Slugging-induced Mechanistic Coupling of Microcrystalline Cellulose-starch Disintegrants for Enhanced Tablet Disintegration.

Disintegrant performance in insoluble, poorly disintegrating matrices is strongly influenced by how the excipients are assembled at the granule level. This study investigated densified microcrystalline cellulose-starch (MCC-starch, 4:1) granular systems as direct compression disintegrants. In the screening stage, co-processed MCC-starch granules prepared by slugging at 10-190 MPa were incorporated into dibasic calcium phosphate (DCP) tablets at 10-15%, w/w. Disintegration behavior exhibited a strong dependence on slugging pressure, with low-pressure, less dense granules failing to disintegrate the tablets within the 15-min test window, while denser granules progressively shifted performance toward rapid disintegration. Based on these trends, granular densification (12.5%, w/w disintegrant; 190 MPa slugging) was examined with different starch types, maize and rice, and blends. Across both starch groups, tablets formulated with co-processed granules disintegrated significantly faster than tablets incorporating physical mixtures of separately densified components, while tablet tensile strength remained comparable between these formulations. Scanning electron microscopy images supported pressure-dependent changes in granule consolidation. Collectively, the results identify intragranular co-location of MCC and starch within a composite granule, rather than densification alone, as the critical determinant of disintegrant efficiency in DCP tablets, driven by the mechanistic coupling of MCC-mediated wicking and localized starch swelling when wetted.