Three-Dimensional Printing Technology in Pharmaceutical Sciences: Personalized Dosage Forms, Polypills, Pediatric Medicines, and Regulatory Considerations

Abstract

Background: Three-dimensional printing, also termed additive manufacturing, represents a paradigm shift in pharmaceutical manufacturing by enabling the layer-by-layer construction of drug products from digital design files, offering capabilities that conventional manufacturing processes cannot match: patient-specific dose customization, complex multi-compartment release geometries, on-demand fabrication of small batches, and the production of polypills combining multiple active pharmaceutical ingredients in a single dosage unit with independently controlled release profiles. The approval of Spritam, a levetiracetam orally disintegrating tablet manufactured by the ZipDose binder jetting technology, by the United States Food and Drug Administration in 2015 established 3D printing as a regulatory-accepted pharmaceutical manufacturing process.

Objective: This review provides a comprehensive critical analysis of 3D printing technologies applicable to pharmaceutical manufacturing, covering printing methods, pharmaceutical materials, formulation design principles, characterization strategies, therapeutic applications in personalized medicine, pediatric and geriatric dosage forms, and polypill development, with emphasis on research and regulatory developments up to 2023.

Results and Discussion: Seven principal 3D printing technologies — fused deposition modeling, semi-solid extrusion, binder jetting, selective laser sintering, stereolithography, inkjet printing, and two-photon polymerization — each offer distinct capabilities and limitations that determine their suitability for specific pharmaceutical applications. Hot-melt extrusion-coupled FDM is the most extensively investigated approach for solid oral dosage forms, enabling fabrication of amorphous solid dispersions, modified-release tablets, and fixed-dose combination products. Spritam remains the only 3D-printed pharmaceutical product with regulatory approval, but more than 150 clinical trials and research programs utilizing 3D printing for pharmaceutical applications had been registered globally by 2023.

Conclusion: Pharmaceutical 3D printing has advanced from laboratory curiosity to a technology with demonstrated clinical feasibility and one regulatory approval, with growing evidence of its particular value in pediatric dosing, personalized medicine, and complex release geometry applications that conventional manufacturing cannot address. Manufacturing scalability, material library expansion, and regulatory framework development are the key barriers to broader clinical translation.