Stability and Crystallization of Indomethacin/ Sucrose Benzoate Co-Amorphous Glasses

Isothermal crystallization of indomethacin and binary miscible mixtures of indomethacin and sucrose benzoate samples are investigated from a super-cooled liquid state using differential scanning calorimetry to study the stability of the systems. These mixtures, classified as co-amorphous systems, are known to demonstrate advantages such as enhanced water solubility and bioavailability relative to the crystalline active pharmaceutical ingredient. The crystallization data for indomethacin and its co-amorphs with sucrose benzoate were modeled using the Avrami equation as a function of time at different temperatures. The derived data are also used to obtain the time-temperature-transformation (TTT) diagram, which is fitted to the nucleation rate theory model. Results reveal that the nose of the TTT diagram shifts to lower temperatures and longer times with the addition of sucrose benzoate. The composition with 49% sucrose benzoate exhibited the highest stability, representing the most stable co-amorphous formulation in this study. In addition, the solubility of IND in SB is examined and found to increase with temperature, as expected.