ABSTRACT
The drug release of felodipine, a water-insoluble drug, was tested by using sodium lauryl sulphate (SLS), polyoxyethylene 20 sorbitan monooleate (Tween) or cetyltrimethylammonium bromide (CTAB) in the test medium as solubilizers. Three slightly different felodipine extended-release (ER) tablets 10 mg based on the gel matrix principle were evaluated under different solubilizer concentrations, agitation intensities and pH. These tablets were also tested in a bioavailability study together with an oral solution. All three solubilizers substantially enhanced the drug solubility and sink conditions were obtained. The choice of solubilizer affected the drug release rate. This is most probably due to physico-chemical interactions between the gel-forming agent and the solubilizers. All in vitro test conditions provided a good correlation (r2 = 0.94-0.97) to in vivo dissolution, as determined by moment analysis. However, a much steeper in vitro/in vivo relationship was obtained for SLS compared to Tween and CTAB reflecting an inferior discrimination between the tablets by use of this anionic solubilizer.
Subject(s)
Felodipine/administration & dosage , Adult , Cetrimonium , Cetrimonium Compounds , Cross-Over Studies , Delayed-Action Preparations , Detergents , Evaluation Studies as Topic , Excipients , Felodipine/chemistry , Felodipine/pharmacokinetics , Humans , Male , Micelles , Polysorbates , Sodium Dodecyl Sulfate , Solutions , Surface-Active Agents , TabletsABSTRACT
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.
Subject(s)
Felodipine/pharmacokinetics , Metoprolol/pharmacokinetics , Adult , Aged , Aging/metabolism , Biological Availability , Delayed-Action Preparations , Drug Combinations , Felodipine/administration & dosage , Food , Humans , Metoprolol/administration & dosageABSTRACT
1. The rate and extent of felodipine absorption from an oral solution, conventional and extended-release tablets were investigated in two groups of healthy volunteers (n = 18 + 15). 2. The antihypertensive effect of felodipine conventional tablets twice daily (n = 71) and extended-release tablets once daily (n = 76) were compared in a parallel-group study in hypertensive patients. 3. As from a solution, felodipine was completely absorbed from the two solid dosage forms. The rate of absorption increased in the order extended-release tablets, conventional tablets, solution. 4. The extended-release tablet gave more sustained plasma concentrations than the conventional tablet. 5. The extended-release tablet given once daily gave similar blood pressure control to the conventional tablet given twice daily.
