Formation and stability of drug nanoparticles obtained from drug/PVP/SDS ternary ground mixture
Formation and stability of drug nanoparticles obtained from drug/PVP/SDS ternary ground mixture
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DOI：
10.1016/s1773-2247(04)50082-5
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发表时间：
2004-11-01
影响因子：
5
通讯作者：
Yamamoto, K
中科院分区：
文献类型：
--
作者：
Pongpeerapat, A;Itoh, K;Yamamoto, K
本研究的目的是研究由难水溶性药物、聚乙烯吡咯烷酮（PVP）和十二烷基硫酸钠（SDS）组成的三元体系制备的药物纳米颗粒的稳定性和形成机制。通过粉末x射线衍射和zeta电位测量研究了药物纳米颗粒的物理状态。将水溶性较差的药物、PVP、KI7、SDS按重量比1:3:1混合，用振动棒磨机研磨30 min。本研究中使用的大多数低水溶性药物在三元混合物（GMs）分散到蒸馏水中后，在亚微米区域形成纳米颗粒。以苯妥英、普罗布考和灰黄霉素为研究对象，研究了药物纳米颗粒形成的稳定性和机理。当三元GMs分散在溶解介质中时，也观察到药物纳米颗粒的形成。在25℃下贮存1个月后，分散颗粒的平均粒径仍小于250 nm，表明药物纳米颗粒具有长期稳定性。药物含量的定量测定表明，在三元GMs中，93%以上的药物被回收为小于0.8 μ m的细颗粒，而在二元GMs、PVP KI7或SDS中几乎没有得到纳米颗粒。对超离心积累的分散颗粒进行粉末x射线衍射分析表明，分散颗粒以细晶形式存在。zeta电位测试表明，PVP和SDS在纳米颗粒表面的吸附有效地抑制了纳米颗粒的团聚，使得纳米颗粒在水介质中稳定存在。
The purpose of this study was to investigate the stability and the formation mechanism of drug nanoparticles obtained from a ternary system consisting of poorly water-soluble drug, polyvinylpyrrolidone (PVP), and sodium dodecyl sulfate (SDS). The physical state of drug nanoparticles was investigated by powder X-ray diffraction and zeta potential measurements. Poorly water-soluble drug, PVP KI7 and SDS were mixed at a weight ratio of 1:3:1 and ground for 30 min by vibrational rod mill. Most of the poorly water-soluble drugs used in this study provided the nanoparticle formation in the submicron region after the ternary ground mixtures (GMs) were dispersed into distilled water. Stability and mechanism of drug nanoparticle formation were investigated by focusing on phenytoin, probucol and griseofulvin. The drug nanoparticle formation was also observed when the ternary GMs were dispersed in the dissolution media. The mean particle size of the dispersed particles was still less than 250 nm after storage at 25 degreesC for one month, indicating the long-term stability, of drug nanoparticles. The quantitative determination of drug content demonstrated that more than 93% of the drug was recovered as fine particles smaller than 0.8 mum from the ternary GMs, whereas the nanoparticles were hardly gained from binary GMs, drug with PVP KI7 or SDS. Powder X-ray diffraction analysis for the dispersed particles accumulated by ultracentrifugation indicated that the dispersed particles existed as fine crystals. The zeta potential measurement revealed that the obtained nanoparticles were stable in aqueous media because the particle agglomeration was effectively inhibited by the adsorption of both PVP and SDS onto the particle surface.