Continuous blending, as a critical step in continuous manufacturing of solid oral dosage forms, has a drastically different powder mixing mechanism from that of batch blenders. In this work, we explored material-sparring methods to develop a continuous blending process, with a particular emphasis on the understanding of the extent of shear that a formulation experiences in the continuous blender. We aim to leverage such mechanistic understanding to explore the process/performance interplay, and further optimize solid dosage formulations.
We characterized the extent of shear experienced by a formulation during blending with two orthogonal methods: a compaction analysis tracking the effect of extended lubrication cased by MgSt, and a color measurement tracking the color of the powder blend caused by a shear-sensitive color tracer. We showed that both methods demonstrated the effect of shear that the blender exerted to the system: with increased amount of shear, the blend showed a drop in tensile strength due to over-lubrication, as well as a change in color appearance caused by the dispersion/de-agglomeration of the colorant particles. Both signals are then used to characterize the effect of shear, compared between batch and continuous blending methods.
We established a toolbox to characterize the amount of shear in blenders, and further develop continuous blending processes. Using two orthogonal shear-sensitive measures, we successfully compared the shear effect of the Gericke continuous blender with the traditional Turbula and Bohle blender. We demonstrated a potential processing advantage of CM blending, which can offer better dispersion & de-agglomeration for very fine particles (like red iron oxide), while reducing the risk of over-lubrication of MgSt. Such advantage can potentially be leveraged in formulation design to create unique process-performance relationships using continuous blending.
Anthony Tantuccio– Merck and Co Inc, West Point, Pennsylvania
William Blincoe– Merck and Co Inc
Jasdeep Mandur– Merck and Co Inc
Brandye Smith-Goettler– Merck and Co Inc
James DiNunzio– Senior Principal Scientist, Merck & Co., Inc., Rahway