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Informationen zum Autor Dennis Douroumis University of Greenwich, UK Alfred Fahr Friedrich-Schiller University of Jena, Germany Klappentext Many newly proposed drugs suffer from poor water solubility, thus presenting major hurdles in the design of suitable formulations for administration to patients. Consequently, the development oftechniques and materials to overcome these hurdles is a major area of research in pharmaceutical companies.Drug Delivery Strategies for Poorly Water-Soluble Drugs provides a comprehensive overview of currently used formulation strategies for hydrophobic drugs, including liposome formulation, cyclodextrin drug carriers, solid lipid nanoparticles, polymeric drug encapsulation delivery systems, self-microemulsifying drug delivery systems, nanocrystals, hydrosol colloidal dispersions, microemulsions, solid dispersions, cosolvent use, dendrimers, polymer- drug conjugates, polymeric micelles, and mesoporous silica nanoparticles. For each approach the book discusses the main instrumentation, operation principles and theoretical background, with a focus on criticalformulation features and clinical studies. Finally, the book includes some recent and novel applications, scale-up considerations and regulatory issues.Drug Delivery Strategies for Poorly Water-Soluble Drugs is an essential multidisciplinary guide to this important area of drug formulation for researchers in industry and academia working in drugdelivery, polymers and biomaterials. Zusammenfassung 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. Inhaltsverzeichnis 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 1.3.1 Linear Growth 9 1.3.2 Cooperative Assembly 10 1.4 Solubility and Partitioning of Drugs 11 1.4.1 Simple Partitioning Equilibria 11 1.4.2 Partitioning and Micellization 13 1.4.3 Hydrophobicity and Ordering of Water 15 1.5 Ways to Model Interactions in Colloidal Systems 16 1.5.1 Electrostatic Interactions: The Poisson-Boltzmann Model 17 1.5.2 Chain Packing Model 21 1.6 Kinetics of Drug Transfer from Mobile Nanocarriers 23 1.6.1 Collision Mechanism 25 1.6.2 Diffusion Mechanism 26 1.6.3 Internal Kinetics 26 1.7 Conclusion 29 Acknowledgments 31 References 31 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 2.2.1 Solubilizing Vehicles with Precipitation Risk upon Dilution 41 2.2.2 Solubilizing Vehicles Maintaining Solubilization Capacity upon Dilution 43 2.2.3 Mechanistic Release Aspects/Transfer Liposomal PWSC 45 2.2.4 In Vivo Consequences 52 2.2.5 Preclinical Parenteral Assessment Liposomal PWSC 56 2.3 Conclusion 59 References 60 3 Drug Solubilizatio...
List of contents
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: Smartcrys
