PSI - Issue 82

Krastena Nikolova et al. / Procedia Structural Integrity 82 (2026) 227–233 K. Nikolova et al./ Structural Integrity Procedia 00 (2026) 000–000

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The aim of the present review paper is to analyze the structure and properties of pharmaceuticals fabricated by 3D printing. 2. Main material 2.1. Precisely dosed dosage forms for pediatric use The production of such dosage forms by conventional methods is often unsuitable for administration to young children due to the difficulty in achieving accurate dosing. In addition, traditionally manufactured pediatric formulations frequently possess an acidic, bitter, or metallic taste (World Health Organization (WHO). Development of Paediatric Medicines: 2012). Taste masking can be achieved through hot melt extrusion techniques. Apart from the challenges of accurate dose adjustment for children, swallowing large capsules or tablets is often problematic because of their size. To overcome these limitations, mini-tablets with a diameter below 5 mm (Thomson S.A. et al. 2009) or tablets designed in the form of chewable candies (Scoutaris N. et al. 2018; Rycerz K. et al. 2019) have been developed. Using semi-solid extrusion (SSE) 3D printing technology, Goyanes et al. formulated chewable isoleucine “prints” (Goyanes A. et al. 2019). Zheng et al. proposed a novel approach for the hospital formulation of medicines by incorporating ground spironolactone and hydrochlorothiazide tablets into excipients to prepare a printable ink, which was then used for the fabrication of 3D-printed tablets with divided doses of the aforementioned drugs (Du J. et al. 2021). The SSE technology has been applied to fabricate bilayer tablets with controlled release (Khaled S.A. et al. 2014), gastric floating tablets (Li Q. et al. 2018), and multi-release tablets (Khaled S.A. et al. 2015), among others. However, SSE-printed tablets typically require prolonged post-processing (approximately 12 hours) to ensure complete solvent evaporation (Khaled S.A. et al. 2015). An alternative approach involves the use of gel-based inks, which can solidify at room temperature through crosslinking. This method has been employed in the manufacture of vitamin formulations containing gums such as arabic and guar gum, as well as hydrocolloids including carrageenan, xanthan, and related polymers (Azam R.S.M. et al. 2018). 3D printing also enables the fabrication of tablets with sustained-release profiles, characterized by a gradual increase in drug release over time. Zhao et al. developed a spherical tablet with a hollow internal tetrahedral cavity, filled with a mixture of the drug substance and poly (vinyl alcohol) (PVA) (Zhao J. et al. 2018). Upon contact with water, the core of the tetrahedral cavity erodes, resulting in enhanced release of the drug over time. Such a release profile is particularly advantageous in the treatment of hypertension, where a dose taken at night reaches its maximum plasma concentration in the morning. Other researchers have impregnated filaments with active pharmaceutical ingredients to generate patterned infill structures in printed tablets. These filaments were produced by extruding a mixture of diltiazem and hydroxypropyl methylcellulose (HPMC) (Kadry H. et al. 2018). Subsequent studies demonstrated that the drug release rate strongly depends on the tablet’s internal geometry (Yang Y. et al. 2018). For instance, hexagonal infill patterns were shown to dissolve more rapidly than alternative designs. Isreb et al. proposed a novel “radiator-type” tablet, with a surface-to mass ratio 7–8 times higher than that of conventionally manufactured tablets (Isreb A. et al. 2019). To facilitate drug release, the printed lamellae were kept thin in order to minimize gel layer formation upon hydration. Another innovative approach is the design of pulsatile tablets, aimed at regulating discrete release intervals of the active substance. In such systems, the inner and outer layers are separated by a drug-free barrier layer (Kadry H. et al. 2018). Using selective laser sintering (SLS) 3D printing, Goyanes et al. produced immediate-release tablets loaded with paracetamol at 5%, 20%, and 35%. These dosage forms demonstrated pH-independent release profiles, with the release rate constant dependent on paracetamol content (Fina F. et al. 2017). Furthermore, by applying hot-melt extrusion followed by fused deposition modeling (FDM), Okwuosa et al. developed theophylline capsules employing polyvinylpyrrolidone (PVP) as an excipient (Okwuosa T. et al. 2016). The use of naturally derived components largely determines the most suitable methods for 3D printing. Fused deposition modeling (FDM) technology is generally unsuitable for processing such materials due to the high temperatures involved. Nevertheless, its application in the pharmaceutical field remains feasible. Frequently, excipients are employed to enable 3D printing, such as alginate, obtained from the cell walls of brown algae or produced by bacterial strains of Azotobacter and Pseudomonas (Szekalska M. et al. 2016). Alginate nanoparticles