Thermodynamic properties of enantiotropic polymorphs of glycolide

Highlights: • Polymorphs of glycolide, form 1 and form 2, were characterized by P-XRD, DSC and TG. • Solubilities of form 1 and 2 in five pure solvents were measured by an isothermal gravimetrical method. • Enantiotropic relationship of form 1 and 2 was confirmed from DSC and solubility results. • The average transition temperature was estimated to be 307.1 ± 6 K. • The dissolution thermodynamic properties of form 1 and 2 were calculated using the NRTL equation. - Abstract: In this work, two different polymorphs (form 1 and form 2) of glycolide were successfully prepared and characterized. The solubility of these two polymorphs in ethyl acetate, 1-propanol, ethanol, 2-propanol and 1-butanol at temperatures from 278.15 K to 328.15 K under atmospheric pressure (0.1 MPa) was experimentally measured by using the isothermal gravimetrical method and correlated by the modified Apelblat model and the van't Hoff equation. For all the selected solvents, the solubility curve of form 1 crossed the solubility curve of form 2 at a transition temperature in the above temperature range. Combining the results of DSC, solubility curves and dissolution data of these two polymorphs, it was confirmed that form 1 and form 2 were enantiotropic. The dissolution thermodynamic properties of glycolide form 1 and form 2 were also calculated.