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Pharma develops 3D vision

Since 3D printing was first covered on this site a little over a year ago, the technology has rarely been out of the news, and often for the wrong reasons
Pharma develops 3D vision

As we revisit the topic in this article, the US Senate has just approved a 10-year extension on a ban on plastic guns invisible to metal detectors, a move that comes as a direct response to the much-publicised creation of a fully 3D-printed gun by Defense Distributed earlier this year.

Other recent cases involving nefarious use of the technology include cloning of the security key used to unlock handcuffs carried by the Dutch police (as with the printed gun the plans were freely distributed via the Internet). Meanwhile, scammers in the US have used 3D printing to disguise the devices used to 'skim' credit card data from unsuspecting ATM users.

Of course, legitimate uses of the technology far outnumber the illicit, and the last few months have also seen a steady stream of research projects that examine how 3D printing can be applied to pharmaceutical research, development and manufacturing in the near-term, as well as providing glimpses of the future medical uses.

The technology itself is evolving fast. Early systems relied on the extrusion of polymer materials but latterly powder-based systems in which lasers fuse materials together are in the ascendency as they combine almost limitless design freedom with robust mechanical properties. More recently, there has been work on jetting-based technologies which allow conductive and dielectric materials to be added into the build via the use of reactive inks and so create much more complex structures.

A team led by Prof Richard Hague, director of the Engineering and Physical Sciences Research Council (EPSRC) Centre for Additive Manufacturing based at Nottingham University in the UK, showcased the potential of the technology at an exhibition at the Science Museum in London that is running until next summer. 

Most people are currently working on single material polymer or metal systems which - while they can make amazing shapes that defy creation using other manufacturing techniques - are generally passive. Hague's research group is working towards multifunctional additive manufacturing, in which electronic, optical or even potentially biological components, or 'interconnects', at the same time. 

Hague's team exhibited a 3D-printed prosthetic arm at the Science Museum, demonstrating how the technology could be used to print customised prosthetics with electronic moving parts and embedded nerve endings on the fingertips. While non-functional, the arm was printed in one go and is both lightweight and articulated. 

“While it doesn't work at the moment it embodies what we are trying to do as a research group, which is print in everything at once,” said Hague at the opening of the exhibition. “Hopefully it will have functionality in future,” he added. 

Other potential applications could be the production of fully operational hearing aids - customised and sculpted to fit the customer - or mobile phones made with built-in circuitry, although he believes that is probably still at least 20 years away.

For the pharmaceutical sector there could be more immediate applications, and researchers at Nottingham University are already exploring how 3D printing can be deployed to create new, complex formulations of medicines that could make delivery of drugs in the body more effective.

For instance, Shaban Khaled et al from the University's School of Pharmacy report in the International Journal of Pharmaceutics how they used a 3D printer to make complex, sustained-release tablets that met and on some variables exceeded the characteristics of a commercially-available product.

The researchers believe that the pharmaceutical industry will have to embrace new ways to manufacture drugs as current approaches - in which they are almost universally manufactured at large centralised plants via processes essentially unchanged in concept for well over a century - will not be able to cope with the shift towards personalised medicine.

“How are the requisite 'unique' medicines for each patient to be manufactured on a routine basis?” they ask, noting that at the moment “no viable method used in manufacturing of solid dosage forms, such as tablets, is suitable”.

While still very much in the early stages of development, the team was able to show for the first time that a room-temperature extrusion printer - using a mix of active ingredient (guaifenesin) and excipients delivered as a paste - could be used to make a relatively complex bilayer tablet incorporating immediate-release and sustained-release layers.

That is pretty impressive given that the printer used was an entry-level desktop version - costing less than $1,000 - and lacked any specialised software to help control the production process.

“We believe that there is clear potential for 3D printing to allow entirely new formulation types, such as new geometries, complex multi-layer or multi-reservoir tablets,” they conclude.

Meanwhile, in the same journal researchers from Abo Akademi University in Finland describe how they used a 3D printing process similar to hot-melt extrusion (HME) to manufacture medical devices impregnated with an antimicrobial compound called nitrofurantoin.

They used the approach to print a catheter that was able to resist colonisation by microorganisms to form biofilms - a significant cause of healthcare-associated infections - and also demonstrated the ability to gradually release the active ingredient in the vicinity of the device.

“The approach taken is very promising and can open up new avenues to manufacture functional medical devices in the future,” they write.

Meanwhile, aside from finding new ways to manufacture drugs and functional medical devices, 3D printing is also starting to be employed in some of the earliest stages of drug discovery. For instance, scientists are starting to make use of the technology to bioprint human tissues - made by delivering cells via a process adapted from inkjet printing on to a supporting scaffold - that can be used to screen drugs and carry out analyses such as toxicological testing.

US company Organovo - which completed a $47m secondary offering in the summer - has said it expects to start selling a toxicology test based on bioprinted liver tissue commercially next year, and is also working in bioprinted models of human tumours. 

3D printing's clearly very early in gestation as a tool for pharmaceutical and medical applications, but few would suggest the technology is not promising, and many of its applications have probably not been envisaged yet. destiny?
Lee Cronin's tantalising vision of making drug compounds on demand using precursors delivered via 3D printers - covered in our previous article - is clearly still a long way off, while the prospect of functional printed organs that could be used in transplant procedures remains vanishingly distant. 

It's clear that there is a fabulous amount of hyperbole surrounding additive manufacturing, and while the stock prices of companies involved in the sector are running extraordinarily high after massive gains in recent months, there are signs that some of the initial furore is wearing off as investors start to understand the limitations of the technology. 

“There will be a correction … and it is up to groups like ours to tell the truth and explain that you can't make everything with it,” said Hague.

There are already signs of downward share-price pressure on a number of companies, notably Voxeljet, ExOne, Stratasys and 3D Systems, amid a growing recognition that there is still a long way to go before it evolves from a great low-volume prototyping technology into something with a significant share of the corporate manufacturing market, let alone widespread domestic use. 

Then again, someone once said PCs would never be found in the home.

Article by
Phil Taylor

freelance journalist specialising in the pharmaceutical industry

13th February 2014

From: Research, Healthcare



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