Chapter 20 - Rational Design of Oral Modified-Release Drug Delivery Systems

Abstract

Modified release (MR) drug delivery systems are developed to modulate the apparent absorption and/or alter the site of release of drugs, in order to achieve specific clinical objectives that cannot be attained with conventional dosage forms. The design objective for modifying oral drug release is to alter the rate of drug input (dissolution/absorption) in the intestinal lumen to achieve a predetermined plasma profile. Common modes of oral MR delivery include: delayed-release, site-specific or timed release, extended-release, and programmed release. Oral MR drug delivery technology has been applied to new product development for several years. Various physical and chemical approaches have been successfully applied to produce well-characterized delivery systems that extend drug input into the GI tract within the specifications of the desired release profile. Today, most proprietary and nonproprietary extended-release (ER) technologies are based on polymeric systems. In a matrix system, the drug substance is homogeneously mixed into the rate-controlling material(s) and other inactive ingredients as a crystalline, amorphous or, in rare cases, molecular dispersion. Hydrophilic matrix systems are polymer-based drug delivery systems in which two competing mechanisms are involved in the drug release: Fickian diffusional release, and relaxational release.