(431c) Continuous Tumble Mixing Characterization Using DEM Simulations

Powder mixing is an essential operation in the manufacture of many pharmaceutical products.  Currently, the pharmaceutical industries are performing this operation in batch mode. The FDA have been working in furtherance the application of the continuous processes as an alternative to batch mixing processes that in principle allows for easier on-line control and optimization of mixing performance. In this study, a new continuous tumble mixer was developed using as a model the batch drum mixers to study granular mixing. The principal results obtained using different flow rates, API concentrations, mixer speeds and feeding angles demonstrated that the tumble mixer is capable of achieving a good mixing based on the RSD values.

Based on these results, a combination of different parameters has been study using Discrete Element Methods (DEM) simulations to analyze the effect of the material properties and equipment parameters on the final uniformity. The blender simulated has exactly the same dimensions of the experimental system, and the experimental design included simulations at 50 and 70 RPM with and without cohesion. The principal parameters used in these simulations include two particle generations, 1 mm particle diameter, and flow rate.

To measure the final uniformity; the effect of cohesion, flow and revolutions per minute have been evaluated using the RSD values. To better understand the powder phenomena inside the mixer, the velocity profile, residence time distribution and Froude Number were used and different areas were selected to study the particle homogeneity. The mixing dynamic was evaluated creating sampling volumes in each exit to measure concentration. Simulation results showed good mixing with RSD values below 3%, similar behavior compared to experimental part, and that the powder behavior inside the mixer change with the flow rate, cohesiveness, and the mixer speed.