Simulation of gastric lipolysis and prediction of felodipine release from a matrix tablet in the fed stomach.
The importance of intragastric lipolysis to felodipine release from a hydrophilic, extended release tablet in the fed stomach was assessed in USP II apparatus with the tablet fixed on a steel wire above the paddle. The release medium, homogenized long-life milk, was gradually digested with shots of acidic solutions of pepsin over the course of the experiment in absence and in presence of biorelevant concentrations of a lipase that was similar to human gastric lipase. Percentage tablet erosion at specific times in the same media was measured in separate experiments. The data were compared to published data for intragastric release in fed healthy adults. In all cases, felodipine release occurred under sink conditions. Lipase facilitated felodipine release from the eroded polymer, bringing the release profile closer to the in vivo data. Likewise, the relationship between tablet erosion and amount of released felodipine reflected the in vivo data only when lipase was added to the medium. It was concluded that modelling intragastric lipolysis is necessary in order to simulate felodipine release from the extended release tablets in the fed stomach.
Laboratory of Biopharmaceutics and Pharmacokinetics, National & Kapodistrian University of Athens, Athens, Greece.
A
A
Diakidou
M
M
Vertzoni
B
B
Abrahamsson
J
J
Dressman
C
C
Reppas
D015736:Felodipine / Q000493:pharmacokinetics*; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D008066:Lipolysis; D012995:Solubility; D013607:Tablets
D013607:Tablets; D015736:Felodipine