5-氟尿嘧啶缓释剂制备及体外释药性能比较*

背景：5-氟尿嘧啶-聚乳酸-乙醇酸共聚物缓释微球在青光眼滤过术后抑制滤过泡的瘢痕化具有潜在应用价值,但微球制备程序复杂,微球载药量一般较低,且药物突释现象明显。目的：比较乳化溶剂挥发法制备的5-氟尿嘧啶-聚乳酸-乙醇酸共聚物微球和喷雾成膜法制备的5-氟尿嘧啶-聚乳酸-乙醇酸共聚物缓释膜两种缓释剂的形态、载药量、体外释放规律,以探讨获得缓释效果较佳的5-氟尿嘧啶缓释剂制备方法。方法：以聚乳酸-乙醇酸共聚物为载体,采用乳化溶剂挥发法制备5-氟尿嘧啶-聚乳酸-乙醇酸共聚物微球;用喷雾成膜法制备5-氟尿嘧啶-聚乳酸-乙醇酸共聚物缓释膜。结果与结论：用乳化溶剂挥发法制备的微球外观圆整,粒径为(4 447.4±359.8) nm,载药量(8.67±0.37)%,包封率为(86.68± 1.92)%;用喷雾成膜法制备的缓释膜表面光滑平整,质量为(13.76±0.26) mg ,直径为6 mm ,厚度为(0.24±0.005) mm,载药量(23.76±0.37)%,包封率为(95.04±1.36)%。缓释剂制备过程未影响5-氟尿嘧啶的药物性能。微球体外释放突释明显,缓释膜的体外释放平稳持久,释放曲线符合Higuchi方程。结果表明缓释膜制备方法更简单易行,且能明显提高缓释剂的载药量,降低突释现象,同时延长药物的缓释时间。关键词：聚乳酸-聚乙醇酸;5-氟尿嘧啶;微球;缓释膜;体外释放doi:10.3969/j.issn.1673-8225.2012.08.022

Preparation and in vitro release test of slow-release 5-fluorouracil

BACKGROUND: Release microspheres of 5-fluorouracil-poly lactic-co-glycolic acid (5-Fu-PLGA) have a potential value in inhibition of scar formation of filtering bleb after glaucoma filtering surgery. However, the preparation of the microspheres is complicated, the drug loading is low, and the phenomenon of sudden release often exists.OBJECTIVE: To compare the shape characteristics, drug loadings and releasing characteristics in vitro of 5-Fu-PLGA microspheres prepared with the emulsion solvent evaporation method and 5-Fu-PLGA slow-release membranes prepared with the spray technique in order to investigate preparation methods of 5-Fu controlled release formulations with more obvious sustained release activity in vitro.METHODS: The 5-Fu-PLGA microspheres were prepared with the emulsion solvent evaporation method on the carrier of poly lactic-co-glycolic acid; the 5-Fu-PLGA slow-release membranes were prepared with spray technique on the carrier.RESULTS AND CONCLUSION: The prepared microspheres had the regular morphology. The average particle size was        (4 447.4±359.8) nm, while the encapsulation efficiency and the drug loading were (86.68±1.92)% and (8.668±0.37)% respectively. The obtained membranes were with smooth surface. The diameter, thickness, drug loading and encapsulation efficiency of the membranes were 6.0 mm, (0.24±0.005) mm, (23.76±0.37)% and (95.04±1.36)% respectively. The drug performance of 5-Fu had not been influenced during preparation. The microspheres had the obvious sudden release in vitro. The slow-release membranes had sustained release activity in vitro, and its release curve was accordance with the Higuchi equation. It is indicated that the preparation is simple, the drug loading is high, the phenomenon of sudden release can be decreased, and the release time is longer of the slow-release membranes.