Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, PR China.
Drug Dev Ind Pharm. 2012 Nov;38(11):1344-53. doi: 10.3109/03639045.2011.650647. Epub 2012 Jan 28.
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.
本研究旨在探讨湿磨药物层层技术，该技术可显著提高非诺贝特丸的溶出速率和口服生物利用度。
将非诺贝特与 HPMC-E5 一起研磨，制备在微米和纳米范围内均匀悬浮液，然后将该悬浮液分层到糖球上以形成丸剂（F1、F2）。
粒径显著减小（从 1000μm减小至 1-10μm和 400nm），但悬浮液中的非诺贝特在 DSC 和 PXRD 研究中保留了其结晶度。F1-F2 和 Antara®胶囊在 60 分钟内 0.01mol/L SDS 溶液中的溶出速率分别为 55.47%、61.27%和 58.43%。此外，将 F1、F2 和 Antara®胶囊口服给予 6 只比格犬以确定生物利用度。F1、F2 的 Cmax（8.21±2.55 和 9.33±2.37μg/mL）和 AUC（0-t）（152.46±78.89 和 172.17±67.58μg/mL·h）均高于 Antara®（6.02±3.34μg/mL 和 89.82±46.46μg/mL·h），且 F1、F2 达到 Cmax 的时间早于 Antara®（F1：2.0±1.1h；F2：1.8±1.2h；Antara®：6.0±8.9h）。
这些结果表明，湿磨药物层层技术是提高非诺贝特溶出速率和生物利用度的有效方法。
