(281f) Enhancing Material Characterizations for Tablet Development Using Split Instrumented Die Technology

In the pursuit of advancing drug product manufacturing, this study employs a state-of-the-art die system facilitating triaxial decompression to investigate the critical unloading and ejection stages of pharmaceutical tablet production. Our experimental setup includes custom-built cylindrical dies integrated with piezoelectric sensors for precise measurements of die-wall pressures throughout the decompression process, and cuboid dies to assess the impact of shape on tablet properties. This combination of advanced instrumentation and die configurations provides unprecedented mechanistic insights into the decompression dynamics and their subsequent impact on tablet integrity.

Our examination spans commonly used excipients—microcrystalline cellulose, crystalline lactose monohydrate, and mannitol. The precise mapping of die-wall pressures facilitated by this technology effectively isolates the effects of unloading from other compaction variables. Although the triaxial decompression system can mitigate defects such as microcracks in certain formulations, its impact on mechanical properties, such as tensile strength, is minimal for materials that already produce defect-free compacts using a rigid die.

On the other hand, our data suggests that the split-able die-wall tooling allows better assessment of materials that are prone to defect formation when made using a rigid die. For these materials, dies with split-able walls enable the production of defect-free compacts, which are crucial for more accurately measuring true bonding strength of the materials; a quantity that better represents the materials' contribution to the bulk mechanical properties of the formulations that include these challenging materials. This enhanced level of material characterization, enabled by our novel instrumentation, offers valuable insights that could contribute to improved practices in material evaluation within the pharmaceutical industry, potentially giving way to better formulation design and optimization that enable faster ‘first-time-right’ tablet development for FIH studies.