Mechanism of the multi-scale structure of starch-based materials in determining the compaction behavior of pharmaceutical powders.

This study aimed to investigate the multiscale structural evolution of starch under mechanical stress and its impact on the mechanical behavior of tablets. The study systematically characterized the multiscale structure, compression behavior, and tablet quality of seven types of starches with different initial structures (native starch, partially hydrolyzed starch, and deeply hydrolyzed starch) before and after dry granulation. The results demonstrate that dry granulation results in a reduction in the short-range and long-range ordered structures of starch (crystallinity decreased by 25.58-61.60%). This stress-induced structural disorder is correlated with increased plastic deformation in native starch and the fragmentation of hydrolyzed starch particles. The enhanced tensile strength (145.95%-228.57%) of partially hydrolyzed starch tablets may result from the increased specific surface area generated by particle fragmentation. In contrast, amorphous maltodextrin after granulation exhibits an enhanced elastic response due to mechanical densification and work hardening, with loss of tabletability. The correlation analysis indicates that the tensile strength of tablets is positively correlated with plastic deformation parameters and roughness, while it is negatively correlated with elastic parameters, short-range order, and crystallinity. These results indicate that the effect of dry granulation on tablet quality depends on the initial structural characteristics. While granulation improves the performance of starch-based tablets with high elastic response by disrupting their ordered structure, it may impair the performance of starch-based tablets with strong plastic deformation capacity due to work hardening. This structure-dependent regulatory relationship provides a theoretical basis for the design of starch-based excipients in solid dosage forms.