Department of Physical Chemistry, Faculty of Pharmacy, Institute of Nanoscience and Nanotechnology, University of Barcelona, Barcelona, Spain.
J Pharm Sci. 2012 Feb;101(2):707-25. doi: 10.1002/jps.22784. Epub 2011 Oct 19.
Flurbiprofen (FB)-loaded nanostructured lipid carriers (NLCs) based on Compritol®888 ATO (C888; FB-C888NLC) were developed for anti-inflammatory ocular therapy. NLCs prepared by high-pressure homogenization technique following a factorial design had low particle size (<199 nm), high entrapment efficiency (∼90%), and long-term physical stability. Previously optimized NLCs based on stearic acid (SA; FB-SANLC) were prepared for comparison studies. Both formulations were dispersed in freshly prepared carbomer hydrogel (HG) to check the suitability of semisolid-based NLC HGs to enhance the corneal residence time. FB-C888NLC remained in the nanometric range, whereas FB-SANLC suffered an increase in particle size up to 5 µm after incorporation. Consequently, modifications in the crystalline lattice structure were observed for FB-SANLC-enriched HG (HG_FB-SANLC) by X-ray diffractometry. Both HG formulations showed plastic and low or no thixotropic properties, making them suitable for ocular application while maintaining its predominant elastic component as an indicator of good physicochemical stability. Formulations depicted sustained FB release. Ex vivo permeation analysis in isolated rabbit cornea revealed enhanced transcorneal drug permeation from the systems. In vivo ocular tolerance was confirmed by the Draize test. Therefore, NLC are promising and effective systems for ocular delivery of FB.
载氟比洛芬（FB）的纳米结构化脂质载体（NLC）基于 Compritol®888 ATO（C888；FB-C888NLC），用于抗炎眼部治疗。通过高压匀质技术制备的 NLC 遵循析因设计，具有较小的粒径（<199nm）、较高的包封效率（约 90%）和长期物理稳定性。先前对基于硬脂酸（SA；FB-SANLC）的优化 NLC 进行了制备，用于比较研究。两种制剂均分散在新制备的卡波姆水凝胶（HG）中，以检查半固体 NLC-HG 对增加角膜滞留时间的适用性。FB-C888NLC 保持在纳米范围内，而 FB-SANLC 在掺入后粒径增加到 5µm。因此，通过 X 射线衍射法观察到 FB-SANLC 富集 HG（HG_FB-SANLC）的晶体点阵结构发生了变化。两种 HG 制剂均表现出塑性和低或无触变特性，使其适合眼部应用，同时保持其主要弹性成分作为良好物理化学稳定性的指标。制剂显示出 FB 的持续释放。在离体兔角膜中的体外渗透分析显示，从这些系统中增强了药物的经角膜渗透。通过 Draize 试验证实了体内眼耐受性。因此，NLC 是 FB 眼部递药的有前途且有效的系统。
