Understanding Continuous Mixing Using Advanced DEM Simulations
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In the pharmaceutical industry, continuous powder mixing plays a crucial role especially in the continuous tableting process providing consistent product quality. Continuous powder mixing involves combining two or more separate streams of powders, often including active pharmaceutical ingredients (APIs) and inactive ingredients (excipients and lubricants), and mixing them into a uniform and processable powder. The importance of mixing comes to light when a blend of excipients, lubricants, and new APIs with specific material properties needs to adhere to predefined tablet quality attributes. However, challenges can arise in the mixing of pharmaceutical powders due to their unique material properties. These powders typically consist of very small particles (around 10-100µm in size) and often exhibit poor flowability, high cohesion, adhesion, and a tendency to segregate. Since not all powders exhibit these properties, the mixing unit has to be able to handle a wide range of powder properties. To address these challenges effectively, advanced techniques such as Discrete Element Method (DEM) simulations are increasingly employed in the pharmaceutical industry. By utilizing DEM simulations, researchers can gain valuable insights into the intricate dynamics of powder mixing. This computational approach allows for a detailed examination of particle interactions, flow patterns, and process parameter dynamics within the continuous mixer. DEM simulations provide a virtual platform for studying various mixing scenarios, optimizing process parameters, and ensuring success during the manufacturing process. In this study, the DEM approach is used to study the mixing of a powder with very high API loading in the mixture. A vertical continuous blender, termed Continuous Mixing Technology (CMT) is simulated. Before employing the DEM in the CMT study, the material characteristics are analyzed and the DEM contact-force model is adjusted to best represent the material at hand. After that, the operating space for the CMT is investigated to find the optimal space for the real process. Multiple innovative mixing approaches were tested virtually to determine their viability for further exploration. This work presents a comprehensive overview of an integrated approach, showcasing the combined simulations and experimental results in Continuous Mixing Technology (CMT).
