Improved dissolution rate and bioavailability of fenofibrate pellets prepared by wet-milled-drug layering.

Objective: The objective of this study is to investigate the wet-milled-drug layering process which could significantly improve the dissolution rate and oral bioavailability of fenofibrate pellets.Methods: Fenofibrate was milled with HPMC-E5 to prepare a uniform suspension in the micrometer and nanometer range, and this suspension was then layered on to sugar spheres to form the pellets (F1, F2).Results: The particle size was significantly reduced (from 1000 µm to 1–10 µm and 400 nm) but the fenofibrate in suspension retained its crystallinity from the results of DSC and PXRD investigations. The dissolution rate of F1-F2 and Antara® capsules was 55.47 %, 61.27 % and 58.43 %, respectively, in 0.01 mol/L SDS solution over 60 min. In addition, F1, F2, and Antara® capsules were given orally to 6 beagle dogs to determine the bioavailability. The Cmax of F1, F2 (8.21 ± 2.55 and 9.33 ± 2.37 μg/mL)and the AUC(0−t) of F1, F2 (152.46 ± 78.89 and 172.17 ± 67.58 μg/mL·h)were higher than those of Antara® (6.02 ± 3.34 ...