3D printing of amorphous solid dispersions: A comparison of fused deposition modeling and drop-on-powder printing

Nowadays, a high number of pipeline drugs are poorly soluble and require solubility enhancement by e.g., manufacturing of amorphous solid dispersion. Pharmaceutical 3D printing has great potential in producing amorphous solid oral dosage forms. However, 3D printing techniques differ greatly in terms of processing as well as tablet properties. In this study, an amorphous formulation, which had been printed via Fused Deposition Modeling and drop-on-powder printing, also known as binder jetting, was characterized in terms of solid-state properties and physical stability. Solid state assessment was performed by differential scanning calorimetry, powder X-ray diffraction and polarized microscopy.

Highlights

• Direct comparison of the 3D printing techniques drop-on-powder and Fused Deposition Modeling using the same raw material.
• Feasibility demonstrated for direct printing of high-dose and physically stable amorphous solid dispersions using both techniques.
• Mechanical properties of formulation greatly influence the processability in both techniques.
• Results indicate an improved mass uniformity for drop-on-powder printed dosage forms.

The supersaturation performance of the amorphous solid dispersion was assessed via non-sink dissolution. We further evaluated both 3D printing techniques regarding their processability as well as tablet conformity in terms of dimension, mass and content. Challenges and limitations of each 3D printing technique were discussed. Both techniques are feasible for the production of amorphous formulations. Results indicated that Fused Deposition Modeling is better suited for production, as the recrystallization tendency was lower. Still, filament production and printing presented a major challenge. Drop-on-powder printing can be a viable alternative for the production of amorphous tablets, when a formulation is not printable by Fused Deposition Modeling.

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Materials

KTZ was used as model compound. KTZ has poor solubility (0.08 mg/mL in phosphate buffer pH 6.8 (Ullrich and Schiffter, 2018)) and melts at 151 °C (Kanaujia et al., 2011). KTZ was purchased from LGM Pharma (Boca Raton, USA). Copovidone, which was used as matrix polymer (Kollidon® VA64, vinylpyrrolidone-vinyl acetate copolymer), was purchased from BASF (Ludwigshafen, Germany). Colloidal silicon dioxide was used as flowability enhancer and was purchased from Evonik Industries (Essen, Germany).

Fasted State Simulated Intestinal Fluid (FASSIF) was purchased from Biorelevant.com Ltd. (London, UK). Hydrochloric acid (HCl 0.1 M), acetonitrile (ACN, hypergrade, purity ≥99.9%), sodium hydroxide solution (1 M), formic acid, ammonia solution (25%), sodium chloride and di‑sodium hydrogen phosphate were purchased from Merck KGaA (Darmstadt, Germany). All reagents used in this study were of analytical grade.

Nadine Gottschalk, Malte Bogdahn, Julian Quodbach, 3D printing of amorphous solid dispersions: A comparison of fused deposition modeling and drop-on-powder printing, International Journal of Pharmaceutics: X, 2023, 100179, ISSN 2590-1567, https://doi.org/10.1016/j.ijpx.2023.100179.