Abstract

Unit dosage form for delivering drugs into the body in a series of sequential, pulsatile releasing events employs conventional pharmaceutical equipment and processes for optimum economy, reliability, and bioavailability. The system can be used with drugs which cannot be released by diffusion through a porous coating, such as water insoluble drugs. A plurality of populations of pellets is provided within a unit dosage form such as a capsule (8) or tablet. The pellets are composed of a core containing the drug (3) and a swelling agent (4) which expands in volume when exposed to water. The core is enclosed within a membrane or coating which is permeable to water. The membrane is composed of a water insoluble and permeable film forming polymer, a water soluble film forming polymer (11) and a permeability reducing agent (14). When the unit dose releases the pellets into the digestive tract, water diffuses through the coating and into the core. As water is taken up by the swelling agent, the core expands, exerting force on the coating until it bursts, releasing the drug. The permeability reducing agent reduces the rate at which water reaches the swelling agent, thereby delaying release time. The water soluble polymer dissolves, weakening the coating so that it bursts sooner. By varying the proportions of the three coating ingredients and/or coating thickness from one pellet population to another, the release timing of the pellets can be very effectively controlled.