Nanoparticulation of Poorly Water Soluble Drugs Using a Wet-Mill Process and Physicochemical Properties of the Nanopowders
Nanoparticulation of Poorly Water Soluble Drugs Using a Wet-Mill Process and Physicochemical Properties of the Nanopowders
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DOI：
10.1248/cpb.57.1050
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发表时间：
2009-10-01
影响因子：
1.7
通讯作者：
Nagata, Shunji
中科院分区：
文献类型：
--
作者：
Tanaka, Yusuke;Inkyo, Mitsugi;Nagata, Shunji
为了改善奥美拉唑、阿苯达唑和那那唑等水溶性较差的药物的溶出和口服吸收性能，采用ULTRA APEX湿磨仪添加不同的分散剂制备纳米粉末配方，并对其理化性能进行了评价。采用Pluronic F-108或F-68作为分散剂，得到纳米级药物颗粒浆液，用于所有模型药物的测试。奥美拉唑是一种热不稳定的药物，在湿磨过程中奥美拉唑纳米颗粒没有被降解，并且在湿磨后24小时内奥美拉唑纳米颗粒没有聚集。这些含有药物纳米颗粒的浆料经过冻干后，得到了细小的固体白色纳米粉末。扫描电子显微镜（SEM）显示模型药物被磨成纳米尺寸。x射线粉末衍射（XRPD）图和差示扫描量热法（DSC）曲线证实，所有研磨后的药物纳米粉均为结晶，尽管研磨后的阿苯达唑纳米粉将其转变为另一种晶体形式。使用ULTRA APEX MILL的湿磨提供了一种非常有效的方法来生产稳定的药物纳米粉末，并且是提高难水溶性和热不稳定药物的生物利用度的非常有用的工具。
In order to improve the dissolution and oral absorption properties of poorly water soluble drugs such as omeprazole, albendazole and danazol, various dispersing agents were added to prepare nanopowder formulations using an ULTRA APEX MILL, which is a wet-mill instrument, and their physicochemical properties were evaluated. Using Pluronic F-108 or F-68 as dispersing agents, slurries containing drug particles having nanometer size were obtained for all model drugs tested. Omeprazole, a heat labile drug, was not degraded by wet-milling and the omeprazole nanoparticles in a milled slurry did not aggregate for 24 h after wet-milling. After lyophilization of these milled slurries containing drug nanoparticles, fine solid white nanopowders were obtained. Scanning electron microscopy (SEM) suggested that the model drugs were milled into nanometer size. Xray powder diffraction (XRPD) patterns and Differential Scanning Calorimetry (DSC) curves confirmed that all milled drug nanopowders were crystalline, although milling of albendazole nanopowder transformed it to another crystal form. Wet-milling using an ULTRA APEX MILL offers a highly effective approach to produce stable drug nanopowders and is a very useful tool for bioavailability enhancement of poorly water soluble and heat labile drugs.