新型可降解聚酯材料地西泮缓释微球的研制  

STUDY ON PREPARATION OF DIAZEPAM-POLY(HYDROXYBUTYRATE- HYDROXYVALERATE)/POLYLACTIDE MICROSPHERES

作　　者：陈建海[1] 陈昆[2] Shagufla M 陈志良 侯连兵 

机构地区：[1]第一军医大学南方医院药理研究所,广东广州510515 [2]南方医院信息科,广东广州510515 [3]Department of Pharmaceutical Science

出　　处：《药学学报》2000年第8期613-616,共4页Acta Pharmaceutica Sinica

基　　金：军队医药卫生研究基金!(98M 0 65)

摘　　要：目的　优化制备工艺 ,用新型的生物可降解材料聚羟基丁酸酯—羟基戊酸酯共聚物 (PHBV)与D ,L 聚乳酸 (PLA)共混物为基材制备以地西泮 (diazepam ,DZP)为模型药物的缓释微球 (MS)。方法　用正交设计优化微球制备工艺 ,用扫描电镜 (SEM)观察微球表面形态。对微球粒径及其分布、体外释药、稳定性及在动物体内药动学进行了测定。结果　微球平均粒径为 (2 0 45± 4 5 0 ) μm ,粒径在 15 5～ 35 2 μm占总数 88%以上。载药量为 (16 95± 0 80 ) % ,包封率为 (6 9 6 8± 1 13) % ;体外释药方程为Q =2 70 2 7t+13 5 0 (γ =0 982 7) ,动物体内实验表明 ,微球的血药浓度 时间曲线下面积AUC是溶液对照组的 2 35倍 ,平均驻留时间MRT是对照组的 3 6 2倍。微球在冰箱4℃与室温 (2 0～ 2 5℃ )条件下性质稳定。结论　微球制备工艺稳定 ,与DZP针剂相比 ,具有明显缓释作用。AIM To optimize the preparation of sustained release microspheres (MS) using the biodegradable materials-poly(hydroxybutyrate-hydroxyvalerate)/ D,L -polylactide blend as the carriers and diazepam (DZP) as a model drug. METHODS The orthogonal test design was used to optimize the technology of preparation with good reproducibility. The surface morphology of the microspheres was observed by scanning electron microscope. The mean diameter and the size distribution of MS, drug release in vitro , stability and pharmacokinetics in rabbit were examined. RESULTS The average particle size was (20 45±4 50) μm with over 88% of the MS being in the range of 15 5～35 2 μm; the drug loading and the incorporation efficiency were 16 95%±0 80% and 69 68%±1 13% respectively; The drug release behavior in vitro could be expressed by the following equation: Q =3 2916 t +13 61 (γ=0 9827); Experiments in rabbits indicate that the area under the plasma concentration-time curve (AUC) was 2 35 times higher than that of DZP solution. The mean residence time (MRT) was 3 62 times longer compared with the original drug DZP solution. The microspheres were stable for 3 months at 4℃ and at room temperature. CONCLUSION The technology of preparation was successful and DZP-PHBV/PLA-MS showed significant sustained release.

关 键 词：地西泮 缓释微球 PHBV 可降解聚酯材料 

分 类 号：R944.9[医药卫生—药剂学]