In vitro and in vivo evaluation of fenofibrate solid dispersion prepared by hot-melt extrusion.
OBJECTIVE
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.


METHODS
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.


RESULTS
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%.


CONCLUSIONS
Hot-melt extrusion is an excellent method to improve the dissolution and therefore the bioavailability of fenofibrate.
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, PR China.
Haibing
H
He
Rui
R
Yang
Xing
X
Tang
D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018592:Cross-Over Studies; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods; D011345:Fenofibrate / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D006358:Hot Temperature; D066298:In Vitro Techniques; D014961:X-Ray Diffraction
D011345:Fenofibrate