Amorphous solid dispersion (ASD) is one of the most promising enabling formulationsfeaturing significant water solubility and bioavailability enhancements for biopharmaceuticalclassification system (BCS) class II and IV drugs. An accurate thermodynamic understandingof the ASD should be established for the ease of development of stable formulation with desiredproduct performances. In this study, we report a first experimental approach combined with classicFlory–Huggins (F–H) modelling to understand the performances of ASD across the entire temperatureand drug composition range. At low temperature and drug loading, water (moisture) was inducedinto the system to increase the mobility and accelerate the amorphous drug-amorphous polymerphase separation (AAPS). The binodal line indicating the boundary between one phase and AAPS offelodipine, PVPK15 and water ternary system was successfully measured, and the correspondingF–H interaction parameters (χ) for FD-PVPK15 binary system were derived. By combiningdissolution/melting depression with AAPS approach, the relationship between temperature anddrug loading with χ (Φ, T) for FD-PVPK15 system was modelled across the entire range asχ = 1.72 − 852/T + 5.17·Φ − 7.85·Φ2. This empirical equation can provide better understandingand prediction for the miscibility and stability of drug-polymer ASD at all conditions.