A Critical Review on Engineering of d-Mannitol Crystals: Properties, Applications, and Polymorphic Control

d-mannitol is a common six-carbon sugar alcohol, which is widely used in food, chemical, pharmaceutical, and other industries. Polymorphism is defined as the ability of materials to crystallize into different crystal structures. It has been reported for a long time that d-mannitol has three polymorphs: β, δ, and α. These different polymorphs have unique physicochemical properties, thus affecting the industrial applications of d-mannitol. In this review, we firstly introduced the characteristics of different d-mannitol polymorphs, e.g., crystal structure, morphology, molecular conformational energy, stability, solubility and the analytical techniques of d-mannitol polymorphisms. Then, we described the different strategies for the preparation of d-mannitol crystals and focused on the polymorphic control of d-mannitol crystals in the products. Furthermore, the factors of the formation of different d-mannitol polymorphisms were summarized. Finally, the application of mannitol polymorphism was summarized. The purpose of this paper is to provide new ideas for a more personalized design of d-mannitol for various applications, especially as a pharmaceutical excipient. Meanwhile, the theoretical overview on polymorphic transformation of d-mannitol may shed some light on the crystal design study of other polycrystalline materials.