Understanding size enlargement and hardening of granules on tabletability of unlubricated granules prepared by dry granulation.

The mechanism of loss of "reworkability" or tabletability of dry granulated microcrystalline cellulose (MCC) was investigated in relation to both granule size enlargement and granule hardness. Slugs of MCC were prepared under three pressures (12.5, 37.5, and 93.8 MPa) and tabletability (tensile strength vs. pressure) of respective granules (three different sizes) was determined. Nominal single granule fracture strength and granule friability were measured. The reduction in tabletability was profound for harder granules, which were obtained from higher slugging pressure. This is consistent with their ability to resist granule fragmentation during tableting. Variation in granule size exhibits negligible effect on tabletability for the lowest slugging pressure and only a small effect for the middle and highest slugging pressure. This observation is again related to different tendency to granule fragmentation during compaction. The results suggest that granule-hardening negatively affects tensile strength more than that of granule size enlargement for MCC.