Design and pharmacokinetics of Logimax, a new extended-release combination tablet of felodipine and metoprolol

Abstract

A new, once-daily combination tablet containing felodipine and metoprolol has been developed, using extended-release techniques to obtain even plasma concentrations throughout the dosing interval. The tablet consists of a hydrophilic matrix containing felodipine in which many small membrane-coated metoprolol pellets are embedded. On contact with gastrointestinal fluids, felodipine is released at an almost constant rate by erosion of the hydrophilic matrix. The release of metoprolol also follows near zero-order kinetics, and is mainly controlled by diffusion through the membrane covering each individual metoprolol bead. Smooth plasma concentration profiles are obtained for both drugs of the combination, similar to those found with the corresponding single-drug formulations: felodipine extended-release tablets and metoprolol controlled-release tablets. The new fixed combination tablet also consistently provides even plasma concentrations of felodipine and metoprolol after administration together with food and in elderly hypertensive patients. The convenience of one tablet per day for effective antihypertensive treatment with a combination of felodipine and metoprolol should improve patient compliance with the prescribed regimen.