3D Printing of Personalised Carvedilol Tablets Using Selective Laser Sintering

Abstract

Selective laser sintering (SLS) has drawn attention for the fabrication of three-dimensional oral dosage forms due to the plurality of drug formulations that can be processed. The aim of this work was to employ SLS with a CO₂ laser for the manufacturing of carvedilol personalised dosage forms of various strengths. Carvedilol (CVD) and vinylpyrrolidone-vinyl acetate copolymer (Kollidon VA64) blends of various ratios were sintered to produce CVD tablets of 3.125, 6.25, and 12.5 mg. The tuning of the SLS processing laser intensity parameter improved printability and impacted the tablet hardness, friability, CVD dissolution rate, and the total amount of drug released. Physicochemical characterization showed the presence of CVD in the amorphous state. X-ray micro-CT analysis demonstrated that the applied CO₂ intensity affected the total tablet porosity, which was reduced with increased laser intensity. The study demonstrated that SLS is a suitable technology for the development of personalised medicines that meet the required specifications and patient needs.

Keywords: 3D printing; carvedilol; oral; personalised medicines; selective laser sintering.

Figure 1

(a) Thermogravimetric analysis of the bulk VA64 and CVD powers to investigate their thermal stability, and (b) DSC thermograms of the bulk CVD and VA64 powders and the 3D-printed tablets at different laser intensities that varied from 25–55%.

Figure 2

(a) SEM image of the CVD/VA 64 physical blend that was used for the printing of formulations 1–8 (30× magnification), and (b) the particle size distribution of the blend.

Figure 3

The 3D-printed tablets with different laser intensities: (a) 100 mg (laser intensities, from left to right, respectively, of 25, 40, and 55%), (b) 200 mg (laser intensities, from left to right, respectively, of 25, 40, and 55%), and (c) 400 mg using a 3.125% CVD blend (laser intensities, from left to right, respectively, of 40 and 55%). The 3D-printed tablets printed with different laser intensities: (d) 100 mg (laser intensities, from left to right, respectively, of 25, 40, and 55%), and (e) 200 mg (laser intensities, from left to right, respectively, of 25, 40, and 55%) with 6.25% loading.

Figure 4

SEM images of the 3D-printed CVD/VA 64 tablets printed at (a) 25% (F1), (b) 40% (F2), and (c) 55% (F3) laser intensities.

Figure 5

XRD graphs of the bulk materials’ physical blends for printing (3.125% CVD loading) and the respective 3D-printed tablets at different laser intensities.

Figure 6

The 3D volume renderings of the SLS-printed specimens (F1) from different views. The top and bottom views are displayed on the left and middle, respectively. On the right, a clipped top view is shown which reveals both the macro-porosity and micro-porosity. Specifically, the top portion of the clipped region is selectively rendered to display the macro-porosity while the bottom portion displays the micro-porosity.

Figure 7

Porosity quantification for the F1–3 printed formulations. (a) The total porosity percentages and their constituent components of the micro- and micro-porosities that resulted from the different laser powers. (b) The total porosity, micro-porosity, and macro-porosity differences between the different laser power printings.

Figure 8

The 3D volume renderings of the SLS-printed specimens printed at 55 W laser power from different views (F3). The top and bottom views are displayed on the left and middle, respectively. On the right, a clipped top view is shown which reveals both the macro-porosity and micro-porosity. Specifically, the top portion of the clipped region is selectively rendered to display the macro-porosity while the bottom portion displays the micro-porosity. Object size: minimum Feret diameter of 5.86 mm, maximum Feret diameter of 11.47 mm, and mean Feret diameter of 9.55 mm. The scale bar is 10 mm.

Figure 9

Dissolution rates of the tablets of various strengths printed at different laser intensities: (a) 3.125 mg, (b) 6.25 mg, (c) 12.5 mg, (d) 6.5 mg, and (e) 12.5 mg strengths.