3D-Printed Isoniazid Tablets for the Treatment and Prevention of TuberculosisPersonalized Dosing and Drug Release

被引:110
|
作者
Oblom, Heidi [1 ]
Zhang, Jiaxiang [2 ]
Pimparade, Manjeet [2 ]
Speer, Isabell [3 ]
Preis, Maren [1 ]
Repka, Michael [2 ,4 ]
Sandler, Niklas [1 ]
机构
[1] Abo Akad Univ, Pharmaceut Sci Lab, Artillerigatan 6A, FIN-20520 Turku, Finland
[2] Univ Mississippi, Dept Pharmaceut & Drug Delivery, University, MS 38677 USA
[3] Heinrich Heine Univ, Inst Pharmaceut & Biopharmaceut, Univ Str 1, D-40225 Dusseldorf, Germany
[4] Univ Mississippi, Pii Ctr Pharmaceut Technol, Oxford, MS 38677 USA
基金
芬兰科学院;
关键词
3D printing; personalized medicine; hot-melt extrusion; immediate release; sustained release; PHARMACEUTICAL EXCIPIENTS; DELIVERY DEVICES; MEDICAL DEVICES; MELT EXTRUSION; 3D; DOSAGE; IMMEDIATE; POLYMERS; PHARMACOKINETICS; FABRICATION;
D O I
10.1208/s12249-018-1233-7
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The aim of the present work was to produce 3D-printed oral dosage forms with a sufficient drug dose displaying various release profiles. Hot-melt extrusion was utilized to produce drug-loaded feedstock material that was subsequently 3D-printed into 6, 8, and 10x2.5mm tablets with 15% and 90% infill levels. The prepared formulations contained 30% (w/w) isoniazid in combination with one or multiple pharmaceutical polymers possessing suitable properties for oral drug delivery. Thirteen formulations were successfully hot-melt extruded of which eight had properties suitable for fused deposition modeling 3D printing. Formulations containing HPC were found to be superior regarding printability in this study. Filaments with a breaking distance below 1.5mm were observed to be too brittle to be fed into the printer. In addition, filaments with high moisture uptake at high relative humidity generally failed to be printable. Different release profiles for the 3D-printed tablets were obtained as a result of using different polymers in the printed formulations. For 8mm tablets printed with 90% infill, 80% isoniazid release was observed between 40 and 852min. Drug release characteristics could further be altered by changing the infill or the size of the printed tablets allowing personalization of the tablets. This study presents novel formulations containing isoniazid for prevention of latent tuberculosis and investigates 3D printing technology for personalized production of oral solid dosage forms enabling adjustable dose and drug release properties.
引用
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页数:13
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