Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hiroshima International University, Kure, Hiroshima, Japan.
Drug Dev Ind Pharm. 2012 Aug;38(8):1015-23. doi: 10.3109/03639045.2011.637051. Epub 2011 Nov 26.
To improve the dissolution and oral absorption properties of probucol, a novel wet-milling process using the ULTRA APEX MILL was investigated. The particle size of bulk probucol powder was 17.1 µm. However, after wet-milling with dispersing agents such as Gelucire 44/14, Gelucire 50/13, vitamin E-TPGS, and Pluronic F-108, the probucol particle sizes decreased to about 77-176 nm. Scanning electron microscopy (SEM) analysis also suggested that the probucol particles were successfully milled into the nanometer range. An in vitro dissolution study showed that the dissolution rates of all nanopowders were several folds higher than those of the corresponding mixed powders. When orally administered to rats, the AUC values of probucol nanopowders treated with Gelucire 44/14 and 50/13, and vitamin E-TPGS were about 3.06-3.54-folds greater than that of the bulk powder. Therefore, through this study, we have developed a new pharmaceutical technique to improve the dissolution rate and oral absorption of probucol using the ULTRA APEX MILL by wet-milling with various dispersing agents.
为了改善普罗布考的溶解和口服吸收性能，研究了一种使用 ULTRA APEX MILL 的新型湿磨工艺。普罗布考原料药的粒径为 17.1μm。然而，在用 Gelucire 44/14、Gelucire 50/13、维生素 E-TPGS 和 Pluronic F-108 等分散剂进行湿磨后，普罗布考的粒径减小到约 77-176nm。扫描电子显微镜（SEM）分析也表明普罗布考颗粒成功地被磨碎到纳米级。体外溶解研究表明，所有纳米粉末的溶解速率都比相应的混合粉末高几倍。当口服给予大鼠时，用 Gelucire 44/14 和 50/13 以及维生素 E-TPGS 处理的普罗布考纳米粉末的 AUC 值约为原料药的 3.06-3.54 倍。因此，通过这项研究，我们使用 ULTRA APEX MILL 通过与各种分散剂湿磨，开发了一种新的制药技术，以提高普罗布考的溶解速率和口服吸收。
