Oral absorption of the antihyperglycaemic agent metformin hydrochloride (MF-HCI) is confined to the upper part of the intestine, therefore rational controlled-release formulations of this drug should ensure a complete release during transit from stomach to jejunum. The aim of this study was the preparation of a system able to sustain release of high MF-HCI doses in compliance with the above requirement. Matrices (6mm diameter; 50 mg weight) comprising varying drug-Precirol ATO 5 ratios were prepared by compression. The matrix containing 70% drug was coated on one face with Eudragit L100-55. Drug release to simulated gastric (SGF), jejunal (SJF) and ileal (SIF) fluids in sequence was studied using a modified USP rotating basket method. Release depended on drug load whereas it was independent of dissolution medium pH and hydrodynamics. Release kinetics were of √t type and were determined by drug diffusion in aqueous pores created in the matrix by drug dissolution. An equation correlating rate-determining factors was developed, whereby the release pattern could be optimized. The half-coated matrix started release in SGF and completed it in SJF. The half-coated matrix, synchronizing drug release and matrix transit across the small intestine, may improve drug bioavailability and reduce side effects.
|Autori:||DI COLO G; ZAMBITO Y; BAGGIANI A; CARELLI V; SERAFINI M.F|
|Titolo:||A site-specific controlled-release system for metformin|
|Anno del prodotto:||2005|
|Digital Object Identifier (DOI):||10.1211/0022357056037|
|Appare nelle tipologie:||1.1 Articolo in rivista|