Título:	Beyond immediate release : FDM‑printed pediatric 6‑Mercaptopurine chewable tablets with spontaneous In situ nanostructure formation
Autor(es):	Oliveira, Gabriel de Sousa Lima, Ana Luiza Granados Muñoz, Pedro Gross, Idejan Padilha Barreto, Livia Cristina Lira de Sá Souza, Patrícia Medeiros de Gratieri, Taís Gelfuso, Guilherme Martins Cunha Filho, Marcílio Sérgio Soares da
ORCID:	https://orcid.org/0009-0005-7175-164X https://orcid.org/0000-0002-2177-8941 https://orcid.org/0000-0001-9787-7076 https://orcid.org/0000-0002-1798-7927 https://orcid.org/0000-0001-8197-4349 https://orcid.org/0000-0003-4022-9187 https://orcid.org/0000-0001-6481-2364 https://orcid.org/0000-0002-1924-7885 https://orcid.org/0000-0002-9167-6852
Afiliação do autor:	University of Brasilia, Laboratory of Food, Drugs, and Cosmetics University of Brasilia, Laboratory of Food, Drugs, and Cosmetics University of Brasilia, Laboratory of Food, Drugs, and Cosmetics University of Brasilia, Laboratory of Food, Drugs, and Cosmetics University of Brasilia, Faculty of Ceilandia University of Brasilia, School of Health Sciences University of Brasilia, Laboratory of Food, Drugs, and Cosmetics University of Brasilia, Laboratory of Food, Drugs, and Cosmetics University of Brasilia, Laboratory of Food, Drugs, and Cosmetics
Assunto:	6-Mercaptopurina Impressão 3D Medicamentos Formulações pediátricas Leucemia linfoblástica aguda Sistemas de liberação de fármacos
Data de publicação:	21-Set-2026
Editora:	Springer
Referência:	OLIVEIRA, Gabriel S. et al. Beyond immediate release: FDM‑printed pediatric 6‑Mercaptopurine chewable tablets with spontaneous In situ nanostructure formation. AAPS PharmSciTech, v. 27, art. n. 302, 2026. DOI: https://doi.org/10.1208/s12249-026-03556-7. Disponível em: https://link.springer.com/article/10.1208/s12249-026-03556-7. Acesso em: 22 out. 2026.
Abstract:	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.
Unidade Acadêmica:	Faculdade de Ciências da Saúde (FS) Departamento de Farmácia (FS FAR) Faculdade de Ciências e Tecnologias em Saúde (FCTS) – Campus UnB Ceilândia
Programa de pós-graduação:	Programa de Pós-Graduação em Ciências da Saúde
Licença:	Open Access This article is licensed under a Creative Commons Attri bution 4.0 International License, which permits use, sharing, adapta tion, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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