University Institute of Pharmaceutical Sciences, Panjab University, Sector-14, Chandigarh, India.
AAPS PharmSciTech. 2018 Apr;19(3):1264-1273. doi: 10.1208/s12249-017-0944-5. Epub 2018 Jan 8.
Aripiprazole (ARP), a second-generation or atypical antipsychotic, is poorly soluble and undergoes extensive hepatic metabolism and P-glycoprotein efflux which lead to reduced in vivo efficacy and increased dose-related side effects. To enhance in vivo efficacy and oral bioavailability of aripiprazole, aripiprazole-loaded solid lipid nanoparticles (SLNs) were developed using tristearin as solid lipid. Tween 80 and sodium taurocholate were used as surfactants to prepare SLNs using microemulsification method. SLNs were characterized for particle size, zeta potential, entrapment efficiency, and crystallinity of lipid and drug. In vitro release studies were performed in water containing 0.5% sodium dodecyl sulfate. Pharmacodynamic evaluation was carried out in laca mice using dizocilpine-induced schizophrenic model where behavioral evaluation revealed better in vivo efficacy of SLNs. Pharmacokinetics of aripiprazole-loaded SLNs after oral administration to conscious male Wistar rats was studied. Bioavailability of aripiprazole was increased 1.6-fold after formulation of aripiprazole into SLNs as compared to plain drug suspension. The results indicated that solid lipid nanoparticles can improve the bioavailability of lipophilic drugs like aripiprazole by enhancement of absorption and minimizing first-pass metabolism.
阿立哌唑（ARP）是一种第二代或非典型抗精神病药，其水溶性差，广泛进行肝代谢和 P-糖蛋白外排，导致体内疗效降低和剂量相关副作用增加。为了提高阿立哌唑的体内疗效和口服生物利用度，用硬脂酸三酯作为固体脂质，采用微乳法制备了载阿立哌唑固体脂质纳米粒（SLNs）。对 SLNs 的粒径、Zeta 电位、包封率和脂质及药物的结晶度进行了表征。在含有 0.5%十二烷基硫酸钠的水中进行了体外释放研究。在使用地佐辛诱导的精神分裂症模型的 laca 小鼠中进行了药效学评价，行为评估显示 SLNs 的体内疗效更好。研究了口服给予清醒雄性 Wistar 大鼠后载阿立哌唑 SLNs 的药代动力学。与普通药物混悬液相比，将阿立哌唑制成 SLNs 后，其生物利用度提高了 1.6 倍。结果表明，固体脂质纳米粒可以通过增强吸收和最小化首过代谢来提高亲脂性药物如阿立哌唑的生物利用度。
