5-氟尿嘧啶聚乳酸缓释片的处方筛选及体外释药机制研究  

Formulation Screening of 5-fluorouracil Polylactic Acid Sustained-release Tablet and Study on Its in vitro Drug-release Mechanism

作　　者：崔丽珺[1] 黄洁 李兴华[3] 康前雁[1] 

机构地区：[1]西安交通大学医学院第一附属医院眼科,西安710061 [2]西安市食品药品检验所,西安710054 [3]西安交通大学医学院第二附属医院药剂科,西安710004

出　　处：《中国药房》2017年第28期3969-3972,共4页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81300765)

摘　　要：目的:筛选5-氟尿嘧啶(5-FU)聚乳酸(PLA)缓释片(5-FU-PLA-DS)的处方,研究其体外释药机制。方法:采用紫外分光光度法测定释放介质中5-FU含量,以模拟体液为释放介质,于37℃水浴中进行体外释放试验。以分子量分别为3 000、6 000、10 000、15 000和20 000的PLA,制备载药量分别为1.5、2.5、3.0 mg/片,直径3.0 mm、厚1.0 mm的15种圆形5-FU-PLA-DS;以有效浓度持续释放时间与累积释放度为指标,筛选最优处方。采用扫描电镜观察5-FU-PLA-DS释药后的形态,评价其释药机制。结果:最优处方中PLA的分子量为20 000,载药量为3.0 mg/片;所制5-FU-PLA-DS可释放119 d,累积释放度为100.63%,有效浓度持续释放91 d。扫描电镜观察显示,5-FU-PLA-DS表面的微球最先接触释放介质而进行蚀解、释放药物,待外层的微球和微球之间的PLA降解后才逐渐暴露出内层的微球进行释药,其释药机制主要为溶蚀和扩散。结论:成功制得5-FU-PLA-DS,其有效浓度持续释放时间长,能够由外向内有步骤地降解,实现不同层次微球的非同步释药。OBJECTIVE：To screen the formulation of 5-fluorouracil（5-FU）polylactic acid（PLA）sustained-release discs（5-FU-PLA-DS）,and study its in vitro drug-release mechanism. METHODS：UV spectrophotometry was used to determine the 5-FU content in the release medium. Using simulate body fluid as release medium,in vitro drug-release test was conducted under 37 ℃water bath. Using PLA with molecular weight of 3 000,6 000,10 000,15 000,20 000,15 species of round 5-FU-PLA-DS with drug containing of 1.5,2.5,3.0 mg/piece and 3.0 mm in diameter and 1.0 mm in thickness were prepared. Using effective concentration sustained release time and cumulative release rate as indexes,the optimal formulation was screened. The form of 5-FU-PLADS was observed by scanning electron microscopy after release,and its release mechanism was evaluated. RESULTS：In the optimal formulation,the PLA molecular weight was 20 000 and drug containing was 3.0 mg/piece. The prepared 5-FU-PLA-DS can release for 119 d,with cumulative release degree of 100.63% and effective concentration sustained for 91 d. Scanning electron microscopy showed that the microspheres at the surface were degraded to the release medium first,and then the microspheres of inner layer exposed and release drug gradually after PLA degraded. The main mechanism of drug-release was melting and diffusion. CONCLUSIONS：5-FU-PLA-DS is successfully prepared,with long release time in effective concentration,can be degraded step by step from outside to inside and achieve non-synchronous drug-release of microspheres at different layers.

关 键 词：5-氟尿嘧啶 聚乳酸 缓释片 体外释放度 扫描电镜 

分 类 号：R943[医药卫生—药剂学]