Simvastatin is a well established oral antihypercholesterolemic agent. This study aimed to formulate simvastatin as orodispersible tablets. The drug was incorporated as a solid dispersion using Pluronic® F68 as carrier. Croscarmellose Na was used as superdisintegrant, microcrystalline cellulose as filler, PVP K-30 as binder and 1:1 magnesium stearate/talc mixture as lubricant. Box- Behnken design was adapted to explore the main and interaction effects of three independent formulation variables on the prepared tablets, namely superdisintegrant concentration (X1), lubricant mixture concentration (X2), and binder concentration (X3). A total of 13 tablet formulations were fabricated in addition, to two replicates of the center point to assess variability and experimental error. The selected dependant variables were the in vitro and in vivo disintegration times, dissolution rate at 4 min, and dissolution efficiency after 30 min. Wetting time, drug content, hardness and friability were also evaluated. Tablet formula, composing of 12% superdisintegrant, 2% lubricant mixture and 3% binder, showed the highest dissolution rate with an acceptable disintegration time (43 sec), hardness, and friability and was chosen as the best formula. An accelerated stability study was conducted for 6 months at 40°C/75% RH. Results showed no significant changes in any of the tested parameters