Abstract
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.
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