Formulation and Physical Characterization of a Novel Sustained-Release Ophthalmic Delivery System for Sparfloxacin: the Effect of the Biological Environment

Aims: The purpose of this study was to prepare and evaluate ocular thermosetting gels containing sparfloxacin-HP-β-CyD. The formulations based mainly on Pluronic F127 alone or combined with other polymers.

Study Design: Experimental study.

Place and Duration of Study: School of Pharmacy, University of East Anglia, Norwich, Norfolk, UK, between July 2010 and January 2011.

Methodology: Sparfloxacin, the more effective fluoroquinolone antibiotic used in ocular infection was prepared in form of 1:2 drug: HP-β-CyD spray dried complex. The complex was characterized by several techniques like DSC, FTIR and SEM. In this study, the possibility of incorporation of this complex into thermosetting gels was investigated using pluronic F127 alone or combined with other polymers. All placebo and medicated formulations were characterized physically (colour, clarity, pH, and drug contents). Rheological tests and texture analysis were performed in both non physiological conditions, and after dilution with the simulated tear fluid, to estimate the effect of the biological environment effect on thermosetting gels properties.

Results: Sparfloxacin-HP-β-CyD complex was successfully prepared and characterized by several techniques, all confirmed complete inclusion between sparfloxacin and HP-β-CyD. The prepared complex showed a significant improvement in the aqueous solubility of Sparfloxacin compared to untreated drug or the physical mixture. Ocular thermosetting gels containing sparfloxacin-HP-β-CyD complex were prepared simply by cold method using 20% Pluronic F127 alone or 15% Pluronic F127 combined with other polymers. All preparations were found colourless or yellow, clear, of acceptable pH, and drug content.

The rheologicaly and texture analysis studies revealed that, the formulations exhibited suitable gelling temperatures, gelling times, and appropriate strength to be used in ocular dosage forms. The biological environment highly affected gel properties according to the polymer type.

Conclusions: Ophthalmic in-situ gelling formulations containing sparfloxacin-HP-β-CyD complex are considered promising delivery systems. They showed good rheological and texturale properties. The results confirmed the possibility of lowering Pluronic F127 concentration by using other polymers in small concentrations. The effect of the biological environment must be considered in developing such formulations.