Origins of the Relative Stabilities of Anhydrous and Hydrated D-Mannitol Crystals

摘要

D-Mannitol, a common bulking agent used in the pharmaceutical. and food industries, is known to crystallize in three anhydrous polymorphs (alpha, beta, and delta) and a hemihydrate form. In this work, solid-state density functional theory simulations and experimental teraherm spectroscopy were used to evaluate the stabilities, thermodynamic relationships, and spectral signatures of these various solids. The thermodynamic analyses of the anhydrous polymorphs identified enantiotropic transitions for beta-delta at approximately room temperature and alpha-delta near the a melting point, but showed alpha and beta to be monotropically related. Computational refinement of the D-mannitol hemihydrate crystal structure and comparison of its Gibbs free energy to the anhydrous forms showed the hemihydrate to be stable only at low temperatures (<253 K), in agreement with experiment, and reveals its conversion to the delta polymorph upon dehydration. Quantification of the intramolecular and intermolecular energies within these solids highlights the competition that exists between molecular conformation and cohesion energies and how a balance of these forces dictates the observed behaviors.