Semisolid extrusion 3D printing for pharmaceutical compounding: influence of active ingredients on alginate-based inks and tailored-dosage forms properties

Falcone G, Amante C, et al.

Carbohydrate Polymer Technologies and Applications

University of Salerno

RESEARCH SUMMARY

This study investigated whether a precrosslinked alginate hydrogel could serve as a versatile semisolid extrusion 3D printing ink for personalized pharmaceutical compounding across different active pharmaceutical ingredients. The authors used ibuprofen, ketoprofen, and ketoprofen lysine salt as model NSAIDs because they differ in aqueous solubility and therefore enter the alginate matrix as either dispersed or solubilized drug phases. Ibuprofen and ketoprofen were physically incorporated as dispersed phases and generally preserved the calcium-alginate network structure, while ketoprofen lysine salt dissolved in the matrix and formed drug-polymer interactions that partially disrupted alginate entanglement. Rheological testing showed that all inks maintained gel-like, shear-thinning behaviour and acceptable recovery for semisolid extrusion. UniVert extrudability testing confirmed that dispersed APIs increased the extrusion force required for continuous flow, while the solubilized KLS reduced extrusion force by weakening network strength. All inks were printable into cylindrical tablets with mass variation below 10%, and most formulations achieved encapsulation efficiency above 90%; the exception was the 10% KLS formulation, where matrix disruption caused liquid leakage during drying and encapsulation efficiency fell to about 60%. Tablet texture testing showed that 5% drug-loaded tablets retained softness comparable to the blank formulation, while 10% ibuprofen and ketoprofen increased stiffness and 10% KLS produced an overly soft, adhesive tablet that did not meet reproducibility requirements. Dissolution testing showed low gastric release below 10%, followed by sustained intestinal release governed mainly by the alginate matrix through Super Case II transport. Overall, the study supports precrosslinked alginate as a flexible ready-to-use SSE ink platform for tailored oral dosage forms, while identifying solubilized high-load APIs as a key limitation for matrix stability.

A CellScale UniVert 1kN equipped with a 200 N load cell was used in two parts of the study. First, it was used to quantify hydrogel-ink extrudability. Drug-free and NSAID-loaded alginate hydrogel inks were loaded into 5 mL syringes fitted with 18-gauge needles and placed in a lab-made syringe tool on the UniVert. Force versus time was recorded at room temperature for 60 seconds at a speed of 0.04 mm/s. Extrusion force was calculated as the mean force after steady-state continuous flow was reached, and force deviation was calculated from the standard deviation of the steady-state extrusion force. The drug-free ink required about 3.30 N, while 5% ibuprofen and 5% ketoprofen increased extrusion force to about 3.80 N and 4.40 N, respectively. In contrast, 5% ketoprofen lysine salt reduced extrusion force by about 20%, consistent with reduced network strength from drug-polymer interactions. At 10% loading, ibuprofen and ketoprofen further increased extrusion force, while KLS further decreased it; all inks showed low force fluctuation, supporting hydrogel homogeneity. Second, the UniVert was used for parallel-plate compression texture testing of dried 3D printed tablets. At least five tablets from each formulation were compressed, and CellScale Data Analysis Software was used to calculate Young’s modulus from the linear region of the stress-strain curve between 1% and 5% compression. These measurements showed that 5% drug-loaded tablets had Young’s modulus values comparable to the blank alginate tablet, 10% ibuprofen and ketoprofen tablets were substantially stiffer, and 10% KLS tablets were much softer and adhesive, supporting the conclusion that API loading and solubility affect final tablet texture.

AUTHORS

Giovanni Falcone, Chiara Amante, Carla Sardo, Pasquale Del Gaudio, Rita P. Aquino, Paola Russo.

PUBLICATION DETAILS

JOURNAL

Carbohydrate Polymer Technologies and Applications

YEAR

2026

INSTITUTIONS

University of Salerno

COUNTRIES

Italy

INSTRUMENT USED

UniVert

TESTING METHODS

Compression Testing

RESEARCH APPLICATIONS

3D Bioprinting & Bioink Materials TestingDrug Screening & Drug Delivery MechanicsHydrogel Mechanical TestingPolymers and Elastomers Testing

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