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目的:制备氟尿嘧啶(fluorouracil,FU)中空微球,并考察其体外释药行为。方法:在单因素考察基础上,选择主药FU(A)、乙基纤维素(ethyl cellulose,EC)(B)和聚乙烯吡咯烷酮(polyvinylpyrrolidone,PVP)(C)为因素,各因素取3个水平进行L9(33)拉丁正交设计试验,以释放度为指标优化处方工艺。结果:基于正交试验释放度指标的综合评分,筛选最佳处方配比为FU(0.6 g)、EC(1 g)、PVP(0.1 g);优化处方工艺制备的氟尿嘧啶中空微球在0.5、1、2、4、8、12、24 h的体外累积释放3批的平均百分率分别为(9.88±0.38)%、(14.64±0.09)%、(23.94±0.67)%、(39.21±0.36)%、(57.53±0.83)%、(67.99±0.58)%、(80.34±0.39)%,P值为0.001;其体外释药模型为:0~8 h按一级方程释药[Ln(1-Q)=-0.072 1t-0.563 7,r=0.998 6,P值为0.001],8~24 h按Higuchi方程释药(Q=0.102 3t1/2+0.398 7,r=0.999 9,P值为0.001)。结论:制备的FU中空微球体外缓释效果良好,有望为FU长效制剂的开发奠定基础。
Objective: To prepare hollow microspheres of fluorouracil (FU) and study its in vitro release behavior. Methods: On the basis of single factor study, the main drugs FU (A), ethyl cellulose (EC) (B) and polyvinylpyrrolidone (PVP) (C) Horizontal L9 (33) Latin orthogonal design test to release as an indicator to optimize the formulation process. Results: Based on the comprehensive evaluation of orthogonal test, the best prescription ratio of FU (0.6 g), EC (1 g) and PVP (0.1 g) was obtained. The optimum preparation of fluorouracil hollow microspheres at 0.5, The average percentage of three batches released cumulatively in vitro was (9.88 ± 0.38)%, (14.64 ± 0.09)%, (23.94 ± 0.67)%, (39.21 ± 0.36)% respectively at 1,2,4,8,12,24 h , (57.53 ± 0.83)%, (67.99 ± 0.58)% and (80.34 ± 0.39)%, respectively. The P value was 0.001. The in vitro release model was as follows: ) = - 0.072 1t-0.563 7, r = 0.998 6, P = 0.001] and Higuchi equation was used for 8-24 h (Q = 0.102 3t1 / 2 + 0.398 7, r = 0.999 9, P = 0.001) . CONCLUSION: The sustained-release effect of FU hollow microspheres prepared in vitro is good, which is expected to lay the foundation for the development of FU long-acting preparation.