(638e) Process Transfer and Optimization of a Commercial Roller Compaction Process Leveraging the Maximum Compressive Stress Model and Design of Experiments

In the pharmaceutical industry roller compaction is becoming more attractive as a method of choice for improving material flow behavior and content uniformity over traditional granulation processes.  This work herein summarizes the scale-up and tech-transfer of a High Drug Load (HDL) and Low Drug Load (LDL) roller compaction granulation (GRN) to a commercial scale compactor.  A Compressive Stresses’ model was employed to scale up the LDL & HDL-GRN processes from an Alexanderwerk WP120 to a Fitzpatrick 7x10 compactor.  Joint process reviews identified critical gaps and/or commercial challenges and were leveraged to define primary development objectives.  During the process validation campaign, poor material flow from the In Bin Hopper (IBH) to the Initial Feed Hopper (IFH) was observed as well as sub-optimized roller compactor operation resulting in various process shut downs and subsequent deviations.  A Design of Experiments (DoE) campaign was successfully employed to balance compaction efficiency and achieve the desired GRN-properties. 

The Maximum Compressive Stress model was able to define the commercial operating parameters that resulted in GRNs with equivalent material properties (PSD, density, porosity, and compactability) as those manufactured at pilot scale.  This enabled the team to rapidly manufacture pivotal Registration Batches at commercial scale.  Material balances of the initial commercial scale batches enabled rapid identification of process risks that resulted in optimizing the process to mitigate preferential API holdup within the material transfer system.  A correlation can also be made between material losses within the material transfer & compaction unit operations and composite assay.  Furthermore, a joint effort was undertaken to successfully execute a commercial scale DoE campaign to optimize the compaction process to reduce equipment stress (i.e., process instability) while yielding GRN properties acceptable for manufacturing bilayer tablets.  GRN properties and operating conditions were not influenced by Roll Speed, however; as expected, Roll Pressure did impact granulation properties.  Characterization of the Roll Pressure operating space enabled optimization of the process to reduce equipment stress without adversely altering the GRN properties.  In conclusion, the LDL and HDL-GRN roller compaction process was successfully qualified and subsequent commercial batches have demonstrated process robustness.