Formation and stability of drug nanoparticles obtained from drug/PVP/SDS ternary ground mixture

Abstract

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 K17 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 nano- particle 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°C 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 ^m from the ternary GMs, whereas the nanoparticles were hardly gained from binary GMs, drug with PVP K17 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.