinic comprehensively discusses the current shortcomings for delivery of classical (small) drugs, macromolecular therapeutics, and recombinant vaccine via the common intravascular and extravascular routes.The book describes the synthetic/chemical engineering methods as well as recombinant, hybridoma, and phage display technologies to fabricate different types of nanoparticulate carriers and drugs. It also reveals the diversified approaches undertaken by harnessing nanotechnology to overcome the multistep extracellular and intracellular barriers and to facilitate the development of novel strategies for therapeutic deTable of ContentsEmergence of nanotherapeutics: Challenges in classical drug transport versus macromolecular drug design. The ultimate destinations for delivery and release of nanotherapeutics. Diversity of bioactive nanoparticles from biological, chemical, and physical perspectives. Fabrication strategies for biofunctional nanoparticles. Interactions and orientation of therapeutic drugs in the vicinity of nanoparticles. Variable interactions of nanoparticles with blood, lymph, and extracellular and intracellular components. Pharmacokinetics and biodistribution of nanoparticles. Specific roles of nanoparticles in various steps of drug transport. Nanotechnology approaches to modulate transport, release, and bioavailability of classical and emerging therapeutics. Nanotechnology in the development of innovative treatment strategies. Nanoparticles for therapeutic delivery in animal models of different cancers. Nanoparticles for therapeutic delivery in animal models of other critical human diseases. Nanomedicine in clinical trials. Approved and commercialized nanomedicine. Current safety issues: Biodegradability, reactivity, and clearance. References.

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Book SynopsisMarine glycobiology is an emerging and exciting area in the field of science and medicine. Glycobiology, the study of the structure and function of carbohydrates and carbohydrate-containing molecules, is fundamental to all biological systems and represents a developing field of science that has made huge advances in the last half-century. This book revolutionizes the concept of marine glycobiology, focusing on the latest principles and applications of marine glycobiology and their relationships.Trade Review"The book describes carbohydrates conjugated with additional molecules – an area that could be called terra incognita, because it has been unexploited until now. An important part of the book constitutes analytical techniques, which are a challenge. Another important aspect is the practical application of those unique compounds: in biomedicine, bio-based technologies. The book contains 6 sections and 38 chapters which thoroughly discuss different aspects of glycoconjugates. The book would be useful for academic research, students, but also for industry, as the inspiration for development of innovative and bioactive products."— Katarzyna Chojnacka, Wroclaw University of Technology, PolandTable of ContentsIntroduction to Marine Glycobiology. Marine Glycoconjugates of Reproduction and Chemical Communications. Marine Glycans. Marine Glycosylation. Marine Glycoproteins. Marine Proteoglycans. Marine Glycolipids. Marine Glycomics. Marine Glycoenzymes. Marine Carbohydrates. Bioinformatics of Glycobiology. Biological Role of Glycoconjugates. Glycoconjugates in Biomedicine and Biotechnology.

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Book SynopsisIndustrial Applications of Marine Biopolymers presents different classes of marine biopolymers and their industrial applications, demonstrating the precious value of ocean resources to society. This timely volume discusses the exceedingly useful polymers derived from these materials that are biodegradable, biocompatible, and at times water soluble. Direct use or chemically modified forms of such biomaterials have many chemical sites, making them suitable for varied types of industrial applications. In addition, this book also addresses current global challenges of conservation, including extended drought conditions and the need for improved agricultural methods, together with new bio-medical developments. It is suitable for anyone who has an interest in the industrial applications of biopolymers.Table of ContentsPart – I Isolation and physicochemical characterization of marine biopolymers. Introduction to marine biopolymers. Isolation of marine biopolymers. Physicochemical characterization of marine biopolymers. Isolation and characterization of chitin and chitosan. Isolation and characterization of alginate from seaweeds. Isolation and characterization of carrageenans and agar / agarose. Influence of physicochemical properties of chitin and chitosan on its potential applications. Structural characteristics of marine biopolymers. Isolation and characterization techniques used for hydroxyapatite. Biosynthesis of marine biopolymers. Electrostatic properties of marine biopolymers. Applications of analytical tools such as NMR, IR and Mass spectrometry to analyse the structural properties of marine biopolymers. Mechanical properties of Marine biopolymers and its derivatives. Use of X-Ray diffraction analysis on Marine biopolymers. Production of marine biopolymers through enzymatics process. Chemical modification of chitin and chitosan for its potential applications. Enzymatic modification of marine biopolymers. Effect of Molecular weight and the degree of deacetylation of chitosan and its determination. Isolation and characterization of hyaluronic acid. Isolation of low-molecular weight biopolymers from marine sources. Physio-chemical characterization of tunicin, laminarin and furcellaran. Isolation and characterization of inorganic biopolymer.Part – II Biological and Biomedical applications of the marine biopolymers Chapter 1: Marine biopolymers for anti-cancer drugs.Chapter 2: Drug Delivery applications of chitin and chitosan.Chapter 3: Gene delivery applications of chitin and chitosan.Chapter 4: Biological activities of Marine biopolymers.Chapter 5: Applications of nano form of biopolymers.Chapter 6: Nanocomposites and nanoparticles of biopolymers in bio-nano-technology.Chapter 7: Antimicrobial activity of marine biopolymers.Chapter 8: Role of Alginate in drug delivery applications.Chapter 9: Application of marine hydroxyapatite scaffolds in bone tissue engineering.Chapter 10: Modified marine polysaccharides and Seaweads in drug delivery applications.Chapter 11: Marine biopolymers as carriers and immunoadjuvants in vaccine delivery.Chapter 12: Antidiabetic activity and anticolestic activity of marine biopolymers.Chapter 13: Antiviral activity of marine biopolymers.Chapter 14: Potential anticoagulant effect of marine derived biopolymers.Chapter 15: Marine biopolymers for antiallergic therapeutics.

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Book SynopsisAqueous-based film coating has become routine in the pharmaceutical industry. This process eliminates the use of organic solvents and thus avoids economic, environmental, and toxicological issues related to residual solvents and solvent recovery. Aqueous-based coating, however, is complex and many variables may impact the final product and its performance. This fourth edition of Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms aims to provide insight into the factors and parameters that should be considered and controlled for the successful development and commercialization of a coated product. The fourth edition has been revised and expanded to reflect the most recent scientific advancements from the literature. The contributing authors explain in detail, using illustrated examples, appropriate steps to solve and ideally avoid formulation, processing, and stability problems and to achieve an optimized dosage form. Trade names and chemical names of comTable of ContentsAqueous-based polymeric coating. Pseudolatex dispersions for controlled drug delivery. Processing and equipment considerations for aqueous-based coatings. Mechanical properties of polymeric films prepared from aqueous dispersions. Defects in aqueous film coated solid oral dosage form. Adhesion of polymeric films. Influence of insoluble additives on the properties of polymeric coating systems. Process and formulation factors affecting drug release from pellets coated with ethylcellulose pseudolatex Aquacoat. Chemistry and application properties of polymethacrylate systems. Application of HPMC and HPMCAS to aqueous film coating of pharmaceutical dosage forms. The applications of formulated systems for aqueous film coating of pharmaceutical solid oral dosage forms. *Substrate considerations when developing an aqueous film coated solid oral dosage form. Polymer interactions with drugs and excipients. Physical aging of polymers and it effect on the stability of solid oral dosage forms.

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Book SynopsisThis book covers the broad field of cellular, molecular, preclinical, and clinical imaging either associated with or combined with photodynamic therapy (PDT). It showcases how this approach is used clinically for cancer, infections, and diseases characterized by unwanted tissue such as atherosclerosis or blindness. Because the photosensitizers are also fluorescent, the book also addresses various imaging systems such as confocal microscopy and small animal imaging systems, and highlights how they have been used to follow and optimize treatment, and to answer important mechanistic questions. Chapters also discuss how imaging has made important contributions to clinical outcomes in skin, bladder, and brain cancers, as well as in the development of theranostic agents for detection and treatment of disease. This book provides a resource for physicians and research scientists in cell biology, microscopy, optics, molecular imaging, oncology, and drug discovery.Trade Review"The editors have skillfully compiled a wide and comprehensive spectrum from contributors around the world on up-to-date imaging technologies for photodynamic therapy (PDT), with a wealth of clinical images." –Optics & Photonics News"The editors have skillfully compiled a wide and comprehensive spectrum from contributors around the world on up-to-date imaging technologies for photodynamic therapy (PDT), with a wealth of clinical images." –Optics & Photonics NewsTable of ContentsINTRODUCTION. Looking out the optical window: Physical principles and instrumentation of imaging in photodynamic therapy. Photochemistry and photophysics of PDT and photosensitizers. IN VITRO MICROSCOPY FOR PHOTOSENSITIZER LOCALIZATION IN CELLS. Phthalocyanines in photodynamic therapy. Singlet oxygen luminescence imaging: A prospective tool in bioscience? Microbial biofilms and antimicrobial photodynamic therapy. High-content imaging for photosensitizer screening. IN VITRO MICROSCOPY OF CELL DAMAGE AND DEATH PROCESSES AFTER PDT. Enhanced efficacy of photodynamic therapy via an iron–lysosome–mitochondria connection: Studies with phthalocyanine 4. Role of cell death pathways in response to photodynamic therapy in gliomas. In search of specific PDT photosensitizers: Subcellular localization and cell death pathways. THERANOSTIC AGENTS AND NANOTECHNOLOGY. Quantum dots in PDT. Tetrapyrrole-based theranostic combinations of photodynamic action and magnetic resonance imaging. Theranostic applications of photodynamic molecular beacons. Tumor-specific imaging and photodynamic therapy targeting the urokinase receptor. SMALL ANIMAL IMAGING. Vascular imaging in photodynamic therapy. Photosensitizer activity imaging on the microscopic scale. Bioluminescence imaging for monitoring the effectiveness of photodynamic therapy for infections in animal models. CLINICAL IMAGING. Imaging of photosensitizers in skin. Brain tumor imaging with ALA. PDT of non-muscle-invasive bladder cancer with Hexylester Aminolevulinate: Optimization of the illumination wavelengths by fluorescence spectroscopy and imaging. Endoscopic imaging and photodynamic therapy. Spectroscopic imaging in prostate PDT. Fluorescent-guided resection in clinical oncology.

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Book SynopsisHydrogels are crosslinked, macromolecular polymeric materials arranged in a three-dimensional network, which can absorb and retain large amounts of water. Hydrogels are commonly used in clinical practice and experimental medicine for a wide range of applications, including drug delivery, tissue engineering and regenerative medicine, diagnostics, cellular immobilization, separation of biomolecules or cells, and barrier materials to regulate biological adhesions. This book elucidates the underlying concepts and emerging applications of hydrogels and will provide key case studies and critical analysis of the existing research.Table of ContentsMicroarchitecture of Water Confined in Hydrogels. The Fate of Thixotropy in Hydrogels. Hydrogel Network Parameters. Mechanisms of drug release from hydrogels in medical applications. Hydrogel Coatings for Medical Device Applications. Hydrogels for Bone Regeneration: An Overview. Hydrogels in Wound Management. Hydrogels for Imaging, Sensing and Diagnostics. Engineering Hyaluronan (HA) Hydrogels with Bioactive and Mechanical Signals. Hydrogel Nanomaterials for Cancer Diagnosis and Therapy. Thermosensitive Hydrogels for Drug Delivery and Tissue Engineering. Silk Hydrogels for Drug and Cell Delivery. In-Situ Forming Phase-inversion Injectable Hydrogels for Controlled Drug Release. Transdermal Applications of Hydrogels. Preparation of Photocurable Hydrogels. Stimuli-Responsive Biomolecular Hydrogels for Medical Applications. Bioengineering Complexity and Tuneability in Hydrogels. Synthetic hydrogels for 3D cell culture.

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Book SynopsisRegulatory affairs and pharmacological drug safety issues of Ayurvedic medicine has been overlooked by practitioners for many years. Research in Ayurveda is now a world-wide phenomenon, and several large pharmaceutical corporations are investing money for novel drug discovery from Ayurvedic sources. This book examines the regulatory and pharmacological aspects and includes extensive data on scientific evaluation carried out on Ayurvedic formulations. It will also serve as a reference book on standardization, pre-clinical studies, and clinical and toxicological studies on Ayurvedic formulations.Table of ContentsRegulatory Affairs in Ayurveda. Introduction to Regulatory Affairs. Introduction to Ayurvedic Pharmacopoeia of India. Drug Cosmetic Act and Ayurvedic Drugs. Ayurvedic Drug Manufacturing License. Good Manufacturing Practices for Ayurvedic, Siddha and Unani Medicines (SCHEDULE T). Ayurvedic Drug Industry. Pharmacovigilance of Ayurvedic Drugs. Heavy Metal Content of Ayurvedic Formulations. Genotoxicity of Ayurvedic Formulations. Aristolochic Acid Distribution in Ayurvedic Formulations. Patent and IPR Issues of Ayurvedic Formulations. Ayurvedic Nutraceuticals. Ayurvedic Cosmetics. Pharmacological Investigations on Ayurvedic Formulations. A-Z of Major Ayurvedic Formulations.

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Book SynopsisAnalyzing Longitudinal Clinical Trial Data: A Practical Guide provides practical and easy to implement approaches for bringing the latest theory on analysis of longitudinal clinical trial data into routine practice.The book, with its example-oriented approach that includes numerous SAS and R code fragments, is an essential resource for statisticians and graduate students specializing in medical research. The authors provide clear descriptions of the relevant statistical theory and illustrate practical considerations for modeling longitudinal data. Topics covered include choice of endpoint and statistical test; modeling means and the correlations between repeated measurements; accounting for covariates; modeling categorical data; model verification; methods for incomplete (missing) data that includes the latest developments in sensitivity analyses, along with approaches for and issues in choosing estimands; and means for preventing missing data. Each chapter sTrade Review"This book deals mostly with longitudinal clinical trial data, but also with the related issue of imputing missing data. The book is an excellent resource overall, as it is fairly comprehensive, well referenced, and clear."~Vance W. Berger, PhD, NIH/NCI/DCP/BRGAnalyzing Longitudinal Clinical Trial Data provides, in a well organized and small format, a fairly easy read that could be helpful for both researchers analyzing longitudinal data collected from clinical trials (or perhaps even observational studies) and instructors teaching undergraduate and graduate courses on clinical trials, longitudinal data, and missing data. The book is divided into four well-structured and complementary sections: background and setting, general modeling strategies and methods, methods for dealing with missing data, and overall guidance (with illustration) for developing a study.~Journal of the American Statistical Association "I recommend this book to anyone who deals with longitudinal clinical trials data at any level with confidence as it concisely presents essential ideas and analysis techniques with illustrative examples, in an intuitively appealing way, both on analytic and conceptual levels. It addresses an important need for practicing (bio)statisticians."~Biometrical JournalTable of ContentsBackground and Setting. Introduction. Objectives and estimands–determining what to estimate. Study design–collecting the intended data. Example data. Mixed effects models review. Modeling the observed data. Choice of dependent variable and statistical test. modeling covariance (correlation). Modeling means over time. Accounting for covariates. Categorical data. Model checking and verification. Methods for dealing with missing Data. Overview of missing data. Simple and ad hoc Approaches for dealing with missing data. Direct maximum likelihood. Multiple imputation. Inverse probability. Methods for incomplete categorical data weighted generalized estimated equations. Doubly robust methods. MNAR methods. Methods for incomplete categorical data. A comprehensive approach to study development and analyses. Developing statistical analysis plans. Example analyses of clinical trial data.

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Book SynopsisPraise for the first edition:Given the author's years of experience as a statistician and as a founder of the first DMC in pharmaceutical industry trials, I highly recommend this booknot only for experts because of its cogent and organized presentation, but more importantly for young investigators who are seeking information about the logistical and philosophical aspects of a DMC. -S. T. Ounpraseuth, The American Statistician In the first edition of this well-regarded book, the author provided a groundbreaking and definitive guide to best practices in pharmaceutical industry data monitoring committees (DMCs). Maintaining all the material from the first edition and adding substantial new material, Data and Safety Monitoring Committees in Clinical Trials, Second Edition is ideal for training professionals to serve on their first DMC as well as for experienced clinical and biostatistical DMC members, sponsor and regTrade Review "The book by Dr. Herson is written amazingly well. The book concentrates on pharmaceutical industrysponsored confirmatory clinical trials and can serve as excellent sources of knowledge for all the aspects of data safety monitoring committee (DMC) activities. A great feature of the book is the “DMCounselor” section at the end of each chapter, covering nearly 70 questions with answers, of which about 33% are for a DMC Chair, 30% for the DMC Biostatistician member, 30% for a DMC physician member, and the rest are for others (e.g., project manager)."~ Daniel Jia, Journal of Biopharmaceutical Statistics"Nicely written and readable cover-to-cover, the author walks through every facet of a Data Monitoring Committee (DMC) beginning with an overview of their past and current place in drug development, to how they are organized and interfaced with other committees, and on to the specifics of how a typical meeting is split into an open and closed session. From there it moves on to clinical issues, including how SAEs are categorized, statistical methods, including Bayesian and frequentist conditional power calculations, common biases and pitfalls, and guidance for how DMC decisions are made. It concludes with emerging issues due to new clinical trial designs mandated by the FDA to speed up the drug development process."~Donna Pauler Ankerst, BiometricsTable of ContentsPreface to the Second Edition. Introduction. Organization of a Safety Monitoring Program for a Confirmatory Trial. Meetings. Clinical Issues. Statistical Issues. Biases and Pitfalls. DMC Decisions. Emerging issues. Appendix.

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Book SynopsisThis insightful work provides a useful introduction to the very large and important field of pharmacokinetics. The authors have selected the Time Constant Approach as a unifying view within which to present important application areas. In addition to providing consistency, their approach provides the novice with an intuitive time view that is meaningful from the outset. This approach allows one to get a "feel" for the data and to relate it to other data in a direct and accessible manner.The Time Constant Approach provides a synthesis of the noncompartmental and compartmental methods, with the advantages of both. It starts by defining a physiologically meaningful model based on the pharmacokinetic processes involved. The Time Constant Approach recognizes pharmacokinetics as a number of processes that move drugs between physiological compartments, each process occurring at its own characteristic length of time, to correlate descriptive pharmacokinetic events with time constants of pharmacokinetic processes. While analogous to the three most common testing approaches for pharmacokinetics (the noncompartmental, compartmental and statistical moment approaches) the Time Constant Approach possesses many advantages.

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Book SynopsisComplete, Authoritative, Unrivaled CollectionClin-Alert, long established as the pre-eminent source of adverse drug reaction/interaction, now brings you Clin-Alert 2000. Presented in a quick reference format, Clin-Alert 2000 allows very easy access by drug class for comparison reports. Pharmacological classes are arranged based on a modified AHFS Therapeutic Classification Code System AND include the addition of a comprehensive section on alternative/herbal medicines.Table of ContentsDrug Classes Include: Alternative Therapies (herbals, supplements). Antihistamines. Anti-infective Agents. Anti-neoplastics. Autonomic Drugs. Blood Formation and Coagulation. Cardiovascular Drugs. CNS Agents (Analgesics, Sedatives, Psychotherapeutics). Dental Agents. Diagnostic Agents. Electrolytic and Water Balance. EENT Preparations. Gastrointestinal Agents. Hormones and Contraceptives. Radioactive Agents. Topical Products. Vaccines. Vitamins. Miscellaneous.

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Book SynopsisIn the fiercely competitive pharmaceutical marketplace, your organization cannot afford to spend excess dollars developing drugs that will fail to get FDA approval or have profoundly poor characteristics. Biochips as Pathways to Drug Discovery takes a comprehensive look at how the industry faces these challenges, using new technologies such as biochips to reduce the cost of drug discovery and improve drug safety. The book explores the tools and skills required at each step of the discovery process when using biochips to determine biological outcomes.The authors provide an in-depth review of the clinical and pharmacogenomic relevance of biochips, ChIP-chip assays, and high-throughput approaches. They discuss how biochips are used to develop biomarkers in the drug discovery process, primarily for gene expression profiling and Single Nucleotide Polymorphism (SNP) analysis. The book includes coverage of experimental theory, quality control, clinical laboratory sampling considerations, database concepts, industrial laboratory design, and the analysis of the resultant large data sets. It discusses the application of biochips to the study of malaria, toxicogenomics, and SNPs, as well as intellectual property and market overviews. The book concludes with a comprehensive overview of how these chips are employed from early target discovery through preclinical toxicology and on through to pharmacogenomic and proof of concept studies in humans. Written in an easily accessible style, the breadth of coverage introduces the subject to those new to the field, while the depth of coverage forms a foundation for future work. The book gives you the knowledge required to leverage the technology into bona fide discoveries. Daniel E. Levy, editor of the Drug Discovery Series, is the founder of DEL BioPharma, a consulting service for drug discovery programs. He also maintains a blog that explores organic chemistry.Trade Review“The authors of this volume provide an in-depth review of the clinical and pharmacogenomic relevance of biochips, ChIP-chip assays, and high-throughput approaches. … The book includes coverage of experimental theory, quality control, clinical laboratory sampling considerations, database concepts, industrial laboratory design, and the analysis of the resultant large data sets. … Written in an easily accessible style, the breadth of coverage introduces the subject to those new to the field, while the depth of coverage forms a foundation for future work.” — In Anticancer Research, Vol. 27, No. 3B, May/June 2007"This book is a must have for students who use biochips in their graduate work or others initiating efforts in these areas . . . In summary, Biochips as Pathways to Drug Discovery provides a broad yet detailed look at the use of DNA microarrays in drug discovery." – Matthew D. Disney, The University at Buffalo, The State University of New York, in ChemMedChem, 2008, No. 3Table of ContentsDNA Biochips — Past, Present, and Future: An Overview. Three-Dimensional HydroArrays: Novel Microarrays for Genomic and Proteomic Studies. Biochip in Malaria for Antiparasitic Discovery. Regional Variations in Intestinal ATP-Binding Cassette Transporter Expression Identified with a Global Error Assessment Model. Toxicogenomics in Drug Safety Evaluation: Bridging Drug Discovery and Development. The Next Generation of Automated Microarray Platforms for a Multiplexed CYP2D6 Assay. Biopsy and RNA Extraction Procedures of Muscle and Adipose Tissue for Microarray Gene-Expression Profiling. ChIP-on-Chip: Analysis of Genomewide Protein Binding and Posttranslational Modifications. DNA Microarrays as Functional Genomics Tools for Cancer Drug Discovery. High-Throughput Microarray Analysis. Laboratory Automation: Strategies for High-Volume Industrial Microarray Programs. Association Studies: Practical and Theoretical Considerations for Drug Discovery, Evaluation, and Beyond. Approaches for Microarray Data Validation. Microarray Enterprise Information Management: What Is It and Why Is It Important? Quality Control of Microarray Data. Microarray Data Normalization and Transformation. Amplification Strategies and DNA Biochips. Ribo-SPIA™, a Rapid Isothermal RNA Amplification Method for Gene Expression Analysis. Genomics, Transcriptomics, and Proteomics: Novel Detection Technologies and Drug Discovery. Intellectual Property Issues for DNA Chips and Microarrays. Biochips: Market Drivers and Commercial Prospect. A Pharmaceutical Perspective for Microarrays and Biochips: Current-Market Overview and Future Trends.

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Book SynopsisClinical trials have become essential research tools for evaluating the benefits and risks of new interventions for the treatment and prevention of diseases, from cardiovascular disease to cancer to AIDS. Based on the authors’ collective experiences in this field, Introduction to Statistical Methods for Clinical Trials presents various statistical topics relevant to the design, monitoring, and analysis of a clinical trial.After reviewing the history, ethics, protocol, and regulatory issues of clinical trials, the book provides guidelines for formulating primary and secondary questions and translating clinical questions into statistical ones. It examines designs used in clinical trials, presents methods for determining sample size, and introduces constrained randomization procedures. The authors also discuss how various types of data must be collected to answer key questions in a trial. In addition, they explore common analysis methods, describe statistical methods that determine what an emerging trend represents, and present issues that arise in the analysis of data. The book concludes with suggestions for reporting trial results that are consistent with universal guidelines recommended by medical journals. Developed from a course taught at the University of Wisconsin for the past 25 years, this textbook provides a solid understanding of the statistical approaches used in the design, conduct, and analysis of clinical trials.Trade Review… There is much good material in this book. The individual chapters are well written and cover the technical aspects as well. A major strength is the ordering of topics to follow the thought process used in the development and implementation of a protocol from defining the question to reporting results. There are careful discussions on fundamental principles and the pivotal role played by statistics is well brought out. … there is much that practicing pharmaceutical statisticians will find useful in this book. They will find the coverage of fundamental principles useful and the technical content of the book a good reference source. …—Pharmaceutical Statistics, 2010… fits the need for a contemporary text and handbook that is oriented toward the clinical trial statistician. I highly recommend it and look forward to using it as both a primary and supplemental text in our curriculum, as well as a research resource.—James J. Dignam, University of Chicago, JASA, March 2009The (technical) statistical content is the main focus of the book and this is what helps it to stand apart from most others on clinical trials (even the more obviously statistically orientated ones). It takes the reader to quite a technical background that would serve him or her well if moving on to research problems in the various areas covered, yet does not lose sight of practical issues. … For those of us with the interest (and need) to grapple with these more statistical issues, I wholeheartedly recommend it.—Biometrics, December 2008…The book is very well written and clear. … the authors generally strike the right balance for the intended audience. The inclusion of many historically important as well as contemporary examples to illustrate various points throughout the text is a major strength, as is the inclusion of several modern topics not seen in other texts. As a basis for a course in clinical trials for graduate students in biostatistics, this book is outstanding. In addition, statisticians in the pharmaceutical industry, government, or academia … will find this text extremely informative and useful.” —Michael P. McDermott, University of Rochester Medical Center, Journal of Biopharmaceutical Statistics, 2008Table of ContentsPreface. Introduction to Clinical Trials. Defining the Question. Study Design. Sample Size. Randomization. Data Collection and Quality Control. Survival Analysis. Longitudinal Data. Quality of Life. Data Monitoring and Interim Analysis. Selected Issues in the Analysis. Closeout and Reporting. Special Topics. Appendix. References. Index.

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Book SynopsisVeterinary students and practicing technicians will find this book to be an important bench manual as well as an educated tool to have on their desk. Also included in the package is a free online resource for testing and additional information.Table of Contents1. THE CLINICAL PATHOLOGY LABORATORY 2. THE CLINICAL PATHOLOGY LABORATORY 3. URINALYSIS LABORATORY 4. PROPER LABORATORY TREATMENT OF BLOOD SMEARS AND CELLS 5. HEMATOLOGY- THE BLOOD SMEAR 6. HEMATOLOGY - THE WHITE BLOOD CELL COUNT AND IDENTIFICATION 7. THE 3-H’S OF HEMATOLOGY 8. COAGULATION TESTING 9. MECHANICAL HEMATOLOGY 10. ANTIGEN-ANTIBODY TESTING 11. COPROPHOLOGICAL TESTING OF GASTROINTESTINAL FUNCTION 12. MICROBIOLOGICAL PREPARATION 13. MICROBIOLOGICAL SUPPLIES AND COLLECTION OF VETERINARY SPECIMENS 14. MICROBIAL CULTURE AND SENSITIVITY AND BIOCHEMICAL TESTING 15. MILK TESTING 16. INTRODUCTION TO CYTOLOGY 17. CYTOLOGY: THE ART OF FINE NEEDLE ASPIRATION 18. NECROPSY: A TECHNICIAN’S ROLE 19. AVIAN, EXOTIC MAMMALS, REPTILES AND FISH 20. RUMEN FLUID COLLECTION AND EVALUATION

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Book SynopsisDrug design is the approach of finding drugs by design, based on their biological targets. Typically a drug target is a key molecule involved in a particular metabolic or signalling pathway that is specific to a disease condition or pathology, or to the infectivity or survival of a microbial pathogen. Some approaches attempt to stop the functioning of the pathway in the diseased state by causing a key molecule to stop functioning. Drugs may be designed that bind to the active region and inhibit this key molecule. However these drugs would also have to be designed in such a way as not to affect any other important molecules that may be similar in appearance to the key molecules. Sequence homologies are often used to identify such risks. Other approaches may be to enhance the normal pathway by promoting specific molecules in the normal pathways that may have been affected in the diseased state. The structure of the drug molecule that can specifically interact with the biomolecules can be modelled using computational tools. These tools can allow a drug molecule to be constructed within the biomolecule using knowledge of its structure and the nature of its active site. Construction of the drug molecule can be made inside out or outside in depending on whether the core or the R-groups are chosen first. However many of these approaches are plagued by the practical problems of chemical synthesis. Newer approaches have also suggested the use of drug molecules that are large and proteinaceous in nature rather than as small molecules. There have also been suggestions to make these using mRNA. Gene silencing may also have therapeutical applications. This book presents leading-edge research from around the world.

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Book SynopsisThis valuable new book, Handbook of Research on Medicinal Chemistry: Innovations and Methodologies, presents some of the latest advancements in the various fields of combinatorial chemistry, drug discovery, biochemical aspects, pharmacology of medicinal agents, current practical problems, and nutraceuticals. The editors keep the drug molecule as the central component of the volume and aim to explain the associated features essential to exhibiting pharmacological activity. With a unique combination of chapters in biology, clinical aspects, biochemistry, synthetic chemistry, medicine and technology, the volume provides broad exposure to the essential aspect of pharmaceuticals. The volume many important aspects of medicinal chemistry, including techniques in drug discovery pharmacological aspects of natural products chemical mediators: druggable targets advances in medicinal chemistry The field of medicinal chemistry is growing at an unprecedented pace, and this volume takes an interdisciplinary approach, covering a range of new research and new practices in the field. The volume takes into account the latest therapeutic guidelines put forward by the World Health Organization and the U.S Food and Drug Administration..Topics include: drug design drug discovery natural products and supplements and nutraceuticals pharmaceutical approaches to sexual dysfunction drug resistance parasites new natural compounds and identification of new targets stereochemistry aspects in medicinal chemistry common drug interactions in daily practices Handbook of Research on Medicinal Chemistry: Innovations and Methodologies will be a valuable addition to the bookshelves of pharmaceutical scientists and faculty as well as for industry professionals.Trade Review"A valuable book that will deliver newer aspects and applications in the field of medicinal chemistry. . . . A very useful reference book that encompasses various principles and applications associated with medicinal chemistry. [It] integrates insights regarding drug discovery, pharmacological aspects of natural products, druggable targets of chemical mediators, and several classes of medicinal agents. . . . It is a good skillful blend of medicinal chemistry, chemical biology, chemical synthesis, pharmacology, formulation, and miscellaneous subjects."—From the Foreword by Vivekananda Mandal, PhD, Former WERC Researcher, Government of Japan; Institute of Pharmaceutical Sciences, Guru Ghasidas University (Central University), India“An excellent resource for cultivating sound research acumen in the area of medicinal chemistry. Unlike most books in the field, this goes beyond purely theoretical knowledge and greatly focuses on experimental procedures and practical approaches to develop a nuance understanding in the field of drug discovery. I thoroughly enjoyed the clear and interesting presentation of the material. Great efforts have been invested to ensure that it is easily accessible to both students and teachers. The book shows promising potential in exploring the field of medicinal chemistry and will prove to be an important aid to the researchers.”—Neelam Singla, PhD, Director, Accura Research Chemicals Pvt. Ltd., Hyderabad, India"A valuable book that will deliver newer aspects and applications in the field of medicinal chemistry. . . . A very useful reference book that encompasses various principles and applications associated with medicinal chemistry. [It] integrates insights regarding drug discovery, pharmacological aspects of natural products, druggable targets of chemical mediators, and several classes of medicinal agents. . . . It is a good skillful blend of medicinal chemistry, chemical biology, chemical synthesis, pharmacology, formulation, and miscellaneous subjects."—From the Foreword by Vivekananda Mandal, PhD, Former WERC Researcher, Government of Japan; Institute of Pharmaceutical Sciences, Guru Ghasidas University (Central University), IndiaTable of ContentsCombinatorial Chemistry: Role in Lead Discovery. Advanced Techniques in Bimolecular Simulations. Retrometabolic Drug Design. Insight Into The Pharmacological Potentials of Camellia sinensis Linn. Pharmaceutical Importance of Natural Aphrodisiac Drugs. Serotonin: Chemical, Biological and Therapeutic Aspects. Eicosanoids: Constitution and Pathophysiological Functions. Development of Antimalarial Drug Analogues to Combat Plasmodium Resistance. Chemistry and Pharmacology of Β-Lactam Analogues. General Anaesthetics. Stereochemical Aspects in Medicinal Chemistry. Pharmaceutical Interactions in Drug Practices.

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Book SynopsisMicrobial lipases are industrially important and have gained attention due to their stability, selectivity, and broad substrate specificity. Lipases are used as medicine, and they also aid in indigestion, heartburn, allergy to gluten in wheat products (celiac disease), Crohn’s disease, and cystic fibrosis. This volume considers the industrial demand for new sources of lipases with different catalytic characteristics that stimulate the isolation, growth, and development of new microbial strains. The volume narrates the challenging metagenomic approach with the isolation of the lipase gene, its cloning into Escherichia coli, culture of the recombinant bacteria, and extraction and assessment of the lipase enzyme. Lipase-producing bacteria are available in different habitats, such as industrial wastes, vegetable oil processing factories, dairy plants, and soils contaminated with oil and oil seeds, among others. This volume is the effort of the authors to document the scientific findings carried out over the last eight years in the area of un-culturable soil microorganisms. The book presents the physic-chemical features of lipases and their specific applications in different commercial industries. The in-depth study looks at metagenomics for lipases from all angles and provides a truly informative resource. It describes the biochemical characterization of lipase enzymes with the high activity in the presence of 1% tributyrin. A wide review has been presented in the book on lipase enzymes purified from a large collection of microbes present in soil, seawater, waste-dumping sites, animal systems (including human beings), and the atmosphere. Stability of enzymes over changing environments of the industry is indeed a big issue, and the book deals at length with the changing temperatures and pH and metal ion concentrations. Table of ContentsIntroduction. Application of Lipases. Metagenomics and Unculturable Bacteria. Accessing Metagenomics. Metagenomics for Lipase. Functional Approach for Metagenomic Library Construction. Overexpression of Recombinant Protein. Biochemical Characterization of Purified Lipase. Genomic Study of Culture Dependent Bacteria. Genomic Study of Culturable Bacteria. Microbial Assay of Culture Supernatant Containing Crude Lipase. Critical Observations.

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Book SynopsisWith chapters from highly skilled, experienced, and renowned scientists and researchers from around the globe, Dendrimers for Drug Delivery provides an abundance of information on dendrimers and their applications in the field of drug delivery.The volume begins with an introduction to dendrimers, summarizing dendrimer applications and the striking features of dendrimers. It goes on to present the details of usual properties, structure, classification, and methods of synthesis, with relevant examples. The toxicity of dendrimers is also discussed. The chapter authors provide an exhaustive amount of information about dendrimers and their biomedical applications, including biocompatibility and toxicity aspects, a very useful feature. This informative volume will be valuable resource that will help readers to create products derived from dendrimers and navigate through the regulatory, manufacturing, and quality control hurdles. It will be an important resource for researchers, scientists, upper-level students, and industry professionals. Table of ContentsDendrimers: Branched Nanoarchitectures and Drug Delivery. Dendrimers: A Tool for Advanced Drug Delivery. Dendrimers: General Features and Applications. Computational Approach to Elucidate Dendrimers. An Overview of Dendrimers and Their Biomedical Applications. Dendrimers for Controlled Release Drug Delivery. Dendrimers in Targeted Drug Delivery. Dendrimers in Oral Drug Delivery. Dendrimers in Gene Delivery. Dendrimers as Nanocarriers for Anticancer Drugs. Dendrimeric Architecture for Effective Antimicrobial Therapy.

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Book SynopsisThis new volume presents a plethora of new research on the use of nanoconjugate nanocarriers in drug delivery. Nanotechnology as drug carriers has been observed to increase the level of sophistication through a variety of ways. It helps to alleviate some of the pitfalls of conventional dosage forms, such as few pitfalls such as non-specific drug delivery, dose dumping, poor patient compliance, toxicities linked with higher doses, etc.With chapters from highly skilled, experienced, and renowned scientists and researchers, Nanoconjugate Nanocarriers for Drug Delivery is divided into four sections, providing an introduction to nanocarriers for drug delivery, physicochemical features of nanocarriers, and specific applications dealing with drug delivery in particular. The materials used as well as formulation and characterization have been discussed in detail. The nanocarriers covered in the book include nanoparticles, vesicular carriers, carriers having carbon as the core constituent, dispersed systems, etc. The book also delves into the interaction and associations between drug delivery research and its therapeutic applications in practice.The book integrates a wide variety of case studies, research, and theories in an attempt to reveal the diversity and capture the novel approaches of nanoconjugate nanocarriers for drug delivery employed by developers and content experts in the field. This timely publication will be an essential reference and current awareness source, building on the available literature in the field of pharmacy and biomedical science, while also providing ideas for further research opportunities in this dynamic field.Table of ContentsNanobiomaterials for Drug Delivery. Role of Surfactants in Nanotechnology-Based Drug Delivery. Smart Polymeric Nanocarriers for Drug Delivery. Gold Nanoconjugates for Smart Drug Delivery and Targeting. Vesicular Drug Carriers as Delivery Systems. siRNA Delivery with Liposomes as Platform Technology. Theranostic Application of Indocyanine Green Liposomes. Aquasomes: A Nanocarrier System. Quantum Dots for Drug Delivery. Graphene and Graphene-Based Materials: Synthesis, Characterization, Toxicity, and Biomedical Applications. Graphene for Drug Delivery: Focus on Antimicrobial Activity. Carbon Nanotubes for Drug Delivery. Nanoemulsion for Drug Delivery. Nanoconjugate Nanocarriers for Drug Delivery in Tropical Medicine. Nanocarrier-Assisted Drug Delivery for Neglected Tropical Diseases. Self-Assembly of Sucrose and Trehalose Alkyl Ethers into Nanoparticles and Nanorods under Aqueous Conditions.

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Book SynopsisThis new volume, Natural Polymers for Pharmaceutical Applications, Volume 1: Plant-Derived Polymers, presents some of the latest research on the applications of natural polymers in drug delivery and therapeutics for healthcare benefits. Polymers and their applications from several plants are discussed in depth, including tamarind gum, gum Arabic, natural carbohydrate polymer gum tragacanth, pectin, guar gum and its derivatives, locust bean gum, sterculia gum, okra gum, and others. The use of the polymers derived from plants as potential pharmaceutical excipients is expanding day by day because of their stability in the biological system, drug-releasing capability, drug-targeting abilities, as well as their bioavailability. Trade Review“A well-engrossed concept on application of natural plant derivatives as pharmaceutical additives. . . . The superlative collection on the application of plant derivatives in design of novel drug delivery systems, such as micro and nanoparticles, throws an insight on the useful applications of plant-derived products. I would say with a definite certitude that the book will prove to be an exemplary reference for academicians and scientist working in the field of plant-derived products for pharmaceutical applications.” - Dr. Tahir Ansari, Assistant Professor, University of Kualalumpur, MalaysiaTable of ContentsVolume 1: Plant-Derived Polymers 1. Pharmaceutical Applications of Tamarind Gum 2. Pharmaceutical Applications of Gum Arabic 3. Recent Advances in Pharmaceutical Applications of Natural Carbohydrate Polymer Gum Tragacanth 4. Application Potential of Pectin in Drug Delivery 5. Guar Gum and Its Derivatives: Pharmaceutical Applications 6. Pharmaceutical Applications of Locust Bean Gum 7. Pharmaceutical Applications of Sterculia Gum 8. Pharmaceutical Applications of Okra Gum 9. Pharmaceutical Applications of Fenugreek Seed Gum

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Book SynopsisMany polymers derived from various marine sources and microorganisms possess some important biological properties such as biocompatibility, biodegradability, and bioadhesivity that make them attractive as pharmaceutical excipients in various pharmaceutical dosage forms. Moreover, these polymers can be modified physically and/or chemically to improve their biomaterial properties.In this volume, Natural Polymers for Pharmaceutical Applications, Volume 2: Marine- and Microbiologically Derived Polymers, looks at how these polymers have been explored and exploited for pharmaceutical uses, such as in tablets, microparticles, nanoparticles, ophthalmic preparations, gels, emulsions, suspensions, etc. Some commonly used marine- and microbiologically derived polymers used as pharmaceutical excipients include alginates, agar-agar, gellan gum, carrageenan; chitosan, xanthan gum, and others. The book focuses on important recent advances from experts around the world on marine-derived polysaccharides and pharmaceutical applications of alginates, agar-agar, gellan gum, carrageenan, chitosan derivatives, xanthan gum. Table of ContentsVolume 2: Marine- and Microbiologically Derived Polymers 1. Marine-Derived Polysaccharides: Pharmaceutical Applications 2. Pharmaceutical Applications of Alginates 3. Pharmaceutical Applications of Agar-Agar 4. Pharmaceutical Applications of Gellan Gum 5. Pharmaceutical Applications of Carrageenan 6. Pharmaceutical Application of Chitosan Derivatives 7. Pharmaceutical Applications of

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Book SynopsisTopical and transdermal drug delivery systems (TDDs) have several advantages over traditional drug delivery methods, as they can be less invasive, more sanitary, more cost-effective, and may result in better patient compliance. TDDs play a significant role in therapeutics with a variety of preparations and approaches designed by expert formulation scientists. This volume integrates a wide variety of case studies, research, and theories to reveal their diversity and capture the novel approaches of transdermal and topical drug delivery employed by developers and content experts in the field. It provides an abundance of important information and state-of-the-art research on topical and transdermal drug delivery systems and addresses the basics of drug delivery systems, strategies to enhance permeation across membranes, and formulation and evaluation of diverse dosage forms.The volume presents an evaluation of the pros and cons of conventional drug delivery systems against TDDs and discusses the nuances of micro- and nano-systems in TDDs. The extraordinary packages of nano systems (vesicular systems, polymeric nanoparticles, nanoemulsion and dendrimers) are broadly discussed, and their applications are reviewed through a transdermal route.The book looks at TDDs and the main nanoparticles used in skin diseases and lesions of the aging, such as psoriasis, vitiligo, cancer, lesions of the aging and others. Chapters also discuss polymeric micelles in topical and transdermal delivery; microneedles; emulsion, nanoemulsion and microemulsion; TDDs in pulmonary drug delivery systems; nanoencapsulated nasal drug delivery systems; skin sensitivity and irritation testing for transposing transdermal drug delivery systems; and regulatory aspects of drug development for dermal products.Topical and Transdermal Drug Delivery Systems: Applications and Prospects will be a valuable resource for pharmaceutical scientists and researchers, industry professionals, and academicians and students of the pharmaceutical and biomedical sciences.Table of ContentsPART I: BASICS OF TRANSDERMAL DRUG DELIVERY SYSTEMS 1. Concepts and Applications in Topical and Transdermal Drug Delivery 2. Micro- and Nano-Systems in Transdermal Drug Delivery System 3. Advanced Topical and Transdermal Drug Delivery (TTDS) Used in Skin Diseases and Lesions of the Aging PART II: DIVERSE TRANSDERMAL DRUG DELIVERY SYSTEMS 4. Polymeric Micelles in Topical and Transdermal Delivery 5. Microneedles: An Innovative Strategy for Skin Drug Delivery, Diagnostic, and Cosmetologic Approaches 6. Emulsion, Nanoemulsion, and Microemulsion in Tdds 7. Pulmonary Drug Delivery Systems 8. Nanoencapsulated Nasal Drug Delivery System PART III: MISCELLANEOUS 9. Skin Sensitivity and Irritation Testing for Transposing Transdermal Drug Delivery System 10. Regulatory Aspects of Drug Development for Dermal Products

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Book SynopsisThe third edition of this popular and highly-regarded guide uncovers the ethics, conventions and often unwritten rules of publishing in peer-reviewed journals and at conferences. It provides clear direction on how to choose the right journal, avoid publication delays, resolve authorship disputes and many other problems associated with being published that pose challenges to new and experienced researchers alike.The A to Z format is highly accessible to readers with different backgrounds and varying levels of publication experience, including students and healthcare professionals, medical researchers and individuals working in drug companies and communications agencies. It will be particularly valuable to anyone involved in planning publications.Trade Review"In short, this is a must-have book for writers, editors and account managers in medical communications agencies in the publications departments of research institutions and pharmaceutical and medical device companies. I also recommend it to my fellow freelance writers as an easy way to ensure that you are ‘on the same page’ as the companies that you are working with when it comes to disseminating medical research findings" – Jane Tricker CMPP, Medical Writing"Like its predecessors this update of Liz Wager’s book is presented concisely, pragmatically and with the inimitable down-to-earth and sharp-witted style familiar to many of us...this book is the source of "Everything You Need to Know About Medical Publishing but Were Afraid to Ask" and could well be one of the best bookshelf investments you make this year". – Moira A Hudson, European Science Editing Journal"The 3rd edition of Getting Research Published successfully instructs in an authoritative, easy to use, and clear and concise manner."—Howard Bauchner, MD, Editor in Chief, JAMA and The JAMA Network "The first thing that strikes you about this book … is its sheer practical nature."—Peter Thorpe, Independent consultant in information and communications management, European Science Editing Journal (of a previous edition)Table of ContentsPUBLICATION STRATEGY – AN OVERVIEW. Step-by-Step Guide to Publication Strategy. Developing a Publication Plan for a Multicentre Study. How Long Will it Take? Working with a Medical Writer. Dr. Seymour and the Disappearing Paper: A Cautionary Tale. A TO Z OF PUBLICATION STRATEGY.

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Book SynopsisDescribing recent developments in the engineering and generation of plants as production platforms for biopharmaceuticals, this book includes both vaccines and monoclonal antibodies. It has a particular emphasis on targeting diseases which predominate in less developed countries, encompassing the current state of technologies and describing expression systems and applications. This book also includes a variety of vaccine case studies, protecting against pervasive infectious diseases such as rabies, influenza and HIV.Table of Contents1: Introduction, and the Promise of a Plant-derived Vaccine for Hepatitis B Virus 2: Protein Body-inducing Fusions for Recombinant Protein Production in Plants 3: Expression of Recombinant Proteins in Plant Cell Culture 4: Plant-derived Monoclonal Antibodies as Human Biologics for Infectious Disease and Cancer 5: Plant-produced Virus-like Particles 6: Expression of the Capsid Protein of Human Papillomavirus in Plants as an Alternative for the Production of Vaccines 7: Patenting of Plant-made Recombinant Pharmaceuticals and Access in the Developing World 8: Case Study 1: Rabies 9: Case Study 2: Plant-made HIV Vaccines and Neutralizing Antibodies 10: Case Study 3: The Search for a Plant-made Vaccine for Pandemic Influenza Virus

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Book SynopsisThe vast majority of drugs are organic molecular entities. A clear understanding of the organic chemistry of drug degradation is essential to maintaining the stability, efficacy, and safety of a drug product throughout its shelf-life. During analytical method development, stability testing, and pharmaceutical manufacturing troubleshooting activities, one of the frequently occurring and usually challenging events would be the identification of drug degradants and understanding of drug degradation mechanisms and pathways. This book is written by a veteran of the pharmaceutical industry who has first-hand experience in drug design and development, drug degradation mechanism studies, analytical development, and manufacturing process troubleshooting and improvement. The author discusses various degradation pathways with an emphasis on the mechanisms of the underlying organic chemistry, which should aid greatly in the efforts of degradant identification, formulation development, analytical development, and manufacturing process improvement. Organic reactions that are significant in drug degradation will first be reviewed and then illustrated by examples of drug degradation reported in the literature. The author brings the book to a close with a final chapter dedicated to the strategy for rapid elucidation of drug degradants with regard to the current regulatory requirements and guidelines. One chapter that should be given special attention is Chapter 3, Oxidative Degradation. Oxidative degradation is one of the most common degradation pathways but perhaps the most complex one. This chapter employs more than sixty drug degradation case studies with in-depth discussion in regard to their unique degradation pathways. With the increasing regulatory requirements on the quality and safety of pharmaceutical products, in particular with regard to drug impurities and degradants, the book will be an invaluable resource for pharmaceutical and analytical scientists who engage in formulation development, analytical development, stability studies, degradant identification, and support of manufacturing process improvement. In addition, it will also be helpful to scientists engaged in drug discovery and development as well as in drug metabolism studies.Trade Review"...the book provides the interested reader with a comprehensive, overview on all relevant aspects of drug degradation chemistries and analytical strategies." -- Prof. Dr. Mario Thevis, German Sport University Cologne (Germany) * ChemMedChem, DOI: 10.1002/cmdc.201300109 *"Overall, Organic Chemistry of Drug Degradation is an interesting read and provides the reader with concise information and up-to-date knowledge on chemical as well as analytical aspects of drug degradation." -- Prof. Dr. Mario Thevis, German Sport University Cologne (Germany) * ChemMedChem, DOI: 10.1002/cmdc.201300109 *"Due to the book’s broad scope and well-balanced coverage of obligatory and new aspects in drug stability research and quality assurance, it is of particular value to students and scientists in the field of pharmaceutical sciences." "The book superbly introduces a broad readership into the arena of drug degradation and impurity testing." -- Prof. Dr. Mario Thevis, German Sport University Cologne (Germany) * ChemMedChem, DOI: 10.1002/cmdc.201300109 *Table of ContentsIntroduction; Hydrolytic Degradation; Oxidative Degradation; Various Types and Mechanisms of Degradation Reactions; Drug-Excipient Interactions and Adduct Formation; Photochemical Degradation; Chemical Degradation of Biological Drugs; Strategies for Elucidation of Degradant Structures and Degradation Pathways; Control of Drug Degradation; Subject index

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Book SynopsisThis handbook, directed at medical professionals and students who are involved in developing the space industry or are academicians doing research in this area, covers current pharmaceutical knowledge about the difference in medication efficacy in space versus on Earth and includes trial results and best practices for the space research and travel industry. The well-known contributors come from an interdisciplinary background and address all aspects of the subject, from the physiological impact of spaceflight to the effects of radiation.As the commercial space industry expands its operations in industry and tourism, the field of space pharmaceuticals is growing commensurately. Existing pharmacological research from space is thoroughly covered in this book, and Earth applications are also described. Potential pharmacological solutions are posed along with the known challenges and examples from existing studies, which are detailed at length. This major reference work is a comprehensive and important medical resource for all space industry players.Table of ContentsSection I: Principles of Pharmaceuticals.- Section II: Effects of Spaceflight on Human Physiology and its Consequences on Drug Treatment.- Section III: Model Organisms for Pharmaceutical Research in Space.- Section IV: Simulated Microgravity for Pharmaceutical Research.- Section V: Translating Knowledge from Spaceflight Research to Earth Applications.- Section VI: Nutritional and Alternative Approaches to Treatment in Space.

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Book SynopsisThis book reviews the principles of design and examples of successful implementation of proteinkinase inhibitors (PKI), and offers a comprehensive and authoritative overview of the history and latest developments in the field. Chapters written by experts from industry and academia cover the function, structure and topology of Proteinkinases, molecular modelling, disclose how to achieve high level of selectivity for kinase inhibitors, and exploit kinase inhibitors for cancer treatment. Particular attention is given to Inhibitors of c-Jun N-terminal kinase 3, and to covalent Janus Kinase 3 Inhibitors. A case study on Receptor Tyrosine Kinases EGFR, VEGFR, PDGFR is also presented in this book.Given its breath, this book will appeal to medicinal chemists, students, researchers and professionals alike.Table of ContentsProteinKinase-Inhibitors: A Story of Success.- Function, Structure and Topology of Proteinkinases.- Molecular Modelling.- Case study on Receptor Tyrosine Kinases EGFR, VEGFR, PDGFR.- Achieving high level of selectivity for kinase inhibitors.- Inhibitors of c-Jun N-terminal kinase 3.- Exploiting kinase inhibitors for cancer treatment - An Overview of Clinical Results and Outlook.- Covalent Janus Kinase 3 Inhibitors.

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