自微乳缓释片中西罗莫司的稳定性提高研究

发布时间：2018-04-22 13:44

  本文选题：西罗莫司 + 自微乳给药系统　； 参考：《中国医院药学杂志》2017年17期

【摘要】：目的:提高自微乳缓释片中西罗莫司(SRL)的稳定性。方法:考察SRL在不同pH条件下的稳定性,再利用柠檬酸或苹果酸调节自微乳的pH并制备缓释片,利用铝塑材料对自微乳缓释片进行包装,考察在高温、高湿和强光照射条件下SRL的含量变化。结果:SRL原料药在高温、高湿和强光照射条件下稳定,市售片中的SRL含量仅在强光照射下少量降低,而自制自微乳缓释片中的SRL在高温和强光照射试验下均不稳定。自微乳的碱性环境可能是导致SRL高温不稳定的主要原因,测定发现SRL稳定的pH为4.5~5.8。利用苹果酸和柠檬酸均可提高自微乳中药物的高温稳定性,使(40±2)℃条件下,缓释片中药物的含量达到98%以上。苹果酸的吸湿性导致片重增加,表面有湿润感,因此确定选用0.20%的柠檬酸作为pH调节剂。光照对自微乳缓释片中的药物有不利影响,采用铝塑包装(内含暗黑色避光层),可使SRL含量由94.06%提高至99.37%。综合应用0.20%柠檬酸和铝塑包装所得的SRL自微乳缓释片在高温、高湿和强光照射条件下,10 d时的含量均在99%以上。结论:经铝塑包装的含0.20%柠檬酸的SRL自微乳缓释片,在高温、高湿、强光照射条件下均具有良好的稳定性。
[Abstract]:Objective: to improve the stability of sirolimus SRL in self-emulsion sustained release tablets. Methods: the stability of SRL under different pH conditions was investigated. The pH of self-microemulsion was adjusted by citric acid or malic acid and sustained release tablets were prepared. The change of SRL content under high humidity and strong light irradiation. Results under the conditions of high temperature, high humidity and strong light irradiation, the content of SRL in commercial tablets decreased only slightly, while the SRL in self-made self-microemulsion sustained release tablets was unstable under high temperature and strong light irradiation. The alkaline environment of the self-microemulsion may be the main cause of the instability of SRL at high temperature. It was found that the stable pH of SRL was 4.5 ~ 5.8. Both malic acid and citric acid could improve the high temperature stability of the drug in the microemulsion, and the content of the drug in the sustained-release tablets could reach more than 98% at 40 卤2 鈩，

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