Drug Delivery Strategies for Poorly Water-Soluble Drugs

Dionysios Douroumis, Alfred Fahr

• Publisher: Wiley
• Year: 2012
• Print ISBN:
  9780470711972
• eBook ISBN:
  9781118444672
• Edition: 1
• Topic: Scienze fisiche
• Subtopic: Chimica organica

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 of
techniques 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 critical
formulation 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 drug
delivery, polymers and biomaterials.

1

Self-Assembled Delivery Vehicles for Poorly Water-Soluble Drugs: Basic Theoretical Considerations and Modeling Concepts

Sylvio May amd Alfred Fahr

1.1 Introduction

Poor solubility is a well-recognized property of many drug molecules [1]. Unprotected administration of poorly water-soluble drugs is problematic. Aggregation, precipitation, uncontrolled binding, and direct exposure to a harsh biological environment render this process inefficient. The putative ‘solution’ of using higher drug concentrations narrows the window between a therapeutic success and unwanted side effects such as locally toxic drug levels. It comes as no surprise that the administration of poorly water-soluble drugs can benefit dramatically from using delivery vehicles. Such vehicles can, in principle, be designed not only to encapsulate a drug and protect it from biological defense mechanisms, but also to release the drug in a controlled manner at the target site and then to be recycled through biodegradation. Different types of delivery vehicles are currently being investigated, including microemulsions [2,3], gels [4], micelles [5,6], liposomes [7], polymersomes [8], dendrimers [9], and nanopcrystals [10], or lipid nanoparticles [11]. Notably, most of these are self-assembled structures. Self-assembly is an ubiquitous process in cellular systems, most strikingly perhaps in the cell membrane where a matrix (lipids) contains highly specialized functional units (poorly water-soluble proteins). Functionalization is an advantage that is also increasingly integrated into drug delivery vehicles. As an example we mention liposomes, which were originally designed as long-circulating transport vehicles for drug molecules [12]. Extending the circulation time by decorating the liposome surface with PEG-chains (stealth liposomes [13]) can be viewed as the first step toward functionalization. Currently designed liposomes raise the concept of functionalization to a new height: they contain targeting ligands and carry out stimuli-sensitive triggering of the drug release [14–16].

Optimizing drug delivery vehicles is promising but also challenging. Self-assembled nanostructures are soft and responsive materials, where entropy becomes an important factor for structure and stability. It is virtually impossible to manipulate one property without affecting others (and sometimes this has drastic implications as one of the authors vividly recalls the disintegration of an entire colloidal formulation upon the replacement of a single -H group by an -OH group in a 1 kDalton drug molecule). Nanocarrier properties are affected by a range of interactions that are well known from colloidal science, including solvation energies, electrostatic and van der Waals interactions, depletion and packing effects, etc. [17,18]. Appreciation and understanding of these interactions are likely to reflect upon nanocarrier design and optimization. For example, one of the challenges that drug encapsulation in nanocarriers faces is related to the retention of the drug in the carrier. A lipophilic drug does not necessarily remain in a rigid lipophilic matrix [19] but is rapidly squeezed out, whereas soft structures (like liposomal membranes) tend to increase the residence time in the membra...

Table of contents

• Cover
• Series
• Title Page
• Copyright
• Dedication
• List of Contributors
• Series Preface
• Preface
• Chapter 1: Self-Assembled Delivery Vehicles for Poorly Water-Soluble Drugs: Basic Theoretical Considerations and Modeling Concepts
• Chapter 2: Liposomes as Intravenous Solubilizers for Poorly Water-Soluble Drugs
• Chapter 3: Drug Solubilization and Stabilization by Cyclodextrin Drug Carriers
• Chapter 4: Solid Lipid Nanoparticles for Drug Delivery
• Chapter 5: Polymeric Drug Delivery Systems for Encapsulating Hydrophobic Drugs
• Chapter 6: Polymeric Drug Delivery Systems for Encapsulating Hydrophobic Drugs
• Chapter 7: Development of Self-Emulsifying Drug Delivery Systems (SEDDS) for Oral Bioavailability Enhancement of Poorly Soluble Drugs
• Chapter 8: Novel Top-Down Technologies: Effective Production of Ultra-Fine Drug Nanocrystals
• Chapter 9: Nanosuspensions with Enhanced Drug Dissolution Rates of Poorly Water-Soluble Drugs
• Chapter 10: Microemulsions for Drug Solubilization and Delivery
• Chapter 11: Hot Melt Extrusion: A Process Overview and Use in Manufacturing Solid Dispersions of Poorly Water-Soluble Drugs
• Chapter 12: Penetration Enhancers, Solvents and the Skin
• Chapter 13: Dendrimers for Enhanced Drug Solubilization
• Chapter 14: Polymeric Micelles for the Delivery of Poorly Soluble Drugs
• Chapter 15: Nanostructured Silicon-Based Materials as a Drug Delivery System for Water-Insoluble Drugs
• Chapter 16: Micro- and Nanosizing of Poorly Soluble Drugs by Grinding Techniques
• Chapter 17: Enhanced Solubility of Poorly Soluble Drugs Via Spray Drying
• Index