Moribe K, Pongpeerapat A, Tozuka Y, Yamamoto K
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
Pharmazie. 2006 Feb;61(2):97-101.
Drug nanoparticle formation from a ternary ground mixture consisting of a poorly water-soluble drug, hydroxypropylmethylcellulose (HPMC), and sodium dodecyl sulfate (SDS) was investigated. Flurbiprofen, which did not show nanoparticle formation by co-grinding with polyvinylpyrrolidone (PVP) and SDS, was used as a model drug. Flurbiprofen, HPMC and SDS were mixed at the weight ratio of 1:3:1 and ground for 30 min in a vibrational rod mill. The drug nanoparticle formation was observed after the ternary ground mixture (GM) was dispersed into distilled water. Molecular interactions both between flurbiprofen and HPMC and between polymer and surfactant were found to be important factors for the nanoparticle formation. The GM was stable for 2 months at the storage condition of 40 degrees C and RH 22%. Mean particle size of the dispersed particles was still less than 350 nm after storage at 25 degrees C for 1 month. It was found that the drug/HPMC/SDS ternary grinding method was applicable not only for flurbiprofen but also for other hydrophobic drugs, such as tolbutamide, probucol, phenytoin and griseofulvin. The drug nanoparticles were also obtained using other cellulose derivatives, indicating that these pharmaceutical excipients were alternative to PVP for the grinding-induced drug nanoparticle formation.
研究了由难溶性药物、羟丙基甲基纤维素（HPMC）和十二烷基硫酸钠（SDS）组成的三元研磨混合物形成药物纳米颗粒的情况。氟比洛芬作为模型药物，它与聚乙烯吡咯烷酮（PVP）和SDS共研磨时未形成纳米颗粒。将氟比洛芬、HPMC和SDS按1:3:1的重量比混合，在振动棒磨机中研磨30分钟。将三元研磨混合物（GM）分散到蒸馏水中后观察到药物纳米颗粒的形成。发现氟比洛芬与HPMC之间以及聚合物与表面活性剂之间的分子相互作用是纳米颗粒形成的重要因素。GM在40℃和相对湿度22%的储存条件下稳定2个月。在25℃储存1个月后，分散颗粒的平均粒径仍小于350nm。发现药物/HPMC/SDS三元研磨方法不仅适用于氟比洛芬，也适用于其他疏水性药物，如甲苯磺丁脲、普罗布考、苯妥英和灰黄霉素。使用其他纤维素衍生物也获得了药物纳米颗粒，这表明这些药用辅料可替代PVP用于研磨诱导的药物纳米颗粒形成。
