Decoupled Semisolid Extrusion and Drop-on-Demand Dispensing for Liposomal Nanomedicine Tableting

Distributed manufacturing of personalized oral nanomedicines requires processing that protects delicate nanocarriers from thermal and mechanical degradation. Tableting of liposomal nanomedicine into solid dosage forms has gained interest by providing enhanced physicochemical stability and room temperature storage, simplifying cold-chain logistics. Nanomedicine advancements have corresponded with the recent push toward an agile decentralized manufacturing paradigm, incorporating additive manufacturing and 3D printing technologies. This study presents a quality by design-guided framework that decouples semisolid extrusion of blank tablet vehicles from drop-on-demand (DoD) microdispensing of liquid liposomal inks. Critical material attributes and critical process parameters were systematically investigated and optimized to preserve liposomal integrity using a lipid bilayer permeability disruption assay and dynamic light scattering size measurements. Decoupling tablet fabrication from the pharmaceutical drug dosing limited the maximum internal processing temperatures to approximately 50 °C for under 5 minutes, safeguarding the thermolabile liposomes. DoD microdispensing across varying nozzle diameters (60 µm and 100 µm) and pressure pulse intensities (5 Pa·s to 30 Pa·s) produced negligible hydrodynamic shear disruption, maintaining bilayer integrity and liposome particle size distribution. Incorporation into solid tablet matrices enhanced 30-day liposome stability at room temperature relative to aqueous controls, which 2 exhibited membrane breakdown after 14 days. Final tableted formulations, including liposomal ciprofloxacin, met United States Pharmacopeia standards for content uniformity, yielding acceptance values ≤ 8.0 % and target dose recoveries within 90 % to 110 %. This decoupled additive manufacturing platform establishes a robust strategy for decentralized, on-demand compounding of shear- and temperature-sensitive solid oral nanomedicines.