Particle engineering enables laser powder bed fusion of highly loaded metoprolol tablets at room temperature.

Abstract

Laser powder bed fusion (LPBF) is a promising additive manufacturing technology for producing personalized pharmaceutical dosage forms at industrial scale. In this process, a laser fuses thin layers of powder composed of an active pharmaceutical ingredient (API) and a binder to build three-dimensional objects layer-by-layer. A key limitation for pharmaceutical application of LPBF is the poor flowability and spreadability of fine and cohesive API powders, especially at high API loadings, which can cause spreading defects and poor process reproducibility. The purpose of this study was to enable LPBF manufacturing of highly loaded metoprolol (MTP) tablets by tailoring powder properties through particle engineering. Tangential spray fluidized bed processing was employed to produce MTP-polymer composite particles with API loadings between 75-90% (w/w). The engineered particles exhibited narrow particle size distributions, good flowability, and favorable spreadability, as determined by the roughness index of the spread powder layers. Tablets were manufactured without preheating the powder, using the laser as the sole energy source. Stimulated Raman scattering microscopy allowed visualization of the fine distribution of MTP and polymer within the tablets across the different API loadings. This particle engineering approach overcomes key material barriers to LPBF of highly loaded drug products and demonstrates that room-temperature manufacturing of metoprolol tablets is feasible. This strategy provides a foundation for extending LPBF to highly dosed APIs, supporting future development of personalized medicines.