Effects of powder flow properties and shear environment on the performance of continuous mixing of pharmaceutical powders

Abstract

This paper focuses on two aspects of continuous powder mixing, namely characterizing the effects of material properties on the bulk powder flow behavior, and developing continuous blending strategies suitable for cohesive materials. The relative effects of process parameters and material properties on the bulk powder flow behavior were analyzed by performing a PLS analysis of the output parameters, including mean residence time, and axial dispersion coefficient as a function of input parameters (impeller speed, flow rate, bulk density and cohesion). The mean residence time was primarily affected by the bulk density and impeller speed, whereas the axial dispersion coefficient was affected by impeller speed and cohesion. Based on previously developed knowledge of mixing performance as a function of process parameters [1] , a design rule to select the optimal number of impeller passes based on the bulk density was proposed. Impeller speed and cohesion showed a significant interacting effect on the output variable, the axial dispersion coefficient. Increase in cohesion leads to increase in the axial dispersion coefficient at higher impeller speeds, whereas a negligible effect of cohesion on the axial dispersion coefficient was observed at lower impeller speeds. In the second part of the paper, a continuous blending methodology for blending cohesive materials was demonstrated. Considering the feeding limitations of cohesive materials, and limitations in the application of shear in the bladed continuous mixer, a combination of high shear and low shear mixing with high-shear mixing as a first step exhibited an optimal mixing strategy. The Gericke mixer was found to be a poor micro-mixer/de-lumper, whereas the Comil was found to be a good micro-mixer and poor macro-mixer. Integrated system with Comil first provided the best possible mixing performance. • Residence time was primarily affected by bulk density and impeller speed. • Axial dispersion was primarily affected by cohesion and impeller speed. • High-shear before low-shear mixing exhibited an optimal continuous mixing strategy.