Study On Nifedipine Sustained-Release Pellets

In this study two kinds of nifedipine 24h sustained-released pellets were prepared by extrusion-spheronisation technology incorporated with solid dispersion technology and by liquid layering fluid-bed coating technology, respectively. Preparation methods for pellets, the sustained-release coating process for pellets, stability, pharmacokinetics were studied and validation in vivo as well. Results indicated that the sustained-release pellets had good appearance and stability, the drug was able to release in vitro over 24h.Ultraviolet spectrophotometry (UV) method was developed for in vitro assay of drug content and release of pellets. High-performance liquid chromatography (HPLC) method with UV detector was applied to determine the solubility of nifedipine in various kinds of solution.The solvent-melting method was selected to prepare the solid dispersion of nifedipine after comparing several methods by dissolution studies. By means of the influence factors test and orthogonal design test, formulation and technology factors on drug release from solid dispersion were investigated and optimized. The relationship between dissolution rates of nifedipine , carrier molecular weight and drug/carrier ration was approached. Dfferential scanning calorimetry (DSC) thermograms showed the absence of diffraction peaks and melting peaks, which indicated the presence of nifedipine in amorphous form.Sustained-release pellets of nifedipine were prepared by extrusion-spheronization technology, and methods used to evaluate the quality of pellets were developed. Appling micromeritical properties and dissolution profiles of pellets as main index, formulation and influence factors of preparing pellets were investigated and optimized. The investigation on the drug release mechanisms indicated that drug release from sustained-release pellets was mainly diffusion-controlled. Results of stability studies on sustained-release pellets of nifedipine showed that the pellets were stable when exposed to high temperature, but sensitive to high humidity and light.Immediate-release pellets of nifedipine were prepared by liquid layering technology and which were coated by a fluid-bed spray processor subsequently. The coating process variables were determined and controlled by dissolution profiles of pellets as main index. Eudragit(?) NE 30D was selected for the excellent drug release character. The anti-tacking agent talc, coating...