Scientists Are Using 3D Printers to Deliver More Effective Tablets for Children

Health

Soon, doctors could administer 3D-printed tablets containing active medication to children. The pills will come in the size and shape, maybe even colour or flavour, selected by the patient. A 3D printed medicine. Credit: © John Gribben for Mosaic In March 2017, 13-year-old Joseph was diagnosed with juvenile arthritis. He has been undergoing treatment at Alder Hey Children’s Hospital in Liverpool ever since.

“He was really, really poorly,” Joseph’s mother, Helen, tells me. “He needed the steroids – there was no getting around that – but one of the side-effects of long-term steroid use is that your body can stop producing its own cortisol.” In effect, his adrenal glands went to sleep.

To replace the lost cortisol, a hormone involved in metabolism and the immune system, Joseph also started taking hydrocortisone tablets in January 2018, and he’ll keep taking them until his adrenal glands start producing cortisol again.

Hydrocortisone, however, is one of many medicines that cause problems for children. In the UK, it is available as 10 mg or 20 mg tablets, and adults generally take two or three whole 10 mg tablets a day. Guidance in the patient information leaflet states that children should take “0.4 to 0.8 mg a day, for every kilogram of your child’s weight in two or three separate doses”.

It is left to parents, therefore, to hack each 10 mg tablet into pieces a few millimetres in size. Joseph takes half a tablet in the morning, another half at midday and a quarter tablet at teatime.

“I’m fine about taking the tablets,” says Joseph, now 15. “But it’s annoying having to cut them up.”

“It is an absolute pain at teatime,” adds Helen, “because they’re not really designed to be broken. They did give us a little cutter, but you really can’t easily cut it into the quarters and they tend to crumble. It’s not an accurate dose.”

This can be a serious problem, explains Matthew Peak, Director of Research at Alder Hey: “If they’re getting an underdose because the quarter that they’ve chopped has got half of what you expect in it, then they start to fall asleep at school in the afternoons. It really affects you.

“Or you might oxidise it. In breaking up the tablet, you would be doing untoward things to the active drugs. There’s all kinds of problems that can arise.”

A few years ago, Peak began to wonder whether it would be possible to offer children and young people like Joseph bespoke tablets – sized to suit them and containing the exact dosage they require. He now believes it is possible, and that the answer could lie in 3D printing.

On the way to Alder Hey – five miles from the hubbub of Liverpool’s city centre – my taxi driver tells me his 11-year-old daughter is treated here for her diabetes. He talks about the place and its “brilliant” care for his child with a wide smile on his face. He seems excited for me, visiting for the first time. And he’s right to be.

Entering through the front doors from an approach lined with shrubs and sculptures, the soaring atrium is lined with bright white walls and wooden panelling. A huge mobile hangs from the ceiling, with painted wooden birds gathered on its branches. Their open beaks seem to burst with playful energy and hope. Beyond them, a treehouse made from glowing Western red cedar contains the hospital’s spiritual sanctuary. Babies and children need formulas that taste nice so that they don’t refuse to take them. Credit: © John Gribben for Mosaic After a warm handshake, Peak leads me upstairs to the light-filled Clinical Research Facility. Here, the floors and walls zing in sunshine yellow, and you can see plants and trees from every window – one of the things that the hospital’s design group insisted upon when the original hospital was knocked down and a modern replacement built.

This is a child-centred hospital: the overall design was inspired by the winner of a drawing competition, and children were involved throughout the design process. Equally, there is a core belief that every child should have an opportunity to participate in clinical research. In 2017/18, more than 9,000 children and young people were enrolled in clinical research studies here.

And in July 2018, Peak’s team at Alder Hey became the first in the world to administer 3D-printed tablets to children as part of a research trial.

First, around 50 healthy children aged 4 to 12 had been asked to swallow traditionally manufactured placebo tablets of three different sizes (6, 8 and 10 mm) to help establish the ideal size and shape for each age group. What’s somewhat surprising is that the pharmaceutical industry has no idea what size tablets are most suitable for each age.

Since July, 20 of these children have gone on to try swallowing tablets made in a specially adapted 3D printer. These tablets can be rougher on the surface than standard, mass-manufactured drugs, and may produce stronger, possibly unpleasant sensations inside the mouth. So, it’s important for the team to establish how children react to them.

Nine-year-old Ollie was one of the children taking part in the trials. “I wanted to be in research that could make taking tablets easier for poorly children,” he says. “I had to swallow three tablets and say if they were hard [to take] or not.” In the next study, he got to try 3D-printed tablets: “I picked an envelope and had to swallow a printed tablet with some water, which was easy! All the tablets were easy to swallow and I would be happy to take them every day if I was poorly.”

Ollie’s father, Tim, is a research nurse at Alder Hey. He’d suggested his son take part based on his own experiences of working in paediatrics for 15 years: “I have seen many situations where the taking of tablets or liquid medication has been very challenging,” he tells me. He thinks the concept of children having medicines printed to a size, shape and even flavour of their choosing would be “fantastic” and would really help with getting children to take the medications prescribed to them – children often struggle to swallow tablets, or hate the taste of a medicine.

Babies and children, with the rest of their lives stretching ahead of them, need formulas that taste nice so that they don’t refuse to take them; they need treatments that are comfortable so that they don’t resist and dread appointments; and they need age-appropriate medication so that prescribed dosages can be given accurately, without splitting tablets, cutting topical patches or diluting liquid medicines.

Within the next two years, the team aims to administer 3D-printed tablets containing active medication to children who need it. Those pills will contain a precise dose of an active drug to fight illness, in a size and shape (and maybe even a colour or flavour) selected by the young patient. The first drug they try will be hydrocortisone – the same drug that Joseph’s family and so many others are currently struggling with.

3D printing has been used to create 3D selfies, chocolate, artificial coral, clothing, cars and even houses. Within industry, its main uses are for rapid prototyping, making proof-of-concept models and creating products. Medical applications have included personalised prosthetics, dental implants and hand braces printed in plastic and metal, as well as accurate models of patients’ organs to help surgeons plan complex procedures. But 3D printing also holds promise for producing bespoke tablet sizes and dosages.

The first – and as yet only – available 3D-printed medicine is Spritam, made by Aprecia Pharmaceuticals. Made with a 3D printer that combines some off-the-shelf parts with Aprecia’s own technologies, Spritam was approved by the US Food and Drug Administration in 2015 to control seizures brought on by epilepsy.

The printer lays down thin sheets of powdered medication, and droplets of water-based fluid bind these layers together at a microscopic level. This approach squeezes in more of the active ingredients than standard manufacturing, which compresses the drug and other components by stamping the preparation into a mould using a machine called a tablet press.

Although the final 3D-printed product is slightly taller and rougher than a standard tablet, the benefit of Spritam is that its porous layers dissolve quickly on the tongue. This makes it easier for patients to take high doses of 1,000 mg of the active drug (levetiracetam) during a seizure. Not all drugs are suited to this method of delivery, but there are various other approaches to 3D printing medicines that could help patients.

Researchers from the University College London School of Pharmacy found that the rate at which a drug is released in the body depends on the ratio between the pill’s surface area and its volume – a pyramid releases a drug faster than a cube or sphere. They established a spinout company, FabRx , in 2014, and believe they will be able to commercialise their ‘printlets’ in the next five to ten years.

Many pharmaceutical companies are also exploring the idea of 3D printing, although it seems unlikely, at least […]

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