2. Academic Validation
  3. Physicochemical characterization and clinical evaluation of 3D-printed subdivided tablets of 6-Mercaptopurine with broad dosage variations

Physicochemical characterization and clinical evaluation of 3D-printed subdivided tablets of 6-Mercaptopurine with broad dosage variations

  • Int J Pharm. 2026 Mar 10:692:126648. doi: 10.1016/j.ijpharm.2026.126648.
Jia Liu 1,  Lu Liu 2,  Haofeng Zheng 1,  Caiye Chen 1,  Baixian Zhou 1,  Changfei Liu 1,  Weiqiang Zeng 3,  Yantong Lu 3,  Kaixia Fu 1,  Sha Lai 4,  Fenglan Song 5,  Saizhu He 6,  Wei Yang 7,  Fan Yang 8
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Teaching and Experimental Center, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China.
  • 2 Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Teaching and Experimental Center, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China; Clifford Hospital, Guangzhou 511495, Guangdong, China.
  • 3 Department of Pharmacy, Shunde Women and Children's Hospital of Guangdong Medical University (Maternity and Child Healthcare Hospital of Shunde Foshan), Foshan 528300, Guangdong, China.
  • 4 Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, Guangdong, China.
  • 5 Teaching and Experimental Center, Guangdong Pharmaceutical University, Zhongshan 528458, Guangdong, China.
  • 6 Department of Pharmacy, Shunde Women and Children's Hospital of Guangdong Medical University (Maternity and Child Healthcare Hospital of Shunde Foshan), Foshan 528300, Guangdong, China. Electronic address: [email protected].
  • 7 Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China. Electronic address: [email protected].
  • 8 Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Teaching and Experimental Center, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China. Electronic address: [email protected].
PMID: 41644072 DOI: 10.1016/j.ijpharm.2026.126648
Abstract

6-Mercaptopurine (6-MP), a first-line drug for the maintenance treatment of acute lymphoblastic leukemia (ALL) in pediatric patients, has an extremely narrow therapeutic window and exhibits considerable dosage variability. This study employed semi-solid extrusion (SSE) 3D printing to fabricate precisely dosed subdivided 6-MP tablets of 1, 3, 5, 15, and 20 mg using two formulations (low-dose and high-dose). Printability-guided optimization was conducted to identify the optimal formulations. The low-dose formulation comprised commercial 6-MP powder, 10% hydroxypropyl methylcellulose (HPMC) hydroalcoholic gel, and a 6:7 (w/w) mixture of cornstarch and microcrystalline cellulose, whereas the high-dose formulation consisted of commercial 6-MP powder, 10% HPMC hydroalcoholic gel, 2% magnesium stearate, and 3% sodium carboxymethyl starch. All five dosage specifications met pharmacopoeial standards for mass uniformity, drug content, content uniformity, and dissolution. High-performance liquid chromatography, powder X-ray diffraction, Fourier transform infrared spectroscopy, and Raman spectroscopy were employed to analyze the physicochemical characterization of 6-MP before and after 3D printing, confirming that the drug content, crystal form, and chemical structure of 6-MP remained unchanged during SSE 3D printing and 7-day storage. Pediatric patients with ALL were treated with either 3D-printed or pharmacist-splitting group subdivided 6-MP doses. Paired t-tests within each group revealed significant differences in white blood cell counts pre-treatment and post-treatment (pharmacist-splitting group: P < 0.01; 3D-printed group: P < 0.001), indicating that both groups exhibited pharmacological activity, with the 3D-printed group achieving improved control of hematological indices. Overall, SSE 3D printing technology enables accurate and safe individualized drug dosing.

Keywords

3D printing; 6-MP; Clinical efficacy; Individualized preparation; Physicochemical characterization.

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