The relevance of granule fragmentation on reduced tabletability of granules from ductile or brittle materials produced by roll compaction/dry granulation.

Roll compaction/dry granulation often results in loss of tabletability. The two main hypotheses for this are granule hardening and granule size enlargement. The aim of this study was to investigate the effect of granule size, roll compaction force, and granule fragmentation upon tableting and its effect on tabletability of granules constituting a ductile or brittle material. Plastically deforming microcrystalline cellulose (MCC) and fragmenting lactose monohydrate (lactose) were roll compacted at five roll compaction forces ranging from 2 to 16 kN/cm. Granule size fractions of 250-355 and 500-710 µm were blended with 10% magnesium stearate (MgSt), compressed into tablets and ground to obtain compressed granules. The predominant deformation behaviour of the particles constituting the granules directly impacted granule deformation upon tableting, as lactose granules fractured extensively upon tableting, whereas MCC granules predominantly deformed by plastic deformation. Increased roll compaction force resulted in more granule hardening of both materials and thereby granules less susceptible to fragmentation upon tableting. Granule hardening accounted for the largest loss of tabletability of MCC granules upon roll compaction. Roll compaction force and granule size had no or negligible effect on tabletability of lactose tablets without MgSt, whereas increased roll compaction force and larger granules decreased tensile strength of tablets containing lactose granules blended with MgSt. This was explained by inter-particle and inter-granular bonds contributing equally to the tensile strength of lactose tablets without MgSt. However, after addition of MgSt, the decreased fragmentation tendency of larger granules compacted at higher roll compaction forces resulted in greater MgSt coverage of the granules upon tableting, thereby decreasing tabletability.