Kumar Varun, Wang Lei, Riebe Mike, Tung Hsien-Hsin, Prud'homme Robert K
Chemical Engineering Department, Princeton University, Princeton New Jersey 08544, USA.
Mol Pharm. 2009 Jul-Aug;6(4):1118-24. doi: 10.1021/mp900002t.
The successful formulation of itraconazole and odanacatib into nanoparticle form with diameters of 145 and 350 nm, respectively, using rapid, block copolymer-directed precipitation is presented. These are the smallest stable nanoparticles that have been reported for these compounds. The difference in size of the nanoparticles for the two compounds is explained by the difference in nucleation rate and its dependence on supersaturation. The conditions for stability after formation are presented: storage at 5 degrees C and removal of residual processing solvent. These requirements are explained in terms of solute solubility and its dependence on both temperature and solvent concentration. The theory of Ostwald ripening provides the framework for understanding the differences in stability observed for the two compounds. The dynamics of the hydrophobic polymer block plays a major role in long-term stability as demonstrated by the behavior of nanoparticles stabilized by poloxamer vs polystyrene-b-polyethylene oxide polymers.
本文介绍了使用快速的、嵌段共聚物导向沉淀法，成功将伊曲康唑和odanacatib分别制成直径为145纳米和350纳米的纳米颗粒。这是已报道的这两种化合物最小的稳定纳米颗粒。两种化合物纳米颗粒大小的差异是由成核速率的差异及其对过饱和度的依赖性来解释的。文中给出了形成后稳定性的条件：在5摄氏度下储存并去除残留的加工溶剂。这些要求是根据溶质溶解度及其对温度和溶剂浓度的依赖性来解释的。奥斯特瓦尔德熟化理论为理解两种化合物稳定性差异提供了框架。疏水性聚合物嵌段的动力学在长期稳定性中起主要作用，泊洛沙姆与聚苯乙烯-b-聚环氧乙烷聚合物稳定的纳米颗粒行为证明了这一点。
