Abhishek Paul ^a, Nicolas Sanchez ^a, Sophie Martin ^a.

^a Process Engineering, CMC Synthetics, Sanofi

Loss of tensile strength, also known as loss of compactability, of dry granulated tablets directly affects tablet critical quality attributes such as disintegration and dissolution ^[1]. One of the main reasons for this loss during roller compaction (RC) is work-hardening of the particles as demonstrated by Farber et al.^[2]. 

In-silico prediction of ribbon strength allows estimation of loss of compactability and simplifies process development with less material usage, especially when in-line process analytical tools are challenging to integrate with existing infrastructure. However, this requires a protocol to predict average tensile strength that accounts for the inhomogeneous ribbon porosity in roller compacted ribbons ^[2].

Our approach involves using a compaction simulator to produce pseudo ribbons (or ‘ribblets’) at multiple porosities and measure the failure strength using at least two compact failure tests. We use the Cohesive Zone Model (CZM) coupled with a finite element representation of ribblets to capture tensile fracture and predict breaking force in multiple compact failure configurations ^[3]. By combining the calibrated CZM model with compaction simulator results, we predict the tensile strength distribution across the ribbon after elastic recovery. Subsequently, a calculated average strength of the ribbon is used to estimate the loss of compactability due to RC for given formulation and process parameters. 

Using this work, we aim to provide process and formulation guidelines on achieving a target tensile strength for RC process such that there is minimum loss in compactability while producing granules with reasonably good flowability.  References:

1. Rajkumar, Arthi D., et al. “The effect of roller compaction and tableting stresses on pharmaceutical tablet performance.” Powder Technology 341 (2019): 23-37.
2. Farber, Leon, et al. “Unified compaction curve model for tensile strength of tablets made by roller compaction and direct compression.” International journal of pharmaceutics 346.1-2 (2008): 17-24.
3. Mazel, Vincent, et al. “Comparing failure tests on pharmaceutical tablets: Interpretation using experimental results and a numerical approach with cohesive zone models.” International Journal of Pharmaceutics 642 (2023): 123166.