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

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.