A two level four factor partial factorial design was adopted, composite of experiment design was applied to optimize a tablet formulation of Tetrabenazine (TBZ) Tablets 25mg containing high percentage of Lactose Anhydrous, Sodium starch Glycolate, Magnesium Stearate and Starch/Lactose Ratio. The particle size distribution of Lactose Anhydrous is used as dependent variable and  Sodium starch Glycolate, Magnesium Stearate and Starch/Lactose Ratio were used as independent variables for optimizing some tablets response parameters. Reponses parameters for final TBZ Tablets were percentage of TBZ dissolve at thirty minutes. Design of Experiments (DOE) is an organized approach to determine the relationship between independent process variables and their effect on the response variable.24 partial factorial design were applied in this research work. The models were validated for accurate prediction of response characteristics and use to identify the optimum formulation. The results that an optimum TBZ 25mg tablets having a volume similar to commercial products can be produced by dry granulation process utilizing Lactose Anhydrous.