目的 制备阿立哌唑自乳化释药系统（ARP-SEDDSs）以提高药物的口服生物利用度。方法 HPLC法检测ARP在不同的油、表面活性剂和助表面活性剂中的溶解度，根据溶解度确定处方组成；采用伪三元相图筛选SEDDSs的处方比例；通过动态光散射、透射电镜、稀释稳定性和体外溶出对ARP-SEDDSs进行表征；大鼠分别ig给予自制ARP-SEDDSs和ARP混悬液（20 mg·kg^-1）后，HPLC法进行药动学研究，考察大鼠ig ARP-SEDDSs的生物利用度。结果 以油酸作为油相，以聚乙二醇15-羟基硬脂酸酯和异丙醇作为表面活性剂和助表面活性剂，优化得到ARP-SEDDSs处方为油酸-聚乙二醇15-羟基硬脂酸酯-异丙醇为2.0∶5.6∶2.4，载药量为10 mg·g^-1；ARP-SEDDSs经水稀释后可快速形成微乳，在透射电镜下可观察到微乳呈类球形，经动态光散射仪检测其平均粒径为（54.6±2.3）nm，聚合物分散性指数（PDI）为0.201±0.011，Zeta电位（-13.5±0.4）mV；ARP-SEDDSs在pH 6.8磷酸盐缓冲液中10 min的药物溶出度接近100%，远高于阿立哌唑口崩片（约10%）。大鼠体内药动学研究表明，与ARP混悬液相比，ARP-SEDDSs相对生物利用度为248.8%。结论 将ARP制备成自乳化释药系统，有助于药物快速溶出，显著提高了ARP的口服生物利用度。

Objective To prepare aripiprazole self-emulsifying drug delivery systems (ARP-SEDDSs) and improve the oral bioavailability in rats. Methods The solubility of ARP in different oils, surfactants and cosurfactants was determined by high performance liquid chromatography (HPLC). Pseudo-ternary phase diagram was used to screen the prescription proportion of SEDDSs. ARP-SEDDSs were characterized by dynamic light scattering, transmission electron microscopy, dilution stability and in vitro dissolution. After rats were administrated with self-made ARP-SEDDS and ARP suspension (20 mg·kg^-1), the pharmacokinetics was studied by HPLC to investigate the bioavailability of rat ig ARP-SEDDS. Results The oleic acid was chosen as the oil phase. Meanwhile, polyoxyl 15 hydroxystearate and isopropanol were chosen as the surfactants and co-surfactants, respectively. The optimized condition was oleic acid : polyethylene glycol 15-hydroxystearate : isopropanol = 2.0: 5.6: 2.4 in mass ratio with drug loading of 10 mg·g^-1. ARP-SEDDSs could quickly form microemulsions after being diluted with water, and the microemulsions could be observed to be spherical under transmission electron microscopy. The average particle size was (54.6±2.3) nm, polymer dispersibility index (PDI) was (0.201±0.011), and the Zeta potential was (-13.5±0.4) mV by dynamic light scattering. The dissolution level of ARP-SEDDSs was nearly 100% after 10 min in pH 6.8 phosphate buffer which was higher than that of aripiprazole orally disintegrating tablets (approximately 10%). The in vivo pharmacokinetic studies in rats showed that ARPSEDDSs significantly improved bioavailability compared with aripiprazole suspensions (the relative bioavailability was 248.8%). Conclusion In this study, aripiprazole was prepared into self-emulsifying drug delivery systems, which was helpful for the rapid dissolution of the drug and significantly improved the oral bioavailability of the drug.

R943