阿立哌唑自乳化释药系统的制备与质量评价  

Preparation and quality evaluation of aripiprazole self-emulsifying drug delivery systems

作　　者：曹桑博 王敏[2] 谢鹏[1] CAO Sangbo;WANG Min;XIE Peng(Department of Pharmacy,Tangshan Union Hospital,Tangshan 063000,China;Tangshan Vocation&Technical College,Tangshan 063000,China)

机构地区：[1]唐山市协和医院药剂科,河北唐山063000 [2]唐山职业技术学院,河北唐山063000

出　　处：《药物评价研究》2023年第3期571-577,共7页Drug Evaluation Research

摘　　要：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.

关 键 词：阿立哌唑 自乳化释药系统 生物利用度 伪三元相图 溶出度 

分 类 号：R943[医药卫生—药剂学]