Preparation And Evaluation Of Nitrendipine Controlled Release Tablets

Hypertension is the most dangerous disease that threatens human being and has close relationship with other cardiovascular diseases. How to effectively and low-costly cure the hypertension disease is the persistent goal of pharmacists. Nitrendipine is the object of this study. We investigated its basic pharmaceutical properties; prepared nitrendipine fast release and sustained release microspheres and its controlled released tablets; studied the influence of controlled release tablets on normal animal blood. Results are showed as follows:(1) Determination of nitrendipine solubility in different solvents: using UV spectrophotometric method, we determined the solubilities of nitrendipine in water, n-propanol-Phosphate buffer, 0.5% Sodium dodecyl sulfate solution. The results showed that nitrendipine has high solubility in 0.5% Sodium dodecyl sulfate solution, but almost insolvable in water, the solubility is 2.14×10-3mg/ml.(2) Lipid water partition coefficient of nitrendipine in different pH:Water dissolubility is necessary to drugs to transport into blood or body fluid, others needs lipid dissolubility to pass biological lipid membrane. The relative extent of lipid solubility and water solubility was defined as lipid water partition coefficient. This experiment determines lipid water partition coefficient through flask-HPLC method. The results showed that under near physiological environment, lipid water partition coefficient of nitrendipine is 3.72.(3) Preparation of Nitrendipine microspheres by Emulsion Solvent Diffusion Method. Fast-and sustained release microspheres of Nitrendipine were prepared by spherical crystallization technique using HPMCP and silica as fast release carriers,EC and Eudragit RS PO as retarding agents,respectively. The results showed that the dissolution from fast-release microspheres was significantly increased when the ratio of 1-HPMCP.silica was up to 1:2:2.The X-ray diffraction and differential thermal analysis results showed that the crystalline peak of Nitrendipine in both microspheres were disappeared,and there were no drug crystals on the surface of the microsphere under scanning electron microscope. It was assumed that the drug was present in amorphous form in solid dispersion.(4) Preparation of controlled release tablets: Estimated by dissolution rates, using orthogonal experimental design, we found out the best prescription of nitrendipine tablets. We determined the tablets properties of controlled release tablets and compared with marketed tablets. The results showed the tablets properties of controlled release tablets were complied with Ch.P.(5) The result showed that the controlled release tablet had better effects than the normal marketed tablets. It suggested that the quick releasing part dissolved quickly and were absorbed to reach the effective blood concentration. Then the controlled releasing part made the action steady and permanent.