Open AccessA site‐specific controlled‐release system for metformin
Author(s) -
Colo Giacomo,
Zambito Ylenia,
Baggiani Andrea,
Carelli Vera,
Serafini Maria Francesca
Publication year - 2005
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1211/0022357056037
Subject(s) - bioavailability , drug , chemistry , chromatography , dosage form , controlled release , matrix (chemical analysis) , dissolution , jejunum , solubility , small intestine , pharmacology , biochemistry , medicine , organic chemistry
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 √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.