Controlled Drug Delivery Systems

Abstract

In most forms of drug delivery, spatial localization and duration of drug concentration are constrained by organ physiology and metabolism. For example, drugs administered orally will distribute to tissues based on the principles of diffusion, permeation, and flow presented in Part II of this book. If the duration of therapy provided by a single administration is insufficient, the drug must be readministered. Localization of drug can be controlled by injection, but only within limited spatial constraints, and effectiveness after an injection is usually short-lived. Controlled-delivery systems offer an alternative approach to regulating both the duration and spatial localization of therapeutic agents. In controlled delivery, the active agent is combined with other (usually synthetic) components to produce a delivery system. Unlike drug modification, which results in new agents that are single molecules, or assemblies of a limited number of molecules, drug delivery systems are usually macroscopic. Like drug modification, controlled-delivery systems frequently involve combinations of active agents with inert polymeric materials. In this text, controlled-delivery systems are distinguished from “sustained-release” drug formulations. Sustained release is often achieved by mixing an active agent with excipients or binders that alter the agent’s rate of dissolution in the intestinal tract or adsorption from a local injection site. The distinction between sustained release (often achieved by drug formulation) and controlled delivery or controlled release is somewhat arbitrary. In our definition, controlled delivery systems must (1) include a component that can be engineered to regulate an essential characteristic (e.g., duration of release, rate of release, or targeting) and (2) have a duration of action longer than a day. Many polymeric materials are available for the development of drug delivery systems (see Appendix A). Non-degradable, hydrophobic polymers have been used the most extensively. Reservoir drug delivery devices, in which a liquid reservoir of drug is enclosed in a silicone elastomer tube, were first demonstrated to provide controlled release of small molecules several decades ago [1]. This discovery eventually led to clinically useful devices, including the Norplant® (Wyeth-Ayerst Laboratories) contraceptive delivery system, which provides reliable delivery of levonorgestrel for 5 years following subcutaneous implantation.