3D printing holds great promise to revolutionize pharmaceutical manufacturing, so for widespread clinical application, it is imperative to evaluate its safety and maximize its benefits. Herein, for the first time, particle emissions of the printing process of a model drug (fluorescein) were monitored in a test chamber to evaluate release. A filament extrusion-type 3D printer was used to make tablets from filaments loaded with fluorescein prepared by hot melt extrusion (HME) or diffusion (passive loading) techniques. Surface contamination of the printer was qualitatively documented. Average concentrations of fluorescein released into air during printing were below the analytical limit of detection for HME and 0.92 ± 0.20 ng/m3 for diffusion. Particle yield from the aerodynamic particle sizer data (#/g extruded) during printing with HME filament (5.01 x 104) was significantly lower (p < 0.05) compared with diffusion filament (1.07 x 106). Mathematical modeling was used to predict where particles might deposit in the respiratory system if inhaled by a worker. Predictions showed larger fractions of particles deposited in the head and pulmonary (alveolar) regions from diffusion-loaded filament compared with HME, albeit non-significant. Fluorescein was transferred onto personal protective equipment (gloves) and printer surfaces, which indicated potential for dermal exposure and cross-contamination. Assuming our results are representative of active pharmaceutical ingredients, they support the importance of controls such as containment to minimize inhalation exposure and housekeeping to minimize dermal exposure and cross-contamination of tablets.
Keywords: Active pharmaceutical ingredient; Exposure controls; Fluorescein; Fused filament fabrication; Hot melt extrusion; Solution loading.
Published by Elsevier B.V.