Pharmaceutical and Analytical Development, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA.
Int J Pharm. 2011 May 16;409(1-2):260-8. doi: 10.1016/j.ijpharm.2011.02.051. Epub 2011 Mar 1.
The purpose of this study was to develop a nanosuspension of a poorly soluble drug by nanomilling process using wet media milling to achieve superior in vitro dissolution and high in vivo exposure in pharmacokinetic studies. A promising nanosuspension was developed with Vitamin E TPGS based formulation with particle size in the nano range. Although the formulation showed significant improvement during in vitro dissolution and in vivo plasma level, probably due to the strong hydrophobic interaction between Vitamin TPGS and the drug molecule, crystal growth was observed during stability studies. A systematic study was done with different combinations of solubilizer/stabilizer system in order to obtain a more stable nanosuspension. Hydroxypropyl methylcellulose (HPMC 3 cps) was found to stabilize the nanosuspension by better surface coverage due to stronger interaction with the drug as compared to other stabilizers used in this study.
本研究的目的是通过湿介质研磨纳米研磨工艺开发一种难溶性药物的纳米混悬剂，以在药代动力学研究中实现优异的体外溶解度和高体内暴露。通过使用基于维生素 E TPGS 的配方，制备了一种具有纳米级粒径的有前途的纳米混悬剂。尽管该配方在体外溶解度和体内血浆水平方面显示出显著改善，但可能由于维生素 TPGS 与药物分子之间的强疏水性相互作用，在稳定性研究中观察到晶体生长。进行了系统研究，以获得更稳定的纳米混悬剂，研究了不同的增溶剂/稳定剂系统的组合。与本研究中使用的其他稳定剂相比，羟丙基甲基纤维素（HPMC 3 cps）由于与药物的相互作用更强，因此能够更好地覆盖表面，从而稳定纳米混悬剂。
