EVALUATION OF SOLUBILIZERS IN THE DRUG-RELEASE TESTING OF HYDROPHILICMATRIX EXTENDED-RELEASE TABLETS OF FELODIPINE

The drug release of felodipine, a water-insoluble drug, was tested by using sodium lauryl sulphate (SLS), polyoxyethylene 20 sorbitan monool eate (Tween) or cetyltrimethylammonium bromide (CTAB) in the test medi um as solubilizers. Three slightly different felodipine extended-relea se (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 togethe r 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 correlatio n (r(2) = 0.94-0.97) to in vivo dissolution, as determined by moment a nalysis. However, a much steeper in vitro/in vivo relationship was obt ained for SLS compared to Tween and CTAB reflecting an inferior discri mination between the tablets by use of this anionic solubilizer.