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Journal of Peking University (Health Sciences) ›› 2022, Vol. 54 ›› Issue (3): 572-577. doi: 10.19723/j.issn.1671-167X.2022.03.026

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Preparation and in vitro evaluation of fused deposition modeling 3D printed compound tablets of captopril and hydrochlorothiazide

Zhi-sheng LI,Hao-nan QIAN,Tian-yuan FAN*()   

  1. Department of Pharmaceutics, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Peking University School of Pharmaceutical Sciences, Beijing 100191, China
  • Received:2021-07-05 Online:2022-06-18 Published:2022-06-14
  • Contact: Tian-yuan FAN E-mail:tianyuan_fan@bjmu.edu.cn

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Abstract:

Objective: To explore the feasibility of preparing compound tablets for the treatment of hypertension by fused deposition modeling (FDM) 3D printing technology and to evaluate the quality of the printed compound tablets in vitro. Methods: Polyvinyl alcohol (PVA) filaments were used as the exci-pient to prepare the shell of tablet. The ellipse-shaped tablets (the length of major axes of ellipse was 20 mm, the length of the minor axes of ellipse was 10 mm, the height of tablet was 5 mm) with two separate compartments were designed and printed using FDM 3D printer. The height of layer was 0.2 mm, and the thickness of roof or floor was 0.6 mm. The thickness of shell was 1.2 mm, and the thickness of the partition wall between the two compartments was 0.6 mm. Two cardiovascular drugs, captopril (CTP) and hydrochlorothiazide (HCT), were selected as model drugs for the printed compound tablet and filled in the two compartments of the tablet, respectively. The microscopic morphology of the tablets was observed by scanning electron microscopy (SEM). The weight variation of the tablets was investigated by electronic scale. The hardness of the tablets was measured by a single-column mechanical test system. The contents of the drugs in the tablets were determined by high performance liquid chromatography (HPLC), and the dissolution apparatus was used to measure the in vitro drug release of the tablets. Results: The prepared FDM 3D printed compound tablets were all in good shape without printing defects. The average weight of the tablets was (644.3±6.55) mg. The content of CTP and HCT was separately (52.3±0.26) mg and (49.6±0.74) mg. A delayed in vitro release profile was observed for CTP and HCT, and the delayed release time for CTP and HCT in vitro was 20 min and 40 min, respectively. The time for 70% of CTP and HCT released was separately 30 min and 60 min. Conclusion: CTP and HCT compound tablets were successfully prepared by FDM 3D printing technology, and the printed tablets were of good qualities.

Key words: Fused deposition modeling, Printing, three-dimensional, Hypertension, Drug combinations, Tablets

CLC Number: 

  • R944.4

Figure 1

Design of the 3D printed compound tablet CTP, captopril; HCT, hydrochlorothiazide."

Figure 2

Photographs of the 3D printed tablets (20.0 mm×10.0 mm×5.0 mm)"

Figure 3

SEM photos for lateral and cross section of the 3D printed tablets A, side view (30×); B, side view (1 000×); C, cross section (30×); D, cross section (inner side of bottom, 1 000×)."

Table 1

Weights and weight variation of the 3D printed tablets"

Number 1 2 3 4 5 6 7 8 9 10
Weight/mg 652.5 632.7 645.6 652.7 650.6 633.9 642.6 644.2 642.9 646.0
Weight variation/% 1.27 -1.80 0.20 1.30 0.98 -1.61 -0.26 -0.02 -0.22 0.22

Figure 4

Stress-deformation curve of the 3D printed tablet"

Figure 5

In vitro dissolution curve of 3D printed tablets CTP, captopril; HCT, hydrochlorothiazide."

1 Tan DK , Maniruzzaman M , Nokhodchi A . Advanced pharmaceutical applications of hot-melt extrusion coupled with fused deposition modelling (FDM) 3D printing for personalised drug delivery[J]. Pharmaceutics, 2018, 10 (4): 203.
doi: 10.3390/pharmaceutics10040203
2 Okafor-Muo OL , Hassanin H , Kayyali R , et al. 3D printing of solid oral dosage forms: Numerous challenges with unique opportunities[J]. J Pharm Sci, 2020, 109 (12): 3535- 3550.
doi: 10.1016/j.xphs.2020.08.029
3 Brambilla CRM , Okafor-Muo OL , Hassanin H , et al. 3D printing of oral solid formulations: A systematic review[J]. Pharmaceutics, 2021, 13 (3): 358.
doi: 10.3390/pharmaceutics13030358
4 Melocchi A , Parietti F , Loreti G , et al. 3D printing by fused deposition modeling (FDM) of a swellable/erodible capsular device for oral pulsatile release of drugs[J]. J Drug Deliv Sci Technol, 2015, 30 (Part B): 360- 367.
doi: 10.1016/j.jddst.2015.07.016
5 Lu J , Lu Y , Wang X , et al. Prevalence, awareness, treatment, and control of hypertension in China: Data from 1.7 million adults in a population-based screening study (China PEACE Million Persons Project)[J]. Lancet, 2017, 390 (10112): 2549- 2558.
doi: 10.1016/S0140-6736(17)32478-9
6 国家卫生计生委合理用药专家委员会, 中国医师协会高血压专业委员会. 高血压合理用药指南(第2版)[J]. 中国医学前沿杂志, 2017, 9 (7): 28- 126.
7 An J , Derington CG , Luong T , et al. Fixed-dose combination medications for treating hypertension: A review of effectiveness, safety, and challenges[J]. Curr Hypertens Rep, 2020, 22 (11): 95.
doi: 10.1007/s11906-020-01109-2
8 国家药典委员会. 中华人民共和国药典(二部)[M]. 北京: 中国医药科技出版社, 2020: 963
9 国家药典委员会. 中华人民共和国药典(四部)[M]. 北京: 中国医药科技出版社, 2020: 112, 137, 478.
10 Ghanizadeh Tabriz A , Nandi U , Hurt AP , et al. 3D printed bilayer tablet with dual controlled drug release for tuberculosis treatment[J]. Int J Pharm, 2021, 593, 120147.
doi: 10.1016/j.ijpharm.2020.120147
11 Charoenying T , Patrojanasophon P , Ngawhirunpat T , et al. Fabrication of floating capsule-in-3D-printed devices as gastro-retentive delivery systems of amoxicillin[J]. J Drug Deliv Sci Technol, 2020, 55, 100393.
12 Wang Y , Sun L , Mei Z , et al. 3D printed biodegradable implants as an individualized drug delivery system for local chemotherapy of osteosarcoma[J]. Materials & Design, 2020, 186, 108336.
doi: 10.1016/j.matdes.2019.108336
13 Kempin W , Domsta V , Grathoff G , et al. Immediate release 3D-printed tablets produced via fused deposition modeling of a thermo-sensitive drug[J]. Pharm Res, 2018, 35 (6): 124.
doi: 10.1007/s11095-018-2405-6
14 Homaee Borujeni S , Mirdamadian SZ , Varshosaz J , et al. Three-dimensional (3D) printed tablets using ethyl cellulose and hydroxypropyl cellulose to achieve zero order sustained release profile[J]. Cellulose, 2020, 27, 1573- 1589.
doi: 10.1007/s10570-019-02881-4
15 Fuenmayor E , Forde M , Healy AV , et al. Comparison of fused filament fabrication to direct compression and injection molding in the manufacture of oral tablets[J]. Int J Pharm, 2019, 558, 328- 340.
doi: 10.1016/j.ijpharm.2019.01.013
16 Yang Y , Wang H , Li H , et al. 3D printed tablets with internal scaffold structure using ethyl cellulose to achieve sustained ibuprofen release[J]. Eur J Pharm Sci, 2018, 115, 11- 18.
doi: 10.1016/j.ejps.2018.01.005
17 Mazzanti V , Malagutti L , Mollica F . FDM 3D printing of polymers containing natural fillers: A review of their mechanical properties[J]. Polymers (Basel), 2019, 11 (7): 1094.
doi: 10.3390/polym11071094
18 Sadia M , Sosnicka A , Arafat B , et al. Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets[J]. Int J Pharm, 2016, 513 (1/2): 659- 668.
19 Melocchi A , Uboldi M , Briatico-Vangosa F , et al. The ChronotopicTM system for pulsatile and colonic delivery of active molecules in the era of precision medicine: Feasibility by 3D printing via fused deposition modeling (FDM)[J]. Pharmaceutics, 2021, 13 (5): 759.
doi: 10.3390/pharmaceutics13050759
20 The U.S. Food and Drug Administration. FDA-approved drugs: Captopril (018343): 2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020504s026lbl.pdf.
21 The U.S. Food and Drug Administration. FDA-approved drugs: Hydrochlorothiazide (084324): 2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018343s087lbl.pdf.
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