Background: Powder-based 3D printing, an advanced additive manufacturing technique, can produce oral disintegrating tablets (ODTs) without disintegrants, creating larger-pored tablets via layer-by-layer powder stacking for better water absorption than traditional tablets. Methods: This study focused on using powder-based 3D printing to fabricate clozapine-based ODTs. Through central composite design (CCD), the formulation of ODTs was optimized for rapid disintegration. Analytical techniques such as X-ray Powder Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Differential Scanning Calorimetry (DSC) were employed to investigate the compatibility between clozapine and excipients. Results: The optimized 3D-printed ODTs exhibited a remarkably short disintegration time of (9.9 ± 0.7) s compared to (40) s for compressed tablets. The contact angle of the 3D-printed ODTs was measured as 60.48 ± 0.36°, indicating favorable wettability for disintegration. Scanning Electron Microscopy (SEM) analysis revealed a porous structure in 3D-printed tablets, with a porosity of 48.97% (over two times higher than that of compressed tablets as determined by mercury injection meter). Conclusions: Collectively, this finding demonstrates the feasibility of fabricating highly hydrophilic and non-distensible ODTs without disintegrants using powder-based 3D printing.

Arctigenin (ATG) is a broad-spectrum antitumor drug with an excellent inhibitory effect on malignant tumors such as breast cancer, glioblastoma, liver cancer, and colon cancer. However, the clinical application of ATG is limited by its poor water solubility and quick hydrolysis in the liver, intestine, and plasma, which might hinder its application. Sialic acid (SA) recognizes selectin receptors overexpressed on the surface of tumor-associated macrophages. In this study, SA was conjugated with octadecylamine (ODA) to prepare SA-ODA, which was employed to prepare SA functionalized nanoliposomes (SA-Lip) to achieve breast cancer targeting. The formulations were finely optimized using the Box–Behnken design to achieve higher ATG loading. The size, ζ potential, entrapment efficiency, drug loading, and release behavior of ATG@SA-Lip were fully investigated in comparison with conventional ATG@Lip. The ATG@SA-Lip displayed more potent cytotoxicity and higher cellular internalization compared to ATG@Sol and ATG@Lip in both MCF7 and 4T1 cells. Notably, ATG@SA-Lip showed the lowest impact on the immune system. Our study demonstrates that SA-Lip has strong potential as a delivery system for the targeted delivery of ATG.