Zero-Order Release from Cylindrical Xerogel Preparation.

Abstract

The objective of this study was to prepare and evaluate the possibility of cylindrical xerogel preparations with zero-order release characteristics. As model polymers, polyvinyl alcohol (PVA), hydroxypropyl methylcellulose (HPMC), and acrylic block copolymers of methacrylic acid and the methacrylate, Eudispert, were selected and formed into xerogel formulations. Tegafur, 5-fluorouracil (5-FU), aspirin, benzoic acid, p-methoxybenzoic acid, theophylline, and salicylamide were employed as model compounds and thereby incorporated into xerogel matrices.In a dissolution test (rotating basket method; pH 7.4), PVA xerogel did not erode nor swell in dissolution medium, and did not exhibit zero-order release, but rather exhibited Fickian's law diffusion followed by the initial burst release profile. In the case of HPMC xerogel, swelling of the polymer was observed to some extent, but the release profile was almost the same as PVA, suggesting the Fickian diffusion of drug from HPMC gel; in contrast, Eudispert gel showed zero-order release in every drug. The polymer was also gradually dissolved into the medium at a zero order release rate.Finally, the Eudispert xerogel containing theophylline was orally administered to beagle dogs, and plasma was withdrawn periodically. The sustained-release characteristics were observed and the possibility of the cylindrical xerogel preparation for oral usage was demonstrated.