The current present study was planned to formulate tacrolimus extended-release tablets to enhance drug activity. Tacrolimus is a calcineurin inhibitor used to treat mild to moderate atopic dermatitis and preclude organ transplant rejection. However, tacrolimus consists of low bioavailability and shorter half-life. Therefore, it was intended to formulate an extended release formulation with suitable polymers to upregulates its therapeutic response.The melt granulation method was used for the preparation of tacrolimus extended release tablets. The central composite design was employed for optimization at two level three factors. Crucial materials properties were the concentration of glyceryl behenate (X1), the concentration of Hypromellose (X2), and the concentration of PEG 6000 (X3).ANOVA has been implemented to interpret the data and design space.The tacrolimus extended release tablet was successfully formulated using melt granulation method and invitro profile of optimized batch compared with marketed formulation. The outcome of the study revealed that optimized formulation of tacrolimus shows 100% release at 12 h. Whereas, marketed formulation (Envarsus XR) also shows 100% release at12 h. Thus, the findings revealed that the optimized formulation was successfully prepared and suitable for extended release nature