水飞蓟素自微乳化浓乳的制备和体内外评价

Preparation and in vitro and in vivo evaluation of silymarin self-microemulsifying concentrated microemulsion

目的:制备和评价水飞蓟素自微乳化浓乳(self-microemulsifying concentrated microemulsion,SCM)。方法:由以前的工作确定微乳的组成;以光散射法测定微乳的粒度及其分布;用透射电镜考察微乳的形态;用加速试验的方法考察SCM的物理和化学稳定性;用透析袋法评价该SCM的释放特征;以市售水飞蓟素胶囊为对照,测定了SCM经家犬口服的生物利用度。结果:SCM在5 min内即可形成粒径均匀、单分散的微乳,其平均粒径为21 nm;所形成微乳乳滴为球形;SCM于加速试验条件下放置6个月,所有指标未见明显变化;SCM和市售水飞蓟素胶囊在12 h的释放百分率分别为(72.5±4.0)%及(44.0±6.9)%;SCM和水飞蓟素胶囊的AUC值分别为(4.78±1.02)和(2.09±0.15)μg.mL-1.h,相对生物利用度为227.2%。结论:本实验研制的SCM可迅速自发形成粒径均匀、液滴呈球形的微乳,且长期放置的稳定性良好,体外释放特征和家犬体内生物利用度均优于市售水飞蓟素胶囊,有望成为水飞蓟素的优良口服制剂。

Objective：To prepare silymarin self-microemulsifying concentrated microemulsion and evaluate its properties in vitro and in vivo. Methods：The compositions of SCM were determined according to previous work. The particle size and distribution of silymarin microemulsion were surveyed by means of dynamic light scattering method. The morphology of silymarin microemulsion was observed through transmission electron microscope. Accelerated tests were used to evaluate physical and chemical stability of silymarin SCM. The in vitro release of silymarin SCM was assessed by dialysis method. The bioavailability of silymarin SCM was determined by oral administration to dogs compared with commercial silymarin capsule. Results：The results of dispersion experiment indicated that the self-microemulsify of silymarin SCM was obtained within five minutes and the mean diameter of mieroemulsion was 21 nm. The shape of silymarin microemulsion appeared spheroid or spheroid-like. The results of the accelerate test for six months showed that the clarity,the size of microemulsion and the silymarin content did not change significantly. The accumulation release percent of silymarin from SCM and conmercial capsule for 12 hours were （72.5 ± 4.0）% and （44.0 ± 6.9） % , respectively. The AUC of silymarin SCM and commercial silymarin capsule were （4.78 ± 1.02） and （2.09 ± 0.15 ） μg·mL^-1. h, respectively. The relative bioavailability was 227.2%. Conclusion：The self-mieroemulsify of silymarin SCM was obtained easily, quickly and with good stability. The bioavailiablity of silymarin by oral administration to dogs was increased significantly. The SCM might be a potential effective preparation for silymarin.