We applied computing-as-a-service to the unattended, system-agnostic, thermodynamic stability prediction of Vitamin E TPGS and Tween 80 pharmaceutical mixtures with a Copovidone VA64 polymer. The computing scheme involved a massively parallelized architecture for molecular dynamics and free energy perturbation from which binodal, spinodal and mechanical mixture critical points were detected on molar Gibbs free energy profiles at a hot melt extrusion temperature of 180 ˚C. We established tight agreement between the computed stability limits of 9.0 and 10.0 wt% vs. the experimental 7 and 9 wt% for the Vitamin E TPGS and Tween 80 systems, respectively, and determined different destabilizing mechanisms applicable to each system. This paradigm supports that computational stability screening may serve as a physically meaningful, resource-efficient, and operationally sensible digital twin to experimental stress-tests of pharmaceutical delivery systems.