The objective of this article was to present some key thermodynamic and physicochemical data for the rational optimization of freeze-drying cycles. First, a ternary system of poly(vinylpyrrolidone) (PVP) + lactose + water was studied over large concentration and temperature ranges by modulated differential scanning calorimetry (MDSC). In parallel with DSC experiments, the binary system PVP + water was investigated by cryomicroscopy. Both methods showed crystallization during cooling in the PVP concentration range lower than 49% (wt) and ice recrystallization during warming in the PVP range between 49% (wt) and 64% (wt). Second, a large experimental study has been carried out to determine the influence of lactose concentration on freezable water fractions and glass-transition temperatures. Finally, the solid/liquid phase diagram of the ternary PVP/water/lactose system was determined. These new experimental data concern the melting and vitreous transition temperatures of this ternary system and could be very useful in the future for optimizing the operating conditions of freeze-drying cycles of thermosensitive pharmaceutical formulations.