Ophthalmic drug delivery system based on the complex of gellan and ofloxacin

Abstract

Complex formation between a natural polysaccharide – gellan and an antimicrobial drug – ofloxacin was studied in aqueous solution. Conductimetric and potentiometric titration curves revealed that gellan and ofloxacin forms a water-soluble complex of composition 2:1 mol/mol stabilized by ionic and hydrogen bonds. The formation of the gellan-ofloxacin complex was confirmed by FTIR spectroscopy, dynamic light scattering, zeta-potential and thermogravimetric analysis. The average hydrodynamic size of the complex was found 307±5 nm and its zeta-potential was negative and equal to -15 mV. Thin films of the gellan-ofloxacin complex, gelled in 0.3 wt.% of CaCl₂, were used to study the release kinetics of ofloxacin in distilled water and phosphate buffer. The drug release kinetics evaluated by UV-Vis spectroscopy at λ_max = 289 nm and calculated by the Ritger-Peppas model correspond to non-Fickian diffusion in distilled water and Case II transport (zero-order kinetics) in phosphate buffer. The cumulative release of ofloxacin from the gellan-ofloxacin films was equal to 96±2% and 36±2% in phosphate buffer and distilled water, respectively. It is expected that the gellan-ofloxacin complex is able to form in situ gel on the surface of the eye and to prolong the drug residence time in the tear fluid.