5-氟尿嘧啶聚乳酸缓释片的制备及其质量控制研究

摘要

目的 制备不同分子量和含药量的5-氟尿嘧啶-聚乳酸缓释片(5-Fu-PLA-DS),并对其进行质量控制研究. 方法 以分子量为3000,6000,10000,15000,20000的聚乳酸,制备含药量分别为1.5,2.5,3.0 mg,直径3.0mm、厚1.0 mm的15种圆形5-Fu-PLA-DS.观察缓释片的表面形态,测定载药率、包封率,并进行稳定性试验. 结果 制得的5-FU-PLA-DS为白色的圆片,质地均匀,表面光滑.PLA分子量越高,缓释片硬度越大,表面越光滑致密;含药量高的缓释片,表面可见颗粒状的微球痕迹.随着5-FU投药量的增加,载药率也逐步增大,3.0 mg含量组的平均载药率达到49.83％.15种5-FU-PLA-DS的平均包封率为(84.14±1.91)％.稳定性试验显示,随时间延长,缓释片载药量稍有降低,空气中比密封保存的载药量损失略多,表面出现微小裂纹. 结论 本法制作工艺简单,方法稳定,缓释片载药量和包封率均达到要求,所用定量检测方法准确可靠,可用于5-FU-PLA-DS的质量控制.%Objective To prepare 5-fluorouracil-polylactic acid sustained-release tablet(5-FU-PLA-DSs) containing different molecular weight polylactic acid and dosage,and to explore the quality control.Methods Fifteen species of round 5-FU-PLA-DS with 3 mm in diameter and 1 mm in thickness were prepared using PLA(molecular weight of 3 000,6 000,10 000,15 000,20 000),containing 1.5,2.5,3.0 mg 5-FU,respectively.The surface morphology and stability of each tablet were observed.The drug-loading rate and encapsulation efficiency were also tested.Results The prepared 5-FU-PLA-DS was white,uniform and smooth.The higher the molecular weight of PLA was,the greater the hardness of tablet was,and the smoother and denser the surface was.The imprint of microspheres was seen on the surface of 5-FU-PLA-DS with high drug content.The drug loading rate increased along with the raised dosage of 5-FU,and the average drug loading rate of 3.0 mg 5-FU reached 49.83％.The average encapsulation efficiency of 15 species of 5-FU-PLA-DS was (84.14 ± 1.91) ％.The stability test showed that the drug loading of 5-FU-PLA-DS was decreased slightly with the prolongation of time,and the loss of drug-loading rate was slightly less in sealed preservation than that exposed to air.Conclusion The technique for the preparation of 5-FU-PLA-DS is simple and stable.The quantitative method is accurate and reliable,which can be used for the quality control.