| The main focus of our research is to investigate continuous powder blending. The unit operation of powder blending is widely used to reduce the heterogeneity degree of product mixture in the manufacture of catalysts, cement, food, metal parts, and many other industrial products. Currently in pharmaceutical industry, continuous powder blending has received more attention as an efficient alternative to the traditional batch blending of powders due to its ability in handling high-flux continuous tablet manufacturing. Numerous previous approaches have been performed focusing on investigating the applicability of continuous manufacturing system. However, the development of reliable industrial system is limited by the inaccuracy of mixing index, the complicated effects of operating conditions and the black-box characterization method, all of which result from the lack of a theoretical model that can quantitatively characterize the whole continuous powder mixing process. Therefore, the overall research objective of this work is to develop a general standard method for quantitative process design and control. In this context, three different specific aims are accomplished. We analyze and distinguish different heterogeneity sources in the continuous blending process and develop a general model of continuous blending. Fourier series is applied to characterize the axial blending component, and a periodic section model is developed to capture the cross-sectional blending component. Based on the modeling work, efficient design, control, and scale-up strategies applicable for practical blending of pharmaceutical powders are determined. The effectiveness of the methodology is demonstrated in particle blending simulations and experiments using industrial mixing apparatuses to check its applicability and robustness in pharmaceutical industrial use. |
