Drug-Delivery by Ion-Exchange. Part IV: Coated Resinate Complexes of Ester Pro-Drugs of Propranolol

Abstract

The micro-encapsulation of cationic exchange resins, loaded with O-n-acyl and O-pivaloyl ester prodrugs of propranolol, by means of gelatin-acacia coacervates is described. Resins loaded at elevated temperatures have delayed release profiles, as have those treated with polyethylene glycol, but drug release still follows particle diffusion models. Drug release from coated resins may be controlled by the weight of coat applied and for a small particle-size pharmaceutical-grade resin the time required for 50% release of complexed propranolol may be extended from 25 minutes to 100 minutes. Double coating procedures may extend this to in excess of 4 hours. The mixing of coated and uncoated particles also offers a means by which release profiles may be controlled and the time necessary for 50% release of O-pivaloylpropranolol may, for example, range from 25 minutes to 250 minutes using mixtures of single-coated particles.

Key Words::

• Coacervation
• controlled-release
• gelatin-acacia
• ion-exchange resins
• propranolol
• resinates