Objective: The purpose of the present investigation is to formulate and evaluation of cubosome loaded in situ gel for fungal keratitis.

Material and Method: The cubosomes were prepared by a top-down approach. Optimization of cubosome using box Behnken design. As formulation (independent) variables, lipid concentration (X1), poloxamer 407 concentration(X2), and homogenizer speed (X3) were used. The dependent variable was particle size (Y1), entrapment efficiency (Y2), and drug release(Y3) were investigated. 3-d surface plots and contour plots were drawn and optimized by feasibility and grid search. Identification of drug and drug-excipient compatibility study was carried out by DSC and FTIR. Particle size, PDI, and Zeta potential were analyzed by a zetatrac particle size analyzer. Entrapment efficiency, Invitro drug release study and SEM study were performed for characterization of nanoparticles. Viscosity, Gelation time and temperature, pH were performed for the characterization of nanoparticle-loaded in situ gel. An ocular irritancy study was performed on a rabbit.

Result and Discussion: Cubosome was prepared by top-down method and optimized by Box-Behnken design and results show that particle size was found to be in the range of 200 to 350 nm, the entrapment efficiency was found to be in the range of 70-90%and drug release was found to be more than 80%. After preparing cubosome, that are incorporated into thermosensitive in situ gel for that carbopol 934: poloxamer 188 in the ratio of 1:20 were selected. The gelation time was found to be 41±1 second and the gelation temperature was found to be 28 ± 0.70 ºc. The checkpoint batch was formulated using the given value having predicted particle size, entrapment efficiency, and drug release respectively 209.106nm, 84.5541%, and 84.3765%, and actual (experimental) value particle size, entrapment efficiency, and drug release respectively 207.88nm, 83.79%, and 82.94%. That shows less % relative error. From the image, the surface of cubosomes can be easily studied as to whether it has a cubic shape. The drug was 90.22 % diffused after 4 hrs. study of the Franz diffusion cell. In the ocular irritancy, study results indicate that the optimized in situ gelling system was non-irritant and well tolerated by the rabbit’s eyes.

Conclusion: In this study cubosome loaded in situ gel for fungal keratitis in the ocular route demonstrate that the ocular route is a promising approach and may improve the retention time of drug by the ocular route and reduce side effects related to other routes also improve patient compliance. This cubogel is an ocular dosage form to boost corneal permeability and bioavailability. The developed novel formulation is promising for the ocular delivery of a drug.