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

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.

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).

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 C(max) 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 μg/mL and 89.82 ± 46.46 μg/mL·h) and, F1, F2 reached their C(max) earlier than Antara® (F1: 2.0 ± 1.1 h; F2: 1.8 ± 1.2 h; Antara®: 6.0 ± 8.9 h).

These results show that the wet-milled-drug layering technique is a powerful method to improve the dissolution rate and the bioavailability of fenofibrate.