(238c) Effect of Powder Cohesion and Mixer Operation Parameters On Blend Uniformity Using a New Low Shear Continuous Tumble Mixer

The study of flow and mixing of granular materials has increased exponentially in computational and experimental studies in the last years especially in batch systems. In most of pharmaceuticals industries powder mixing is an important operation used daily, and due to the Process Analytical Technology (PAT) initiative these industries need to move on to continuous systems and to be in the capacity to control instabilities on line to make processes more efficient.

 In this work, a new continuous low shear mixing device consisting of two, short, acrylic, hollow concentric cylinders has been developed to study granular mixing. The inside cylinder has multiple orifices of 4 mm of diameter and the complete mixer moves counter clockwise making part of the powders to form an avalanche while at the same time powders escape from the inside cylinder to the outside cylinder where the sample is collected to obtain the degree of mixing achieved. The complete system consists of two feeders that deliver the active pharmaceutical ingredient and the excipients. The experimental design was set to obtain three different formulations (2.5, 10.5 and 20% API) each one at three flow rates and four mixer different velocities. Results show an effective mix with values of RSD lower than 6% demonstrating that the operating conditions and powder properties such as particle size distribution and powder cohesion affect considerably the homogeneity, hold up and the average residence time of the mixer.

 The experimental part will be completed with simulations of the continuous mixing process using DEM (discrete element method) to study the powder phenomena including the pattern flows, avalanche deformation and flow through tumble orifices to relate these with the properties of the materials characterized previously.