Fenofibrate solid dispersion pellets prepared by fluid-bed coating: physical characterization, improved dissolution and oral bioavailability in beagle dogs

Abstract

Abstract:

Solid dispersion of fenofibrate (FNB), a poorly water-soluble drug, was prepared by a fluid-bed coating technique with PEG 6000 as the carrier. The physical state was characterized by DSC and X-ray powder diffractometry, which indicated the existence of fenofibrate in crystalline form in the solid dispersion. In vitro dissolution was studied in water containing 1% sodium lauryl sulfate, FASSIF and FESSIF. Significant enhancement in dissolution was achieved at PEG/FNB ratio of 4/1 with near complete dissolution within 30 min. Moderate improvement in dissolution rate was observed at smaller PEG/FNB ratios. Oral bioavailability was studied in beagle dogs after oral administration of fenofibrate solid dispersion pellets by monitoring fenofibric acid in plasma. The oral bioavailability of PEG/FNB 3/1 and 4/1 solid dispersion pellets was improved by 3.4 and 4.4-fold as compared to Lipanthyl^®, a commercial micronized fenofibrate formulation. There was a strong dependence of oral bioavailability on the in vitro dissolution rate. Good correlation was observed between the in vivo absorption fraction and the in vitro dissolution rate in each of the dissolution media, water containing 1% sodium lauryl sulfate, FASSIF and FESSIF. It could be concluded that PEG/FNB solid dispersion pellets were able to improve the dissolution and oral bioavailability of fenofibrate.

Key words: Solid dispersion, Solid dispersion, Pellets, Pellets, Fluid-bed, Fluid-bed, Coating, Coating, Fenofibrate, Fenofibrate, Bioavailability, Bioavailability

CLC Number:

945.1

Supporting:

Ning Tang, Jie Lai, Ya-Pin Chen, Yi Lu^*, Wei Wu^*. Fenofibrate solid dispersion pellets prepared by fluid-bed coating: physical characterization, improved dissolution and oral bioavailability in beagle dogs[J]. .

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Fenofibrate solid dispersion pellets prepared by fluid-bed coating: physical characterization, improved dissolution and oral bioavailability in beagle dogs

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