Clinical investigation showed that itraconazole exhibit various adverse effect such as nausea, vomiting, and other gastric disturbances. To minimize these side effects, itraconazolenanocochleatesformulation was developed and delivered to topical site which can minimize the frequency and intensity of adverse effect. The need of these study due to the drug has low bioavailability (55%) because of low aqueous solubility and first pass effect. Nano-cochleates are prepared by trapping method by using the phosphatidyl serine as a lipid and calcium chloride as a metal cation. In the current study design expert base risk assessment was exploited for the preparation of itraconazole loaded nano-cochleae. The Box-Behnken design was utilize for risk assessment and optimization for various formulation and process parameter. Five central point were utilized in this design for the accomplishment of the goal.The optimized formula yielded 247nm particle size, 0.364 PDI, -30.8mV zeta potential, and 93% entrapment efficiency. An optimized batch in-vitro drug release study was carried out. The selected formulation was loaded into HPMC K 5M gel for in-vitro testing. The antifungal study on Trichophyton rubrum (T. rubrum) culture revealed an 18.5±0.5mm zone of inhibition with the nano-cochleate formulation. A design expert assist in understanding the interaction between process and formulation parameters. In the future, the prepared nanocochleate gel could be a potential alternative for topical fungal infection.