丹参素钠-PLGA缓释微球的制备及药剂学性能评价

Preparation and Pharmaceutical Properties of Salvianic Acid A Sodium-PLGA Sustained Release Microspheres

目的:优选丹参素钠-聚乳酸-羟基乙酸共聚物(PLGA)缓释微球的处方工艺并考察其药剂学性能。方法:采用W/O/O型乳化溶剂挥发法制备丹参素钠-PLGA微球,以载药量、包封率及收率为考察指标,通过单因素试验优选处方工艺,并考察其体外释药性能。采用激光粒度分析仪、扫描电子显微镜和X射线衍射法对该微球进行表征。结果:选取内水相体积300μL,PLGA质量浓度125 g·L^(-1),二氯甲烷-丙酮(3∶7),外油相为液体石蜡200 m L,加入正己烷6 m L,0.25%司盘80为乳化剂,1 400 r·min^(-1)搅拌4 h。丹参素钠-PLGA微球平均载药量(20.71±1.42)%,平均包封率(63.27±1.70)%,平均收率(99.10±0.83)%,体外累积释放率达98%需要120 h。平均粒径(71.72±1.71)μm,表面圆整光滑,内部含有蜂窝状孔洞。部分药物可能以晶体状态分散于载体材料中。结论:W/O/O型乳化溶剂挥发法成功制备了丹参素钠-PLGA微球,优选的处方工艺稳定合理,可为丹参素钠制剂的开发提供参考。

Objective： To select the best formula and technology for the preparation of salvianie acid A sodium-poly （lactide-glycolic acid） （PLGA） sustained release mierospheres and to discuss its pharmaceutical properties. Method： W/O/O emulsified solvent evaporation method was used to prepare the microspheres, taking drug loading, encapsulation efficiency and yield as indexes, single factor tests were used to optimize formulation, and its in vitro release was investigated. Laser particle size analyzer, scanning electron microscopy and X-ray diffraction （ XRD ） volume of internal methylene chloride were used to characterise the microspheres. Result： Optimum formulation was determined, phase was 300 μL, concentration of PLGA50/50 COOH was 125 g·L^-1, the proportion of and acetone was 3 ： 7, the volume of liquid paraffin was 200 mL as external oil phase,concentration of span80 was 0.25% , stirring speed was 1 400 r·min^-1, stirring time was 4 h, volume of n- hexane was 6 mL. Drug loading, encapsulation efficiency and yield were （20.71 ±1.42） % , （63.27 ±1.70） % and （99.10 ± 0.83）% , respectively. Cumulative release in vitro of 98% required 120 h. Mean particle diameter was （71.72 ± 1.71 ） μm. Surfaces of salvianic acid A sodium-PLGA sustained release microspheres were smooth and spherical with honeycomb-like inner structure. XRD indicated that some drug may dispersed as crystals in carrier materials. Conclusion： Salvianic acid A sodium-PLGA sustained release microspheres can be prepared by W/O/O emulsified solvent evaporation method. This optimized process is simple and reasonable, which is base for further research of salvianic acid A sodium preparation.