Study Of Metoprolol Succinate Sustained Release Tablets

Metoprolol is a selectiveβ1-receptor blocker of heart,which was developed at 1970s,used for the treatment of hypertension, angina pectoris, myocardial infarction, hypertrophic cardiomyopathy, aortic dissection, arrhythmia, hyperthyroidism, and so on. It is still a commonly used drug in clinical. Nowadays tartrate metoprolol and metoprolol succinate are the common metoprolol sustained-release tablets circulated on the market. There are more and more people who choose metoprolol succinate as model drug for sustained-release research for its low solubility. Metoprolol succinate was chosen as model drug in this paper, and powder of direct pressure was chosen as the method for preparing gel matrix sustained-release tablets and coated hydroxypropyl methylcellulose matrix sustained-released tablets.First, UV spectrophotometry was developed for the content and drug release;The mixture with MS,HPMC,CMC and other accessories' fluidity was studied, it showed that the mixture owned a good fluidity, can be direct powder compressed.Then, drug release during 0～20 hours in vitro was chosen as the standard to study the effect of single factor such as the viscosity and amount of HPMC,the type and amount of EC,the viscosity and amount of CMC,the type of fills,preparation methods,the hardness,pH of medium on the release of MS from gel matrix sustained-release tablets;Empirical Evidence showed that the speed of release reduced as the amount of HPMC and CMC increased;the release of drug can not be slowed down by the addition of EC;the viscosity of CMC,the type of fills,preparation methods and the hardness did not have a significant effect on the release. In addition, the effect of hardness, amount of PEG400, membrane weight, different pH of medium were studied; Empirical Evidence showed that membrane weight, amount of PEG400 had a significant effect on the release while the hardness, pH of medium, rotating basket did not have a significant effect.On this basis, the L9(34) orthogonal test was used to optimize the prescription , and at last, a gel matrix sustained-release tablets and a coated hydroxypropyl methylcellulose matrix sustained-released tablets were obtained. The release profile of gel matrix sustained-release tablets showed a good sustained release role, The release profiles of MS gel matrix sustained-release tablets followed Higuchi equation and Peppas equation well. It suggested that the release of MS could be described as the result of synergy between dissolution and drug diffusion, Peppas modification formula had been used to describe the percentage of dissolution and drug diffusion during drug release. The result showed that during the drug release, the percentage of drug diffusion reduced while percentage of dissolution increased.The release profiles of MS coated hydroxypropyl methylcellulose matrix sustained-released tablets showed that dissolution curve of drug release followed zero-order release pattern during the prophase of the release(0~4 hours) ,according with Fick diffusion, while the release of MS could be described as the result of synergy between dissolution and drug diffusion during the anaphase. The study of stability of the coated hydroxypropyl methylcellulose matrix sustained-released tablets showed that high humidity and high temperature had a significant effect on the release, while light did not have. Humidity and temperature should be paied attention to while conserving the coated hydroxypropyl methylcellulose matrix sustained-released tablets.