Research

Pakistani researchers use FDM 3D printing to create tablets with enhanced dosage control

Researchers from旁遮普大学,Mirpur University of Science & Technology,Bahaudin Zakaria UniversityLahore College for Women University,使用3D打印优化了可控剂量的抗生素片剂。

Utilizing Fused Deposition Modelling (FDM) technology, the research team 3D printed tablets of equal size, but with varying percentages of infill and drug concentration. The team identified a direct link between the release rate of the antibiotic, and the tablet’s infill percentage, which enabled them to control its dosage by adjusting its printing parameters. Future applications of the technique could lead to the development of personalized medicine for antibiotic patients, and enhanced clinical outcomes for the severely ill.

The Pakistani researchers used FDM 3D printing to create tablets with different percentages of infill (pictured). Photo via the Future Medicine journal.
The Pakistani researchers used FDM 3D printing to create tablets with different percentages of infill (pictured). Photo via the Future Medicine journal.

3D打印的抗生素应用

抗生素是临床医生在与病原体和管理重症疾病的斗争中的重要武器,有可能提高患者护理甚至降低死亡率。采用优化的剂量方法对于获得这些好处并抑制耐药病原体的发展至关重要。

Ideally, the dosage of these drugs would be customized to the patient, and focused on the specific disease to avoid the risks of over or under-dosage. While this isn’t currently commercially plausible, pharmaceutical companies are increasingly turning towards alternative manufacturing methods to develop customized-dosage capable tablets.

The advantage of using 3D printing to produce drugs is that it allows for different geometrical structures to be built in a layer-by-layer fashion, and when guided by a digital model, the release of the dosage can be controlled. A multitude of AM methods have already been tested by other researchers to 3D print tablets, but the Pakistani team opted for FDM due to its accuracy, adaptability and cost-effectiveness. Moreover, the simplified development processes and enhanced in-built quality of dosage forms by FDM, make it an attractive technique for the production of customized drug-delivery systems.

使用FDM 3D打印,该团队试图控制称为环丙沙星盐酸盐(环丙沙星-HCl)的广泛光谱抗生素的剂量。该药物对复杂和简单的尿液,严重的低呼吸道,胆囊和腹腔内感染有效。尽管如此,为了有效地抵抗这些疾病,每个患者的适当剂量将取决于疾病的先进程度以及年龄和体重等因素。

In addition, only a small number of strength variants for the drug have been made commercially available, and bulk-purchasing in hospital settings hasn’t been feasible or economical. As a result, the research team began developing ciprofloxacin-HCl tablets with differing dosages, in order to optimize its efficacy against multiple infections, and make it customizable to each patient.

The team found that the tablets displayed a mechanical strength of 340 to 400N for those with 25 percent infill, and close to 495N for the higher percentage tablets. Image via the Future Medicine journal.
The team found that the tablets displayed a mechanical strength of 340 to 400N for those with 25 percent infill, and close to 495N for the higher percentage tablets. Image via the Future Medicine journal.

Producing the 3D printed tablets

这些片剂是使用聚乙烯醇(PVA)生物相容性和水溶性聚合物创建的,这是由于其相对低的熔点在190至210°C之间,使用热融化(HME)技术制造了药物负载的PVA丝(HME)技术。Makerbot3 d打印机,复制ciprofloxacin-HCl平板电脑in specific strengths. The polymer melts were extruded through a circular die of 1.75 mm, and guided onto a conveyor belt for cooling and to ensure uniformity of diameter. Extruded filaments were then stored in air-tight containers, with a total of eight formulations containing strengths of between five and twenty percent (w/w) ciprofloxacin-HC, which were fabricated in 50g batches.

进行了挤出细丝的机械测试,以检查其在药物负荷和成分方面的可打印性,并将药物与市售的药物进行比较。结果表明,将药物比例提高到15%或更高,导致机械较弱的丝,这些丝不容易通过FDM工艺打印出来。另一方面,药物比例为10%或以下的细丝更强,可以成功制造。这是由于以下事实:Makerbot 3D打印机需要以1.75毫米的灯丝直径使用,以达到所需的3D打印精度所需的水平。

Critically, the team found that dissolution patterns could be altered by changing the printing parameters, and tablets were successfully printed with 25, 50, 75 and 100 percent infill percentages. Moreover, while the increase in infill percentage predictably increased the tablet’s weight, the size of the tablets stayed almost the same. The drugs also demonstrated high reproducibility and resistance to damage on handling, showing a mechanical strength of 340 to 400N for the 25 percent tablets, and close to 495N for the higher percentage tablets.

While the 25 percent infill tablets were observed to give complete drug release within four hours, the 50, 75 and 100 percent tablets showed a slower release after an initial burst. This indicated that the rate of drug release could be slowed down with a higher infill percentage. In the case of low (25 percent) polymer infill tablets, dissolution was also found to be fast due to the presence of channels in the tablet structure by virtue of its design. As more of its surface area was exposed to the dissolution medium, the drug release was mainly dissolution dependent.

研究小组得出结论,FDM 3D打印可以有效地用定制的口服剂量来制造环丙沙星-HCl。释放图案是通过调整打印参数来量身定制的,并通过降低片剂的填充百分比获得了快速的药物释放。在3D打印中的进展,不仅可以导致具有特定于患者的剂量的片剂,而且还可以提高重症患者的生存率。

“This work is potentially significant for optimized antibiotic dosing, which in turn leads to enhanced clinical outcome,” said the research team. “Further advancement and sophistication in the field will allow this promising move to become an authentic method of producing personalized medicines.”

Tablets used in additive applications

在过去的几年中,3D打印已被用来生产平板电脑来对抗一系列不同的疾病。一组研究人员University College London(UCL) for instance, used3D printing to create opioid tablets(tramadol) with alcohol-resistant and abuse-deterrent properties. The researchers created the tablets to combat the growing global health crisis of opioid abuse caused by the over-prescription of high-strength painkillers.

Global pharmaceutical companyMerck, worked withAMCM, 一个EOS Group建造定制添加剂制造机的公司,使用粉末床融合技术开发和生产3D印刷平板电脑。该伙伴关系被视为“迈向行业数字化的一步。”

British 3D printed pharmaceuticals companyFabRx,使用3D打印来开发儿童个性化药物与罕见的代谢疾病,枫糖浆尿液疾病(MSUD)。FabRX的3D印刷咀嚼片称为“ Printlets”,为制备定制的治疗剂量提供了快速自动的替代方案。

The researchers’ findings are detailed in their paper titled “Fabrication of modified-release custom-designed ciprofloxacin tablets via fused deposition modeling 3D printing” published by theFuture Medicine杂志。该报告由Nasir Abbas,Nadia Qamar,Amjad Hussain,Sumera Latif,Muhammad Sohail Arshad,Qazi Amir Ijaz,Faisal Mahmood和Nadeem Irfan Bukhari合着。

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Featured image shows a 3D printed tablet produced by the Pakistani research team. Image via the Future Medicine journal.