Handbook of Polymers for Pharmaceutical Technologies, Structure and Chemistry

Vijay Kumar Thakur (Ph.D.) 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 Gellan as Novel Pharmaceutical Excipient 1Priya Vashisth, Harmeet Singh, Parul A. Pruthi and Vikas Pruthi1.1 Introduction 11.2 Structural Properties of Gellan 21.3 Physiochemical Properties of Gellan 41.3.1 Gelling Features and Texture Properties 41.3.2 Rheology 61.3.3 Biosafety and Toxicological Studies 61.4 Pharmaceutical Applications of Gellan 71.4.1 Gellan-Based Pharmaceutical Formulations 71.4.2 Role of Gellan Excipients in Drug Delivery and Wound Healing 111.5 Conclusion and Future Perspectives 16References 162 Application of Polymer Combinations in Extended Release Hydrophilic Matrices 23Ali Nokhodchi, Dasha Palmer, Kofi Asare-Addo, Marina Levina and Ali Rajabi-Siahboomi2.1 Extended Release Matrices 232.1.1 Polymers Used in ER Matrices 242.1.2 Water-Soluble (Hydrophilic) Polymers 242.1.3 Water-Insoluble Polymers 242.1.4 Fatty Acids/Alcohols/Waxes 252.2 Polymer Combinations Used in ER matrices 252.2.1 Compatibility and Miscibility of Polymers 252.2.2 Combination of Non-Ionic Polymers 262.3 Combination of Non-Ionic with Ionic Polymers 272.4 Combinations of Ionic Polymers 272.5 Other Polymer Combinations 282.6 Effect of Dissolution Method (Media) on Drug Release from ER Matrices Containing Polymer Combinations 282.7 Main Mechanisms of Drug-Polymer and/or Polymer-Polymer Interaction in ER Formulations 302.8 Summary and Conclusions 39References 403 Reagents for the Covalent Attachment of mPEG to Peptides and Proteins 51Marianela González, Victoria A. Vaillard and Santiago E. Vaillard3.1 Introduction 513.2 General Considerations about PEG Reagents and PEGylation Reactions 543.3 PEGylation of Amino Groups 573.3.1 PEGylation by Urethane Linkage Formation 583.3.2 PEGylation by Amide Linkage Formation 603.3.3 PEGylation by Reductive Amination 653.3.4 PEGylation by Alkylation 673.4 PEGylation of Th iol Groups 693.5 Reversible PEGylation 733.6 Enzymatic PEGylation 763.7 PEGylation of Carbohydrates Residues 773.8 PEGylation by Click Chemistry 773.9 Other PEGylations 793.9.1 PEGylation at Arginine 793.9.2 PEGylation at Tirosine 793.9.3 PEGylation at Histidine 803.9.4 PEGylation at Carboxylic Groups 813.9.5 PEGylation with mPEG Isothiocyanate 813.10 Actual Trends 813.11 Conclusions 82Acknowledgements 83References 834 Critical Points and Phase Transitions in Polymeric Matrices for Controlled Drug Release 101A. Aguilar-de-Leyva, M.D. Campiñez, M. Casas and I. Caraballo4.1 Introduction 1014.2 Matrix Systems 1024.2.1 Inert Matrices 1034.2.2 Hydrophilic Matrices 1044.2.3 Lipidic Matrices 1044.3 Polymers Employed in the Manufacture of Matrix Systems 1044.3.1 Polymers for Inert Matrices 1054.3.2 Polymers for Hydrophilic Matrices 1074.4 Polymer Properties Aff ecting Drug Release from Matrix Systems 1114.4.1 Mechanical Properties 1114.4.2 Particle Size 1124.4.3 Viscosity 1124.4.4 Molecular Size 1134.4.5 Substituent Content 1134.5 Percolation Th eory 1134.5.1 Basic Concepts 1144.5.2 Fundamental Equation 1164.5.3 Percolation Models 1164.5.4 Application of the Percolation Th eory to the Design of Controlled Release System 1174.6 Critical Points in Matrix Systems 1174.6.1 Critical Points in Inert Matrices 1174.6.2 Critical Points in Hydrophilic Matrices 1234.6.3 Critical Points in Multiparticular Matrix Systems 1284.6.4 Critical Points in Matrix Tablets Prepared by Ultrasound-Assisted Compression 1294.7 Case-Study: Characterization of a New Biodegradable Polyurethane PU (TEG-HMDI) as Matrix-Forming Excipient for Controlled Drug Delivery 1304.7.1 Rheological Studies 1304.7.2 Preparation of Matrix Tablets 1314.7.3 Drug Release Studies 1314.7.4 Estimation of Excipient Percolation Th reshold 1314.8 Conclusions and Future Perspectives 133References 1355 Polymeric Systems in Quick Dissolving Novel Films 143Prithviraj Chakraborty, Amitava Ghosh and Debarupa D. Chakraborty5.1 Introduction 1435.1.1 Drug Delivery Systems for Intraoral Application 1445.1.2 Quick Dissolving Novel Pharmaceutical Films/Wafer Dosage Form 1445.1.3 Buccoadhesive Wafer Dosage Form Advantages over Conventional Oral Dosage Forms 1465.2 Preparation Methods of Novel Quick Dissolving Films 1465.2.1 Hot-Melt Extrusion Process 1465.2.2 Solvent Casting Method 1475.3 Polymers and Blends for Utilization in Diff erent Quick Dissolving Films 1475.4 Polymers in Novel Quick Dissolving Films 1495.4.1 Hydroxypropyl Cellulose (Cellulose, 2-hydroxypropyl ether) 1495.4.2 Hydroxypropyl Methyl Cellulose (Cellulose Hydroxypropyl Methyl Ether) 1505.4.3 Pullulan 1515.4.4 Carboxymethyl Cellulose 1525.4.5 Polyvinyl Pyrollidone 1535.4.6 Sodium Alginate 1545.4.7 Polymethacrylates 1555.4.8 Microcrystalline Cellulose 1575.5 Role of Plasticizers in Novel Quick Dissolving Film 1585.6 Characterization Procedure Listed in the Literature for Fast Dissolving Films 1595.6.1 Thickness and Weight Variation 1595.6.2 Film Flexibility 1605.6.3 Tensile Strength 1605.6.4 Tear Resistance 1605.6.5 Young’s Modulus 1615.6.6 Folding Endurance 1615.6.7 ATR-FTIR Spectroscopy 1615.6.8 Thermal Analysis and Differential Scanning Calorimetry (DSC) 1615.6.9 Disintegration Test 1615.6.10 X-ray Diffraction Study or Crystallinity Study of Films 1625.6.11 Morphological Study 1625.7 Conclusion and Future Perspectives 163References 1636 Biomaterial Design for Human ESCs and iPSCs on Feeder-Free Culture toward Pharmaceutical Usage of Stem Cells 167Akon Higuchi, S. Suresh Kumar, Murugan A. Munusamy and Abdullah A Alarfaj6.1 Introduction 1676.2 Analysis of the Pluripotency of hPSCs 1736.3 Physical Cues of Biomaterials that Guide Maintenance of PSC Pluripotency 1746.3.1 Effect of Biomaterial Elasticity on hPSC Culture 1766.3.2 Effect of Biomaterial Hydrophilicity on hPSC Culture 1776.4 Two-Dimensional (2D) Culture of hPSCs on Biomaterials 1806.4.1 hPSC Culture on ECM-Immobilized Surfaces in 2D 1806.4.2 hPSC Culture on Oligopeptide-Immobilized Surfaces in 2D 1846.4.3 hPSC Culture on Recombinant E-cadherin Substratum in 2D 1866.4.4 hPSC Culture on Polysaccharide-Immobilized Surfaces in 2D 1876.4.5 hPSC Culture on Synthetic Surfaces in 2D 1896.5 Three-Dimensional (3D) Culture of hPSCs on Biomaterials 1936.5.1 3D Culture of hPSCs on Microcarriers 1936.5.2 3D Culture of hPSCs Entrapped in Hydrogels (Microcapsules) 2006.6 hPSC Culture on PDL-Coated Dishes with the Addition of Specific Small Molecules 2056.7 Conclusion and Future Perspective 205Acknowledgements 206References 2067 New Perspectives on Herbal Nanomedicine 215Sourabh Jain, Aakanchha Jain, Vikas Jain and Dharmveer Kohli7.1 Introduction 2157.1.1 Novel Herbal Drug Formulations 2167.2 Phytosomes 2177.3 Liposomes 2187.3.1 Classification of Liposomes by Work and Mode of Delivery 2197.3.2 Classification of Liposomes by Size and Range of Bilayers 2197.4 Nanoparticles 2207.4.1 Merits of Nanoparticles as Drug Delivery Systems 2227.5 Nanoemulsions/Microemulsions 2227.5.1 Merits of Nanoemulsions 2227.6 Microspheres 2237.6.1 Classifications of Polymers Used in Microspheres 2247.7 Microcapsules 2257.7.1 Morphological Features of Microcapsules 2257.8 Nanocrystals 2257.8.1 Methods for Formulation of Nanocrystals 2267.9 Ethosomes 2277.10 Transfersomes 2287.10.1 Relevant Characteristics of Transferosomes 2287.10.2 Transferosomes as Herbal Formulation 2297.10.3 Limitations of Transfersomes 2297.11 Nanoscale Herbal Decoction 2307.12 Natural Polymers in Nanodrug Delivery 2307.13 Future Prospects 231References 2328 Endogenous Polymers as Biomaterials for Nanoparticulate Gene Therapy 237Giovanni K. Zorzi, Begoña Seijo and Alejandro Sanchez8.1 Introduction 2378.2 Polymeric Nanoparticles in Gene Th erapy: Main Characteristics of Currently Proposed Nanosystems Based on Endogenous Polymers 2398.2.1 Strategies Based on Use of Endogenous Polymers as Biomaterials 2398.2.2 Physicochemical Characteristics of Nanosystems Based on Endogenous Polymers 2468.2.3 Nanoparticle Internalization 2498.3 Specific Features of Endogenous Polymers that Can Open New Prospects in Nanoparticulate Gene Therapy 2508.3.1 Proteins 2508.3.2 Carbohydrates 2558.4 Conclusion and Future Perspective 258References 2599. Molecularly Imprinted Polymers as Biomimetic Molecules: Synthesis and their Pharmaceutical Applications 267Mohammad Reza Ganjali, Morteza Rezapour, Farnoush Faridbod and Parviz Norouzi19.1 Introduction 2679.2 Preparation of Molecularly Imprinted Polymers (MIPs) 2689.2.1 Reaction Components 2689.2.2 Imprinting Modes 2719.2.3 Polymerization 2749.2.4 Physical Forms of MIPs 2759.2.5 Removing the Template 2769.3 Applications of Imprinted Polymers 2769.3.1 Imprinted Polymers in Drug Delivery 2769.3.2 Imprinted Polymers in Separation of Pharmaceuticals 2869.3.3 MIPs in Devices for Sensing Pharmaceutical Species 289References 30010 Biobased Pharmaceutical Polymer Nanocomposite: Synthesis, Chemistry and Antifungal Study 327Fahmina Zafar, Eram Sharmin, Sheikh Shreaz, Hina Zafar, Muzaff ar Ul Hassan Mir, Jawad M. Behbehani and Sharif Ahmad10.1 Introduction 32810.1.1 Vegetable Seed Oils(VO) 32910.1.2 Polyesteramides (PEAs) 33110.1.3 Zinc Oxide Nanoparticles 33210.1.4 Green Chemistry 33310.1.5 Microwave-Assisted Reactions 33410.2 Experimental Protocol 33510.2.1 Procedure for Transformation of RCO to N,N-bis(2 Hydroxyethyl)Ricinolamide (MicHERA) 33510.2.2 Procedure for the Transformation of MicHERA to PERA/Nano-ZnO Bionanocomposite 33610.2.3 Procedure for Transformation of MicHERA to PERA 33610.2.4 Fungal Isolates Used and Minimum Inhibitory Concentration (MIC90) Determination 33610.2.5 Disc Diffusion Halo Assays 33710.2.6 Growth Curve Studies 33710.2.7 Proton Efflux Measurements 33710.2.8 Measurement of Intracellular pH (pHi) 33810.3 Results 33810.3.1 Synthesis 33810.3.2 Minimal Inhibitory Concentration 34110.3.3 Disc Diffusion 34110.3.4 Growth Studies (Turbidometric Measurement) 34210.3.5 Proton Efflux Measurements 34210.3.6 Measurement of Intracellular pH 34410.4 Discussion 34410.5 Conclusion 346Acknowledgements 347References 34711. Improving Matters of the Heart: Th e Use of Select Pharmaceutical Polymers in Cardiovascular Intervention 351Ashim Malhotra11.1 Pharmaceutical Polymers Used for Drug-Eluting Stents 35111.1.1 Introduction and Historical Perspective 35111.1.2 Polymers Used in Drug-Eluting Stents 35211.1.3 Polymers Used for Paclitaxel Stents 35311.2 Pharmaceutical Polymers Used in Cardiovascular Prostheses 35411.2.1 Introduction and Historical Perspective 35411.2.2 Factors Affecting Selection of Polymer 35611.2.3 Specific Polymers Used in Cardiovascular Applications 35611.3 Pharmaceutical Polymers Used for Gene Therapy 35911.3.1 Introduction to Cardiovascular Gene Therapy 35911.3.2 Cardiovascular Gene Delivery Systems 35911.3.3 Ideal Polymeric Characteristics for Use in Gene Therapy 36011.3.4 Polymers Used in the Design of Cardiovascular Vectors 36011.3.5 Ultrasound-Targeted Microbubble Destruction (UTMD) for Cardiovascular Gene Therapy 36011.4 Pharmaceutical Polymers Used in Tissue Engineering 36111.5 Injectable Biopolymers 36311.5.1 Introduction and Historical Perspective 36311.5.2 Cardiac Restructuring 36311.5.3 Select Biopolymer Agents Used as Bioinjectables in Cardiovascular Intervention 36411.6 Vascular Restructuring 36511.7 Conclusions and Future Directions 365Acknowledgement 366References 36612 Polymeric Prosthetic Systems for Site-Specifi c Drug Administration: Physical and Chemical Properties 369Marián Parisi, Verónica E. Manzano, Sabrina Flor, María H. Lissarrague, Laura Ribba1, Silvia Lucangioli, Norma B. D’Accorsoand Silvia Goyanes12.1 Introduction 37012.2 Polymers Used in Medical Devices: General Features 37312.3 Risks Associated with Surgical Procedures 37412.4 Applications in Bone Tissue Engineering 37512.4.1 Surgical Applications of PMMA 37612.4.2 Antibiotic Treatment Commonly Used in Orthopedic Procedure Involving PMMA Bone Cement 38312.4.3 General Drawbacks of Antibiotic-Loaded Bone Cements 38412.4.4 PMMA Modified Materials 38612.5 Applications in Cardiovascular Tissue Engineering 38812.5.1 Cardiovascular Devices 39112.5.2 Drug Treatments Commonly Used in Cardiovascular Devices 39612.5.3 Polyurethane Modified Materials 39812.6 Future Perspectives 40012.7 Conclusions 403Acknowledgements 404References 40413 Prospects of Guar Gum and Its Derivatives as Biomaterials 413D. Sathya Seeli and M. Prabaharan13.1 Introduction 41313.2 Developments of Guar Gum and Its Derivatives 41413.2.1 Drug Delivery Systems (DDSs) 41413.2.2 Tissue Engineering Scaffolds 42313.2.3 Wound Healing Materials 42513.2.4 Biosensors 42513.2.5 Antimicrobial Agents 42813.3 Conclusions 429References 42914 Polymers for Peptide/Protein Drug Delivery 433M.T. Chevalier, J.S. Gonzalez and V.A. Alvarez14.1 Biodegradable Polymers 43314.2 Why Protein and Peptide Encapsulation? 43414.3 Surface Functionalization 43514.4 Poly Lactic Acid (PLA) 43714.4.1 Polymer Structure and Main Characteristics 43714.4.2 Encapsulation of Peptides/Proteins in PLA 43814.5 Poly(lactic-co-glycolic acid) (PLGA) 44014.5.1 Polymer Structure and Main Characteristics 44014.5.2 Encapsulation of Peptides/Proteins in PLGA 44114.6 Chitosan 44614.6.1 Chitosan Structure and Main Characteristics 44614.6.2 Encapsulation of Peptides/Proteins 44714.6.3 Peptides and Proteins Encapsulated in Chitosan 44814.7 Final Comments and Future Perspectives 450References 45015 Eco-Friendly Graft ed Polysaccharides for Pharmaceutical Formulation: Structure and Chemistry 457Sumit Mishra, Kartick Prasad Dey and Srijita Bharti15.1 Introduction 45715.1.1 Targeted Drug Delivery 45815.1.2 Controlled Drug Delivery 45815.1.3 Current Status of Controlled Drug Release Technologies 45915.1.4 Pharmaceutical Formulation 46015.1.5 Stages and Timeline 46015.1.6 Types of Pharmaceutical Formulation 46015.2 Polysaccharides 46215.2.1 Chemistry of Polysaccharides 46315.2.2 Grafted Polysaccharides 46315.2.3 Drug Delivery System by Grafted Polysaccharides 46415.2.4 Concept of Drug Delivery Matrix 46515.2.5 Concept of Inter-Polymer Network (IPN) 46615.2.6 ‘In-Vitro’ Drug Release Study 46715.2.7 Mechanism of Drug Release 46815.3 Conclusions 471References 47116 Pharmaceutical Natural Polymers: Structure and Chemistry 477George Dan Mogoºanu1 and Alexandru Mihai Grumezescu16.1 Introduction 47716.2 Natural Polymers 47816.2.1 Polysaccharides 47816.2.2 Peptides and Proteins 49416.2.3 Resins and Related Compounds 497Acknowledgments 498References 498Index 521Information about the Series 529