超临界流体技术制备5-氟尿嘧啶聚乳酸微球  

Preparation of 5-fluorouracil-poly(L-lactide) microparticles by supercritical fluids technique

作　　者：蒲曦鸣[1] 陈爱政[1] 康云清[1] 尹光福[1] 廖立[1] 

机构地区：[1]四川大学材料科学与工程学院,四川成都610064

出　　处：《华西药学杂志》2006年第6期515-517,共3页West China Journal of Pharmaceutical Sciences

基　　金：教育部优秀青年教师基金资助项目(2002123)

摘　　要：目的 以5-氟尿嘧啶（5-Fu）为模型药物，制备氟尿嘧啶聚乳酸微球。方法 采用超临界流体强制分散溶液技术，将5-Fu微粒化，并制备5-Fu聚乳酸微球。通过扫描电镜、激光粒度仪检测微球外形及粒径分布；气相色谱法测定二氯甲烷的残留量；恒温振荡透析法检测药物的释放度。结果 25℃时，微粒化后5-Fu的乙醇饱和溶液浓度为6．43mg·ml^-1，较原料药的2．32mg·ml^-1有显著提高；所制备载药微球球形较好，表面光滑。粒径分布窄，粒径范围0．615—1．990μm，平均粒径为0．980μm；二氯甲烷残留量为0．0046％；微球载药量为2．6％。包封率为17．8％，药物释放呈缓释模式，无突释效应。结论 超临界流体强制分散技术是制备5-Fu聚乳酸微球的可行方法。OBJECTIVE To prepare 5 - fluorouracil - poly （ L - lactide） （5 - Fu - PLLA ） microparticles by supercritical fluids technique. METHODS 5 - Fu was first mieronized by solution -enhanced dispersion by supercritical CO2 （SEDS）. And then was used as model drug to prepare 5 - Fu - PLLA microparticles with PLLA in SEDS again. Scanning electron electron microscopy and zetasizer provided evidences about surface morphology, particle size and particle size distribution of the 5 - Fu - PLLA samples, Headspaee gas chromatography was performed to test the residual dichloromethane （DCM） in 5 - Fu - PLLA micropartieles. The constant temperature vibration dialysis assay was utilized to detect the rate of release. RESULTS The saturated concentration of mieronized 5 - Fu in ethanol at 25℃ was significantly increased from 2.32 mg·ml^-1 to 6.43 mg·ml^-1 compared with original 5 - Fu. The 5 - Fu - PLLA microparticles exhibited a rather spherical shape, smooth surface, and a narrow particle size distribution, ranged from 0. 615 μm to 1. 990 pan with a mean particle size of 0. 980 μm. The DCM residue in 5 -Fu- PLLA mieroparticles was 0. 0046%. The average amount of drug - loaded in 5 - Fu - PLLA micropartieles was 2.6%, while the corresponding average encapsulation efficiency was 17.8%. The drug release of 5 - Fu - PLLA micropartieles was mainly in a first - order kinetics without microparticles burst effect. CONCLUSION The SEDS process is a promising method to prepare 5 - Fu - PLLA.

关 键 词：超临界流体强制分散溶液技术 氟尿嘧啶 聚乳酸 微球 

分 类 号：R94[医药卫生—药剂学]