(569a) Scale-Up of the Roller Compaction Process: A Practical and Dimensionless Approach

Scale-up of the Roller Compaction Process: A Practical and Dimensionless Approach

Roller compaction is a continuous dry granulation process commonly used in the pharmaceutical industry to improve powder flow and blend uniformity via powder densification.  In the roller compaction process, powder is fed between two counter-rotating rolls.  The friction between the powder and the rotating roll surface draws the powder through the gap between the rolls and maximum compaction (densification) occurs when the separation between the rolls is at its minimum.  The resultant compacts, or briquettes, are then milled to achieve the desired granule size.

While the roller compaction process appears simple, efforts to quantitatively model the process have proven challenging due to complex material behavior in the feeding and compaction zones.  To date, implementation of roller compaction models to experimental work has been limited because these models typically require large experimental data sets or obscure input parameters that are difficult to obtain experimentally.  In this work, an alternative approach has been established, expanding upon the widely-used roller compaction model, Johanson’s model, to enable its incorporation into a daily work-flow.  The proposed method requires minimal amounts of material (< 1 kg drug blend) and only standard, routinely-measured parameters as inputs.  An excellent correlation between simulated and experimental results has been achieved for placebo and active blends up to 22%w/w drug-load.  Furthermore, a dimensionless relationship between key process parameters and final compact properties was elucidated.  This dimensionless parameter, referred to as the modified-Bingham number (B_m*), highlights the importance of balancing yield and viscous stresses during roller compaction to achieve optimal output properties.  By maintaining a constant ratio of yield-to-viscous stresses, as indicated by a constant B_m*, consistent products were attained between two scales of operation.  B_m* was shown to provide guidance towards determining the design space for formulation development, as well as to facilitate scale-up development.