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