DEXTRAN HYDROGELS FOR COLON-SPECIFIC DRUG-DELIVERY .4. COMPARATIVE RELEASE STUDY OF HYDROCORTISONE AND PREDNISOLONE SODIUM-PHOSPHATE

The release mechanisms of two model drugs from monolithic hydrogel devices based on dextran have been studied. The dextran hydrogel devices have previously been proposed for colonic drug delivery. The release of hydrocortisone, a hydrophobic drug, was found to be diffusion-controlled and proportional to the cross-linking density of dextran hydrogels. This suggests that release is governed by the << partition >> mechanism for solute transport in hydrogels. The release of prednisolone sodium phosphate, a hydrophilic drug, however, was found to be swelling-controlled and inversely proportional to the cross-linking density, suggesting a release by the << pore >> mechanism. Drug release was found to be successfully triggered after the addition of a dextranase preparation used as a model for colonic microbial dextranases. In the presence of dextranase, the hydrogels were degraded by surface erosion, and the drug release was found to be partially controlled by degradation. The contribution from degradation on the release depended on the hydrophobicity of the drug and the cross-linking density of the hydrogel.