Optimizing flurbiprofen-loaded NLC by central composite factorial design for oculardelivery

Abstract

The purpose of this study was to design and optimize a new topical deliverysystem for ocular administration of flurbiprofen (FB), based on lipidnanoparticles. These particles, called nanostructured lipid carriers (NLC), werecomposed of a fatty acid (stearic acid (SA)) as the solid lipid and a mixture ofMiglyol® 812 and castor oil (CO) as the liquid lipids, prepared by the hot high pressurehomogenization method. After selecting the critical variables influencing thephysicochemical characteristics of the NLC (the liquid lipid (i.e. oil) concentration withrespect to the total lipid (cOil/L (wt%)), the surfactant and the flurbiprofenconcentration, on particle size, polydispersity index and encapsulation efficiency), athree-factor five-level central rotatable composite design was employed to plan andperform the experiments. Morphological examination, crystallinity and stabilitystudies were also performed to accomplish the optimization study. The resultsshowed that increasing cOil/L (wt%) was followed by an enhanced tendency toproduce smaller particles, but the liquid to solid lipid proportion should not exceed30 wt% due to destabilization problems. Therefore, a 70:30 ratio of SA to oil (miglyol + CO) was selected to develop an optimal NLC formulation. The smaller particlesobtained when increasing surfactant concentration led to the selection of 3.2 wt% ofTween® 80 (non-ionic surfactant). The positive effect of the increase in FB concentrationon the encapsulation efficiency (EE) and its total solubilization in the lipidmatrix led to the selection of 0.25 wt% of FB in the formulation. The optimalNLC showed an appropriate average size for ophthalmic administration(228.3 nm) with a narrow size distribution (0.156), negatively charged surface (−33.3 mV) andhigh EE (∼90%). The in vitro experiments proved that sustained release FB was achieved using NLC asdrug carriers. Optimal NLC formulation did not show toxicity on ocular tissues.