The interplay between compression mechanisms and compaction pressure in relation to the loss of tabletability of dry granulated particles

The study investigated the sequential relationship between composition, fracture strength, degree of fragmentation, and loss of tabletability (LoT) of dry granulated particles to get a deeper insight into the underlying causes controlling the LoT. Surrogate granules, consistent in dimension and composed of a systematic variation of a brittle (lactose) and plastic powder (microcrystalline cellulose), were prepared by compaction. These granules were then compressed into tablets at low compression pressures, considered to correspond to the compression phase during which the main fragmentation occurs. The mechanically weak tablets were gently deaggregated into compressed granules, and the proportion of formed fragments was determined using dry powder laser diffractometry and by sieving as an indication of the degree of granule fragmentation. The compressed granules comprised three sub-populations of particles, i.e., non-fragmented granules, fragmented granules, and fine particles, with fragmentation ceasing already within the restricted pressure range applied. The degree of granule fragmentation was dependent on composition and showed an inverted relationship with granule fracture strength. For tablets formed at 100 MPa, the LoT was primarily controlled by the degree of fragmentation, while for tablets formed at 300 MPa, the LoT was affected by a combination of granule fragmentation and deformation. Thus, the relative impact of fragmentation and deformation on the LoT is dependent on the tableting pressure. • Granule fragmentation depends on the mechanical properties of the raw materials. • The degree of granule fragmentation related inversely to granule fracture strength. • Granule fragmentation ceased at low strain and tablet pressure when compressed. • Granule fragmentation dictates the loss of tabletability at low tablet pressures. • At high pressures, loss of tabletability depends on fragmentation and deformation.