Progress in pharmaceutical crystallographic study of mannitol

As a pharmaceutical excipient with low caloric value, low hygroscopicity, and high stability, mannitol is widely used in various dosage forms, such as solid, lyophilized and inhalation preparations, etc. It has different crystal structures (α, β and δ) and cocrystal, and the changes in the crystal structure will affect formulation properties of pharmaceutical formulations. This paper reviews structural features, physicochemical properties, and preparation methods of mannitol polymorphs and cocrystal formation, with emphasis on polymorphic transformation pathways, monitoring methods and the effect of polymorphic transformation on properties and application in pharmaceutical formulations, including tabletability, disintegration and dissolution properties. By systematically summarizing the crystallographic study of mannitol, this study attempts to provide new ideas for the development of novel pharmaceutical excipients and applications in pharmaceutical formulations.