Beyond Immediate Release: FDM-Printed Pediatric 6-Mercaptopurine Chewable Tablets with Spontaneous In Situ Nanostructure Formation

Pediatric maintenance therapy for acute lymphoblastic leukemia requires prolonged daily administration of 6-mercaptopurine (6-MP), a drug characterized by a narrow therapeutic index and substantial interindividual variability, creating a need for flexible and patient-friendly dosage forms. This study aimed to develop pediatric chewable tablets 6-MP using hot-melt extrusion and fused deposition modeling (FDM) 3D printing. Preformulation studies and rheological characterization were performed to support formulation development. The influence of internal architecture on porosity, disintegration, mechanical properties, and chewability was investigated by varying infill density. Among the evaluated architectures, 30% infill provided the best balance between structural integrity, porosity, rapid disintegration, and softening after saliva exposure, ensuring adequate chewability. Tablets exhibited accurate drug content (99.5 ± 2.2%). Beyond their immediate-release behavior, complete drug release was achieved within 15 min, while colloidal nanostructures were spontaneously formed, associating approximately 11% of dissolved 6-MP, suggesting a hybrid release mechanism combining rapid drug availability with nano-mediated modulation. Dynamic light scattering and transmission electron microscopy confirmed these findings. Overall, the developed platform demonstrates the potential of FDM-based structural engineering to produce personalized pediatric medicines and reveals that thermally processed polymeric matrices may function as dynamic drug delivery systems rather than conventional immediate-release dosage forms.