Dynamic scaling approach for a continuous horizontal blender using a small-scale image of an industrial-scale blender

While scaling in pharmaceutical development is a well-established concept, continuous processes are often lacking on small scale equipment and translation experience to employ it. Especially when aiming for direct compression processes. Therefore, in this study, an industrial-scale blender will be scaled down, and the scaling approach will be evaluated. In this study, a potential scaling approach is evaluated and demonstrated to highlight considerations that must be applied for scaling. This approach consists of achieving geometric and dynamic similarity by scaling the vessel volume by a factor of ten and maintaining a consistent Froude number ratio for impeller speed. The feasibility of this scaling approach is investigated with well-flowing and cohesive materials of different particle aspect ratios (spherical, fibrous) by comparing the number of blade passes, blender fill level, and blend uniformity. The key findings of our study are the quantitative feasibility of scaling for spherical, and well flowing materials. For flowing, but fibrous materials the quantitative scaling approach was successful for the centre points, but challenges with intensified pro-cess conditions arose. Cohesive, and irregular shaped materials, proved to be qualitatively scalable with the presented approach. Therefore, risk assessment can be conducted even in early clinical trial manufacturing with the small-scale equipment enabling knowledge transfer from early to late stage development. These findings contribute to a deeper understanding of scaling processes (material attribute dependency, process limitations) in continuous horizontal blending and provide a framework (keeping number of blade passes and fill level constant) for optimizing blending operations across scales.