3D Printing of Antiemetics: Rheology Serving Personalized Medicine

Introduction
Semi-solid extrusion (SSE) 3D printing is an additive manufacturing technology producing personalized pharmaceutical dosage forms, adjustable in dimensions, dosage strength, and release profile. The dexamethasone-ondansetron combination, recommended for the prophylaxis of moderately emetogenic chemotherapy, could benefit from this technology to manufacture combined orodispersible dosage forms in pediatrics. The success of printing largely depends on the rheological profile of the hydrogel.

Objective
To optimize the physicochemical characteristics of the gel in order to identify a paste with an optimal rheological profile, ensuring orodispersible dosage forms according to the European Pharmacopoeia.

Materials and Methods
Some Hydrogels containing dexamethasone and ondansetron were formulated. Printing was performed by SSE using an M3DIMAKER 2 system (FabRx) in single-layer geometry (cuboid: 10 × 10 × 4 mm). Rheological characterization was carried out using an MCR302 rheometer (Anton Paar): viscosity measurements, amplitude sweeps (storage modulus G′ and loss modulus G″), thixotropy (structural recovery after shear stress), thermal stability (temperature sweeps from 20 to 60 °C). The formulations were subjected to disintegration testing, water loss evaluation, assay of active ingredients, uniformity of mass, and microbiological stability assessment (TSA agar, 35 °C, 6 days) according to the European Pharmacopoeia.

Results
Among 23 formulations, three pastes were selected: P17 (alginate and high glycerol content), P19 (without alginate, enriched in croscarmellose and water), and P22 (Tween 80, reduced water and glycerol).
All hydrogels exhibited shear-thinning behavior, a prerequisite in SSE. Formulations with a high viscoelastic storage modulus G′ (> 1000 Pa) without crossover with G″, such as P17, indicated a rigid structure, leading to difficult extrusion and irregular deposition. Intermediate profiles (G′ ≈ 500 Pa; G″ ≈ 200 Pa), such as P19, enabled homogeneous extrusion. Pronounced thixotropy favored rapid recovery of the initial viscosity, preventing collapse of the hydrogel and ensuring three-dimensional structural stability. P22 displayed a tan δ = 1, reflecting a rigidity–fluidity balance, over a broad range, confirmed by a frequency sweep with stable elastic dominance (G′ > G″, tan δ < 1) without transition between 20 and 60 °C. These three pastes demonstrated shear-thinning behavior, suitable for SSE (improved printing resolution, mechanical integrity).
Water loss stabilized at 11.1% (P17) and 10.2% (P22) after 18 h, compared with 14.9% for P19. Disintegration times were 218 s (P17, non-compliant), 77 s (P19), and 73 s (P22): compliant. P22 met the requirements for mass uniformity (497.5 mg; CV = 2.2%, N = 32) and assay (CV ondansetron = 3.14%; dexamethasone = 11.8%).
No microbial contamination was observed at D0 or after 3 months.

Conclusion
P22 presents an optimal rheological profile; complementary evaluations (dissolution, stability, DSC, XRPD) are required for full validation

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