张继芬 张焦 王帆 王帅 王玫 易涛

[摘要]研制葛根素纳米晶自稳定Pickering乳液（puerarin nanocrystalline selfstabilized Pickering emulsion，PuNSSPE），采用BoxBehnken设计效应面法优化处方以提高其稳定性，研究药物浓度、水相pH和水油体积比对乳液的分层指数、乳液层的药物含量和乳滴粒径变化的影响。结果显示，当葛根素浓度为05%，水相pH为9，水油体积比为9时，能得到最稳定的PuNSSPE，乳滴粒径为（1270±117） μm，乳液层的药物浓度为（449±021） g·L-1，室温放置6个月后均无明显变化，稳定性好。采用扫描电镜、激光共聚焦显微镜和荧光倒置显微镜对乳滴结构进行表征，结果显示葛根素纳米晶能吸附于油滴界面形成稳定的球状核壳结构，这可能是PuNSSPE能够长期稳定的微观结构原因。

[关键词]葛根素； 纳米晶； Pickering乳液； 稳定性； BoxBehnken； 效应面法

Stability optimization of puerarin nanocrystalline selfstabilizied

Pickering emulsion by response surface methodology

ZHANG Jifen1， ZHANG Jiao1， WANG Fan1， WANG Shuai1， WANG Mei1， YI Tao2*

1 College of Pharmaceutical Sciences， Southwest University， Chongqing 400716， China；

2 School of Health Sciences， Macau Polytechnic Institute， Macau 999078）

[Abstract]A new Pickering emulsion， puerarin nanocrystalline selfstabilized Pickering emulsion （PuNSSPE） was developed BoxBehnken design was used for optimizing the preparation formulation of PuNSSPE to improve its stability， and the effects of concentration of puerarin， volume ratio of water to oil， and pH value of water phase on the stratification index of emulsion， droplet size and drug concentration in emulsion were investigated Results showed that the optimized PuNSSPE could be prepared with the concentration of puerarin of 05%， the volume ratio of water to oil of 9∶1 and the pH of water of 9 The size of emulsion droplet of optimized PuNSSPE was （1270±117） μm and the drug content was （449±021） g·L-1 The above indexes had no significant changes within the storage of 6 months at room temperature， indicating good stability Microstructure characterizations by scanning electron micrograph， confocal laser scanning microscope and fluorescence microscope showed that the optimized PuNSSPE had a stable coreshell structure of emulsion droplet formed by the adsorption of puerarin nanocrystallines at the surface of oil droplets， which may be the microstructure reason for the long stability of PuNSSPE.

[Key words]puerarin； nanocrystalline； Pickering emulsion； stability； Boxbehnken design； response surface methodology

Pickering乳液是一種以固体微粒，如二氧化硅[1]、二氧化钛[2]等作为稳定剂的乳液。固体微粒不可逆地吸附于油水界面，形成稳定的膜状结构，阻止液滴合并而稳定乳液。与传统乳液相比，Pickering乳液不需要使用表面活性剂，安全性更高，且具有更好的热力学稳定性[1]，是一种潜在的优良给药系统，已在皮肤局部给药[34]、口服给药[56]中有所研究应用。课题组以难溶性药物自身纳米晶作为固体微粒稳定剂制备一种新型Pickering乳液，即药物纳米晶自稳定Pickering乳液（nanocrystalline selfstabilized Pickering emulsion，NSSPE）；与传统Pickering乳液比较，无异种固体微粒的存在，进一步增强了安全性；而药物除了溶解于油相，还大量吸附于油水界面，可提高制剂载药量，已成功用于提高水飞蓟宾的口服生物利用度[7]。endprint

通脉复方由葛根、川芎、丹参配伍组成，具有活血通脉的功效，可用于缺血性心脑血管疾病，动脉硬化，脑血栓，脑缺血，冠心病，心绞痛的治疗。……