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

230 4

loaded with oxaliplatin have been investigated for targeted delivery to colon cancer cells, employing a combined approach of hot-melt extrusion (HME) and FDM (Mirdamadian S.Z. et al. 2022). Furthermore, by simultaneously utilizing FDM and HME technologies, researchers have developed tablet formulations with pectin and sarpogrelate, resulting in a 3D-printed gastroretentive tablet capable of floating in the gastric medium for more than 10 hours (Lee S.H. et al. 2022). 2.2. Bilayer tablets Bilayer tablets represent biphasic systems typically composed of two different active pharmaceutical ingredients (APIs) with distinct release profiles. They have recently gained significant attention due to their potential to achieve synergistic therapeutic effects, improved treatment efficacy, reduced pill burden for patients, and straightforward, rapid manufacturing (He W. et al. 2014). Commonly, one layer ensures immediate release, while the second layer provides sustained release. A successful example includes the development of a 600 mg guaifenesin bilayer tablet produced by 3D printing, intended for the treatment of respiratory tract infections. One layer provided immediate release to relieve acute symptoms, while the second enabled sustained release to maintain therapeutic plasma levels (Khaled S.A. et al. 2014). Similarly, a bilayer tablet for diabetes treatment was fabricated using a one-step compression method (He W. et al. 2014). In this formulation, the first layer contained pioglitazone, a polymer, and a disintegrant for rapid onset of action, while the second layer incorporated metformin with sustained release, achieved through the use of HPMC. Complete release of pioglitazone occurred within 5 minutes, whereas metformin was released over a 12-hour period. 2.2. Polypill With advancing age and the increased prevalence of cardiovascular disorders, elderly patients are often required to take multiple medications either simultaneously or at different intervals. 3D printing technology enables the development of a polypill, which combines all active pharmaceutical ingredients (APIs) and their respective doses tailored to the patient, while accounting for individual dosing schedules. In cases of incompatibility between the co administered drugs, this can be addressed by using a chemically compatible excipient as a barrier or by separating the APIs into distinct layers of the tablet (Awad A. et al. 2018). Maroni proposed an approach for the co-delivery of two chemically incompatible drugs or dosage forms with different compositions (Maroni A. et al. 2017).A multilayered polypill can not only provide different doses at scheduled time intervals, but also allow modification of the release order by adjusting the sequence of the printed layers. Using an emulsion-gelation technique, alginate beads loaded with telmisartan were developed, demonstrating a high efficiency factor and sustained release over 12 hours (Uthumansha U. et al. 2023). 2.3. 3D printing of biopharmaceuticals and nanomedicine products In addition to the dosage forms mentioned above, recent years have seen growing efforts in the 3D printing of biopharmaceuticals and nanomedicines. One example includes a 3D-printed tablet containing alkaline phosphatase for the treatment of ulcerative colitis, designed with a colon-targeted release profile to avoid premature release in the gastric environment (Serrano D.R. et al. 2013). To prevent enzyme degradation during printing, a powder-based printing technique was employed. Furthermore, the printed dosage form was coated with polyethylene glycol (PEG) to ensure colonic release. 3D printing is also increasingly applied to the fabrication of nanomedicines. However, challenges arise due to the tendency of nanoparticles to aggregate, which can compromise the structural integrity of the printed form. To overcome this, research groups recommend pre-treating nanosuspensions with ultrasound, incorporating surfactants, and other stabilizing approaches (Fisusi F.A. et al. 2016). There is considerable interest in 3D-printed nanomedicines based on curcumin, owing to its antioxidant and anticancer properties. However, its lipophilic nature complicates processing. To address this, polymeric nanocapsules loaded with curcumin were incorporated into a 3D-printed carboxymethyl cellulose hydrogel using pressure-assisted microsyringes (PAM). The resulting formulation released polyphenols partially over an 8-hour period, but not completely (Xu W. et al. 2021). Moreover, self-nanoemulsifying