(41g) A Scalable Continuous Process for ASD Tablet Production: Integration of Hot Melt Extrusion and Direct Compaction

The pharmaceutical industry is progressively transitioning from batch to continuous manufacturing, enabling shorter process cycles, reduced storage and production costs, minimized material losses, and enhanced process efficiency through maximized equipment utilization and reduced downtime. Beyond these advantages, continuous manufacturing facilitates real-time quality control, advanced process monitoring, rapid process parameter adjustments, and full automation of the production chain. Through these capabilities, better product quality can be achieved.

This study presents a systematic approach for processing the model active pharmaceutical ingredient (API) itraconazole into an amorphous solid dispersion (ASD) via hot melt extrusion (HME) and subsequent direct compaction (DC) into tablets within a fully integrated continuous manufacturing process. In the initial phase, small-scale feasibility studies were conducted, supported by one-dimensional (1D) HME simulations, to optimize process parameters of the individual unit operations. The second phase involved the implementation in a large-scale continuous manufacturing process. The first step in this manufacturing process is the ASD formation via HME using a large-scale ZSK18 extruder. The extrudates are then continuously pelletized and milled to achieve a controlled particle size distribution (PSD) suitable for direct compaction (DC). A vacuum transport system conveys the milled material to the DC unit, consisting of two feeders, a high-shear fluidizing blender, and a rotary tablet press. The final tablets are analysed in terms of their critical quality attributes, including content uniformity and dissolution profile.

This work focuses on the formation of an ASD via HME and its subsequent integration into a continuous, direct compaction process, demonstrating its feasibility for scalable and efficient production for solid oral dosage forms.