Design and Optimization of Ciprofloxacin Hydrochloride Nanoemulsion for Effective Ocular Delivery: In Vitro, Ex Vivo and In Vivo Characterization

Abstract

Ciprofloxacin hydrochloride nanoemulsions consisting of oil and surfactant mixtures were prepared and studied for the properties such as morphology, particle size, zeta potential, pH, rheological behavior, drug content, antimicrobial activity and in vitro drug release behavior, ex vivo permeation, ocular irritancy and in vivo pharmacokinetics in aqueous humour as well as plasma. Design expert was used to designing and optimizing the formulation and the effects of formulation ingredients on droplet size and % drug release which sequentially affect the drug bioavailability were studied. The in-vitro diffusion studies revealed that the prepared formulations exhibited sustained drug release for 24h. The optimized formulation was subjected to transmission electron microscopy, ex vivo corneal permeability studies and eye irritability test where the results showed the spherical nano sized globules, the enhanced drug permeation through the bovine cornea with greater flux value compared to the simple drug solution at 4h time point and found nonirritant with a total score of 2 in Draize eye test. The pharmacokinetic assessment of optimized formulation was done both in aqueous humor and plasma of rabbit models to compare the AUC values of optimized formulation with that of marketed ciprofloxacin solution. The results demonstrated the improved corneal absorption and less systemic absorption of optimized formulation when compared to marketed formulation.