Background:
Fenofibrate (FNB) is an effective drug for the treatment of hypertriglyceridemia,
hypercholesterolemia as well as mixed hyperlipidemia. However, due to its poor aqueous solubility,
FNB has the problem of poor oral absorption followed by low bioavailability.
Objective:
The aim of this research was to construct FNB amorphous solid dispersion employing PVP
VA64 as the carrier by hot-melt extrusion method, in order to improve the oral bioavailability. Additionally,
the cell transport experiment was conducted to further investigate the mechanism of promoted
osmotic absorption.
Methods:
The physical state of the obtained solid dispersion was characterized using SEM, DSC and
XRD. Besides, in vitro Caco-2 cells were used to evaluate the cytotoxicity of the carrier and mimic
gastrointestinal drug permeation. At last, in vitro dissolution test and in vivo bioavailability study were
also carried out.
Results:
The prepared FNB solid dispersion was found to be an amorphous state after hot-melt extrusion
process. In vitro cytotoxicity test on Caco-2 cells confirmed the excellent biocompatibility of the
carrier PVP VA64. Besides, transwell cell transport assay and in vitro dissolution test revealed that
FNB released from amorphous solid dispersion was equipped with an improved transmembrane transport
and dissolution rate. Moreover, pharmacokinetic study in beagle dogs showed that comparing with
commercial micronized product Lipanthyl®, the oral bioavailability of FNB solid dispersion was significantly
enhanced (2.45 fold).
Conclusion:
In conclusion, PVP VA64 can be regarded as a promising polymer to enhance the
bioavailability of poorly water-soluble drugs such as FNB processed by hot-melt extrusion. Besides,
investigations on the mechanism of the enhanced penetration are expected to lay a foundation on the
subsequent development of effective and practical solid dispersion.
Dissolution Enhancement of Raltegravir by Hot Melt Extrusion Technique
