Study On Nitrendipine In-situ Forming Gel And Biodegradable Microspheres

Recently, the studies on sustained/controlled-release injection have become focuses in pharmaceutical studies. In these studies, the formulations such as microspheres, microcapsules, nanoparticles and gels were made containing drugs, in which macromolecules were used as carriers and new pharmaceutical techniques were introduced. Nitrendipine, which is an effective antihypertension drug and has a very low solubility in vitro, was selected as the model drug to prepare in-situ forming gel and biodegradable microspheres by grinding method and quasi-emulsion solvent diffusion method, respectively. The aim of this paper is to prolong the drug's action time and decrease administration times.High performance liquid chromatography (HPLC) method was developed for in vitro assay of drug content in NTD in-situ forming gel and microspheres. Ultraviolet-visible spectrophotometry (UV) method was used to study the release of drug from the two formulations. HPLC method was also applied to determine the concentration of the related substance of nitrendipine.Grinding method was selected to prepare in-situ forming gel of nitrendipine, and the evaluation indexes were found to control the quality of nitrendipine in-situ forming gel. By means of the single factor test, formulation factors on drug content and release from in-situ forming gel were investigated and optimized. The in-situ forming gel of nitrendipine with optimum formulation was prepared and it's release, stability, safety and other physical and chemical property were characterized. The release test disclosed that the release of drug from the formulation was mainly diffusion-controlled and erosion-controlled. Influence parameter studies showed that the formulation of nitrendipine was stable under high temperature, but unstable under high humidity and high light. By accelerating test, the stability of the formulation was strengthened in ampoule. The safety test showed that the formulation had no acute toxicity and hemolysis, but had slight stimulation. The in-situ forming gel of nitrendipine could be used as the muscular injection.The biodegradable microspheres of nitrendipine were prepared by quasi-emulsion solvent diffusion method, and the evaluation indexes were found to control the quality of the microspheres. Applying drug loading, incorporation efficiency and release profiles as main indexes, formulation factors and technology factors were investigated and optimized by the single factor test. The...