Development and In-Vitro Characterization of a Personalized, pH-Responsive Polypill for Dual-Drug Delivery via Multi-Material FDM 3D Printing

Abstract

This study explores the development of a personalized polypill designed to deliver two drugs with distinct, pH-sensitive release profiles using multi-material 3D printing via fused deposition modeling (FDM). The aim was to engineer a single tablet capable of releasing each drug independently at its intended site within the gastrointestinal tract. To achieve this, two drug-loaded filaments were prepared through hot-melt extrusion (HME). One filament, intended for immediate release, incorporated paracetamol within a polyvinyl alcohol (PVA) matrix. The other, designed for enteric release, embedded mesalazine in Eudragit L100. These filaments were used to print a core-shell tablet, with the mesalazine-containing core fully enclosed by the paracetamol-based shell. The printed tablets were evaluated for their physical integrity, chemical composition, and drug release behavior. In vitro dissolution testing was conducted using a USP Apparatus II paddle system, simulating gastrointestinal conditions through a pH-shift protocol—starting with 0.1N hydrochloric acid for two hours, followed by a phosphate buffer at pH 7.4. Results showed that the extrusion process produced filaments with uniform drug distribution and excellent printability. The tablets demonstrated high dimensional accuracy and allowed for precise, customizable dosing. During dissolution, the outer shell released over 95% of paracetamol rapidly in the acidic phase, while the mesalazine core remained intact. Upon transitioning to the neutral pH environment, the enteric coating dissolved, enabling a complete and controlled release of mesalazine. Overall, the findings highlight the promise of multi-material FDM 3D printing in fabricating sophisticated, pH-responsive polypills. This approach offers a viable pathway for creating patient-specific combination therapies with tailored dosing and release kinetics, potentially transforming personalized medicine.