盐酸川芎嗪肺靶向微球的研究

用乳化法制备盐酸川芎嗪明肢微球,优化了工艺。对微球的外观、粒径与其分布、含量、体外释药、稳定性及体内分布等进行研究。结果表明平均粒径为12.65μm,粒径范围5.0～24.9μm占总数的87.5%,球内含药量平均为16.49%±0.49%(n=3),冰箱或室温放置稳定,体外释药符合一级动力学规律,释药t_1/2比原药延长约5倍。小鼠静注微球后20 min,在肺内的相对分布百分率明显高于其它组织与血液,与溶液对照组相比,提高近6倍。

STUDIES ON GELATIN MICKOSPHERE LOADED LIGUSTRAZINE HYDROCHLORIDE FOR LUNG TARGETING

The effect of ligustrazine hydrochloride (LTH) on depressing pulmonary arteryhypertension has been proved in recent studies.In an attempt to prepare a lung targeting dosage form,ligustrazine hydrochloride gelatin microspheres (LTH-GMS)were prepared by the method of emulsionprocess,using 2:1 as the weight ratio of LTH to gelatin. The preparation technique was optimizedand the apl1earance,particle size and size distribution,LTH content,in vitro release,stability,and in vivo distribution of LTH-GMS were studied.The results showed that the mean diameter of LTH-GMSmeasured by Coulter counter was 12.65μm,87.5% of the microspheres ranging from 5 to 24.9μm.The average content of LTH in LTHGMS was 16.49%±0.49%(n=3)with an average extent ofentrapment of abOut 89%and the LTH-GMS were stable for three months when stored in refrigeratoror at rcom temperature. The release profile in vitro(pH 7.8～8.0 phosphate buffer)can be describedby first-order kinetic equation. The release t_1/2 of LTH when given LTH-GMS was about 6 times asmuch as that of original LTH, The relative distribution percentage of LTH-GMS in lung whendetermined 20 min after iv administration to mice was significantly higher than those of LTH-GMS inother tissues and blood,and was about 6 times as much as that of the LTH solution control group inlung under the same conditions.