(656g) Hybrid Modeling of Roller Compaction and Tableting for Accelerated Oral Tablet Product

Dry granulation is a technique to improve the bulk density and flow of formulated drug substance powders by increasing the particle size. The powder blend is passed in between a pair of counter-rotating rollers which compacts the blend into a ribbon, which is subsequently milled into a granulation. Extra-granular formulation components are blended into the granulation prior to compression within a rotary tablet press. Traditional dry granulation process development involved a series of experimental evaluations, which allowed formulators and process scientists to determine an operating region for the roller compactor, and the subsequent tablet press. Such evaluations tend to be resource and time intensive and are particularly challenging to execute in the early development stages when drug substance availability is limited. This is particularly relevant to projects with accelerated timelines. In such situations, computer simulation methods offer an excellent alternative, allowing the exploration of operating regions with minimal a priori experimental characterization. In addition, regions beyond typical experimental studies can be explored using simulations.

In this work, we develop computational methods to model roller compaction and tableting processes and propose their use in combination. The resulting end-to-end model utilizes minimal experimental data. These proposed models are a combination of first-principles methods and their extensions using physics-based data-driven models. These models allow us to accelerate process development by identifying suitable process operating regions to achieve a target ribbon solid fraction, and subsequent tablet solid fraction and hardness specifications. We compare our model predictions with available data from an accelerated tablet drug product and find reasonable agreement. These models allow for faster process development and identification of process parameters for scale-up, which allows project teams to accomplish accelerated technology transfers and rapid manufacturing campaigns. These models are at the forefront of our digitalization initiatives in dry granulation process development, enabling us to reduce developmental time and resources.