Direct extrusion additive manufacturing of personalized theophylline-loaded tablets using granules and powders as feedstock materials

Traditional pharmaceutical manufacturing is heavily optimized for mass production, utilizing high-throughput processing methods to ensure economic viability and strict uniformity. However, these rigid, centralized systems inherently lack the operational flexibility required to address the emerging paradigm of personalized medicine, which demands custom dosages tailored to individual patient characteristics. Additive Manufacturing (AM) has emerged as a disruptive technology capable of fabricating complex geometries unattainable via traditional processes. This approach enables precise control over drug dosages and their release profiles, offering a viable path to fulfill specific clinical needs. However, conventional filament-based AM requires a multi-step workflow involving intermediate filament fabrication via Hot Melt Extrusion (HME). This process imposes strict material constraints and subjects Active Pharmaceutical Ingredients (APIs) to a dual heating cycle, significantly increasing the risk of thermal degradation and processing failures. To circumvent these limitations, this thesis explores and optimizes Direct Extrusion Additive Manufacturing (DEAM), a process designed for the single-step fabrication of personalized tablets. By integrating a miniaturized plasticizing screw into a commercial Fused Deposition Modeling (FDM) printer, this setup enables the direct processing of granules and powder blends, thereby eliminating the intermediate filament production phase entirely. This work systematically evaluates the influence of critical process settings, specifically the temperature profile, screw design and rotation speed on the stability and consistency of the extrusion flow to identify optimal printing windows. Two distinct polymeric matrices are evaluated: Soluplus® and Kollidon® VA 64, alongside theophylline as Active Pharmaceutical Ingredient (API). Additionally, the study establishes empirical relationships between tablet mass, infill percentage and geometric scale to provide a predictive framework for dosage personalization in clinical applications. Ultimately, this research establishes the overall feasibility of DEAM technology, validating its technical reliability, the reproducibility of the produced dosage forms and its potential as a transformative manufacturing platform for the decentralized production of customized medicines in hospital or pharmacy settings.