Cross-linked amylose tablets containing alpha-amylase: an enzymatically-controlled drug release system.
An oral controlled release system based on direct compression of cross-linked amylose (CLA) and drug powders was previously introduced. For drugs with limited solubility or for some drugs for which solubility can be influenced by variation of gastro-intestinal pH, a system is required to accelerate drug release. This paper describes a novel enzymatically-controlled drug release (ECDR) system based on the addition of alpha-amylase to CLA tablets, which can modulate the release kinetics of drugs. The alpha-amylase within the tablets is able to hydrolyze alpha-1-4-glucosidic bonds present in the CLA semisynthetic substrate. Increasing amounts of alpha-amylase (5 to 25 EU) within the tablets induced a significant decrease in release time from 24 to 6 h. High amounts of external alpha-amylase (300-6000 EU/l) had a slight effect on the release rate. Drug release from the ECDR system seems to be controlled by two sequential mechanisms: (a) hydration and swelling of CLA tablets followed by (b) internal enzymatic hydrolysis of the hydrated gel phase.
Dumoulin
Y
Y
Faculty of Pharmacy, University of Montreal, C.P. 6128, Succ. Centre-Ville, Montreal, Quebec, Canada.
Cartilier
L H
LH
Mateescu
M A
MA
D000688:Amylose / Q000737:chemistry / Q000493:pharmacokinetics*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D006868:Hydrolysis; D066298:In Vitro Techniques; D013607:Tablets; D013997:Time Factors; D000516:alpha-Amylases / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D013607:Tablets; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D000688:Amylose; D000516:alpha-Amylases