Molecular Dynamics and Physical Stability of Pharmaceutical Co-amorphous Systems: Correlation Between Structural Relaxation Times Measured by Kohlrausch-Williams-Watts With the Width of the Glass Transition Temperature (ΔTg) and the Onset of Crystallization

The study aims to characterize the structural relaxation times of quench-cooled co-amorphous systems using Kohlrausch-Williams-Watts (KWW) and to correlate the relaxation data with the onset of crystallization. Comparisonwas also made between the relaxation times obtained by KWW and the width of glass transition temperature (Delta T-g) methods (simple and quick). Differential scanning calorimetry, Fourier-transformed infrared spectroscopy, and polarized light microscopy were used to characterize the systems. Results showed that co-amorphous systems yielded a single T-g and Delta C-p, suggesting the binary mixtures exist as a single amorphous phase. A narrow step change at Tg indicates the systems were fragile glasses. In co-amorphous nap-indo and para-indo, experimental T(g)s were in good agreement with the predicted T-g. However, the T-g of co-amorphous nap-cim and indo-cim were 20 degrees C higher than the predicted T-g, possibly due to stronger molecular interactions. Structural relaxation times below the experimental Tg were successfully characterized using the KWW and Delta T-g methods. The comparison plot showed that KWW data are directly proportional to the 1/2 power of Delta T-g data, after adjusting for a small offset. A moderate positive correlation was observed between the onset of crystallization and the KWW data. Structural relaxation times may be useful predictor of physical stability of co-amorphous systems. (C) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.