Influence of powder properties on CMT performance- a DEM study
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Continuous manufacturing is gaining traction in the pharmaceutical industry due to its potential to enhance product quality and flexibility and speed up the drug production-to-shelf path. In continuous production, powder mixing is crucial to ensuring consistent product quality. This process involves blending multiple powders —active pharmaceutical ingredients (APIs) and excipients—into a uniform, processable mixture suitable for compression. Mixing becomes particularly challenging when dealing with powders that exhibit poor flowability, high cohesion, adhesion, and segregation tendencies, all of which can affect final product quality. Discrete Element Method (DEM) simulations are increasingly employed to address these challenges, providing detailed insights into particle interactions, flow dynamics, and mixing efficiency. DEM enables the virtual investigation of process behavior, optimizing operating conditions before implementation in real-world manufacturing. In this study, we investigate how material parameters influence process behavior, particularly focusing on hold-up mass (HUM) stability, valve opening, and particle mean residence time (MRT) as quality parameters. Using several thousand DEM-generated virtual materials that closely represent a wide range of real powders, we explore the behavior of challenging materials with low Flow Function Coefficient (FFC). Since easily flowing materials are typically easy to handle, we concentrate on the region of challenging materials to determine the failure limits under different impeller speeds and mass loads, identifying the boundaries of stable operation. A vertical continuous blender, Continuous Mixing Technology (CMT), is simulated to evaluate how these material characteristics interact with process conditions. The process space investigated represents a relevant, real industrial operating space. The investigation focuses on the interplay between material properties and operational parameters, particularly in conditions where failure risks are high. This work presents a comprehensive approach, utilizing DEM simulations to represent real, challenging pharmaceutical powders, providing valuable insights into continuous powder mixing and helping to establish robust and scalable processes.