Effect of non-uniform initial drug concentration distribution on the kinetics of drug release from glassy hydrogel matrices

Abstract

The effect of non-uniform initial drug concentration distribution, on the kinetics of drug release from polymer matrices has been examined theoretically. The results indicate that a constant-rate of drug release can be achieved, via a specific sigmoidal drug concentration distribution without the need to have a saturated drug reservoir as in a membrane-reservoir system. To test this concept, a novel approach has been developed, which utilizes the non-Fickian swelling behaviour in glassy hydrogels to develop an inflection-point containing drug concentration profile, followed by a freeze-drying step to rapidly remove the swelling solvent and immobilize in-situ the desired sigmoidal drug concentration distribution. The drug release from such a system generally exhibits a characteristic time-lag and a constant-rate release region similar to that of a membrane-reservoir system. The applicability of the present concept and process has been demonstrated experimentally with the release of oxprenolol HCl from hydrogel beads; based on 2-hydroxyethyl methacrylate polymerized with a polymeric crosslinking agent.