Development and Evaluation of a Water Soluble Fluorometholone Eye Drop Formulation Employing Polymeric Micelle

摘要

Low aqueous solubility of drug causes difficulties in preparation and inconvenience of administration. Polymeric micelles of fluorometholone (FML) using solid dispersion technique were prepared to develop an eye drop formulation with enhanced water solubility. Solid dispersions of FML were prepared at various FML:Soluplus^® w/w ratios using solvent evaporation method. A physical mixture was also prepared. Physicochemical characterization was performed with various methods. Ex vivo porcine corneal permeation of polymeric micelle, physical mixture, and commercial product were compared. FML solid dispersion (1:15) showed the highest solubility, which was c.a. 169.6- and 15.3-fold higher than that of pure FML and physical mixture. Characterization showed that the crystalline form of FML changed to amorphous state and polymeric micelles were formed in round micelle. Flucon^®, a commercial product of FML, showed significantly large particle size and high poly dispersity index. In contrast, FML polymeric micelle showed submicron size with uniform size distribution. Ex vivo porcine corneal permeation study showed that permeation by polymeric micelles was significantly higher than that by the commercial product and physical mixture. In addition, confocal laser scanning microscopic analysis supported the enhanced porcine corneal tissue permeation property of polymeric micelle. In conclusion, polymeric micelle prepared with solid dispersion using Soluplus^® can be a potential nanomedicine for ocular delivery of poorly water-soluble FML.