Cross-linked amylose tablets containing alpha-amylase: an enzymatically-controlled drug release system

An oral controlled release system based on direct compression of cross-link ed amylose (CLA) and drug powders was previously introduced. For drugs with limited solubility or for some drugs for which solubility can be influence d by variation of gastro-intestinal pH, a system is required to accelerate drug release. This paper describes a novel enzymatically-controlled drug re lease (ECDR) system based on the addition of alpha-amylase to CLA tablets, which can modulate the release kinetics of drugs. The a-amylase within the tablets is able to hydrolyze alpha-1-4-glucosidic bonds present in the CLA semisynthetic substrate. Increasing amounts of a-amylase (5 to 25 EU) withi n the tablets induced a significant decrease in release time from 24 to 6 h . High amounts of external alpha-amylase (300-6000 EU/1) had a slight effec t on the release rate. Drug release from the ECDR system seems to be contro lled by two sequential mechanisms: (a) hydration and swelling of CLA tablet s followed by (b) internal enzymatic hydrolysis of the hydrated gel phase. (C) 1999 Published by Elsevier Science B.V. All rights reserved.