In vitro evaluation of a system for pH-controlled peroral delivery of metformin

Oral absorption of the antihyperglycaemic agent metformin ((MFHCl)-H-.) is confined to the upper part of the intestine, therefore control led-re lease oral formulations of this drug should ensure a complete release during transit from stomach to jejunum. Compressed matrix tablets based on pH-sensitive poly(ethylene oxide) (PEO)-Eudragit L100 (EUD L) Compounds have shown in vitro a compliance with the above requirement. The polymer compounds were prepared by a coevaporation process. The release pattern of (MFHCl)-H-. from matrices depended on the PEO-EUD L ratio in the coevaporate. The 1:1 (w/w) ratio was unable to control (MFHCl)-H-. release in simulated gastric fluid (SGF, pH 1.2). because the matrix material was excessively hydrophilic. Nevertheless, the release rate in SGF could be modulated by increasing the EUD L fraction in the coevaporate. With a PEO (M-w, 400 kDa)-EUD L ( 1:2, w/w) ratio the percent dose released in 2 h to SGF, where the coevaporate was insoluble, was around 23 or 50% with 10 or 20% loading dose. The release was then completed within the successive 2 h of elution with simulated jejunal fluid (SJF, pH 6.8) where EUD L and the coevaporate gradually dissolved. Release in SGF was controlled by matrix swelling and/or drug diffusion in matrix, whereas matrix dissolution controlled release in SJF. The unique release-controlling properties of the polymer compounds were due to PEO-EUD L macromolecular interactions. Matrices show promise of a gradual and complete release of (MFHCl)-H-. from stomach to jejunum, unaffected by gastric pH fluctuations. This mode of administration might allow the use of lower therapeutic doses compared to existing immediate- or sustained-release products, thus minimising side effects. (C) 2002 Elsevier Science B.V. All rights reserved.