Development and optimization of ofloxacin as solid lipid nanoparticles for enhancement of its ocular activity

Abstract

Ofloxacin (Ofx) is one of the most commonly available ocular antibiotic solutions. Unfortunately, it suffers from rapid tear turnover and therefore requires administration every 4 h or even every hour for serious eye infections; moreover, its solubility is pH-dependent and very low at the pH of corneal fluid (7.2–7.4), and it can form a white crystalline deposit on the cornea. Hence, the aim of this investigation was to load Ofx into solid lipid nanoparticles (SLNs) to address its limitations. SLNs were prepared using hot homogenization followed by ultrasonication techniques at a pH of 7.4. The Box-Behnken design addressed the influence of the formulation factors, namely, the effects of the percentages of Compritol, Gelucire 44/14, and stearylamine on the particle size, zeta potential, entrapment efficiency, percentage of Ofx release after 1 h, and time required to release 50% of the drug. The obtained optimal Ofx-SLN was evaluated for its transcorneal permeation, antimicrobial activity, and amount of Ofx present in the aqueous humor as compared with Ofx aqueous suspension, and commercially available Ofx eye drop. The optimum formulation exhibited a particle size of 34 nm, zeta potential of 22 mV, entrapment efficiency of 82%, Ofx release of 9% after 1 h, and time to release of 50% of the drug of 5 h. It produced a 1.5-fold and 3-fold increase in the cumulative amount permeated and cumulative percentage permeated, respectively, compared with other tested formulations. Furthermore, the optimized Ofx-SLN had a high level over the minimum inhibitory concentration in the aqueous humor of rabbits for longer periods compared with a commercial preparation. These data proved that a once-a-day dose of an Ofx-SLN dispersion would produce the required effects of prolonged transcorneal permeation, enhanced ophthalmic bioavailability, diminished need for recurrent administration.