Abstract
To develop a calorimetry-based model for estimating the time-dependence of molecular mobility during the isothermal relaxation of amorphous organic compounds below their glass transition temperature (Tg). The time-dependent enthalpy relaxation times of amorphous sorbitol, indomethacin, trehalose and sucrose were estimated based on the nonlinear Adam-Gibbs equation. Fragility was determined from the scanning rate dependence of Tg. Time evolution of the fictive temperature was determined from Tg, the heat capacity of the amorphous and crystalline forms, and from the enthalpy relaxation data. Relaxation time changes significantly upon annealing for all compounds studied. The magnitude of the increase in relaxation time does not depend on any one parameter but on four parameters: Tg, fragility, and the crystal-liquid and glass-liquid heat capacity differences. The obtained mobility data for indomethacin and sucrose, both stored at Tg-16 K, correlated much better with their different crystallization tendencies than did the Kohlrausch-Williams-Watts (KWW) equation. The observed changes in relaxation time help explain and address the limitations of the KWW approach. Due consideration of the time-dependence of molecular mobility upon storage is a key element for improving the understanding necessary for stabilizing amorphous formulations.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
