Hamid Reza Fard Masoumi, Mahiran Basri, Wan Sarah Samiun, Zahra Izadiyan, Chaw Jiang Lim Nanodelivery Group, Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Abstract: Aripiprazole is considered as a third-generation antipsychotic drug with excellent therapeutic efficacy in controlling schizophrenia symptoms and was the first atypical anti­psychotic agent to be approved by the US Food and Drug Administration. Formulation of nanoemulsion-containing aripiprazole was carried out using high shear and high pressure homo­genizers. Mixture experimental design was selected to optimize the composition of nanoemulsion. A very small droplet size of emulsion can provide an effective encapsulation for delivery system in the body. The effects of palm kernel oil ester (3–6 wt%), lecithin (2–3 wt%), Tween 80 (0.5–1 wt%), glycerol (1.5–3 wt%), and water (87–93 wt%) on the droplet size of aripiprazole nanoemulsions were investigated. The mathematical model showed that the optimum formulation for preparation of aripiprazole nanoemulsion having the desirable criteria was 3.00% of palm kernel oil ester, 2.00% of lecithin, 1.00% of Tween 80, 2.25% of glycerol, and 91.75% of water. Under optimum formulation, the corresponding predicted response value for droplet size was 64.24 nm, which showed an excellent agreement with the actual value (62.23 nm) with residual standard error <3.2%. Keywords: schizoaffective disorder, antipsychotic drug, bipolar I disorder, D-optimal mixture design, optimization formulation