Novel approach to zero-order drug delivery via immobilized nonuniform drug distribution in glassy hydrogels

A novel approach to zero-order drug delivery from glassy hydrogel matrices via an immobilized, sigmoidal, initial drug distribution has been developed. The method utilizes a controlled-extraction process on initially dry, drug-loaded hydrogels to generate an inflection-point-containing drug concentration profile followed by a vacuum freeze-drying step to rapidly remove the swelling solvent and immobilize in situ a nonuniform drug distribution. The drug release from such a system generally exhibits typical zero-order characteristics similar to that of a membrane-reservoir device. However, a saturated reservoir of active ingredient as in the membrane-reservoir device is not required because the constant release is achieved via an initially nonuniform concentration distribution instead of the constant activity in a reservoir. The applicability of the present concept and process has been demonstrated experimentally with the release of oxprenolol hydrochloride from hydrogel beads based on 2-hydroxyethyl methacrylate polymerized with a polymeric cross-linking agent.