(707b) Study the Effect of the Low Shear Continuous Tumble Mixer Parameters On Powder Phenomena, Residence Time, and Blend Uniformity

Miguel Florián, Carlos Velázquez,and Rafael Méndez.

Department of Chemical Engineering, University of Puerto Rico at Mayaguez, PO Box 9000 Mayaguez PR 00681, Puerto Rico

Industries such as the pharmaceutical, food, cosmetic, catalysis, ceramic, and detergent have as a common denominator the granular material mixing step. This operation is performed primarily in batch mode, with some limitations, such as sampling methodology, sample homogeneity determination, and unknown process scale-up behavior. All these limitations hinder the possibility of achieving optimal production, reducing product quality, performance and often lead to batch failures. The pharmaceutical industry started recently to consider continuous manufacturing to be in the capacity to control instabilities on line, to make processes more efficient, optimizing the production and reducing the principal problems of the batch process. One of the more important operations is the powder mixing, which could be the principal process in the drug manufacturing. In this work, a new continuous low shear mixing device consisting of two, short, acrylic, hollow concentric cylinders has been developed using as a model the batch drum mixers to study granular mixing. The complete system consists of two feeders that deliver the active pharmaceutical ingredient and the excipients. The principal goal is understand the effect of the three different flow rate, three API concentrations (2.5, 20.5 and 20%), three speed mixer rotations (30, 50 and 70 RPM) and feeding angle on the relative standard deviation (RSD) of the mixing achieved. The experimental part is complemented with DEM simulations of the continuous mixing process to study the cohesion effect, velocity profile, particle trajectory and the powder phenomena includes the pattern flows, avalanche deformation and flow through tumble orifices to relate these with the properties of the materials characterized previously. A set of experiments with the same operational parameters and particle characteristics similar to the simulations was run to validate these process obtaining similar results with the experimental part. Simulations results show a good agreement with the experimental based on the mixing RSD, the velocity profile and avalanche behavior. The principal results obtained demonstrated that the tumble mixer is capable of achieving a good mixing index based on the RSD of the outlet concentration, the mixing homogeneity was affected by the operation conditions and powder properties such as the particle size distribution and the cohesion, hold up and the average residence time of the mixer.