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The concept of controlled release has attracted increasing attention over the last two decades, with the applications of this technology proliferating in diverse fields in­ cluding medicine, agriculture and biotechnology. Research and developmental efforts related to controlled release are multiplying in both industry and academia. The reason for this phenomenal growth is obvious. The use of a variety of biologically active agents, such as drugs, fertilizers and pesticides, has become an integral part of modern society. Along with the use of these reagents has evolved an awareness that their uncontrolled application almost inevitably induces harmful effects on the health of humans and their surrounding environments. To eliminate or minimize these harmful effects necessitates the controlled release of these chemicals. Moreover, the controlled release of substances, not usually considered toxic or hazardous, e.g., some catalysts and nutrients, can enhance their effectiveness. The number and variety of controlled release systems, differing in their physical and chemical makeup, are increasing rapidly. Proliferation almost always demands correlation, generalization and unification; it requires both the development of underlying theories of their behavior and the mechanistic interpretation of their performance. This, in turn, requires a statistical and mathematical (quantitative) treatment of the scientific information and technical data pertaining to them. A quantitative treatment can also facilitate the formulation of procedures for computer-aided design of these systems through a priori prediction of their per­ formance for a variety of design parameters.

Inhaltsverzeichnis

Frontmatter

1. Introduction

Abstract
In the search for safe, economical, and efficient means of providing for the health and well-being of mankind, modern science has produced numerous active agents that manipulate the biological environment around and within us. Nevertheless, the use of these active agents is fraught with inefficiencies stemming from an inability to deliver these agents to their targets at the right time and in the right amounts. This results in their loss and in undesirable side effects and leads to a regimen requiring repeated treatment to produce and sustain the desired effect. With drugs, periodic dosage produces peaks and valleys in the concentration of the drug in the blood stream, possibly between harmful and ineffective levels (see Fig. 1.1). Agricultural chemicals such as pesticides, fertilizers, herbicides, and fumigants create the same problems when applied directly. To counter these problems, scientists have conventionally looked to altering the persistency and effectiveness of the reagents through modification of the reagents themselves. However, this approach tends to be difficult, time consuming, and expensive.
Liang-tseng Fan, Satish Kumar Singh

2. Diffusion-Controlled Release

Abstract
Molecular diffusion through polymers and synthetic membranes is an effective, simple and yet reliable means of attaining the controlled release of a variety of active agents. The principal devices utilizing this phenomenon are of the reservoir and monolithic types. In a reservoir device, the active agent is contained within the rate-controlling membrane, while in a monolithic device, the active agent is homogeneously dissolved or dispersed throughout the polymer matrix.
Liang-tseng Fan, Satish Kumar Singh

3. Chemical Reaction Controlled Release

Abstract
The polymer utilized in diffusion-controlled release devices or systems plays a relatively passive role. It serves simply as a carrier and retards the rate at which the active agent is delivered to the target. Nevertheless, some polymeric carriers are designed to play a more active role in the release process. These polymers undergo chemical reactions at the target site, thereby enabling the active agent to be delivered. Such chemically activated systems fall into two broad categories (Langer, 1980; Baker, 1987):
i.
Physical immobilization systems, also called erodible or (bio)degradable systems in each of which the active agent, physically immobilized within the polymer network, is released by erosion of this network (Fig. 3.1a)
 
ii.
Chemical immobilization systems, in each of which the active agent is either chemically bonded to the polymer carrier backbone (pendant chain) or is part of the backbone itself (polyagents). Release occurs by hydrolytic or enzymatic degradation of the appropriate bonds (Fig. 3.1b).
 
Liang-tseng Fan, Satish Kumar Singh

4. Swelling-Controlled Release

Abstract
Consider a monolithic polymeric device containing an active agent introduced into the elution medium. If the elution medium is not thermodynamically compatible with the polymer or if the polymer is well above its glass transition temperature, the morphological structure is time independent and the device belongs to the diffusion-controlled category. However, if the elution medium or a constituent component is thermodynamically compatible with a polymer in the glassy state, its glass transition temperature may be lowered below the system temperature. Subsequently, the glassy polymer begins to undergo a glass-to-gel transition. The polymer chains in the gel state, being more mobile than those in the glassy state, allow the active agent to diffuse (more rapidly) out of the matrix. Such a device in which the change of polymer morphology, caused by interaction with the elution medium, controls or influences the release is classified as being swelling controlled. A distinction has been made between two types of systems formed by such swellable polymers (Peppas, 1984). A swellable controlled-release system comprising the first type, consists of a hydrophilic polymer that undergoes swelling more or less continuously throughout the matrix. This glass-to-gel transition loosens the matrix and the active agent is able to diffuse out, with the release rate determined by the diffusion process. A swelling-controlled system belonging to the second type, comprises a polymeric system exhibiting spatially discontinuous swelling.
Liang-tseng Fan, Satish Kumar Singh

5. Special Controlled-Release Systems

Abstract
In this chapter, we shall briefly examine some controlled-release systems not widely modeled mathematically. Nevertheless, these systems are interesting since they offer a wide range of performance capabilities, and also constitute interesting modeling problems.
Liang-tseng Fan, Satish Kumar Singh

6. Stochastic Model for Diffusion in Porous or Heterogeneous Polymer Matrix

Abstract
A number of new polymeric materials are being explored for possible utilization as carriers for the controlled release of biologically active agents. The morphological structure of most polymers is heterogeneous, consisting of two phases, namely crystalline and amorphous. These two phases are present in varying amounts depending on the composition and the thermal and processing history of the polymer, and are dispersed throughout the body of the polymer. Transport of active agents in such materials is influenced therefore by their molecular structure since the permeabilities of the two phases are different. Crystalline domains in a semi-crystalline polymer are virtually impermeable relative to the amorphous phase; consequently, the diffusing molecule has to follow a tortuous path through the permeable amorphous phase. This permeable phase is interspersed between the impermeable domains serving as boundaries or walls. It is evident that the characteristics of transport in the permeable-impermeable domains of a heterogeneous polymer are similar to those in a porous medium. Thus the release of an active agent from either the heterogeneous polymer or the porous matrix carrier can be analyzed analogously (see, e.g., Peterlin, 1979, Harland and Peppas, 1986).
Liang-tseng Fan, Satish Kumar Singh

7. Epilogue

Abstract
As stated in the preface of this monograph, a quantitative treatment can facilitate computer-aided design of controlled-release devices or systems. In theory, the mathematical models presented in this monograph could be employed to design these devices. In reality, however, the resultant device cannot be expected to perform optimally over the whole range of possible “environmental” conditions.
Liang-tseng Fan, Satish Kumar Singh

Backmatter

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