Surfactants and Polymers

in Drug Delivery
Martin Malmsten
Institute for Surface Chemistry and
Royal Institute of Technology
Stockholm, Sweden

Marcel Dekker, Inc.

New York Basel

TM

Copyright 2002 by Marcel Dekker, Inc. All Rights Reserved.

ISBN: 0-8247-0804-0
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Preface

Surfactant and polymer systems play an important role in modern drug delivery,
where they may allow control of the drug release rate, enhance effective drug
solubility, minimize drug degradation, contribute to reduced drug toxicity, and
facilitate control of drug uptake. In all, they contribute signicantly to therapeutic
efciency. However, although understanding of the physicochemical properties
and behavior of surfactants and polymers in solution and at interfaces has undergone dramatic development in the past couple of decades, the new ndings have
generally not been fully implemented in drug delivery, most likely as a result of
lack of interdisciplinary communication. Things are gradually changing, however, and scientists and engineers in both academia and industry are paying increasing attention to physicochemical aspects of surfactant and polymer systems
and recognizing their importance for the design and controlled use of advanced
drug delivery formulations. This is fueled by the development of new biopharmaceuticals in the wake of recent advances in genomics and proteomics. In parallel,
a push for advanced drug delivery formulations based on surfactants and polymers has originated from the development of many new synthetic drugs that are
sparingly soluble and noncrystallizing compounds, which often are difcult to
formulate by traditional means. Here, surfactant and polymer systems of various
types offer real potential.
The present book represents an attempt to discuss the basics of surfactant

Copyright 2002 by Marcel Dekker, Inc. All Rights Reserved.

and polymer surface activity and self-assembly, the various types of structures
formed by such compounds, and how they may be used in drug delivery. For this
purpose, individual chapters are devoted to micelles, liquid crystalline phases,
liposomes, microemulsions, emulsions, gels, and solid particles. Because biodegradation of surfactant and polymer systems has a particularly important effect
on their use in drug delivery, a separate chapter is devoted to this topic. Finally,
further processing of such formulations, for example, through spray-drying and
freeze-drying, is discussed.
I would like to thank Professors Bjorn Lindman, Thomas Arnebrant, and
Per Claesson for fruitful discussions on these topics and for helpful comments
on the manuscript. I also express my gratitude to Maud Norberg for her skillful
help with the gures and Britt Nystrom for help with literature issues.
Martin Malmsten

Copyright 2002 by Marcel Dekker, Inc. All Rights Reserved.

Contents

Preface
1.

Introduction
1.1 Introduction to Surfactants
1.2 Introduction to Polymers
1.3 Surface Activity of Drugs
1.4 Introduction to Drug Delivery
Bibliography

2.

Micelles
2.1 Structure and Dynamics of Micellar Systems
2.2 Block Copolymer Micelles
2.3 Characterization of Micellar Systems
2.4 Micellar Systems in Drug Delivery
Bibliography

3.

Liquid Crystalline Phases

3.1 Association Structures and Packing
3.2 Phase Diagrams
3.3 Association in Nonionic Surfactant Systems
3.4 Association in Ionic Surfactant Systems
3.5 Cubic Phases

Copyright 2002 by Marcel Dekker, Inc. All Rights Reserved.

3.6 Liquid Crystalline Phases Formed by PEO-PPO-PEO

Block Copolymers
3.7 Characterization of Liquid Crystalline Phases
3.8 Liquid Crystalline Phases as Drug Delivery Systems
3.9 Liquid Crystalline Phases in Drug Delivery Applications
Bibliography
4.

Liposomes
4.1 Preparation and Properties of Liposome Systems
4.2 Solubilization and Release from Liposomes
4.3 Methods for Investigating Liposome Systems
4.4 Liposomes in Drug Delivery
4.5 Other Types of Dispersed Liquid Crystalline Phases
Bibliography

5.

Microemulsions
5.1 Basics of Microemulsions
5.2 Characterization of Microemulsions
5.3 Drug Release from Microemulsions
5.4 Microemulsions in Drug Delivery
Bibliography

6.

Emulsions
6.1 Formation of Emulsions
6.2 Structure of Emulsions
6.3 Phase Inversion of Emulsions
6.4 Rheology of Emulsions
6.5 Destabilization of Emulsions
6.6 Multiple Emulsions
6.7 Emulsions in Drug Delivery
6.8 Emulsions as Precursors for SLN
Bibliography

7.

Aerosols, Bubbles, and Foams

7.1 Aerosols
7.2 Bubbles and Foams
7.3 Pharmaceutical Applications of Aerosols
7.4 Pharmaceutical Applications of Bubbles and Foams
Bibliography

8.

Polymer Solutions and Gels

8.1 Polymer Solutions
8.2 Polymer-Surfactant Interactions
8.3 Polymer Gels
8.4 Characterization of Polymer Solutions and Gels

Copyright 2002 by Marcel Dekker, Inc. All Rights Reserved.

8.5 Responsive Polymer Systems

8.6 Polymer Solutions and Gels in Drug Delivery
Bibliography
9.

Polymer Particles
9.1 Interaction Between Particles
9.2 Interaction Between Particles and Surfaces
9.3 Methods for Studying Polymer Particle Systems
9.4 Polymer Particles in Drug Delivery
9.5 Bioadhesion
9.6 Oral Vaccines
Bibliography

10.

Degradation of Surfactants and Polymers in Drug Delivery

10.1 Biodegradation of Polymers
10.2 Biodegradation of Phospholipids
Bibliography

11.

Drying of Formulations Containing Surfactants and Polymers

11.1 Spray-Drying
11.2 Freeze-Drying
11.3 Drying of Self-Assembled Structures
Bibliography

Copyright 2002 by Marcel Dekker, Inc. All Rights Reserved.