Handbook of Polymers for Pharmaceutical Technologies, Processing and Application

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Polymers are one of the most fascinating materials of the present era finding their applications in almost every aspects of life. Polymers are either directly available in nature or are chemically synthesized and used depending upon the targeted applications. Advances in polymer science and the introduction of new polymers have resulted in the significant development of polymers with unique properties. Different kinds of polymers have been and will be one of the key in several applications in many of the advanced pharmaceutical research being carried out over the globe. This 4-partset of books contains precisely referenced chapters, emphasizing different kinds of polymers with basic fundamentals and practicality for application in diverse pharmaceutical technologies. The volumes aim at explaining basics of polymers based materials from different resources and their chemistry along with practical applications which present a future direction in the pharmaceutical industry. Each volume offer deep insight into the subject being treated. Volume 1: Structure and ChemistryVolume 2: Processing and ApplicationsVolume 3: Biodegradable PolymersVolume 4: Bioactive and Compatible Synthetic/Hybrid Polymers

FORMATHardcover LANGUAGEEnglish CONDITIONBrand New Author Biography

Vijay Kumar Thakur, PhD, is a Staff Scientist in the School of Mechanical and Materials Engineering at Washington State University, U.S.A. He has published more than 100 research articles, patents and conference proceedings in the field of polymers and materials science and has published ten books and 25 book chapters on the advanced state-of-the-art of polymers/ materials science. He has extensive expertise in the synthesis of polymers (natural/ synthetic), nano materials, nanocomposites, biocomposites, graft copolymers, high performance capacitors and electrochromic materials. Manju Kumari Thakur works in the Department of Chemistry, Himachal Pradesh University, Simla, India.

Table of Contents

Preface xvii 1 Particle Engineering of Polymers into Multifunctional Interactive Excipients 1Sharad Mangal, Ian Larson, Felix Meiser and David AV Morton 1.1 Introduction 1 1.2 Polymers as Excipients 3 1.3 Material Properties Affecting Binder Activity 6 1.3.1 Particle Size 6 1.3.2 Deformation Mechanisms 7 1.3.3 Glass Transition Temperature (Tg) 8 1.4 Strategies for Improving Polymeric Filler-Binder Performance for Direct Compression 8 1.4.1 Interactive Mixing 12 1.4.2 Challenges to Interactive Mixing 13 1.4.3 Controlling Interparticle Cohesion 14 1.5 Preparation and Characterization of Interactive Excipients 14 1.5.1 Particle Size and Size Distribution of Excipients 15 1.5.2 Effect of L-leucine on Surface Morphology 16 1.5.3 Effect of L-leucine on Surface Composition 16 1.5.4 Effect of L-leucine on Surface Energy 17 1.5.5 Effect of L-leucine on Interparticle Cohesion 18 1.6 Performance of Interactive Excipients 18 1.6.1 Blending Ability 18 1.6.2 Effect on Flow 20 1.6.3 Binder Activity 20 1.7 Investigation of the Effect of Polymer Mechanical Properties 23 1.8 Conclusion 25 References 26 2 The Art of Making Polymeric Membranes 33K.C. Khulbe, T. Matsuura and C. Feng 2.1 Introduction 33 2.2 Types of Membranes 35 2.2.1 Porous Membranes 35 2.2.2 Nonporous Membranes 36 2.2.3 Liquid Membranes (Carrier Mediated Transport) 36 2.2.4 Asymmetric Membranes 36 2.3 Preparation of Membranes 36 2.3.1 Phase Inversion/Separation 37 2.3.2 Vapor-Induced Phase Separation (VIPS) 37 2.3.3 Thermally-Induced Phase Separation (TIPS) 37 2.3.4 Immersion Precipitation 38 2.3.5 Film/Dry Casting Technique 38 2.3.6 Track Etching 39 2.3.7 Electrospinning 39 2.3.8 Spraying 42 2.3.9 Foaming 42 2.3.10 Particle Leaching 43 2.3.11 Precipitation from the Vapor Phase 43 2.3.12 Emulsion Freeze-Drying 43 2.3.13 Sintering 44 2.3.14 Stretching 44 2.3.15 Composite/Supported 44 2.3.16 Mixed Matrix Membranes (MMMs) 45 2.3.17 Hollow Fiber Membranes 46 2.3.18 Metal-Organic Frameworks (MOFs) 48 2.4 Modification of Membranes 49 2.4.1 Modification of Polymeric Membrane by Additives/Blending 49 2.4.2 Coating 50 2.4.3 Surface Modification by Chemical Reaction 50 2.4.4 Interfacial Polymerization (IP)/Copolymerization 50 2.4.5 Plasma Polymerization/Treatment 52 2.4.6 Surface Modification by Irradiation of High Energy Particles 52 2.4.7 UV Irradiation 53 2.4.8 Ion-Beam Irradiation 53 2.4.9 Surface Modification by Heat Treatment 53 2.4.10 Graft Polymerization/Grafting 53 2.4.11 Other Techniques 53 2.5 Characterization of Membrane by Different Techniques 54 2.5.1 Conventional Physical Methods to Determine Pore Size and Pore Size Distribution 55 2.5.2 Morphology 58 2.5.3 Thermal Properties 60 2.5.4 Mechanical Properties 60 2.6 Summary 61 References 62 3 Development of Microstructuring Technologies of Polycarbonate for Establishing Advanced Cell Cultivation Systems 67Uta Fernekorn, Jörg Hampl, Frank Weise, Sukhdeep Singh, Justyna Tobola and Andreas Schober 3.1 Introduction 67 3.2 Material Properties of Polycarbonate 71 3.2.1 Physical Properties 71 3.2.2 Chemical Properties 72 3.2.3 Biological Properties 72 3.3 Use of Polycarbonate Foils in Structuration Processes 75 3.3.1 Hot Embossing 75 3.3.2 Thermoforming 77 3.4 Simulation of Microstructuring of a Polycarbonate Foil 79 3.5 Chemical Functionalization of Polycarbonate 81 3.6 Surface Micropatterning of Polycarbonate 84 3.7 Application Examples 86 3.7.1 3D Liver Cell Cultivation in Polycarbonate Scaffolds 86 3.7.2 3D Lung Cell Cultivation in Semi-Actively Perfused Systems 87 3.7.3 Guiding 3D Cocultivation of Cells by Micropatterning Techniques 87 3.8 Conclusion and Further Perspectives 88 Acknowledgements 89 References 89 4 In-Situ Gelling Thermosensitive Hydrogels for Protein Delivery Applications 95Roberta Censi, Alessandra Dubbini and Piera Di Martino 4.1 Introduction 96 4.2 Polymers for the Design of Hydrogels 97 4.2.1 Polymer Architectures 97 4.2.2 Natural, Synthetic and Hybrid Hydrogels 97 4.2.3 Crosslinking Methods 99 4.2.4 Thermogelling Polymer Hydrogels 100 4.3 Pharmaceutical Applications of Hydrogels: Protein Delivery 107 4.3.1 Strategies for Protein Release from Hydrogels 109 4.4 Application of Hydrogels for Protein Delivery in Tissue Engineering 112 4.5 Conclusions 113 References 114 5 Polymers as Formulation Excipients for Hot-Melt Extrusion Processing of Pharmaceuticals 121Kyriakos Kachrimanis and Ioannis Nikolakakis 5.1 Introduction 121 5.1.1 Overview of Hot-Melt Extrusion (HME) 121 5.1.2 Solubility/Dissolution Enhancement by Solid Dispersions 123 5.2 Polymers for HME Processing 127 5.2.1 Basic Requirements 127 5.2.2 Suitability – Examples 128 5.3 Polymer Selection for the HME Process 130 5.3.1 Thermodynamic Considerations – Drug-Polymer Solubility and Miscibility 130 5.4 Processing of HME Formulations 135 5.4.1 Physical Properties of Feeding Material – Flowability, Packing and Friction 135 5.5 Improvements in Processing 141 5.5.1 Equipment Modifications 141 5.5.2 Plasticizers 142 5.6 Conclusion and Future Perspective 144 References 144 6 Poly Lactic-Co-Glycolic Acid (PLGA) Copolymer and Its Pharmaceutical Application 151Abhijeet Pandey, Darshana S. Jain, Subhashis Chakraborty 6.1 Introduction 151 6.2 Physicochemical Properties 152 6.3 Biodegradation 153 6.4 Biocompatibiliy, Toxicty and Pharmacokinetics 154 6.5 Mechanism of Drug Release 155 6.6 PLGA-Based DDS 157 6.7 Bone Regeneration 158 6.8 Pulmonary Delivery 160 6.9 Gene Therapy 162 6.10 Tumor Trageting 162 6.11 Miscellaneous Drug Delivery Applications 164 6.12 Conclusion 165 References 165 7 Pharmaceutical Applications of Polymeric Membranes 173Stefan Ioan Voicu 7.1 Introduction 173 7.2 Obtaining Pure and Ultrapure Water for Pharmaceutical Usage 178 7.3 Wastewater Treatment for Pharmaceutics 180 7.4 Controlled Drug Delivery Devices Based on Membrane Materials 183 7.5 Molecularly Imprinted Membranes 185 7.6 Conclusions 190 References 191 8 Application of PVC in Construction of Ion-Selective Electrodes for Pharmaceutical Analysis: A Review of Polymer Electrodes for Nonsteroidal, Anti-Inflammatory Drugs 195Joanna Lenik 8.1 Introduction 195 8.2 Properties and Usage of Poly(vinyl)chloride (PVC) 197 8.3 PVC Application and Properties in Construction of Potentiometric Sensors for Drug Detection 199 8.3.1 Role of Polymer Membrane Components 202 8.4 Ion-Selective, Classic, Liquid Electrodes (ISEs) 205 8.5 Ion-Selective Solid-State Electrodes 206 8.5.1 Ion-Selective Coated-Wire Electrodes (CWE) 206 8.5.2 Ion-Selective BMSA Electrodes 207 8.5.3 Electrodes Based on Conductive Polymers (SC-ISEs ) 208 8.6 Application of Polymer-Based ISEs for Determination of Analgetic, Anti-Inflammatory and Antipyretic Drugs: Literature Review (2000-2014) 211 8.6.1 Electrodes for Determination of Narcotic Medicines 211 8.6.2 Electrode Sensitive to Dextromethorphan 211 8.6.3 Electrode Sensitive to Tramadol 212 8.6.4 Electrodes for Determination of Non-Narcotic Drugs 212 8.6.5 Salicylate Electrode 214 8.6.6 Ibuprofen Electrode 214 8.6.7 Ketoprofen Electrodes 216 8.6.8 Piroxicam Electrode 216 8.6.9 Tenoxicam Electrode 217 8.6.10 Naproxen Electrodes 217 8.6.11 Indomethacin Electrodes 217 8.6.12 Sulindac Electrode 218 8.6.13 Diclofenac Electrodes 218 8.7 Conclusion 218 References 222 9 Synthesis and Preservation of Polymer Nanoparticles for Pharmaceutical Applications 229Antonello A. Barresi, Marco Vanni, Davide Fissore and Tereza Zelenková 9.1 Introduction: Polymer Nanoparticles Production 229 9.2 Production of Polymer Nanoparticles by Solvent Displacement Using Intensive Mixers 238 9.2.1 Influence of Polymer-Solvent Type and Hydrodynamics on Particle Size 243 9.2.2 Dependence on Operating Conditions – Polymer and Drug Concentration, Solvent/Antisolvent Ratio, Processing Conditions 248 9.2.3 Process Design: Selection of Mixing Device, Scale Up and Process Transfer 256 9.3 Freeze-Drying of Nanoparticles 264 9.4 Conclusions and Perspectives 268 Acknowledgements 272 References 272 10 Pharmaceutical Applications of Maleic Anhydride/Acid Copolymers 281Irina Popescu 10.1 Introduction 281 10.2 Maleic Copolymers as Macromolecular Drugs 283 10.3 Maleic Copolymer Conjugates 285 10.3.1 Polymer-Protein Conjugates 286 10.3.2 Polymer-Drug Conjugates 288 10.4 Noncovalent Drug Delivery Systems 291 10.4.1 Enteric Coatings 291 10.4.2 Solid Dispersions 292 10.4.3 Polymeric Films and Hydrogels 293 10.4.4 Microspheres and Microcapsules 294 10.4.5 Nanoparticles 295 10.4.6 Micelles 295 10.5 Conclusion 296 References 296 11 Stimuli-Sensitive Polymeric Nanomedicines for Cancer Imaging and Therapy 311F. Perche, S. Biswas and V. P. Torchilin 11.1 Introduction 311 11.2 Pathophysiological and Physical Triggers 314 11.2.1 Acidosis 314 11.2.2 Reductive Stress 319 11.2.3 Tumor Hypoxia 320 11.2.4 Cancer Associated Extracellular Enzymes 322 11.2.5 Magneto-Responsive Polymers 324 11.2.6 Temperature-Sensitive Dendrimers 325 11.2.7 Photoresponsive Polymers 326 11.3 Stimuli-Responsive Polymers for Patient Selection and Treatment Monitoring 327 11.3.1 Selection of Patients Amenable to Nanomedicine Treatment 328 11.3.2 Selection of Patients for pH-Sensitive Nanocarriers 329 11.3.3 Selection of Patients for Redox-Sensitive Nanocarriers 329 11.3.4 Mapping of Dominant Active Pathways Using Enzyme-Sensitive Probes 330 11.3.5 Selection of Patients for Molecularly-Targeted Therapies 330 11.3.6 Evaluation of Response to Treatment 331 11.4 Conclusions and Future Perspectives 331 Acknowledgments 333 References 333 12 Artificial Intelligence Techniques Used for Modeling of Processes Involving Polymers for Pharmaceutical Applications 345Silvia Curteanu 12.1 Introduction 345 12.2 Artificial Neural Networks 347 12.2.1 Elements and Structure 347 12.2.2 Working Methodology 349 12.2.3 Variants of ANN Modeling 350 12.3 Support Vector Machines 352 12.3.1 General Aspects 352 12.3.2 SVM Modeling Methodology 353 12.4 Modeling of Processes Involving Polymers for Pharmaceutical Applications 354 12.4.1 Neural Networks Used for Modeling of Processes Involving Pharmaceutical Polymers 354 12.4.2 Support Vector Machines Used for Modeling of Processes Involving Pharmaceutical Polymers 359 12.5 Conclusion and Future Perspective 360 References 361 13 Review of Current Pharmaceutical Applications of Polysiloxanes (Silicones) 363Krystyna Mojsiewicz-Pieñkowska 13.1 Introduction 363 13.2 Variety of Polysiloxane – Structure, Synthesis, Properties 364 13.2.1 Basic Silicone Chemistry 364 13.2.2 Properties of Silicones 364 13.3 Polysiloxanes as Active Pharmaceutical Ingredient (API) 368 13.3.1 Mechanism of Action of Dimethicone and Simethicone 370 13.3.2 Current Legislative Standards Related to Oral Application of Dimethicone and Simethicone (PDMS) 370 13.3.3 Admissible Doses for Dimethicone and Simethicone (PDMS) 372 13.4 Polysiloxanes as Excipients 373 13.4.1 Skin Adhesive Patches 375 13.4.2 Carrier for Controlled-Release Drugs 375 13.5 Conclusion and Future Perspective 377 References 378 14 Polymer-Doped Nano-Optical Sensors for Pharmaceutical Analysis 383M. S. Attia and M. S. A. Abdel-Mottaleb 14.1 Introduction 383 14.1.1 Sol-Gel Process 383 14.1.2 Molecular Imprinting Nanomaterial Polymer 386 14.1.3 Poly(methyl methacrylate) Polymer (PMMA) 390 14.2 Processing 392 14.2.1 Sol-Gel Technique 392 14.2.2 Molecular Imprinted Nanomaterials 394 14.2.3 Preparation of Optical Sensor Doped in PMMA Matrix 396 14.2.4 Determination of Pharmaceutical Drug in Pharmaceutical Preparations 396 14.2.5 Determination of Pharmaceutical Drug in Serum Solution 397 14.3 Application of Optical Sensor for Pharmaceutical Drug Determination 397 14.3.1 TEOS-Doped Nano-Optical Sensor for Pharmaceutical Determinations 397 14.3.2 Molecular Imprinted Nano-Polymer 401 14.3.3 Sensor Embedded in Polymethymethacrylate 404 14.4 Conclusion 405 References 405 15 Polymer-Based Augmentation of Immunosuppressive Formulations: Application of Polymer Technology in Transplant Medicine 411Ian C. Doyle and Ashim Malhotra 15.1 Introduction 411 15.2 Polymer-Based Immunosuppressive Formulations 414 15.2.1 Sirolimus 414 15.2.2 Cyclosporine A 424 15.2.3 Tacrolimus 429 15.2.4 Mycophenolic Acid 431 15.3 Conclusion and Future Perspective 433 References 434 16 Polymeric Materials in Ocular Drug Delivery Systems 439M. E. Pina, P. Coimbra, P. Ferreira, P. Alves, A. I. Figueiredo and M. H. Gil 16.1 Introduction 439 16.2 A Brief Description of Ocular Anatomy and Physiology 440 16.2.1 Anatomy of the Human Eye 440 16.2.2 Routes of Ocular Drug Delivery 441 16.2.3 Barriers in Ocular Drug Delivery 444 16.3 Polymeric Ocular Drug Delivery Systems 445 16.3.1 Non-Biodegradable Polymeric Ocular Drug Delivery Systems 446 16.3.2 Biodegradable Polymeric Ocular Drug Delivery Systems 449 16.4 Conclusion and Future Perspective 455 References 455 Index 459

Details ISBN1119041384 Year 2015 ISBN-10 1119041384 ISBN-13 9781119041382 Format Hardcover Subtitle Processing and Applications Short Title HANDBK OF POLYMERS FOR PHARMAC Edition Description Volume 2 Language English Media Book DEWEY 615.19 Place of Publication New York Country of Publication United States Pages 496 Illustrations Yes Author Manju Kumari Thakur UK Release Date 2015-09-22 AU Release Date 2015-08-10 NZ Release Date 2015-08-10 Publisher John Wiley & Sons Inc Publication Date 2015-09-22 Imprint Wiley-Scrivener Edited by Manju Kumari Thakur Audience Professional & Vocational US Release Date 2015-09-22 Series Handbook of Polymers for Pharmaceutical Technologies We've got this

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