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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。
OBJECTIVE To optimize the preparation process and prepare diazepam with a new biodegradable material, polyhydroxybutyrate-hydroxyvalerate copolymer (PHBV) and D, L polylactic acid (PLA) DZP) as a model drug sustained release microspheres (MS). Methods The preparation of microspheres was optimized by orthogonal design. The surface morphology of microspheres was observed by scanning electron microscopy (SEM). Microsphere size and distribution, in vitro release, stability and pharmacokinetics in animals were determined. Results The average diameter of the microspheres was (20 45 ± 45 0) μm, and the diameter was in the range of 15 5 ~ 35 2 μm, accounting for 88% of the total. The drug release rate was (16 95 ± 0 80)% and the encapsulation efficiency was (6 9 6 8 ± 1 13)%. The in vitro drug release equation was Q = 2 70 2 7t + 135 0 (γ = 0 982 7) The in vivo experiments in vivo showed that the area under the plasma concentration-time curve (AUC) of the microspheres was 235 times that of the solution control group, and the MRT of the mean residence time was 362 times that of the control group. Microspheres in the refrigerator at 4 ℃ and room temperature (20 ~ 25 ℃) under the conditions of stability. Conclusion Microspheres preparation process is stable, compared with DZP injection, has a significant sustained release.