Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, PO Box 56, 00014 Helsinki, Finland.
Int J Pharm. 2011 Jun 15;411(1-2):215-22. doi: 10.1016/j.ijpharm.2011.03.050. Epub 2011 Mar 31.
Nanosizing techniques are important tools for improving the bioavailability of water insoluble drugs. Here, a rapid wet milling method was employed to prepare nanosuspensions: 4 types of stabilizers at 4 different concentrations were tested on 2 structurally different drug compounds: indomethacin and itraconazole. Photon correlation spectroscopy (PCS) results showed that the finest nanosuspensions were obtained when 80 wt% (to drug amount) pluronic F68 was the stabilizer for indomethacin and 60 wt% pluronic F127 for itraconazole. Compared to physical mixtures, dissolution rates of the nanosuspensions showed significant increases. The morphology of nanoparticles was observed by transmission electron microscopy (TEM). Crystalline state of the drugs before and after milling was confirmed using differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). The physical and chemical stabilities of the nanosuspensions after storage for 2 months at room temperature and at 4°C were investigated using PCS, TEM and HPLC. No obvious changes in particle size and morphology and no chemical degradation of the drug ingredients were seen.
纳米化技术是提高水不溶性药物生物利用度的重要手段。在这里，采用了一种快速湿磨法来制备纳米混悬剂：在 2 种结构不同的药物化合物（吲哚美辛和伊曲康唑）上测试了 4 种不同浓度的稳定剂。光相关光谱（PCS）结果表明，当稳定剂为 80wt%（相对于药物量）的泊洛沙姆 F68 时，可获得最细的纳米混悬剂，而对于伊曲康唑则为 60wt%的泊洛沙姆 F127。与物理混合物相比，纳米混悬剂的溶解速率显著提高。通过透射电子显微镜（TEM）观察了纳米粒子的形态。使用差示扫描量热法（DSC）和 X 射线粉末衍射（XRPD）确认了药物在研磨前后的结晶状态。在室温下和 4°C 下储存 2 个月后，使用 PCS、TEM 和 HPLC 研究了纳米混悬剂的物理和化学稳定性。未观察到粒径和形态的明显变化，药物成分也未发生化学降解。
