Investigating the Mechanical Behaviour of Viscoelastic and Brittle Pharmaceutical Excipients During Tabletting: Revealing the Unobvious Potential of Advanced Compaction Simulation

<b>Background</b>: The compaction of formulation blends is a critical stage in pharmaceutical tablet manufacturing, particularly when drug substances or functional excipients exhibit limited flowability and tabletability. <b>Objectives</b>: This study systematically examined the mechanical behaviour of viscoelastic microcrystalline cellulose (MCC) and brittle anhydrous dibasic calcium phosphate (DCPA), as well as their mixtures, to check how deformation mechanisms influence powder handling and tablet performance. <b>Methods</b>: A compaction simulator, mimicking a small rotary tablet press, was used to evaluate tablet weight variability, densification profiles, die-filling height, force-displacement behaviour, and in-die Heckel analysis. Additional assessments included compression times, breaking force, tensile strength, elastic recovery, as well as in-die and out-of-die tablet thickness across various compositions and compaction pressures. <b>Results/Conclusions</b>: Bulk density values from the simulator showed strong correlation with pharmacopeial measurements (R² ≥ 0.997). Measurable differences in true density and cohesiveness led to poor flowability for MCC and good flow for DCPA, with mixtures containing higher DCPA concentration displaying markedly improved flow characteristic. Compaction analyses confirmed extensive plastic deformation for MCC and fragmentation for DCPA. Increasing MCC content elevated die-fill height, compaction energy, and tablet weight variability, whereas higher DCPA fractions decreased apparent density of tablets and reduced energy demand. Tabletability and compressibility profiles reflected that MCC generated hard tablets but exhibited higher elastic recovery, while DCPA formed softer tablets with closer to linear strength-pressure relationships. Energy profiling demonstrated that MCC stored more elastic energy and required higher overall compression work, whereas DCPA reduced elastic accumulation. Overall, blending viscoelastic and brittle excipients offers a robust strategy for optimizing manufacturability, mechanical strength, and energy efficiency in tablet production.