目的 制備阿立哌唑自乳化釋藥系統(tǒng)（ARP-SEDDSs）以提高藥物的口服生物利用度。方法 HPLC法檢測(cè)ARP在不同的油、表面活性劑和助表面活性劑中的溶解度，根據(jù)溶解度確定處方組成；采用偽三元相圖篩選SEDDSs的處方比例；通過動(dòng)態(tài)光散射、透射電鏡、稀釋穩(wěn)定性和體外溶出對(duì)ARP-SEDDSs進(jìn)行表征；大鼠分別ig給予自制ARP-SEDDSs和ARP混懸液（20 mg·kg^-1）后，HPLC法進(jìn)行藥動(dòng)學(xué)研究，考察大鼠ig ARP-SEDDSs的生物利用度。結(jié)果 以油酸作為油相，以聚乙二醇15-羥基硬脂酸酯和異丙醇作為表面活性劑和助表面活性劑，優(yōu)化得到ARP-SEDDSs處方為油酸-聚乙二醇15-羥基硬脂酸酯-異丙醇為2.0∶5.6∶2.4，載藥量為10 mg·g^-1；ARP-SEDDSs經(jīng)水稀釋后可快速形成微乳，在透射電鏡下可觀察到微乳呈類球形，經(jīng)動(dòng)態(tài)光散射儀檢測(cè)其平均粒徑為（54.6±2.3）nm，聚合物分散性指數(shù)（PDI）為0.201±0.011，Zeta電位（-13.5±0.4）mV；ARP-SEDDSs在pH 6.8磷酸鹽緩沖液中10 min的藥物溶出度接近100%，遠(yuǎn)高于阿立哌唑口崩片（約10%）。大鼠體內(nèi)藥動(dòng)學(xué)研究表明，與ARP混懸液相比，ARP-SEDDSs相對(duì)生物利用度為248.8%。結(jié)論 將ARP制備成自乳化釋藥系統(tǒng)，有助于藥物快速溶出，顯著提高了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