Study On Nitrendipine Immediate-Release And 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. Nitrendipine, 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 solvent evaporation-deposition method, immediate-release pellets by centrifugal granulation technology, and sustained-release pellets by extrusion-spheronization technology, respectively. The aim of this paper is to improve or to control the dissolution rate in vitro and absorption in vivo of nitrendipine.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 concentration of related substance of nitrendipine.The solvent evaporation-deposition method was selected to prepare the solid dispersion of nitrendipine 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. Solid dispersion of nitrendipine 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 nitrendipine dissolved in the first 10 min was more than 80%, x-ray diffraction analysis (XRD) and differential scanning calorimetry (DSC)...