title: Improved dissolution rate and bioavailability of fenofibrate pellets prepared by wet-milled-drug layering.
abstract: 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).
  
  
  CONCLUSIONS
  These results show that the wet-milled-drug layering technique is a powerful method to improve the dissolution rate and the bioavailability of fenofibrate.
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, PR China.
authors.forename: Puxiu
authors.initials: P
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Luo
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Miao
authors.forename: Lin
authors.initials: L
authors.lastname: Ying
authors.forename: Haibing
authors.initials: H
authors.lastname: He
authors.forename: Cuifang
authors.initials: C
authors.lastname: Cai
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D004285:Dogs; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D004356:Drug Storage; D011345:Fenofibrate / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D012995:Solubility; D013499:Surface Properties; D013817:Thermography; D014961:X-Ray Diffraction
chemical_list: D000960:Hypolipidemic Agents; D011345:Fenofibrate