(553c) De-Agglomeration Rate Determination Using Specific Energy Input for Intensifier Bar Blending

Sommer, T., Eli Lilly and Company
Pletcher, T., Eli Lilly and Company
Hilden, J., Eli Lilly and Company
Schrad, M., Eli Lilly and Company
Sloan, J. T., Eli Lilly and Company

Tumble bin blending with intensifier bars (I-bars) has gained popularity in the pharmaceutical industry due to the increased shear provided to the blending process by the I-bar.  This increased shear promotes de-agglomeration of blend components and uniform dispersion in low drug load formulations.  Previous development studies had shown that this de-agglomeration rate could be modeled as a first order ideal mixing process to result in a de-agglomeration rate equation and associated rate constant.

In the work presented here, an alternative first principles model was derived leveraging analogues from comminution theory to characterize the first order de-agglomeration rate constant as a function of the I-bar specific energy input.  Studies were then run at varying bin sizes, bin fill levels, and I-bar speeds to test this model using red iron oxide as a surrogate for agglomerated drug substance.  Results of the study are analyzed to determine the validity of using measured cumulative specific energy input to determine de-agglomeration endpoint.  Additionally, the results of this specific energy model are compared to those of the ideal mixing model.