Comparative Analysis of the Compression Performance of Polymorphic D-Mannitol Using a Multidimensional Framework

The purpose of this study was to conduct a comprehensive, multidimensional measurement and comparison of polymorphic mannitol in order to gain a deeper understanding of its polymorphism. The morphology, density, flowability, tabletability, disintegrability, and dissolution behavior of different polymorphic forms of mannitol were first compared. Then, the differences in tabletability, disintegrability, and dissolution behavior of the polymorphs were further elucidated via nanoindentation, atomic force microscopy (AFM), and cryo-scanning electron microscopy (cryo-SEM). Measurements of density, particle size, angle of repose, and texture parameters indicated that β-mannitol exhibited a lower cohesive index and cake strength, resulting in superior flowability. Nanoindentation and tensile strength data showed that δ-mannitol demonstrated a greater plastic deformation energy, leading to enhanced tabletability. Cryo-SEM and disintegration studies revealed that tablets containing α-mannitol had the loosest surface structure and the shortest disintegration time, although the roughness of the particle surface negatively impacted disintegration. In vitro release and AFM results showed that β-mannitol had weaker binding interactions with drug particles and exhibited a stronger release effect on curcumin. This comprehensive comparison of polymorphic mannitol enhances our understanding of its properties and supports its potential application in solid dosage forms, providing a reference for further exploration in other fields.