Diclofenac sodium is a non steroidal anti-inflamation drug that generally has been used as rheumatoid arthritis treatment. Formulation of diclofenac sodium in Fast disintegrating tablet dosage form is an appropiate alternative to enhance patient compliance and rapidly disintegrated in the mouth. This research was aimed to optimize the formulation of diclofenac sodium Fast disintegrating tablet using Primojel, Primellose, and effervescent component by simplex lattice design method.Optimum region was determined by simplex lattice design with several responses i.e. hardness, friability, wetting time, in vitro and in vivo disintegration time, amount of drug released at 1 min and dissolution efficiency during 5 min using Design Expert software. The results showed that effervescent components significantly affected on an increase wetting time, in vitro and in vivo disintegration time, and the drug release. Primojel was the most dominant component affected on an increase friability, meanwhile Primellose affected on an increase hardness. The most optimum formula was obtained on Primojel 11,12 mg, Primellose 2,88 mg and effevescent components 8,00 mg.