Objective: The aim of this study was to evaluate and optimize the amorphous solid dispersion of a low-soluble BCS Class IV anti-platelet drug using factorial design in line with the Quality by Design (QbD) principle. Methods: Ticagrelor, a low-soluble anti-platelet agent, was used as the model drug for the current study. A solid dispersion technique was explored to improve the dissolution of ticagrelor. The extent of amorphization of ticagrelor with the solid dispersion approach was evaluated with powder X-Ray diffraction (p-XRD) and differential scanning calorimetry (DSC). The principle of factorial design (FD) was adopted to optimize the formulation of ticagrelor solid dispersion. Design Expert® 13 (Stat-Ease Inc., Minneapolis, MN, USA) was explored for the Design of experiments (DoE) and Statistical evaluation. The experiments were designed with three factors at two levels (a 23-factor design) and two responses. The significance of the model was evaluated by analysis of variance (ANOVA) and fit statistics. Various statistical parameters such as sequential p-values, lack of fit, squared correlation coefficient (R2), adjusted R2, and adequate precision were considered in fit statistics. Results: The crystalline ticagrelor has completely amorphized, as indicated by the powder x-ray diffraction (p-XRD) and differential scanning calorimetry (DSC) of the solid dispersion of ticagrelor prepared with copovidone VA 64 and vitamin E TPGS through solvent evaporation technique. An increase in ticagrelor dissolution by 10.7 fold was possible through solid dispersion technology. The lack of fit F-values of 0.11 and 0.00 in the factorial model for response dissolution at 10 min and disintegration time, respectively, are indicative of a good fit. The ANOVA and the fit statistics for the selected factorial model were found to be significant. Conclusion: A solid dispersion technique with carrier copovidone VA 64 and vitamin E TPGS could enhance the dissolution of ticagrelor significantly, to an extent of 10.7 fold. Factorial design is an important tool in optimizing the amorphous solid dispersion of ticagrelor and establishing the design space.