Characterization of Target Topical Ocular Delivery form of Levofloxacin

Abstract

In the present work we developed and optimized levofloxacin loaded PLGA nanodispersions for enhanced ocular delivery of levofloxacin. The optimized nanodispersions were prepared by double emulsification solvent evaporation method using high pressure homogenizer. Particle size of nanodispersion was found to be dependent on PLGA concentration, PLGA:drug ratio, PVA concentration and Water:Oil phase volume ratio whereas drug encapsulation was related to PLGA concentration and PLGA:drug ratio. Encapsulation efficiency of optimized nanodispersion was 78% with a mean particle size of around 178 ± 12 nm which makes them a suitable candidate for ocular administration. The plasma half-life of levofloxacin was estimated to be 13 hours. Drug release kinetic studies of a sustained release profile of levofloxacin from nanodispersions was studied. Plasma concentrations of levofloxacin were measured in 21 male and female adult subjects receiving bilateral topical ocular doses of levofloxacin solution every 8 hours for a total of 13 doses. Biphasic extended-release profile was produced in vitro. The mean steady-state Cmax and AUC were 2.87 ± 0.23 ng/mL and 44.5 ng·hr/mL, respectively. These systemic exposure values were at least 1000 times lower than the mean Cmax and AUC reported after therapeutic 400 mg oral doses of levofloxacin. Prevent ocular drainage of levofloxacin in nanodisperssion form enhanced ocular bioavailability by 3.7-fold. The antibacterial activities of the nanosuspension were performed against S. aureus and P. aeroginosa. The levofloxacin-loaded PLGA nanosuspensions showed uniform in vitro corneal permeability across isolated goat cornea, indicating the suitability of the nanosuspension formulation in the ophthalmic delivery of levofloxacin. The optimised nano-suspension was found to be more active against S. aureus and P. aeruginosa compared to the marketed eye drops.