Molecular Dynamics of Amorphous Sulfamethazine With Structurally Related Sulfonamide Impurities Evaluated Using Thermal Analysis

In this study, the effects of structurally related organic impurities on the molecular dynamics of amorphous sulfamethazine were evaluated using thermal analysis. Sulfanilamide (SNA), sulfamerazine (SMR), and sulfadimethoxine were used as virtual impurities of sulfamethazine. The amorphous state was prepared in situ in differential scanning calorimetry by quenching the melted physical mixtures of sulfamethazine and each impurity compound in the differential scanning calorimetry pan. In the following heating process, the glass transition temperatures (Tg) of each were measured. The fragility parameters were estimated from the width of Tg. The Tg of amorphous sulfamethazine with those impurities changed in accordance with the manner set forth in the Gordon-Taylor equation. The fragility parameter slightly increased when a small amount of SNA or SMR was incorporated. Moreover, the probability of a measurement in which crystallization of sulfamethazine was observed above its Tg, increased at a low-concentration range of SNA, SMR, or sulfadimethoxine. It was considered that the existence of a small amount of impurity would induce heterogeneity in the molecular density of the amorphous state, which would be associated with the local fluctuation. It was suggested that the change in the molecular dynamics would be related to the probability of crystallization of sulfamethazine.