Handbook of Polymers for Pharmaceutical Technologies, Processing and Applications

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.

• Preface xvii1 Particle Engineering of Polymers into Multifunctional Interactive Excipients 1Sharad Mangal, Ian Larson, Felix Meiser and David AV Morton1.1 Introduction 11.2 Polymers as Excipients 31.3 Material Properties Affecting Binder Activity 61.3.1 Particle Size 61.3.2 Deformation Mechanisms 71.3.3 Glass Transition Temperature (Tg) 81.4 Strategies for Improving Polymeric Filler-Binder Performance for Direct Compression 81.4.1 Interactive Mixing 121.4.2 Challenges to Interactive Mixing 131.4.3 Controlling Interparticle Cohesion 141.5 Preparation and Characterization of Interactive Excipients 141.5.1 Particle Size and Size Distribution of Excipients 151.5.2 Effect of L-leucine on Surface Morphology 161.5.3 Effect of L-leucine on Surface Composition 161.5.4 Effect of L-leucine on Surface Energy 171.5.5 Effect of L-leucine on Interparticle Cohesion 181.6 Performance of Interactive Excipients 181.6.1 Blending Ability 181.6.2 Effect on Flow 201.6.3 Binder Activity 201.7 Investigation of the Effect of Polymer Mechanical Properties 231.8 Conclusion 25References 262 The Art of Making Polymeric Membranes 33K.C. Khulbe, T. Matsuura and C. Feng2.1 Introduction 332.2 Types of Membranes 352.2.1 Porous Membranes 352.2.2 Nonporous Membranes 362.2.3 Liquid Membranes (Carrier Mediated Transport) 362.2.4 Asymmetric Membranes 362.3 Preparation of Membranes 362.3.1 Phase Inversion/Separation 372.3.2 Vapor-Induced Phase Separation (VIPS) 372.3.3 Thermally-Induced Phase Separation (TIPS) 372.3.4 Immersion Precipitation 382.3.5 Film/Dry Casting Technique 382.3.6 Track Etching 392.3.7 Electrospinning 392.3.8 Spraying 422.3.9 Foaming 422.3.10 Particle Leaching 432.3.11 Precipitation from the Vapor Phase 432.3.12 Emulsion Freeze-Drying 432.3.13 Sintering 442.3.14 Stretching 442.3.15 Composite/Supported 442.3.16 Mixed Matrix Membranes (MMMs) 452.3.17 Hollow Fiber Membranes 462.3.18 Metal-Organic Frameworks (MOFs) 482.4 Modification of Membranes 492.4.1 Modification of Polymeric Membrane by Additives/Blending 492.4.2 Coating 502.4.3 Surface Modification by Chemical Reaction 502.4.4 Interfacial Polymerization (IP)/Copolymerization 502.4.5 Plasma Polymerization/Treatment 522.4.6 Surface Modification by Irradiation of High Energy Particles 522.4.7 UV Irradiation 532.4.8 Ion-Beam Irradiation 532.4.9 Surface Modification by Heat Treatment 532.4.10 Graft Polymerization/Grafting 532.4.11 Other Techniques 532.5 Characterization of Membrane by Different Techniques 542.5.1 Conventional Physical Methods to Determine Pore Size and Pore Size Distribution 552.5.2 Morphology 582.5.3 Thermal Properties 602.5.4 Mechanical Properties 602.6 Summary 61References 623 Development of Microstructuring Technologies of Polycarbonate for Establishing Advanced Cell Cultivation Systems 67Uta Fernekorn, Jörg Hampl, Frank Weise, Sukhdeep Singh, Justyna Tobola and Andreas Schober3.1 Introduction 673.2 Material Properties of Polycarbonate 713.2.1 Physical Properties 713.2.2 Chemical Properties 723.2.3 Biological Properties 723.3 Use of Polycarbonate Foils in Structuration Processes 753.3.1 Hot Embossing 753.3.2 Thermoforming 773.4 Simulation of Microstructuring of a Polycarbonate Foil 793.5 Chemical Functionalization of Polycarbonate 813.6 Surface Micropatterning of Polycarbonate 843.7 Application Examples 863.7.1 3D Liver Cell Cultivation in Polycarbonate Scaffolds 863.7.2 3D Lung Cell Cultivation in Semi-Actively Perfused Systems 873.7.3 Guiding 3D Cocultivation of Cells by Micropatterning Techniques 873.8 Conclusion and Further Perspectives 88Acknowledgements 89References 894 In-Situ Gelling Thermosensitive Hydrogels for Protein Delivery Applications 95Roberta Censi, Alessandra Dubbini and Piera Di Martino4.1 Introduction 964.2 Polymers for the Design of Hydrogels 974.2.1 Polymer Architectures 974.2.2 Natural, Synthetic and Hybrid Hydrogels 974.2.3 Crosslinking Methods 994.2.4 Thermogelling Polymer Hydrogels 1004.3 Pharmaceutical Applications of Hydrogels: Protein Delivery 1074.3.1 Strategies for Protein Release from Hydrogels 1094.4 Application of Hydrogels for Protein Delivery in Tissue Engineering 1124.5 Conclusions 113References 1145 Polymers as Formulation Excipients for Hot-Melt Extrusion Processing of Pharmaceuticals 121Kyriakos Kachrimanis and Ioannis Nikolakakis5.1 Introduction 1215.1.1 Overview of Hot-Melt Extrusion (HME) 1215.1.2 Solubility/Dissolution Enhancement by Solid Dispersions 1235.2 Polymers for HME Processing 1275.2.1 Basic Requirements 1275.2.2 Suitability – Examples 1285.3 Polymer Selection for the HME Process 1305.3.1 Thermodynamic Considerations – Drug-Polymer Solubility and Miscibility 1305.4 Processing of HME Formulations 1355.4.1 Physical Properties of Feeding Material – Flowability, Packing and Friction 1355.5 Improvements in Processing 1415.5.1 Equipment Modifications 1415.5.2 Plasticizers 1425.6 Conclusion and Future Perspective 144References 1446 Poly Lactic-Co-Glycolic Acid (PLGA) Copolymer and Its Pharmaceutical Application 151Abhijeet Pandey, Darshana S. Jain, Subhashis Chakraborty6.1 Introduction 1516.2 Physicochemical Properties 1526.3 Biodegradation 1536.4 Biocompatibiliy, Toxicty and Pharmacokinetics 1546.5 Mechanism of Drug Release 1556.6 PLGA-Based DDS 1576.7 Bone Regeneration 1586.8 Pulmonary Delivery 1606.9 Gene Therapy 1626.10 Tumor Trageting 1626.11 Miscellaneous Drug Delivery Applications 1646.12 Conclusion 165References 1657 Pharmaceutical Applications of Polymeric Membranes 173Stefan Ioan Voicu7.1 Introduction 1737.2 Obtaining Pure and Ultrapure Water for Pharmaceutical Usage 1787.3 Wastewater Treatment for Pharmaceutics 1807.4 Controlled Drug Delivery Devices Based on Membrane Materials 1837.5 Molecularly Imprinted Membranes 1857.6 Conclusions 190References 1918 Application of PVC in Construction of Ion-Selective Electrodes for Pharmaceutical Analysis: A Review of Polymer Electrodes for Nonsteroidal, Anti-Inflammatory Drugs 195Joanna Lenik8.1 Introduction 1958.2 Properties and Usage of Poly(vinyl)chloride (PVC) 1978.3 PVC Application and Properties in Construction of Potentiometric Sensors for Drug Detection 1998.3.1 Role of Polymer Membrane Components 2028.4 Ion-Selective, Classic, Liquid Electrodes (ISEs) 2058.5 Ion-Selective Solid-State Electrodes 2068.5.1 Ion-Selective Coated-Wire Electrodes (CWE) 2068.5.2 Ion-Selective BMSA Electrodes 2078.5.3 Electrodes Based on Conductive Polymers (SC-ISEs ) 2088.6 Application of Polymer-Based ISEs for Determination of Analgetic, Anti-Inflammatory and Antipyretic Drugs: Literature Review (2000-2014) 2118.6.1 Electrodes for Determination of Narcotic Medicines 2118.6.2 Electrode Sensitive to Dextromethorphan 2118.6.3 Electrode Sensitive to Tramadol 2128.6.4 Electrodes for Determination of Non-Narcotic Drugs 2128.6.5 Salicylate Electrode 2148.6.6 Ibuprofen Electrode 2148.6.7 Ketoprofen Electrodes 2168.6.8 Piroxicam Electrode 2168.6.9 Tenoxicam Electrode 2178.6.10 Naproxen Electrodes 2178.6.11 Indomethacin Electrodes 2178.6.12 Sulindac Electrode 2188.6.13 Diclofenac Electrodes 2188.7 Conclusion 218References 2229 Synthesis and Preservation of Polymer Nanoparticles for Pharmaceutical Applications 229Antonello A. Barresi, Marco Vanni, Davide Fissore and Tereza Zelenková9.1 Introduction: Polymer Nanoparticles Production 2299.2 Production of Polymer Nanoparticles by Solvent Displacement Using Intensive Mixers 2389.2.1 Influence of Polymer-Solvent Type and Hydrodynamics on Particle Size 2439.2.2 Dependence on Operating Conditions – Polymer and Drug Concentration, Solvent/Antisolvent Ratio, Processing Conditions 2489.2.3 Process Design: Selection of Mixing Device, Scale Up and Process Transfer 2569.3 Freeze-Drying of Nanoparticles 2649.4 Conclusions and Perspectives 268Acknowledgements 272References 27210 Pharmaceutical Applications of Maleic Anhydride/Acid Copolymers 281Irina Popescu10.1 Introduction 28110.2 Maleic Copolymers as Macromolecular Drugs 28310.3 Maleic Copolymer Conjugates 28510.3.1 Polymer-Protein Conjugates 28610.3.2 Polymer-Drug Conjugates 28810.4 Noncovalent Drug Delivery Systems 29110.4.1 Enteric Coatings 29110.4.2 Solid Dispersions 29210.4.3 Polymeric Films and Hydrogels 29310.4.4 Microspheres and Microcapsules 29410.4.5 Nanoparticles 29510.4.6 Micelles 29510.5 Conclusion 296References 29611 Stimuli-Sensitive Polymeric Nanomedicines for Cancer Imaging and Therapy 311F. Perche, S. Biswas and V. P. Torchilin11.1 Introduction 31111.2 Pathophysiological and Physical Triggers 31411.2.1 Acidosis 31411.2.2 Reductive Stress 31911.2.3 Tumor Hypoxia 32011.2.4 Cancer Associated Extracellular Enzymes 32211.2.5 Magneto-Responsive Polymers 32411.2.6 Temperature-Sensitive Dendrimers 32511.2.7 Photoresponsive Polymers 32611.3 Stimuli-Responsive Polymers for Patient Selection and Treatment Monitoring 32711.3.1 Selection of Patients Amenable to Nanomedicine Treatment 32811.3.2 Selection of Patients for pH-Sensitive Nanocarriers 32911.3.3 Selection of Patients for Redox-Sensitive Nanocarriers 32911.3.4 Mapping of Dominant Active Pathways Using Enzyme-Sensitive Probes 33011.3.5 Selection of Patients for Molecularly-Targeted Therapies 33011.3.6 Evaluation of Response to Treatment 33111.4 Conclusions and Future Perspectives 331Acknowledgments 333References 33312 Artificial Intelligence Techniques Used for Modeling of Processes Involving Polymers for Pharmaceutical Applications 345Silvia Curteanu12.1 Introduction 34512.2 Artificial Neural Networks 34712.2.1 Elements and Structure 34712.2.2 Working Methodology 34912.2.3 Variants of ANN Modeling 35012.3 Support Vector Machines 35212.3.1 General Aspects 35212.3.2 SVM Modeling Methodology 35312.4 Modeling of Processes Involving Polymers for Pharmaceutical Applications 35412.4.1 Neural Networks Used for Modeling of Processes Involving Pharmaceutical Polymers 35412.4.2 Support Vector Machines Used for Modeling of Processes Involving Pharmaceutical Polymers 35912.5 Conclusion and Future Perspective 360References 36113 Review of Current Pharmaceutical Applications of Polysiloxanes (Silicones) 363Krystyna Mojsiewicz-Pieñkowska 13.1 Introduction 36313.2 Variety of Polysiloxane – Structure, Synthesis, Properties 36413.2.1 Basic Silicone Chemistry 36413.2.2 Properties of Silicones 36413.3 Polysiloxanes as Active Pharmaceutical Ingredient (API) 36813.3.1 Mechanism of Action of Dimethicone and Simethicone 37013.3.2 Current Legislative Standards Related to Oral Application of Dimethicone and Simethicone (PDMS) 37013.3.3 Admissible Doses for Dimethicone and Simethicone (PDMS) 37213.4 Polysiloxanes as Excipients 37313.4.1 Skin Adhesive Patches 37513.4.2 Carrier for Controlled-Release Drugs 37513.5 Conclusion and Future Perspective 377References 37814 Polymer-Doped Nano-Optical Sensors for Pharmaceutical Analysis 383M. S. Attia and M. S. A. Abdel-Mottaleb14.1 Introduction 38314.1.1 Sol-Gel Process 38314.1.2 Molecular Imprinting Nanomaterial Polymer 38614.1.3 Poly(methyl methacrylate) Polymer (PMMA) 39014.2 Processing 39214.2.1 Sol-Gel Technique 39214.2.2 Molecular Imprinted Nanomaterials 39414.2.3 Preparation of Optical Sensor Doped in PMMA Matrix 39614.2.4 Determination of Pharmaceutical Drug in Pharmaceutical Preparations 39614.2.5 Determination of Pharmaceutical Drug in Serum Solution 39714.3 Application of Optical Sensor for Pharmaceutical Drug Determination 39714.3.1 TEOS-Doped Nano-Optical Sensor for Pharmaceutical Determinations 39714.3.2 Molecular Imprinted Nano-Polymer 40114.3.3 Sensor Embedded in Polymethymethacrylate 40414.4 Conclusion 405References 40515 Polymer-Based Augmentation of Immunosuppressive Formulations: Application of Polymer Technology in Transplant Medicine 411Ian C. Doyle and Ashim Malhotra15.1 Introduction 41115.2 Polymer-Based Immunosuppressive Formulations 41415.2.1 Sirolimus 41415.2.2 Cyclosporine A 42415.2.3 Tacrolimus 42915.2.4 Mycophenolic Acid 43115.3 Conclusion and Future Perspective 433References 43416 Polymeric Materials in Ocular Drug Delivery Systems 439M. E. Pina, P. Coimbra, P. Ferreira, P. Alves, A. I. Figueiredo and M. H. Gil16.1 Introduction 43916.2 A Brief Description of Ocular Anatomy and Physiology 44016.2.1 Anatomy of the Human Eye 44016.2.2 Routes of Ocular Drug Delivery 44116.2.3 Barriers in Ocular Drug Delivery 44416.3 Polymeric Ocular Drug Delivery Systems 44516.3.1 Non-Biodegradable Polymeric Ocular Drug Delivery Systems 44616.3.2 Biodegradable Polymeric Ocular Drug Delivery Systems 44916.4 Conclusion and Future Perspective 455References 455Index 459