Due to high global warming potential (GWP) of hydrofluorocarbons (HFCs), the separation and recovery of HFCs from different refrigerant mixtures is an important issue. Most HFC mixtures are azeotropic in nature, thereby rendering the conventional distillation-based separation difficult and energy intensive. Extractive distillation (ED) with ionic liquid (IL) as solvent provides an attractive strategy for selective separation of HFC mixtures. However, systematic design and optimization of ED-based separation processes is nontrivial. In this work, we present SPICE_ED which is a software framework for the detailed design, synthesis, and techno-economic analysis of ED-based separation processes. The framework employs a building block representation followed by superstructure optimization that is able to automatically generate numerous design solutions and screen the best without requiring prior expert knowledge of candidate configurations. For a given IL as solvent and a set of design specifications, one can automatically determine the feasibility of the solvent and obtain the optimal process flowsheets that correspond to minimum energy consumption, minimum separation cost, or minimum emission/waste. We demonstrate the capability of SPICE_ED for the separation of R-410A (50 wt % R-32 and 50 wt % R-125) using [bmim][PF 6 ], a commonly used IL. Our optimized design requires an equivalent work of only 338.2 kJ/kg R-410A, which is about 48% less than the previously reported value of 656 kJ/kg. The newly identified design also achieves more than 47% and 27% reductions in CO 2 -equivalent emission (sustainability) and cost, respectively. Through multiobjective optimization, we further identify an operating regime to separate R-410A at a near-minimum cost without significantly increasing the energy consumption and emission. The processes obtained from SPICE_ED show excellent agreement with the key performance metrics when simulated in Aspen Plus, thereby establishing confidence in our designs as realistic and implementable.