Use of osmotically active therapeutic agents in monolithic systems

Abstract

The functionality of a new class of monolithic systems for the controlled release of drugs is discussed. The systems consist of uniformly dispersed particles of osmotically active therapeutic agents (drugs) in biocompatible polymeric matrices. The drug particles are encapsulated by polymers to form a multiplicity of microcapsules throughout the matrix. These osmotic film systems display zero-order drug delivery kinetics. The principal energy source governing the release of agents is osmotic in nature. When such a film is placed in an aqueous infinite sink, the film imbibes water into the outermost layer of the dispersion at a rate dictated by permeability of the polymer. Water transport into the film continues until volumetric rupture of the drug-containing capsules occurs, after which time saturated drug solution is pumped through channels created by the rupture. This process repeats itself in a serial fashion until the system is exhausted of agent. Due to the osmotic functionality of these systems, reduction of the thermodynamic activity of water outside the system can proportionally reduce the release of agent. In this paper the effects of varying drug particle size, osmotic pressure gradients, system area, drug type, polymer type, and temperature upon the drug release kinetics are presented. Application of this new technology has allowed the fabrication of several useful drug therapeutic systems. © 1980.