关键词: 缓释微球, 硝苯地平, 丙烯酸树脂, 释放速率

Abstract: Sustained-release Eudragit RL/RS microspheres encapsulating nifedipine were prepared using the acetone/liquid paraffin emulsion-solvent evaporation method. The influence of different preparation factors on release of the drug in vitro was investigated. The release rate of nifedipine from the microspheres increased with increasing Eudragit RL/RS ratio and stirring rate during the preparation, and with decreasing the polymer concentration of internal phase and microsphere size. It was found that a linear relationship existed between the microsphere size and the time of 50% drug release. The drug release rate increased with increasing nifedipine content from 4.2 to 16.7% and was more rapid than the dissolution rate of pure nifedipine particles. However, the release rate of the microspheres with 26.6% drug content decreased significantly and was slower than the dissolution rate of pure drug particles. This was attributed mainly to the nifedipine dispersion state in the microspheres as confirmed by the differential thermal analysis and X-ray diffraction study, which showed that nifedipine was present in an amorphous or molecular state in the microspheres with 4.2, 9.4 and 16.7% drug, whereas partly in the crystalline state in the microspheres with 26.6% drug. The amounts released for less than 70% nifedipine can be fitted to Higuchi square-root of time model, independent of polymer ratio, drug content and microsphere size.

Key words: Sustained-release microspheres, Nifedipine, Eudragit RL/RS, Release rate