a Department of Pharmaceutics and Industrial Pharmacy , Al-Ahram Canadian University , Cairo , Egypt.
b Department of Pharmaceutics and Industrial Pharmacy , Cairo University , Cairo , Egypt.
Drug Dev Ind Pharm. 2018 Sep;44(9):1443-1450. doi: 10.1080/03639045.2018.1459675. Epub 2018 Apr 18.
Dapoxetine (D) suffers from poor oral bioavailability (42%) due to extensive metabolism in the liver. The aim of this study was to enhance the bioavailability of D via preparing instantly-dispersible nanocarrier powder system (IDNPs) for intranasal delivery of D. IDNPs were prepared using the thin film hydration technique, followed by freeze-drying to obtain easily reconstituted powder providing rapid and ready method of administration. The produced nanocarrier systems were evaluated for drug content, entrapment efficiency percentage, particle size, polydispersity index, zeta potential, and drug payload. The optimized nanocarrier system was morphologically evaluated via transmission electron microscopy and the optimized freeze-dried IDNPs were evaluated for ex-vivo permeation and in-vivo pharmacokinetic studies in rabbits following intranasal and oral administration. The relative bioavailability of D after intranasal administration of freeze-dried IDNPs was about 235.41% compared to its corresponding oral nanocarrier formulation. The enhanced D permeation and improved bioavailability suggest that IDNPs could be a promising model for intranasal delivery of drugs suffering from hepatic first pass effect.
达泊西汀（D）由于在肝脏中广泛代谢，口服生物利用度（42%）较差。本研究旨在通过制备即刻分散纳米载体粉末系统（IDNPs）来提高 D 的生物利用度，用于 D 的鼻内给药。IDNPs 是通过薄膜水化技术制备的，然后进行冷冻干燥以获得易于重构的粉末，从而提供快速和方便的给药方法。所制备的纳米载体系统的药物含量、包封效率百分比、粒径、多分散指数、Zeta 电位和载药量进行了评估。通过透射电子显微镜对优化的纳米载体系统进行了形态学评价，并对优化的冷冻干燥 IDNPs 进行了体外渗透和兔体内药代动力学研究，分别通过鼻内和口服给药。与相应的口服纳米载体制剂相比，D 经鼻内给予冷冻干燥 IDNPs 后的相对生物利用度约为 235.41%。D 的渗透增强和生物利用度提高表明，IDNPs 可能是一种有前途的治疗肝脏首过效应药物的鼻内给药模型。
