Indexed on: 09 Feb '10Published on: 09 Feb '10Published in: Drug development and industrial pharmacy
This article aimed to develop fenofibrate solid dispersion with high bioavailability using hot-melt extrusion and compare the difference of Eudragit E100 and polyvinylpyrrolidone-vinyl acetate copolymer S630 (PVP-VA) in dissolution.Solid dispersion with carrier of Eudragit E100 or PVP-VA was prepared by hot-melt extrusion and then characterized by differential scanning calorimetry (DSC), X-ray diffraction, in vitro dissolution test, and in vivo bioavailability study.Fenofibrate exited as noncrystal state in these two kinds of solid dispersions that can be proved by DSC and X-ray diffraction. Eudragit E100 1:2 solid dispersion has the dissolution of 84% and 65% at 60 minutes in 0.1M HCl and water, respectively. Eudragit E100 1:4 solid dispersion has lower dissolution in 0.1M HCl and higher dissolution in water; the values are 73.6% and 87.3%. PVP-VA 1:2 solid dispersion has the dissolution of 60% and 65% at 60 minutes in 0.1M HCl and water, respectively. PVP-VA 1:4 solid dispersion has higher dissolution in 0.1M HCl and lower dissolution in water; the values are 64% and 53%. The different dissolution of fenofibrate from the two polymers is because of their different solubility and gelling tendency. When Eudragit E100 1:4 solid dispersion was administrated to beagle dogs, its relative bioavailability to micronization Lipanthyl capsule was 177.1%.Hot-melt extrusion is an excellent method to improve the dissolution and therefore the bioavailability of fenofibrate.