GRINDING

POORLY WATER-SOLUBLE DRUG

POLYVINYLPYRROLIDONE

SODIUM DODECYL SULFATE

修了年:2006

千大院医薬甲博第33号

Ternary ground mixtures (GMs) of drug/PVP K17/SDS were prepared with seventeen poorly water-soluble drugs. Most of the poorly water-soluble drugs provided the nanoparticle formation after dispersing the ternary GMs into distilled water. Stability of drug nanoparticles in suspension was investigated by focusing on phenytoin, probucol and griseofulvin. Mean particle size of the dispersed particles was still less than 250 nm after the storage at 25°C for 1 month, indicating the long-term stability of drug nanoparticles. Quantitative determination of drug content demonstrated that more than 930f drug was recovered as nanoparticles smaller than 0.8 ?m from the ternary GMs, whereas the nanoparticles were hardly gained from binary GMs, drug with PVP K17 or SDS.Effects of PVP molecular weight on the nanoparticle formation and intermolecular interactions among probucol/PVP/SDS ternary GM were investigated. Particle size analysis demonstrated that probucol nanoparticles were obtained effectively when the low molecular weight PVP was used. The PXRD results indicated that drug amorphization during grinding was accelerated with decrease in PVP molecular weight. The solid-state 13C CP/MAS NMR results indicated that low molecular weight PVP interacted with probucol and SDS more strongly than the high molecular weight PVP in the ternary GM....