Novel water soluble sterile natamycin formulation (Natasol) for fungal keratitis

The purpose of this study was to develop, characterize and evaluate novel water soluble formulation for its topical and intrastromal application. Natamycin complexed with cyclodextrin was characterized by Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The complexed powder was used to formulate 1% w/v aqueous natamycin formulation (Natasol 1%) for topical use. The developed formulation was subjected to stability testing at various conditions. Single and multi-dose trans-corneal permeation of Natasol 1% was evaluated in New Zealand Albino rabbits in comparison with marketed 5% natamycin suspension. Sterile unpreserved Natasol (0.01% w/v natamycin) formulation was also developed for intrastromal injection. Both formulations were evaluated for the ocular toxicity. FTIR and DSC studies revealed successful complexation of natamycin that further protected the degradation at various stability conditions. Single dose trans-corneal permeation studies revealed that Natasol 1% attained Cmax at one hr and maintain its intraocular concentration 5 and 2.5 times higher at 4th and 6th hr compared to 5% natamycin suspension. Multi-dose kinetics revealed the steady state pharmacokinetics after hourly and two hourly dosing schedules. Topical Natasol 1% and sterile unpreserved Natasol 0.01% intrastromal injection, did not show any ocular toxicity in the animals. To conclude, the newly developed topical 1% w/v natamycin formulation was found to be non-inferior to 5% natamycin topical suspension. It is expected to increase patient compliance for the treatment of fungal keratitis.