Selective laser sintering additive manufacturing of dosage forms: Effect of powder formulation and process parameters on the physical properties of printed tablets

被引:29
作者
Tikhomirov, Evgenii [1 ]
ahlen, Michelle [1 ]
Di Gallo, Nicole [2 ]
Stromme, Maria [1 ]
Kipping, Thomas [2 ]
Quodbach, Julian [3 ]
Lindh, Jonas [1 ]
机构
[1] Uppsala Univ, Dept Mat Sci & Engn, Div Nanotechnol & Funct Mat, Angstrom Lab, Box 35, SE-75103 Uppsala, Sweden
[2] Merck KGaA, Frankfurter Str 250, D-033001 Darmstadt, Germany
[3] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Dept Pharmaceut, Univ Weg 99, NL-3584 CG Utrecht, Netherlands
关键词
Additive manufacturing; Three-dimensional printing; Selective laser sintering; Personalized medicines; Drug manufacturing;
D O I
10.1016/j.ijpharm.2023.122780
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Large batches of placebo and drug-loaded solid dosage forms were successfully fabricated using selective laser sintering (SLS) 3D printing in this study. The tablet batches were prepared using either copovidone (N-vinyl-2-pyrrolidone and vinyl acetate, PVP/VA) or polyvinyl alcohol (PVA) and activated carbon (AC) as radiation absorbent, which was added to improve the sintering of the polymer. The physical properties of the dosage forms were evaluated at different pigment concentrations (i.e., 0.5 and 1.0 wt%) and at different laser energy inputs. The mass, hardness, and friability of the tablets were found to be tunable and structures with greater mass and mechanical strength were obtained with increasing carbon concentration and energy input. Amorphization of the active pharmaceutical ingredient in the drug-loaded batches, containing 10 wt% naproxen and 1 wt% AC, was achieved in-situ during printing. Thus, amorphous solid dispersions were prepared in a single-step process and produced tablets with mass losses below 1 wt%. These findings show how the properties of dosage forms can be tuned by careful selection of the process parameters and the powder formulation. SLS 3D printing can therefore be considered to be an interesting and promising technique for the fabrication of personalized medicines.
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页数:11
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