title: Reduced tabletability of roller compacted granules as a result of granule size enlargement.
abstract: The mechanism for the frequently observed "loss of reworkability or tabletability" of dry-granulated (DG) powders was investigated in detail using microcrystalline cellulose (MCC). It was hypothesized that granule size enlargement is the primary mechanism to the phenomenon. Detrimental effects of size enlargement on tabletability of plastic materials are predictable based on the physical model of interparticulate bonding within a tablet. In absence of extensive fracture of particles/granules, larger particles/granules exhibit lower surface area available for bonding thus lower tensile strength when compressed under identical conditions. Size effects were first demonstrated using different grades of MCC powders, both whole and sieved, of different particle size distributions. Regardless grade and sieve fraction, larger particles always resulted in lower tabletability, that is, lower tensile strength at the same compaction pressure. It was subsequently shown that enlargement of granules also reduced powder tabletability regardless grade of MCC. Tabletability of sieved granules after roller compacted for one, two, and four times decreased monotonically with increasing granule size but independent of the total number of roller compaction. Moreover, tabletability of fine granules (44-106 microm) was higher than that of coarse MCC powder (Avicel PH-200). These results suggest that the primary mechanism for reduced tabletabilty of DG granules of MCC is granule size enlargement rather than "work-hardening."
authors.affiliation: Pfizer Global Research and Development, 7000 Portage Road, Portage, Michigan 48329, USA.
authors.forename: Changquan Calvin
authors.initials: CC
authors.lastname: Sun
authors.forename: Micah W
authors.initials: MW
authors.lastname: Himmelspach
mesh_terms: D002482:Cellulose / Q000737:chemistry; D004339:Drug Compounding; D010316:Particle Size; D013607:Tablets / Q000737:chemistry*
chemical_list: D013607:Tablets; D002482:Cellulose; C109691:microcrystalline cellulose