Study on powder physical and compression properties of mannitol: Similarity, variation, and classification

Abstract

The global supply of mannitol offers diverse grades, typically categorized by manufacturers into “spray-dried” or “granulated” types for direct compression (DC). However, relying solely on these nominal process labels can be misleading for formulation development. This study established a quantitative, functionality-based classification system by systematically evaluating thirteen commercial mannitol grades through multivariate statistical analysis. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) revealed that the manufacturing process label does not strictly dictate functional performance. Notably, three specific granulated grades were found to functionally cluster with spray-dried materials (Cluster 1) due to their shared porous micromorphology and high specific surface area, exhibiting superior tabletability (k_a) and compressibility (k_G). In contrast, Cluster 2, characterized by dense crystalline structures, demonstrated distinct mechanical behaviors dominated by high elasticity (k_FES) and fragmentation tendency (f). Partial least squares (PLS) regression further elucidated the critical mechanisms governing tablet quality, identifying yield pressure (P_y) and tabletability (k_a) as the primary positive determinants for tensile strength, while excessive fragmentation and elastic recovery negatively impacted mechanical integrity. A trade-off was also observed where enhanced compressibility facilitated rapid disintegration, whereas excessive interparticle bonding could delay it. In summary, this property-driven classification framework provides a more rational strategy for excipient selection than commercial labels, enabling the identification of optimal materials for robust DC formulations based on intrinsic functional attributes.