Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt, Cairo, Egypt.
Department of Pharmaceutical Technology, Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Cairo, Egypt.
AAPS PharmSciTech. 2018 Nov;19(8):3751-3762. doi: 10.1208/s12249-018-1145-6. Epub 2018 Sep 26.
The aim of this study was to design a novel carrier for enhancing the bioavailability of the poorly water-soluble drug, aripiprazole (ARP). Silicosan, the applied carrier, was obtained by chemical interaction between tetraethyl orthosilicate (TEOS) and chitosan HCl. Different ARP-loaded silicosan particles were successfully prepared in absence and presence of one of the following surfactants; Tween 80, Poloxamer 407 and cetyltrimethylammonium bromide (CTAB). The prepared ARP-loaded silicosan particles were thoroughly investigated for their structures using FTIR, XRD, and DSC analysis as well as their particle size, zeta potential, flowability, drug content, and in vitro drug release efficiencies. The prepared ARP-loaded silicosan particles were characterized by amorphous structure, high drug entrapment efficiency and a remarkable improvement in the release of aripiprazole in simulated gastric fluid. SEM and EDX revealed that the morphology and silica atom content in the prepared ARP-loaded silicosan particles were affected by the used surfactant in their formulations. The selected ARP-loaded silicosan particles were subjected to in vivo study using rabbits. The obtained pharmacokinetic results showed that the relative bioavailability for orally administered ARP-loaded silicosan particles (SC-2-CTAB) was 66% higher relative to the oral suspension (AUC was 16.38 ± 3.21 and 27.23 ± 2.35 ng.h/mL for drug powder and SC-2-CTAB formulation, respectively). The obtained results suggested the unique-structured silicosan particles to be used as successful vehicle for ARP.
本研究旨在设计一种新型载体，以提高水溶性差的药物阿立哌唑（ARP）的生物利用度。应用的载体硅烷通过四乙氧基硅烷（TEOS）和盐酸壳聚糖之间的化学相互作用获得。在不存在和存在以下表面活性剂之一的情况下，成功地制备了不同载有 ARP 的硅烷纳米粒子：聚氧乙烯山梨醇酐单油酸酯 80（Tween 80）、泊洛沙姆 407 和十六烷基三甲基溴化铵（CTAB）。使用傅里叶变换红外光谱（FTIR）、X 射线衍射（XRD）和差示扫描量热法（DSC）分析以及粒度、Zeta 电位、流动性、药物含量和体外药物释放效率对制备的载有 ARP 的硅烷纳米粒子的结构进行了全面研究。制备的载有 ARP 的硅烷纳米粒子具有无定形结构、高药物包封效率和在模拟胃液中显著提高阿立哌唑释放的特点。SEM 和 EDX 表明，所制备的载有 ARP 的硅烷纳米粒子的形态和硅原子含量受其制剂中所用表面活性剂的影响。选择的载有 ARP 的硅烷纳米粒子在兔体内进行了研究。获得的药代动力学结果表明，口服载有 ARP 的硅烷纳米粒子（SC-2-CTAB）的相对生物利用度比口服混悬剂高 66%（AUC 分别为 16.38±3.21 和 27.23±2.35ng.h/mL 用于药物粉末和 SC-2-CTAB 制剂）。结果表明，具有独特结构的硅烷纳米粒子可用作 ARP 的成功载体。
