The aim of this work was to apply the simplex lattice design in the formulation development of lozenges containing Vernonia cinerea extract. The different ratios of three diluents; milk powder, xylitol, and inulin were investigated. The preformulation parameters of powder mixtures were evaluated. The compressed lozenges were evaluated for their weight variation, thickness, hardness, friability, and disintegration time. Results showed that the ratios of the three diluents affected the preformulation parameters. The angle of repose data revealed that all 12 powder mixtures had excellent flow property. The formulation containing milk powder had the highest values of Carr’s index and Hausner ratio, indicating the poor compressibility. While formulation containing inulin had the best compressibility. A formulation containing xylitol had the lowest moisture content. The compressed lozenges had a weight variation of less than 5%, a diameter of 1.5 mm, a thickness of 5-6 mm, and a hardness of 2-12 kP. The 8 of 12 formulations had friability of less than 1%. Use of milk powder provided the longest disintegration time. The desired properties of developed lozenge achieved when the medium amount of xylitol and inulin and low amount of milk powder were used. The optimal diluent ratio providing the weight variation not more than 5%, the hardness of 5-8 kP, friability not more than 1%, and disintegration time not more than 30 min was an equal weight ratio of milk powder, xylitol, and inulin.