Handbook of Polymers for Pharmaceutical Technologies. Structure and Chemistry. Volume 1

  • ID: 3335854
  • Book
  • 552 Pages
  • John Wiley and Sons Ltd
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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 Chemistry
Volume 2: Processing and Applications
Volume 3: Biodegradable Polymers
Volume 4: Bioactive and Compatible Synthetic/Hybrid Polymers

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Preface xvii

1 Gellan as Novel Pharmaceutical Excipient 1Priya Vashisth, Harmeet Singh, Parul A. Pruthi and Vikas Pruthi

1.1 Introduction 1

1.2 Structural Properties of Gellan 2

1.3 Physiochemical Properties of Gellan 4

1.3.1 Gelling Features and Texture Properties 4

1.3.2 Rheology 6

1.3.3 Biosafety and Toxicological Studies 6

1.4 Pharmaceutical Applications of Gellan 7

1.4.1 Gellan–Based Pharmaceutical Formulations 7

1.4.2 Role of Gellan Excipients in Drug Delivery and Wound Healing 11

1.5 Conclusion and Future Perspectives 16

References 16

2 Application of Polymer Combinations in Extended Release Hydrophilic Matrices 23Ali Nokhodchi, Dasha Palmer, Kofi Asare–Addo, Marina Levina and Ali Rajabi–Siahboomi

2.1 Extended Release Matrices 23

2.1.1 Polymers Used in ER Matrices 24

2.1.2 Water–Soluble (Hydrophilic) Polymers 24

2.1.3 Water–Insoluble Polymers 24

2.1.4 Fatty Acids/Alcohols/Waxes 25

2.2 Polymer Combinations Used in ER matrices 25

2.2.1 Compatibility and Miscibility of Polymers 25

2.2.2 Combination of Non–Ionic Polymers 26

2.3 Combination of Non–Ionic with Ionic Polymers 27

2.4 Combinations of Ionic Polymers 27

2.5 Other Polymer Combinations 28

2.6 Effect of Dissolution Method (Media) on Drug Release from ER Matrices Containing Polymer Combinations 28

2.7 Main Mechanisms of Drug–Polymer and/or Polymer–Polymer Interaction in ER Formulations 30

2.8 Summary and Conclusions 39

References 40

3 Reagents for the Covalent Attachment of mPEG to Peptides and Proteins 51Marianela González, Victoria A. Vaillard and Santiago E. Vaillard

3.1 Introduction 51

3.2 General Considerations about PEG Reagents and PEGylation Reactions 54

3.3 PEGylation of Amino Groups 57

3.3.1 PEGylation by Urethane Linkage Formation 58

3.3.2 PEGylation by Amide Linkage Formation 60

3.3.3 PEGylation by Reductive Amination 65

3.3.4 PEGylation by Alkylation 67

3.4 PEGylation of Th iol Groups 69

3.5 Reversible PEGylation 73

3.6 Enzymatic PEGylation 76

3.7 PEGylation of Carbohydrates Residues 77

3.8 PEGylation by Click Chemistry 77

3.9 Other PEGylations 79

3.9.1 PEGylation at Arginine 79

3.9.2 PEGylation at Tirosine 79

3.9.3 PEGylation at Histidine 80

3.9.4 PEGylation at Carboxylic Groups 81

3.9.5 PEGylation with mPEG Isothiocyanate 81

3.10 Actual Trends 81

3.11 Conclusions 82

Acknowledgements 83

References 83

4 Critical Points and Phase Transitions in Polymeric Matrices for Controlled Drug Release 101A. Aguilar–de–Leyva, M.D. Campiñez, M. Casas and I. Caraballo

4.1 Introduction 101

4.2 Matrix Systems 102

4.2.1 Inert Matrices 103

4.2.2 Hydrophilic Matrices 104

4.2.3 Lipidic Matrices 104

4.3 Polymers Employed in the Manufacture of Matrix Systems 104

4.3.1 Polymers for Inert Matrices 105

4.3.2 Polymers for Hydrophilic Matrices 107

4.4 Polymer Properties Aff ecting Drug Release from Matrix Systems 111

4.4.1 Mechanical Properties 111

4.4.2 Particle Size 112

4.4.3 Viscosity 112

4.4.4 Molecular Size 113

4.4.5 Substituent Content 113

4.5 Percolation Th eory 113

4.5.1 Basic Concepts 114

4.5.2 Fundamental Equation 116

4.5.3 Percolation Models 116

4.5.4 Application of the Percolation Th eory to the Design of Controlled Release System 117

4.6 Critical Points in Matrix Systems 117

4.6.1 Critical Points in Inert Matrices 117

4.6.2 Critical Points in Hydrophilic Matrices 123

4.6.3 Critical Points in Multiparticular Matrix Systems 128

4.6.4 Critical Points in Matrix Tablets Prepared by Ultrasound–Assisted Compression 129

4.7 Case–Study: Characterization of a New Biodegradable Polyurethane PU (TEG–HMDI) as Matrix–Forming Excipient for Controlled Drug Delivery 130

4.7.1 Rheological Studies 130

4.7.2 Preparation of Matrix Tablets 131

4.7.3 Drug Release Studies 131

4.7.4 Estimation of Excipient Percolation Th reshold 131

4.8 Conclusions and Future Perspectives 133

References 135

5 Polymeric Systems in Quick Dissolving Novel Films 143Prithviraj Chakraborty, Amitava Ghosh and Debarupa D. Chakraborty

5.1 Introduction 143

5.1.1 Drug Delivery Systems for Intraoral Application 144

5.1.2 Quick Dissolving Novel Pharmaceutical Films/Wafer Dosage Form 144

5.1.3 Buccoadhesive Wafer Dosage Form Advantages over Conventional Oral Dosage Forms 146

5.2 Preparation Methods of Novel Quick Dissolving Films 146

5.2.1 Hot–Melt Extrusion Process 146

5.2.2 Solvent Casting Method 147

5.3 Polymers and Blends for Utilization in Diff erent Quick Dissolving Films 147

5.4 Polymers in Novel Quick Dissolving Films 149

5.4.1 Hydroxypropyl Cellulose (Cellulose, 2–hydroxypropyl ether) 149

5.4.2 Hydroxypropyl Methyl Cellulose (Cellulose Hydroxypropyl Methyl Ether) 150

5.4.3 Pullulan 151

5.4.4 Carboxymethyl Cellulose 152

5.4.5 Polyvinyl Pyrollidone 153

5.4.6 Sodium Alginate 154

5.4.7 Polymethacrylates 155

5.4.8 Microcrystalline Cellulose 157

5.5 Role of Plasticizers in Novel Quick Dissolving Film 158

5.6 Characterization Procedure Listed in the Literature for Fast Dissolving Films 159

5.6.1 Thickness and Weight Variation 159

5.6.2 Film Flexibility 160

5.6.3 Tensile Strength 160

5.6.4 Tear Resistance 160

5.6.5 Young s Modulus 161

5.6.6 Folding Endurance 161

5.6.7 ATR–FTIR Spectroscopy 161

5.6.8 Thermal Analysis and Differential Scanning Calorimetry (DSC) 161

5.6.9 Disintegration Test 161

5.6.10 X–ray Diffraction Study or Crystallinity Study of Films 162

5.6.11 Morphological Study 162

5.7 Conclusion and Future Perspectives 163

References 163

6 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 Alarfaj

6.1 Introduction 167

6.2 Analysis of the Pluripotency of hPSCs 173

6.3 Physical Cues of Biomaterials that Guide Maintenance of PSC Pluripotency 174

6.3.1 Effect of Biomaterial Elasticity on hPSC Culture 176

6.3.2 Effect of Biomaterial Hydrophilicity on hPSC Culture 177

6.4 Two–Dimensional (2D) Culture of hPSCs on Biomaterials 180

6.4.1 hPSC Culture on ECM–Immobilized Surfaces in 2D 180

6.4.2 hPSC Culture on Oligopeptide–Immobilized Surfaces in 2D 184

6.4.3 hPSC Culture on Recombinant E–cadherin Substratum in 2D 186

6.4.4 hPSC Culture on Polysaccharide–Immobilized Surfaces in 2D 187

6.4.5 hPSC Culture on Synthetic Surfaces in 2D 189

6.5 Three–Dimensional (3D) Culture of hPSCs on Biomaterials 193

6.5.1 3D Culture of hPSCs on Microcarriers 193

6.5.2 3D Culture of hPSCs Entrapped in Hydrogels (Microcapsules) 200

6.6 hPSC Culture on PDL–Coated Dishes with the Addition of Specific Small Molecules 205

6.7 Conclusion and Future Perspective 205

Acknowledgements 206

References 206

7 New Perspectives on Herbal Nanomedicine 215Sourabh Jain, Aakanchha Jain, Vikas Jain and Dharmveer Kohli

7.1 Introduction 215

7.1.1 Novel Herbal Drug Formulations 216

7.2 Phytosomes 217

7.3 Liposomes 218

7.3.1 Classification of Liposomes by Work and Mode of Delivery 219

7.3.2 Classification of Liposomes by Size and Range of Bilayers 219

7.4 Nanoparticles 220

7.4.1 Merits of Nanoparticles as Drug Delivery Systems 222

7.5 Nanoemulsions/Microemulsions 222

7.5.1 Merits of Nanoemulsions 222

7.6 Microspheres 223

7.6.1 Classifications of Polymers Used in Microspheres 224

7.7 Microcapsules 225

7.7.1 Morphological Features of Microcapsules 225

7.8 Nanocrystals 225

7.8.1 Methods for Formulation of Nanocrystals 226

7.9 Ethosomes 227

7.10 Transfersomes 228

7.10.1 Relevant Characteristics of Transferosomes 228

7.10.2 Transferosomes as Herbal Formulation 229

7.10.3 Limitations of Transfersomes 229

7.11 Nanoscale Herbal Decoction 230

7.12 Natural Polymers in Nanodrug Delivery 230

7.13 Future Prospects 231

References 232

8 Endogenous Polymers as Biomaterials for Nanoparticulate Gene Therapy 237Giovanni K. Zorzi, Begoña Seijo and Alejandro Sanchez

8.1 Introduction 237

8.2 Polymeric Nanoparticles in Gene Th erapy: Main Characteristics of Currently Proposed Nanosystems Based on Endogenous Polymers 239

8.2.1 Strategies Based on Use of Endogenous Polymers as Biomaterials 239

8.2.2 Physicochemical Characteristics of Nanosystems Based on Endogenous Polymers 246

8.2.3 Nanoparticle Internalization 249

8.3 Specific Features of Endogenous Polymers that Can Open New Prospects in Nanoparticulate Gene Therapy 250

8.3.1 Proteins 250

8.3.2 Carbohydrates 255

8.4 Conclusion and Future Perspective 258

References 259

9. Molecularly Imprinted Polymers as Biomimetic Molecules: Synthesis and their Pharmaceutical Applications 267Mohammad Reza Ganjali, Morteza Rezapour, Farnoush Faridbod and Parviz Norouzi1

9.1 Introduction 267

9.2 Preparation of Molecularly Imprinted Polymers (MIPs) 268

9.2.1 Reaction Components 268

9.2.2 Imprinting Modes 271

9.2.3 Polymerization 274

9.2.4 Physical Forms of MIPs 275

9.2.5 Removing the Template 276

9.3 Applications of Imprinted Polymers 276

9.3.1 Imprinted Polymers in Drug Delivery 276

9.3.2 Imprinted Polymers in Separation of Pharmaceuticals 286

9.3.3 MIPs in Devices for Sensing Pharmaceutical Species 289

References 300

10 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 Ahmad

10.1 Introduction 328

10.1.1 Vegetable Seed Oils(VO) 329

10.1.2 Polyesteramides (PEAs) 331

10.1.3 Zinc Oxide Nanoparticles 332

10.1.4 Green Chemistry 333

10.1.5 Microwave–Assisted Reactions 334

10.2 Experimental Protocol 335

10.2.1 Procedure for Transformation of RCO to N,N–bis(2 Hydroxyethyl)Ricinolamide (MicHERA) 335

10.2.2 Procedure for the Transformation of MicHERA to PERA/Nano–ZnO Bionanocomposite 336

10.2.3 Procedure for Transformation of MicHERA to PERA 336

10.2.4 Fungal Isolates Used and Minimum Inhibitory Concentration (MIC90) Determination 336

10.2.5 Disc Diffusion Halo Assays 337

10.2.6 Growth Curve Studies 337

10.2.7 Proton Efflux Measurements 337

10.2.8 Measurement of Intracellular pH (pHi) 338

10.3 Results 338

10.3.1 Synthesis 338

10.3.2 Minimal Inhibitory Concentration 341

10.3.3 Disc Diffusion 341

10.3.4 Growth Studies (Turbidometric Measurement) 342

10.3.5 Proton Efflux Measurements 342

10.3.6 Measurement of Intracellular pH 344

10.4 Discussion 344

10.5 Conclusion 346

Acknowledgements 347

References 347

11. Improving Matters of the Heart: Th e Use of Select Pharmaceutical Polymers in Cardiovascular Intervention 351Ashim Malhotra

11.1 Pharmaceutical Polymers Used for Drug–Eluting Stents 351

11.1.1 Introduction and Historical Perspective 351

11.1.2 Polymers Used in Drug–Eluting Stents 352

11.1.3 Polymers Used for Paclitaxel Stents 353

11.2 Pharmaceutical Polymers Used in Cardiovascular Prostheses 354

11.2.1 Introduction and Historical Perspective 354

11.2.2 Factors Affecting Selection of Polymer 356

11.2.3 Specific Polymers Used in Cardiovascular Applications 356

11.3 Pharmaceutical Polymers Used for Gene Therapy 359

11.3.1 Introduction to Cardiovascular Gene Therapy 359

11.3.2 Cardiovascular Gene Delivery Systems 359

11.3.3 Ideal Polymeric Characteristics for Use in Gene Therapy 360

11.3.4 Polymers Used in the Design of Cardiovascular Vectors 360

11.3.5 Ultrasound–Targeted Microbubble Destruction (UTMD) for Cardiovascular Gene Therapy 360

11.4 Pharmaceutical Polymers Used in Tissue Engineering 361

11.5 Injectable Biopolymers 363

11.5.1 Introduction and Historical Perspective 363

11.5.2 Cardiac Restructuring 363

11.5.3 Select Biopolymer Agents Used as Bioinjectables in Cardiovascular Intervention 364

11.6 Vascular Restructuring 365

11.7 Conclusions and Future Directions 365

Acknowledgement 366

References 366

12 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 Goyanes

12.1 Introduction 370

12.2 Polymers Used in Medical Devices: General Features 373

12.3 Risks Associated with Surgical Procedures 374

12.4 Applications in Bone Tissue Engineering 375

12.4.1 Surgical Applications of PMMA 376

12.4.2 Antibiotic Treatment Commonly Used in Orthopedic Procedure Involving PMMA Bone Cement 383

12.4.3 General Drawbacks of Antibiotic–Loaded Bone Cements 384

12.4.4 PMMA Modified Materials 386

12.5 Applications in Cardiovascular Tissue Engineering 388

12.5.1 Cardiovascular Devices 391

12.5.2 Drug Treatments Commonly Used in Cardiovascular Devices 396

12.5.3 Polyurethane Modified Materials 398

12.6 Future Perspectives 400

12.7 Conclusions 403

Acknowledgements 404

References 404

13 Prospects of Guar Gum and Its Derivatives as Biomaterials 413D. Sathya Seeli and M. Prabaharan

13.1 Introduction 413

13.2 Developments of Guar Gum and Its Derivatives 414

13.2.1 Drug Delivery Systems (DDSs) 414

13.2.2 Tissue Engineering Scaffolds 423

13.2.3 Wound Healing Materials 425

13.2.4 Biosensors 425

13.2.5 Antimicrobial Agents 428

13.3 Conclusions 429

References 429

14 Polymers for Peptide/Protein Drug Delivery 433M.T. Chevalier, J.S. Gonzalez and V.A. Alvarez

14.1 Biodegradable Polymers 433

14.2 Why Protein and Peptide Encapsulation? 434

14.3 Surface Functionalization 435

14.4 Poly Lactic Acid (PLA) 437

14.4.1 Polymer Structure and Main Characteristics 437

14.4.2 Encapsulation of Peptides/Proteins in PLA 438

14.5 Poly(lactic–co–glycolic acid) (PLGA) 440

14.5.1 Polymer Structure and Main Characteristics 440

14.5.2 Encapsulation of Peptides/Proteins in PLGA 441

14.6 Chitosan 446

14.6.1 Chitosan Structure and Main Characteristics 446

14.6.2 Encapsulation of Peptides/Proteins 447

14.6.3 Peptides and Proteins Encapsulated in Chitosan 448

14.7 Final Comments and Future Perspectives 450

References 450

15 Eco–Friendly Graft ed Polysaccharides for Pharmaceutical Formulation: Structure and Chemistry 457Sumit Mishra, Kartick Prasad Dey and Srijita Bharti

15.1 Introduction 457

15.1.1 Targeted Drug Delivery 458

15.1.2 Controlled Drug Delivery 458

15.1.3 Current Status of Controlled Drug Release Technologies 459

15.1.4 Pharmaceutical Formulation 460

15.1.5 Stages and Timeline 460

15.1.6 Types of Pharmaceutical Formulation 460

15.2 Polysaccharides 462

15.2.1 Chemistry of Polysaccharides 463

15.2.2 Grafted Polysaccharides 463

15.2.3 Drug Delivery System by Grafted Polysaccharides 464

15.2.4 Concept of Drug Delivery Matrix 465

15.2.5 Concept of Inter–Polymer Network (IPN) 466

15.2.6 In–Vitro Drug Release Study 467

15.2.7 Mechanism of Drug Release 468

15.3 Conclusions 471

References 471

16 Pharmaceutical Natural Polymers: Structure and Chemistry 477George Dan Mogoºanu1 and Alexandru Mihai Grumezescu

16.1 Introduction 477

16.2 Natural Polymers 478

16.2.1 Polysaccharides 478

16.2.2 Peptides and Proteins 494

16.2.3 Resins and Related Compounds 497

Acknowledgments 498

References 498

Index 521

Information about the Series 529

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