(M0930-03-14) Styl’One Nano Compaction Simulation Studies and Utilization of a Digital Tableting Platform in Formulation Development

Purpose: This study describes the application of the STYL’One Nano Compaction Simulator in conjunction with a Virtual Tablet Designer Platform in the material characterization and formulation development of consumer health drug products.

Methods: STYL’One Nano Compaction Simulation Measurements: Compaction simulation studies were performed using the STYL’One Nano Compaction Simulator. These studies included the In-Die and Out-of-Die measurements. In-Die Measurements: Performed in triplicate at two different linear speeds (low & high speed). Out-of-Die Measurements: Performed in quintuplicate (n=5) at five different pressure levels of 50, 100, 150, 200, and 250 Mpa. Virtual Tablet Designer Platform (VTDP: A database (name & composition) of all the raw materials (individual ingredients and formulation blends) measured in the compaction simulation studies was created in the VTDP. Excel files generated as an output from the In-Die measurements were modified to a file format that is uploadable to the VTDP. The tablet height, mass, and hardness for the five tablets produced at each pressure level in the Out-of-Die measurements were measured and entered into the output excel file generated from the Out-of-Die measurements. The excel file was then modified to a file format that is uploadable to the VTDP. In-Die data calibration: A Sun model calibration was run to get the true density of the materials, that was needed to run a Heckel analysis in the computation of strain rate sensitivity (SRS) of the materials. Out-of-Die data calibration: This was performed for each material to generate the compressibility, compactibility, tabletability, elastic recovery, and ejection stress profile plots for the materials. Composition Designer (part of the VTDP): The calibrated In-Die and Out-of-Die data for the individual raw materials and formulation blends was evaluated with the composition designer.

Results: Material characterization of individual ingredients and formulation blends of proposed bi-layer tablets was successfully conducted using the STYL’One Nano Compaction Simulator and a virtual tablet designer platform. The strain rate sensitivities, compressibility, compactibility, tabletability, elastic recovery, and ejection stress profile plots for the materials generated through model calibration on the VTDP, were evaluated with the composition designer (part of the VTDP) to propose a formulation composition based on the desired/target solid dosage form attributes like tablet hardness. A summary of the results from the In-Die and Out-of-Die data calibrations and Composition Designer evaluation, are as shown in figures 1, 2, and 3, respectively.

Conclusion: Material characterization using the STYL’One Nano Compaction Simulator in conjunction with the Virtual Tablet Designer Platform is an important approach in the pre-formulation development of drug products that is based on mixture rules where the properties of a formulation can be inferred from the properties of its components. This approach provided advantages over the conventional trial-and-error/ time-consuming DOE formulation development studies like better process understanding, more time for innovation, less experiments required, less API/ excipient amounts required, and use of validated models.

References: R. Cabiscol, J. H. Finke, H. Zetzener, A. Kwade, “Characterization of mechanical property distributions on tablet surfaces,” vol. 10, no. 4, p. 184, 2018.
R. J. Roberts, R. C. Rowe, “The compaction of pharmaceutical and other model materials – a pragmatic approach,” vol. 42, no. 4, pp. 903-911, 2001.

Acknowledgements: Bayer AG - Engineering and Technology team.


Summary of In-Die VTDP Calibrated Data


Summary of Out-of-Die VTDP Calibrated Data


Composition Designer Proposed Formulation