Background: Research in developing formulations of drug for allergic and respiratory disorders which are capable of rapid disintegration and quickly dissolves when placed on the tounge is necessary. Objective: Therefore the objective of the present study was formulated Cetirizine HCl in fast disintegrating tablet (FDT) dosage forms with variation of superdisintegrant crospovidone and croscarmellose sodium. Materials and Methods: FDT of Cetirizine HCl was manufactured by direct compression. Furthermore, the tablet was evaluated with physical properties and the results were analyzed using Design expert 10.1.3 program to bring in simplex lattice design (SLD) equation to get the optimum formula. Data which had been obtained was then analyzed by one sample t-test with confidence interval 95%. Results: Based on the research results, the combinations of crospovidone and croscarmellose sodium was able to reduce the response of physical properties such as weight variation, hardness, friability, disintegration time, and wetting time. The optimum formula consist of 0.15 mg of crospovidone and 5.85 mg of croscarmellose sodium in 100 mg tablet, which resulted in 3.4 kg of hardness response, 0.34% of friability, 2.38 seconds of wetting time, and 3.97 seconds of disintegration time. Analysis of one sample t-test showed that there was no significant difference between the parameter values predicted results with the results of the research, so it can be concluded that SLD equation can be used to develop a formula that gives optimum parameters of FDT. Conclusion: Based on these results, combinations of crospovidone and croscarmellose sodium was able to produce FDT of Cetirizine HCl.