Study On Nimodipine Sustained-Release Pellets

The enhancement of dissolution rate in vitro and oral bioavailability in vivo of poorly water-soluble drugs remains one of the most challenging aspects of modern pharmaceutics. Nimodipine, which is a dihydropyridines calcium channel antagonist and has a very low solubility in vitro, was selected as the model drug to prepare solid dispersion by hot-melt extrusion technique, immediate-release pellets by centrifugal granulation technology, and sustained-release pellets by a fluid-bed spray processor, respectively. The aim of this paper is to improve or to control the dissolution rate in vitro and absorption in vivo of nimodipine.Ultraviolet spectrophotometry (UV) method was developed for in vitro assay of drug content and release of pellets.Hot-Melt extrusion technique was selected to prepare the solid dispersion of nimodipine after comparing several methods by dissolution studies. By means of the influence factors test, formulation and technology factors on drug release from solid dispersion were investigated . Solid dispersion of nimodipine with optimal formulation was prepared under optimal technology and it's dissolution and physical state property were characterized. Dissolution studies showed that the percentage of nimodipine dissolved in the first 5min was more than 85%, x-ray diffraction analysis (XRD) , differential scanning calorimetry (DSC) thermograms and fourier transform-infrared spectroscopy (FT-IR) showed the absence of diffraction peaks and melting peaks, which indicating the presence of nitrendipine in amorphous form.Immediate-release pellets of nimodipine were prepared by centrifugal granulation technology, and methods used to evaluate the quality of pellets were developed. Appling dissolution profiles of pellets as main index, formulation and technology factors of preparing pellets were investigated and optimized.Sustained-release pellets of nimodipine were prepared by a fluid-bed spray processor . Appling drug release profiles as main index, technology factors of preparing pellets were investigated, and formulation factors of pellet's coat were investigated and optimized by the influence factors test .The investigation on the drug release mechanisms indicated that the drug release profiles in vitro from sustained-release pellets mainly followed Hixson-Crowell erosion equation.