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The goal of the study was to analyze the impact of human serum albumin (HSA) quality (stabilized or nonstabilized HSA), the addition of NaCl, and the HSA stabilizers Naoctanoate and Na-N-acetyltryptophanate on the freezing behavior of mannitol-HSA formulations. The focus was on crystallization, Tg' (glass transition temperature of the maximally freeze-concentrated phase), and Tc (collapse temperature). Differential scanning calorimetry (DSC), cryomicroscopy, and low-temperature x-ray powder diffraction (LTXRD) were used to study the frozen state. In mannitol-HSA formulations. mannitol crystallization was inhibited and Tg' lowered to a greater extent by stabilized HSA (containing Na-octanoate, Na-N-aceyltraptophanate, and NaCl) than by unstabilized HSA. Detailed DSC and LTXRD studies showed that in the concentrations used for stabilizing HSA, NaCl led to changes in the freezing behavior, an effect that was less pronounced for the other stabilizers. NaCl further lowered the Tc, which was determined by cryomicroscopy. As the freezing behavior governs the lyophilization process, the changes have to be taken into consideration for the development of a lyophilization cycle, to avoid collapse and instabilities.