熔融沉积成型3D打印法莫替丁口服脉冲制剂的研究

doi:10.5246/jcps.2022.09.055

中国药学(英文版) ›› 2022, Vol. 31 ›› Issue (9): 657-664.DOI: 10.5246/jcps.2022.09.055

• 【研究论文】 • 下一篇

熔融沉积成型3D打印法莫替丁口服脉冲制剂的研究

李芮¹^,²^,^#, 徐翔宇³^,^#, 陈迪¹^,², 张悦¹^,², 钱浩楠¹^,², 臧根奥³, 闫光荣³^,^*(), 范田园¹^,²^,^*()

1. 北京大学天然药物及仿生药物国家重点实验室, 北京 100191
2. 北京大学药学院分子药剂学与新释药系统北京市重点实验室, 北京 100191
3. 北京航空航天大学机械工程及自动化学院, 北京 100191

收稿日期:2022-03-12 修回日期:2022-04-11 接受日期:2022-05-24 出版日期:2022-09-30 发布日期:2022-09-30
通讯作者: 闫光荣, 范田园
作者简介:
+ Tel.: +86-10-82805123, E-mail: tianyuan_fan@bjmu.edu.cn
+ E-mail: yangr@buaa.edu.cn

Fused deposition modeling 3D printed oral famotidine pulsatile release tablets

Rui Li¹^,²^,^#, Xiangyu Xu³^,^#, Di Chen¹^,², Yue Zhang¹^,², Haonan Qian¹^,², Genao Zang³, Guangrong Yan³^,^*(), Tianyuan Fan¹^,²^,^*()

1 The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
2 Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
3 School of Mechanical Engineering and Automation, Beihang University, Beijing 100191, China

Received:2022-03-12 Revised:2022-04-11 Accepted:2022-05-24 Online:2022-09-30 Published:2022-09-30
Contact: Guangrong Yan, Tianyuan Fan
About author:
# These authors contributed equally to this work.

摘要/Abstract

摘要：

为了制备具有不同药物延迟释放时间, 按照患者需求实现个性化给药的脉冲制剂, 本研究将熔融沉积成型(fused deposition modeling, FDM) 3D打印技术引入制剂领域, 探讨了以该技术结合传统工艺制备核壳型口服脉冲制剂的可行性。该制剂的"核"是以传统工艺制备的市售片剂, 而不含药物的外层壳是以FDM 3D打印技术制备的。本研究采用不同参数设计了三种外壳的片剂, 并对其形态、尺寸、片重、硬度和体外释药进行了表征和评价。结果表明3D打印片剂外型完好, 无缺陷。脉冲片剂的大小、片重、硬度及体外释药行为均与外壳参数相关, 通过调节外壳参数可以实现药物个性化的体外5–7小时的延迟释放。本研究探索了制备脉冲制剂的新方法和实现脉冲制剂个性化给药的新途径。

关键词: FDM 3D打印, 脉冲释放, 口服制剂, 法莫替丁

Abstract:

The aim of this study was to prepare pulsatile release tablets which provide different drug delayed-release time and realize personalized administration according to the needs of patients. Fused deposition modeling (FDM) 3D printing technology was introduced into the field of pharmaceutics in this study, and the feasibility to prepare core-shell pulsatile release tablets was explored by combing 3D printing technology with the traditional manufacturing technology. The core of the pulsatile tablets was a commercial tablet obtained from the traditional technology, and the drug-free shell was prepared by the FDM 3D printing technology. Three kinds of tablet shells were designed using different parameters. Furthermore, the morphology, size, weight, hardness, and in vitro drug release of the 3D printed famotidine pusatile tablets were characterized and evaluated. The results showed that the 3D printed tablets appeared intact without any defects. Different parameters of outer shell affected the size, weight, hardness, and in vitro drug release of the tablets. The tablets achieved a personalized delayed release time varying from 5 to 7 h in vitro. In this way, a new method for preparing pulsatile release tablets and a new way for the personalized administration of pulsatile tablets were explored in this study.

Key words: FDM 3D printing, Pulsatile release, Oral preparation, Famotidine

Supporting:

李芮, 徐翔宇, 陈迪, 张悦, 钱浩楠, 臧根奥, 闫光荣, 范田园. 熔融沉积成型3D打印法莫替丁口服脉冲制剂的研究[J]. 中国药学(英文版), 2022, 31(9): 657-664.

Rui Li, Xiangyu Xu, Di Chen, Yue Zhang, Haonan Qian, Genao Zang, Guangrong Yan, Tianyuan Fan. Fused deposition modeling 3D printed oral famotidine pulsatile release tablets[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(9): 657-664.

图/表 6

Table 1. Parameters of the three kinds of 3D printed pulsatile tablets.

Figure 1. Illustration of the applied force to 3D printed pulsed tablets: direction I (A) and II (B).

Figure 2. Images of filament (A), T-266 (B), T-366 (C) and T-399 (D).

Table 2. The measured weight and size of the 3D printed famotidine pulsatile tablets.

Table 3. The hardness of the 3D printed famotidine pulsatile tablets.

Figure 3. The drug release curves of conventional tablets and 3D printed tablets (n = 3).

参考文献 28

[1]	Long, J.; Gholizadeh, H.; Lu, J.; Bunt, C.; Seyfoddin, A. Application of fused deposition modelling (FDM) method of 3D printing in drug delivery. Curr. Pharm. Des. 2017, 23, 433–439.
[2]	Awad, A.; Trenfield, S.J.; Gaisford, S.; Basit, A.W. 3D printed medicines: a new branch of digital healthcare. Int. J. Pharm. 2018, 548, 586–596.
[3]	Konta, A.; García-Piña, M.; Serrano, D. Personalised 3D printed medicines: which techniques and polymers are more successful? Bioengineering. 2017, 4, 79.
[4]	Jamróz, W.; Kurek, M.; Czech, A.; Szafraniec, J.; Gawlak, K.; Jachowicz, R. 3D printing of tablets containing amorphous aripiprazole by filaments co-extrusion. Eur. J. Pharm. Biopharm. 2018, 131, 44–47.
[5]	Trenfield, S.J.; Goyanes, A.; Telford, R.; Wilsdon, D.; Rowland, M.; Gaisford, S.; Basit, A.W. 3D printed drug products: Non-destructive dose verification using a rapid point-and-shoot approach. Int. J. Pharm. 2018, 549, 283–292.
[6]	Prasad, L.K.; Smyth, H. 3D Printing technologies for drug delivery: a review. Drug Dev. Ind. Pharm. 2016, 42, 1019–1031.
[7]	Kempin, W.; Franz, C.; Koster, L.C.; Schneider, F.; Bogdahn, M.; Weitschies, W.; Seidlitz, A. Assessment of different polymers and drug loads for fused deposition modeling of drug loaded implants. Eur. J. Pharm. Biopharm. 2017, 115, 84–93.
[8]	Zhang, J.X.; Yang, W.W.; Vo, A.Q.; Feng, X.; Ye, X.Y.; Kim, D.W.; Repka, M.A. Hydroxypropyl methylcellulose-based controlled release dosage by melt extrusion and 3D printing: structure and drug release correlation. Carbohydr. Polym. 2017, 177, 49–57.
[9]	Melocchi, A.; Parietti, F.; Loreti, G.; Maroni, A.; Gazzaniga, A.; Zema, L. 3D printing by fused deposition modeling (FDM) of a swellable/erodible capsular device for oral pulsatile release of drugs. J. Drug Deliv. Sci. Technol. 2015, 30, 360–367.
[10]	Patil, S.S.; Shahiwala, A. Patented pulsatile drug delivery technologies for chronotherapy. Expert Opin. Ther. Pat. 2014, 24, 845–856.
[11]	Jain, D.; Raturi, R.; Jain, V.; Bansal, P.; Singh, R. Recent technologies in pulsatile drug delivery systems. Biomatter. 2011, 1, 57–65.
[12]	Díaz Nebreda, A.; Zappia, C.D.; Rodríguez González, A.; Sahores, A.; Sosa, M.; Burghi, V.; Monczor, F.; Davio, C.; Fernández, N.; Shayo, C. Involvement of histamine H1 and H₂ receptor inverse agonists in receptor’s crossregulation. Eur. J. Pharmacol. 2019, 847, 42–52.
[13]	Agarwal, V.; Bansal, M. Design and optimization of a chronotherapeutic dosage form for treatment of nocturnal acid breakthrough. Curr. Drug Deliv. 2012, 9, 608–616.
[14]	Agarwal, V.; Bansal, M. Statistical optimization and fabrication of a press coated pulsatile dosage form to treat nocturnal acid breakthrough. Curr. Drug Deliv. 2013, 10, 444–452.
[15]	Chen, D.; Xu, X.Y.; Li, R.; Zang, G.N.; Zhang, Y.; Wang, M.R.; Xiong, M.F.; Xu, J.R.; Wang, T.; Fu, H.; Hu, Q.; Wu, B.; Yan, G.R.; Fan, T.Y. Preparation and in vitro evaluation of FDM 3D-printed ellipsoid-shaped gastric floating tablets with low infill percentages. AAPS PharmSci. 2019, 21, 6.
[16]	Fu, J.H.; Yin, H.; Yu, X.; Xie, C.; Jiang, H.L.; Jin, Y.G.; Sheng, F.G. Combination of 3D printing technologies and compressed tablets for preparation of riboflavin floating tablet-in-device (TiD) systems. Int. J. Pharm. 2018, 549, 370–379.
[17]	Maroni, A.; Melocchi, A.; Parietti, F.; Foppoli, A.; Zema, L.; Gazzaniga, A. 3D printed multi-compartment capsular devices for two-pulse oral drug delivery. J. Control. Release. 2017, 268, 10–18.
[18]	Melocchi, A.; Parietti, F.; Maroni, A.; Foppoli, A.; Gazzaniga, A.; Zema, L. Hot-melt extruded filaments based on pharmaceutical grade polymers for 3D printing by fused deposition modeling. Int. J. Pharm. 2016, 509, 255–263.
[19]	Isreb, A.; Baj, K.; Wojsz, M.; Isreb, M.; Peak, M.; Alhnan, M.A. 3D printed oral theophylline doses with innovative ‘radiator-like’ design: impact of polyethylene oxide (PEO) molecular weight. Int. J. Pharm. 2019, 564, 98–105.
[20]	Pereira, B.C.; Isreb, A.; Forbes, R.T.; Dores, F.; Habashy, R.; Petit, J.B.; Alhnan, M.A.; Oga, E.F. ‘Temporary Plasticiser’: a novel solution to fabricate 3D printed patient-centred cardiovascular ‘Polypill’ architectures. Eur. J. Pharm. Biopharm. 2019, 135, 94–103.
[21]	Yang, Y.; Wang, H.H.; Li, H.C.; Ou, Z.M.; Yang, G.S. 3D printed tablets with internal scaffold structure using ethyl cellulose to achieve sustained ibuprofen release. Eur. J. Pharm. Sci. 2018, 115, 11–18.
[22]	Aho, J.; Bøtker, J.P.; Genina, N.; Edinger, M.; Arnfast, L.; Rantanen, J. Roadmap to 3D-printed oral pharmaceutical dosage forms: feedstock filament properties and characterization for fused deposition modeling. J. Pharm. Sci. 2019, 108, 26–35.
[23]	Matijašić, G.; Gretić, M.; Kezerić, K.; Petanjek, J.; Vukelić, E. Preparation of filaments and the 3D printing of dronedarone HCl tablets for treating cardiac arrhythmias. AAPS PharmSci. 2019, 20, 310.
[24]	Arafat, B.; Wojsz, M.; Isreb, A.; Forbes, R.T.; Isreb, M.; Ahmed, W.; Arafat, T.; Alhnan, M.A. Tablet fragmentation without a disintegrant: a novel design approach for accelerating disintegration and drug release from 3D printed cellulosic tablets. Eur. J. Pharm. Sci. 2018, 118, 191–199.
[25]	Palekar, S.; Nukala, P.K.; Mishra, S.M.; Kipping, T.; Patel, K. Application of 3D printing technology and quality by design approach for development of age-appropriate pediatric formulation of baclofen. Int. J. Pharm. 2019, 556, 106–116.
[26]	Khaled, S.A.; Alexander, M.R.; Wildman, R.D.; Wallace, M.J.; Sharpe, S.; Yoo, J.; Roberts, C.J. 3D extrusion printing of high drug loading immediate release paracetamol tablets. Int. J. Pharm. 2018, 538, 223–230.
[27]	Tan, D.; Maniruzzaman, M.; Nokhodchi, A. Advanced pharmaceutical applications of hot-melt extrusion coupled with fused deposition modelling (FDM) 3D printing for personalised drug delivery. Pharmaceutics. 2018, 10, 203.
[28]	Li, Q.J.; Guan, X.Y.; Cui, M.S.; Zhu, Z.H.; Chen, K.; Wen, H.Y.; Jia, D.Y.; Hou, J.; Xu, W.T.; Yang, X.G.; Pan, W.S. Preparation and investigation of novel gastro-floating tablets with 3D extrusion-based printing. Int. J. Pharm. 2018, 535, 325–332.

熔融沉积成型3D打印法莫替丁口服脉冲制剂的研究

Fused deposition modeling 3D printed oral famotidine pulsatile release tablets

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 6

参考文献 28

相关文章 2

编辑推荐

Metrics

本文评价

[1]	胡连栋^1*, 刘慈¹, 徐文². 地克珠利口服制剂在家兔体内的药动学研究[J]. , 2009, 18(3): 273-277.
[2]	吴涛, 曾环想^*, 陈济民, 潘卫三. 法莫替丁缓释片的相对生物利用度研究[J]. , 1998, 7(4): 191-196.