3D Screen Printing Enables Application of Integrated QR Codes on Pharmaceutical Dosage Forms in Mass Production – A Game Changer
Full Article available here.
Introduction
Quick Response (QR) codes have been in use since the 1990s. They were initially developed as a way to track components of vehicles at Denso Wave (a Japanese company and a subsidiary of Toyota) through the supply chain.
Since then, their use has steadily increased. The widespread availability and decreasing costs of entry for mobile devices such as smartphones and tablets that can quickly read QR codes have significantly contributed to their quick adoption. A QR code is simply a two-dimensional barcode. It looks like a crossword puzzle with black and white squares called modules.
The square grid-like design allows for increased storage of information compared to a standard one-dimensional bar code. QR codes can store about 7,000 digits (around 4,000 characters) of information, such as linking to a specific website. It includes a high level of integrated redundancy, allowing for the QR code to be readable even if a substantial portion (around 30%) of the code has been damaged.
Today, QR codes are ubiquitous and can be found everywhere, from construction through social media to banking. The flexibility of their design and the ability to quickly update their information makes them easily amenable to a wide range of applications, including healthcare.
QR codes have already proven to be highly beneficial in healthcare, such as patient tracking, drug safety, and many other use cases (Figure 1). They can be used to digitally store product safety, and medication interactions, among others, as well the ability to update this information in real-time for patients and health care providers.
Moreover, implementing QR codes directly on dosage forms is an efficient means of combating counterfeit medicines. This review investigates the potential for using QR codes in medicine, with a special focus on their application for pharmaceuticals using 3D printing technology, including screen printing.
Tablet Level Labeling
Additive manufacturing is an increasingly disruptive force in pharmaceutical development. 3D printing (3DP) approaches enable custom geometry, size, content, and release characteristics of active pharmaceutical ingredients (API).
At the same time, digital modeling has allowed for a new level of freedom in drug design. These opportunities have led to a boom in 3DP technologies for pharmaceutical development. Although conceptually similar, each uses its own method to deposit each layer of material and cure it.
There are two primary approaches for additive manufacturing: personalized drug development and production for the mass market. The ability to produce custom drugs for the mass market has a lot of appeal for responding to changing needs at scale and have been a major focus of recent technological developments.
However, concerns over the scalability of 3DP technologies, low mechanical resistance, low printing resolution, and limited material choices have so far limited their practical implementation. Currently, only a single 3D-printed pharmaceutical, the antiepileptic drug Spritam® is FDA-approved and marketed.
The first types of 3DP pharmaceuticals were developed using continuous inkjet printing. Since then, advances in inkjet printing as well as newer technologies, most notably: extrusion-based printing (fused deposition modeling (FDM), and screen printing), powder-based printing (powder bed and powder jetting), selective laser sintering (SLS) printing, have aimed to print instead pharmaceuticals for the mass market.
Among the 3DP technologies, extrusion-based printing, such as FDM, direct ink writing (DIW), and, most recently, 3D screen printing (3DSP), have shown the greatest promise due to their low cost and flexibility.
All extrusion-based 3D printers have two principal components: 1. The extruder (which deposits the precise quantity of material over a specific distance) and 2. The positioning system.
The printable material (i.e., ink), in the form of a viscous melt or liquid, is extruded through a nozzle (in the case of FDM and DIW) or through tissue (in the case of 3DSP). While the nozzle gets only a single printer, the tissue, as a function of its area, mediates the extrusion of paste for multiple objects at the same time.
The new kid on the extrusion-based printing block is 3DSP. 3DSP is a type of extrusion printing that uses a screen mesh to transfer a semisolid, API-containing paste onto a substrate, except in areas made impermeable to the paste by a blocking stencil. The deposited layer is then dried. The next layer is printed precisely on top of the previous one after lifting the screen by the dried layer thickness. 3DSP has the potential for mass customization, enabling the buildup of thousands of units per screen simultaneously.
The number of units printed simultaneously is largely defined by the ratio of screen size to unit size. This differentiates screen printing from other 3DP technologies, whose capacity is limited by the number of printing heads.
Exentis Group [24], based in Switzerland, has developed the patented 3DSP technology for a broad range of industrial applications, such as renewable energy sources, the automotive industry, aerospace, and biotechnology. The Exentis 3DSP enables the production of several hundred items with the option for mass production of an upscaling to several million a day.
Laxxon Medical Corp holds the exclusive worldwide license to explore this 3DSP technology for all kinds of pharmaceutical applications.
Laxxon Medical Corp. is developing a screen-printing approach for printing pharmaceuticals for the mass market. This approach is based on classic flatbed screen printing that is widely used in industrial applications. Proof-of-concept work with 3DSP (SPID®-Technology) has shown that it is possible inter alia to print QR codes directly on tablets as small as r = 5 mm during and as an integrated part of the manufacturing process (Figure 2).
Using this approach, the QR code is part of a one-stop manufacturing process of the tablet. 3DSP could also be used to print API containing QR codes and/or inks which make the tablet easier to identify, harder to counterfeit, and increases product safety.
There are at least two ways that a QR code can be printed directly on tablets. The first is to print the code on top of the tablet using different kinds of ink. Inkjet printing, for example, has previously been shown as a viable strategy for printing QR codes directly on oral dosage formulations. Work by Edinger et al. showed that it was possible to print specific amounts of the neuroleptic drug haloperidol as a QR code on an edible orodispersible substrate.
Here, researchers used the QR code to identify the API, dose, patient name, administration route, expiration date, manufacturer ID, and batch number as a proof-of-concept. Further work by Trenfield et al. combined both 2D and 3D inkjet printing technologies in a single-step manufacturing process to create drug-loaded tablets with a combined QR code identifier that used anti-counterfeit ink.
In both cases, a personalized medicine approach was investigated instead of a mass customization strategy, but there is clear potential for both strategies.
A. QR code screen with different sizes (diameter) and QR code designs used within the 3D Screen Printing Unit EX 301i.
B. Tablets were printed with 92 levels of each 0.025 mm. Afterward, at the end of the manufacturing process, 2 additional layers with the QR code pattern were applied. A mixture of black and blue (2:1) commercial food dye was utilized for coloring the QR code. Example QR code printed on a 9.5 mm size tablet.
C. More complex QR Code (allows larger amounts of data) were printed on different-sized tablets 14.5, 11.5, and 9.5 mm (from left to right).
The ability to print a QR code directly on the tablet would be a major benefit for patients and health care professionals (HCPs). It would allow them to confidently identify the medication and access all relevant product information, even without the need of any secondary packing information.
This could be helpful to older patients who may be taking multiple medications and who may separate their pills into pill boxes without any identifying information. It is also of great interest to patients who may be visually impaired and have trouble identifying their medication even with the packaging information available.
Also, patient safety could increase through automated dispensing enabled through this QR code marking. This is especially important in the hospital setting, a situation characterized by frequent medication changes and increasing patient turnover. Checking drug data against patient data, both in an electronic format and at the point of dispense, could maximize patient safety.
An alternative to printing the QR code on the tablet itself is to embed the code into the tablet. One such proposal used grooving to offset the surface inward to create light and dark regions resulting from ambient occlusion. This could allow for tablets with rough surface structures as well as a wide range of surface colors to have a readable QR code.
While conceivable, the outlined solution is complex as its implementation requires the sequential application of two technically different processes. In contrast, 3DSP is capable of yielding tablets with embedded QR codes by applying two additional steps of the very same production process.
First, a negative print is administered on top of the printed tablet's body using the "negative" screen, then resulting recesses are filled using the "positive" screen and a colored paste. Requirements are well within the scope of the screen-printing technology, namely, two more screens and two pastes with different colors. Where needed, the QR code could be sealed by applying a thin layer of transparent paste.
Full article available here.
Laxxon Medical is dedicated to engineering patented 3D pharmaceutical solutions which optimize products and benefit patients. Our goal is to establish SPID®-Technology as a manufacturing process that has the individual and the pharmaceutical partner in mind.