John Wiley & Sons Drug Delivery Strategies for Poorly Water-Soluble Drugs Cover Many newly proposed drugs suffer from poor water solubility, thus presenting major hurdles in the de.. Product #: 978-0-470-71197-2 Regular price: $144.86 $144.86 In Stock

Drug Delivery Strategies for Poorly Water-Soluble Drugs

Douroumis, Dionysios / Fahr, Alfred

Advances in Pharmaceutical Technology

Cover

1. Edition January 2013
626 Pages, Hardcover
Wiley & Sons Ltd

ISBN: 978-0-470-71197-2
John Wiley & Sons

Short Description

Many newly proposed drugs suffer from poor water solubility, thus presenting major hurdles in the design of suitable formulations for administration to patients. This work addresses the latest techniques and materials to overcome these hurdles, providing a thorough review of current formulation strategies for a wide range of hydrophobic drugs. With a focus on critical formulation features and clinical studies, the book covers instrumentation, operation principles, applications, scale-up considerations, regulatory issues, and more. An essential guide for researchers in drug delivery, polymers, and biomaterials.

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Many newly proposed drugs suffer from poor water solubility, thus presenting major hurdles in the design of suitable formulations for administration to patients. This work addresses the latest techniques and materials to overcome these hurdles, providing a thorough review of current formulation strategies for a wide range of hydrophobic drugs. With a focus on critical formulation features and clinical studies, the book covers instrumentation, operation principles, applications, scale-up considerations, regulatory issues, and more. An essential guide for researchers in drug delivery, polymers, and biomaterials.

List of Contributors xvii

Series Preface xxi

Preface xxiii

1 Self-Assembled Delivery Vehicles for Poorly Water-Soluble Drugs: Basic Theoretical Considerations and Modeling Concepts 1
Sylvio May and Alfred Fahr

1.1 Introduction 1

1.2 Brief Reminder of Equilibrium Thermodynamics 3

1.3 Principles of Self-Assembly in Dilute Solutions 7

1.4 Solubility and Partitioning of Drugs 11

1.5 Ways to Model Interactions in Colloidal Systems 16

1.6 Kinetics of Drug Transfer from Mobile Nanocarriers 23

1.7 Conclusion 29

2 Liposomes as Intravenous Solubilizers for Poorly Water-Soluble Drugs 37
Peter van Hoogevest, Mathew Leigh and Alfred Fahr

2.1 Introduction 37

2.2 Intravenous Administration of Poorly Water-Soluble Compounds (PWSC) 40

2.3 Conclusion 59

3 Drug Solubilization and Stabilization by Cyclodextrin Drug Carriers 67
Thorsteinn Loftsson and Marcus E. Brewster

3.1 Introduction 67

3.2 Structure and Physiochemical Properties 68

3.3 Cyclodextrin Complexes and Phase Solubility Diagrams 72

3.4 Cyclodextrin Complexes 76

3.5 Effects on Drug Stability 77

3.6 Cyclodextrins and Drug Permeation through Biological Membranes 80

3.7 Drug Solubilization in Pharmaceutical Formulations 82

3.8 Toxicology and Pharmacokinetics 89

3.9 Regulatory Issues 90

3.10 Conclusion 91

4 Solid Lipid Nanoparticles for Drug Delivery 103
Sonja Joseph and Heike Bunjes

4.1 Introduction 103

4.2 Preparation Procedures for Solid Lipid Nanoparticles 104

4.3 Structural Parameters and Their Influence on Product Quality and Pharmaceutical Performance 116

4.4 Incorporation of Poorly Soluble Drugs and In Vitro Release 123

4.5 Safety Aspects, Toxicity and Pharmacokinetic Profiles 129

4.6 Conclusion 133

5 Polymeric Drug Delivery Systems for Encapsulating Hydrophobic Drugs 151
Naveed Ahmed, C.E. Mora-Huertas, Chiraz Jaafar-Maalej, Hatem Fessi and Abdelhamid Elaissari

5.1 Introduction 151

5.2 Safety and Biocompatibility of Polymers 152

5.3 Encapsulation Techniques of Hydrophobic Drugs 156

5.4 Behavior of Nanoparticles as Drug Delivery Systems 173

5.5 Conclusion 177

6 Polymeric Drug Delivery Systems for Encapsulating Hydrophobic Drugs 199
Dagmar Fischer

6.1 Introduction 199

6.2 Drug Encapsulation by Monomer Polymerization 200

6.3 Polymeric Nanospheres and Nanocapsules Produced by Polymerization 209

6.4 Formulation Components 210

6.5 Control of Particle Morphology 212

6.6 Toxicity and In Vivo Performance 213

6.7 Scale-Up Considerations 214

6.8 Conclusion 217

7 Development of Self-Emulsifying Drug Delivery Systems (SEDDS) for Oral Bioavailability Enhancement of Poorly Soluble Drugs 225
Dimitrios G. Fatouros and Anette Mullertz

7.1 Introduction 225

7.2 Lipid Processing and Drug Solubilization 226

7.3 Self-Emulsifying Drug Delivery Systems 227

7.4 In Vitro Digestion Model 232

7.5 Enhancement of Oral Absorption by SEDDS 235

7.6 Conclusion 238

8 Novel Top-Down Technologies: Effective Production of Ultra-Fine Drug Nanocrystals 247
C.M. Keck, S. Kobierski, R. Mauludin and R.H. Muller

8.1 Introduction: General Benefits of Drug Nanocrystals (First Generation) 247

8.2 Ultra-Fine Drug Nanocrystals (

8.3 Production of First Generation Nanocrystals: A Brief Overview 250

8.4 Production of Ultra-Fine Drug Nanocrystals: Smartcrystals 252

8.5 Conclusion 259

9 Nanosuspensions with Enhanced Drug Dissolution Rates of Poorly Water-Soluble Drugs 265
Dennis Douroumis

9.1 Introduction 265

9.2 Crystal Growth and Nucleation Theory 266

9.3 Creating Supersaturation and Stable Nanosuspensions 269

9.4 Antisolvent Precipitation Via Mixer Processing 272

9.5 Antisolvent Precipitation by Using Ultrasonication 277

9.6 Nanoprecipitation Using Microfluidic Reactors 278

9.7 Particle Engineering by Spray: Freezing into Liquid 279

9.8 Precipitation by Rapid Expansion from Supercritical to Aqueous Solution 280

9.9 Conclusion 282

10 Microemulsions for Drug Solubilization and Delivery 287
X.Q. Wang and Q. Zhang

10.1 Introduction 287

10.2 Microemulsion Formation and Phase Behavior 289

10.3 HLB, PIT and Microemulsion Stability 293

10.4 Microemulsion Physico-Chemical Characterization 293

10.5 Components of Microemulsion Formulations 295

10.6 Preparation Methods 303

10.7 In Vitro and In Vivo Biological Studies 303

10.8 Recent Developments and Future Directions 314

11 Hot Melt Extrusion: A Process Overview and Use in Manufacturing Solid Dispersions of Poorly Water-Soluble Drugs 325
Shu Li, David S. Jones and Gavin P. Andrews

11.1 Introduction: Present Challenges to Oral Drug Delivery 325

11.2 Solid Drug Dispersions for Enhanced Drug Solubility 327

11.3 Hot Melt Extrusion (HME) as a Drug Delivery Technology 329

11.4 Solubility Enhancement Using HME 340

11.5 Representative Case Studies with Enhanced Solubility 344

11.6 Conclusion 347

12 Penetration Enhancers, Solvents and the Skin 359
Jonathan Hadgraft and Majella E. Lane

12.1 Introduction 359

12.2 Interactions of Solvents and Enhancers with the Skin 360

12.3 Skin Permeation Enhancement of Ibuprofen 363

12.4 Conclusion 369

13 Dendrimers for Enhanced Drug Solubilization 373
Narendra K. Jain and Rakesh K. Tekade

13.1 Introduction 373

13.2 Current Solubilization Strategies 374

13.3 Origin of Dendrimers 374

13.4 What Are Dendrimers? 375

13.5 Synthesis of Dendritic Architecture 375

13.6 Structure and Intrinsic Properties of Dendrimeric Compartments 377

13.7 Dendrimers in Solubilization 378

13.8 Factors Affecting Dendrimer-Mediated Solubilization and Drug Delivery 381

13.9 Drug-Dendrimer Conjugation Approaches 386

13.10 Dendrimers' Biocompatibility and Toxicity 393

13.11 Classification of PEGylated Dendrimers 394

13.12 Conclusion 399

14 Polymeric Micelles for the Delivery of Poorly Soluble Drugs 411
Swati Biswas, Onkar S. Vaze, Sara Movassaghian and Vladimir P. Torchilin

14.1 Micelles and Micellization 411

14.2 Chemical Nature and Formation Mechanism of Polymeric Micelles 416

14.3 Polymeric Micelles: Unique Nanomedicine Platforms 419

14.4 Determination of Physico-Chemical Characteristics of Polymeric Micelles 430

14.5 Drug Loading 435

14.6 Biodistribution and Toxicity 439

14.7 Targeting Micellar Nanocarriers: Example: Drug Delivery to Tumors 443

14.8 Site-Specific Micellar-Drug Release Strategies 449

14.9 Intracellular Delivery of Micelles 452

14.10 Multifunctional Micellar Nanocarriers 453

14.11 Conclusion 455

15 Nanostructured Silicon-Based Materials as a Drug Delivery System for Water-Insoluble Drugs 477
Vesa-Pekka Lehto, Jarno Salonen, H´elder A. Santos and Joakim Riikonen

15.1 Introduction 477

15.2 Control of Particle Size and Pore Morphology 478

15.3 Surface Functionalization 482

15.4 Biocompatibility and Cytotoxicity 485

15.5 Nanostructured Silicon Materials as DDS 492

15.6 Conclusion 502

16 Micro- and Nanosizing of Poorly Soluble Drugs by Grinding Techniques 509
Stefan Scheler

16.1 Introduction 509

16.2 Kinetics of Drug Dissolution 510

16.3 Micronization and Nanosizing of Drugs 510

16.4 Theory of Grinding Operations 512

16.5 Influence of the Stabilizer 520

16.6 Milling Equipment and Technology 527

16.7 Process Development from Laboratory to Commercial Scale 535

16.8 Application and Biopharmaceutical Properties 537

16.9 Conclusion 543

17 Enhanced Solubility of Poorly Soluble Drugs Via Spray Drying 551
Cordin Arpagaus, David R¨utti and Marco Meuri

17.1 Introduction 551

17.2 Advantages of Spray Drying 553

17.3 Principles and Instrumentation of Spray Drying Processes 553

17.4 Optimizing Spray Drying Process Parameters 563

17.5 Spray Drying of Water-Insoluble Drugs: Case Studies 566

17.6 Conclusion 582

References 583

Index 587