Additive manufacturing or 3D printing refers to processes where products are made layer-by-layer. One of these technologies, inkjet printing, has shown potential in the manufacture of pharmaceutical products, including solid oral dosage forms. Rather than using typical powder compression methods, tablets could be made by the deposition of micro-sized droplets, selectively jetted onto a substrate. These droplets, instead of containing a colored ink as in most inkjet systems, would instead contain a drug – and can be repeatedly deposited until a 3D product is created.
The conventional route for tablet manufacture is a long and multi-step process that is well-suited for the mass manufacture of tablets, but offers limited avenues for personalized medicine. For the latter, inkjet printing could have a major impact as it would be possible to offer complex therapies customized to individual patients with consideration to their age, gender, weight and medical condition. Personalization can come in the form of multiple drugs in a single tablet, patient-specific dosing and/or multiple or multifunctional materials for controlling drug release. The highly programmable nature of inkjet printing would make it easy to meet the personalized demands of custom therapies.
I recently completed my doctoral research at the UK’s Centre for Additive Manufacturing (part of the University of Nottingham) where I investigated inkjet printing for oral pharmaceutical tablets. Previously, solvent-based inkjet printing had been used to create oral formulations with the use of an edible substrate – meaning the printing technique was used as a dosing technology, rather than an individual manufacturing process. There have also been hot-melt inkjet and UV-curable inkjet formulations, but they have been limited to a single material for the tablet. My research focused on using solvent-based formulations to create wholly inkjet printed freestanding tablets (i.e., without the use of an edible substrate). Using multiple materials, I was able to illustrate a highly controlled drug release. To achieve this control, I designed and printed reservoir devices, which consisted of a polymer-drug internal core, an impermeable shell and a release-controlling membrane allowing for one-directional drug release.
The first stage of my research involved developing the internal core of the device. Recently published in the International Journal of Pharmaceutics (1), one unique aspect of this work is the use of a water-based formulation to create freestanding tablets for the core. With this formulation, the risk of toxic solvents or hazardous uncured materials was removed and no extreme conditions were required to create the printed tablets. We were able to show the consequences of printing drug-containing materials layer-by-layer and, more importantly, to conclusively prove that the drug was distributed homogenously throughout the tablet and in its desired polymorphic form. Drug release studies showed that complete drug release was rapid (approximately seven minutes) and the formulation developed could potentially be used for any water-soluble drug.
My next research focus was to introduce a degree of control into the system. By formulating (with an organic solvent) a hydrophobic and hydrophilic polymer blend, I was able to print a release-controlling membrane. By varying the ink formulation, printing parameters and geometry of the device, I was able to create tablets capable of delivering sustained and controlled release (from seven minutes to over seven hours) with significant consistency. In addition to simply extending release, I created specific release profiles, such as delayed and bimodal (initially fast, transitioning to slow).
Even though much has been achieved with additive techniques for pharmaceutical products, there are shortcomings that need addressing, including the low output of most 3D printers and the relatively high costs of printers that offer high accuracy and reliability. Although this is a significant issue in the academic research setting, these problems can be resolved by greater cooperation between pharmaceutical companies and large 3D printer manufacturers through the optimization of printer specifications and parameters. Another significant factor holding back 3D printing from being adopted by the pharmaceutical industry is the lack of knowledge of the technology, particularly in regulatory agencies.
Despite these drawbacks, interest from pharmaceutical companies in additive manufacturing for tablet production is growing. Major companies, including GlaxoSmithKline, AstraZeneca and Pfizer, have all worked with leading academic institutions in the UK to further understand the technology’s feasibility, advantages and constraints for pharmaceutical production. A company called FabRx, created by academics at University College London, has also been set up to create personalized medicines using a variety of different 3D printing technologies. More recently, a collaboration between AstraZeneca, Xaar, an inkjet technology company, and Added Scientific, an additive manufacturing research company, finished their investigation into the feasibility of using inkjet printing for the manufacture of personalized dosages on an industrial scale. To date, only Aprecia Pharmaceuticals in the US has produced an FDA approved oral pharmaceutical product made using 3D printing (Spritam uses a binder jetting technology). But it highlights that there are ways to overcome the drawbacks of 3D printing and allow it to be used by the pharmaceutical industry for commercial medicines.
The majority of inkjet printing research for pharmaceuticals has been from academia, but as industry gets involved, so must the regulatory agencies. Only together can we drive such technologies into more routine use.
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References
- HK Cader et al., “Water-based 3D inkjet printing of an oral pharmaceutical dosage form,” Int. J. Pharm., 10, 359-368 (2019).
