Theoretical approaches are formulated to investigate the molecular mobility under various cooling rates of amorphous drugs. We describe the structural relaxation of a tagged molecule as a coupled process of cage-scale dynamics and collective molecular rearrangement beyond the first coordination shell. The coupling between local and non-local dynamics behaves distinctly in different substances. Theoretical calculations for the structural relaxation time, glass transition temperature, and dynamic fragility are carried out over twenty-two amorphous drugs and polymers. Numerical results have a quantitatively good accordance with experimental data and the extracted physical quantities using the Vogel-Fulcher-Tammann fit function and machine learning. The machine learning method reveals the linear relation between the glass transition temperature and the melting point, which is a key factor for pharmaceutical solubility. Our predictive approaches are reliable tools for developing drug formulations.
This journal is © The Royal Society of Chemistry.