Clozapine is atypical antipsychotic agent used in treatment of patients with schizophrenia, it is available in oral route, Clozapine is class II drug having a poor bioavability (27%), hence the aim of present study to develop proniosomes of Clozapine for brain targeted delivery through olfactory pathway. Proniosomes drug delivery system is a promising drug delivery system derived from Niosomes, Proniosomes proves to be potential carriers for efficient drug delivery for Lipophilic and amphphillc drug using oral route, nasal route, transdermal route and other route. 3-factor and 3 levels box Behnken design used to explain multiple regression analysis and counter plot response. The independent variable selected were Cholesterol, Span 60 and Sonication time; dependent variables % entrapment efficiency, particle size analysis and PDI value. Based on Box-Behnken design 17 runs trials studied and optimized. The formulation evaluate for Scanning electron Microscopy (SEM), FT-IR Study, DSC Study, Particle size analysis. From DOE the derived polynomial equation and counter plots give support to predicating the values of selected independent variable for the preparation of the optimum formulation with required properties