title: A site-specific controlled-release system for metformin.
abstract: Oral absorption of the antihyperglycaemic agent metformin hydrochloride (MF-HCl) 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-HCl doses in compliance with the above requirement. Matrices (6 mm 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 radical 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.
authors.affiliation: Department of Bioorganic Chemistry and Biopharmaceutics, University of Pisa, Via Bonanno 33, 56126 Pisa, Italy. giadic@farm.unipi.it
authors.forename: Giacomo
authors.initials: G
authors.lastname: Di Colo
authors.forename: Ylenia
authors.initials: Y
authors.lastname: Zambito
authors.forename: Andrea
authors.initials: A
authors.lastname: Baggiani
authors.forename: Vera
authors.initials: V
authors.lastname: Carelli
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Serafini
mesh_terms: D001682:Biological Availability; D004339:Drug Compounding; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D007082:Ileum / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D007700:Kinetics; D008687:Metformin / Q000737:chemistry* / Q000493:pharmacokinetics; D008954:Models, Biological; D009928:Organ Specificity; D012995:Solubility; D013608:Tablets, Enteric-Coated
chemical_list: D007004:Hypoglycemic Agents; D013608:Tablets, Enteric-Coated; D008687:Metformin