Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain.
Departamento de Quimica y Ciencias Exactas, Universidad Tecnica Particular de Loja, Loja 1101608, Ecuador.
CNS Neurol Disord Drug Targets. 2018 Apr 26;17(1):43-53. doi: 10.2174/1871527317666180104122347.
Donepezil (DPZ) is widely prescribed as a specific and reversible acetylcholinesterase inhibitor for the symptomatic treatment of mild to moderate Alzheimer's disease (AD).
Considering the therapeutic potential of DPZ and the advantages offered by the intranasal route as an alternative for drug administration, the aim of this study was the development and characterization of a DPZ microemulsion (ME) for nose-to-brain delivery.
The ME was developed by construction of pseudoternary phase diagrams and characterized by dynamic light scattering and transmission electron microscopy. Flow properties and viscosity, as well as optical stability and stability under storage at different temperatures were evaluated. Finally, in vitro release and ex vivo permeation studies through porcine nasal mucosa were accomplished.
A transparent and homogeneous DPZ-ME (12.5 mg/ml) was obtained. The pH and viscosity were 6.38 and 44.69 mPa·s, respectively, indicating nasal irritation prevention and low viscosity. The mean droplet size was 58.9±3.2 nm with a polydispersity index of 0.19±0.04. The morphological analysis revealed the spherical shape of droplets, as well as their smooth and regular surface. Optical stability evidenced no destabilization processes. DPZ release profile indicated that the ME followed a hyperbolic kinetic model while the ex vivo permeation profile showed that the highest permeation occurred during initial 4 h and the maximum permeated amount was approximately 2000 µg, which corresponds to 80% of the starting amount of drug.
We conclude that our nasal ME could be considered as a new potential tool for further investigation in the AD.
多奈哌齐（DPZ）作为一种特异性和可逆的乙酰胆碱酯酶抑制剂，被广泛用于治疗轻度至中度阿尔茨海默病（AD）的症状。
鉴于 DPZ 的治疗潜力以及鼻腔给药作为替代给药途径的优势，本研究旨在开发和表征 DPZ 微乳（ME）用于鼻内递药。
通过构建伪三元相图来开发 ME，并通过动态光散射和透射电子显微镜对其进行表征。评估了流动特性和粘度、光学稳定性以及在不同温度下储存的稳定性。最后，通过猪鼻黏膜进行了体外释放和体外渗透研究。
得到了透明且均匀的 DPZ-ME（12.5 mg/ml）。pH 值和粘度分别为 6.38 和 44.69 mPa·s，表明可预防鼻内刺激和低粘度。平均粒径为 58.9±3.2 nm，多分散指数为 0.19±0.04。形态分析显示出球形液滴，以及其光滑和规则的表面。光学稳定性表明没有失稳过程。DPZ 释放曲线表明 ME 遵循双曲动力学模型，而体外渗透曲线表明在最初的 4 小时内渗透最高，最大渗透量约为 2000 µg，相当于起始药物量的 80%。
我们得出结论，我们的鼻腔 ME 可以被认为是进一步研究 AD 的一种新的潜在工具。
