Evaluation of solubilizers in the drug release testing of hydrophilic matrix 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 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.
Pharmaceutical R&D, Astra Hässle, Mölndal, Sweden.
B
B
Abrahamsson
D
D
Johansson
A
A
Torstensson
K
K
Wingstrand
D000328:Adult; D000077286:Cetrimonium; D002593:Cetrimonium Compounds; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D003902:Detergents; D005069:Evaluation Studies as Topic; D005079:Excipients; D015736:Felodipine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008823:Micelles; D011136:Polysorbates; D012967:Sodium Dodecyl Sulfate; D012996:Solutions; D013501:Surface-Active Agents; D013607:Tablets
D002593:Cetrimonium Compounds; D003692:Delayed-Action Preparations; D003902:Detergents; D005079:Excipients; D008823:Micelles; D011136:Polysorbates; D012996:Solutions; D013501:Surface-Active Agents; D013607:Tablets; D012967:Sodium Dodecyl Sulfate; D015736:Felodipine; D000077286:Cetrimonium