Study On Preparation, Quality Control And Stability Of Sim86-5Tablet

Hydrochloric Dronedarone, namely Sim86-5, is a class III antiarrhythmic drug, developed by Sanofi-Aventis. It can significantly reduce the incidence and mortality rate of patients with atrial fibrillation.With dissolution, angle of repose, bulk density, maximum hardness and friability as the main indexes, studies about the composition and preparation process of Hydrochloric Dronedarone were carried out in this text. The stress tests, in which Hydrochloric Dronedarone was placed under high temperature (60℃) or high humidity (RH90%±5%), or the condition of illumination(45001x±5001x) for ten days, showed that no index of the product had got significant change.Then, research was made to control the quality of Hydrochloric Dronedarone from two aspects, the quality and the stability.The quality study.①Hydrochloric Dronedarone was film-coated tablets, white or off-white after removing the coating, and solubility was over426mg/1000mL in the HCl(pH=1.0, containing0.5wt%of Tween80) and the PBS(pH=6.8, containing0.2wt%of Tween80).②Three different methods were used to identify Hydrochloric Dronedarone, wherein the other components didn’t interfere in the color reaction identification and HPLC identification, so those two methods could be used for the identification③A HPLC method was established for the determination of related substances and the content assay in the study. In the related substances study, linear range of Hydrochloric Dronedarone was0.122～6.097μg-mL-1and the correlation coefficient was0.9998. The HPLC method was proved to be accurate, reliable and easy to operate. Ten impurities were detected from three batches, all coming from the bulk drug. Every single impurity was less than0.05%, and the results of impurity purity were qualified. In the study of content, linear range of Hydrochloric Dronedarone was100.2～501.0μg-mL-1and the correlation coefficient was0.9999. The HPLC method was accurate, reliable and easy to operate. Results of content assay were100.9%,98.50%and99.19%, respectively.④The results of moisture content test were2.1%,2.1%and2.2%, respectively. The results of weight difference test, microbial limits test and polymorphs test were proved to be qualified.⑤Dissolution was determined by UV spectrophotometry in this study. Linear range of Hydrochloric Dronedarone was2.13～25.52μg·mL-1and the correlation coefficient was0.9998. The dissolution of three batches was all qualified. The stability study. The accelerated test and long-term test showed that appearance, dissolution, content, related substances of Hydrochloric Dronedarone had no significant change. Results were consistent with relevented requirements. The qualiy of Hydrochloric Dronedarone was proved to be stabile and it should be kept under seal at room temperature.