Singaporean researchers are adding to the biomedical 3D-printing trend by gearing the technology toward the creation of affordable, on-demand and personalized pills.
With their template-based prototype published in the April edition of the International Journal of Pharmaceutics, the research team invented a simple way to make 3D-printed, customizable drugs that meet patients' unique needs, overcoming what they view as limitations with mass-produced over-the-counter and prescription medications.
Normally, pharmaceutical organizations manufacture drugs at a huge scale, providing diverse groups of people with the same pill. In order to customize doses, patients must sometimes manually break pills into smaller pieces, which can lead to people inadvertently taking the wrong amount.
"Each individual has differing biological cycles and would require customized medication," said Soh Siow Ling, an assistant professor of biomolecular engineering at the National University of Singapore and the lead author of the study.
The molding method that Siow Ling offers is the cornerstone of his invention. Rather than create the drug itself, the team came up with a template-centered tactic that gives the casing of the tablet various geometric shapes, sizes and heights that can control the dosage and release of the medication.
Siow Ling's first paper regarding a customizable drug tablet was published in 2015, and since then, he says, he has perfected the technology so precisely that it will be available soon. The team's work was funded by the A*STAR - P&G Joint Fund under a five-year Master Research Collaboration Agreement, with A*STAR referring to Singapore's Agency for Science, Technology and Research, and P&G to the American-based Proctor & Gamble.
"The technology is very mature based on all the work that we have done so far," Siow Ling told The Academic Times, "and we are currently in talks with companies for commercializing it."
3D printing has been invading the biomedical sector, enabling new approaches to creating dental replacements and prosthetics, for example.
Driven by the need for convenience, Siow Ling's approach uses a standard 3D printer that is widely accessible. It's called a Fused Deposition Modeling, or FDM printer, and can be purchased for about $200.
"The technology can be in the form of dispensing machines that can be placed at any location to be made widely available for the general population," he said, noting that it can also be used in rural areas with fewer medical resources and smaller facilities.
These researchers aren't the first to dabble with the idea. In 2016, the same year that Siow Ling patented his own prototype, the company Aprecia Pharmaceuticals was the first to announce a 3D-printed drug that could instantly be made available to the public, one called Spritam.
This medication helps control seizures in epileptic patients, can hold any dose needed and is made using the company's original ZipDose technology, a 3D-printing technique that layers the powdered drug upon itself. However, while ZipDose made the pill easy to swallow because the powder disintegrates quickly, it was difficult to commercialize because of the high specificity and cost of necessary tools.
To cover his bases further, Siow Ling sought to ensure that his technique would not pose difficulties with feeding the machine sticky chemicals, which could form clogs in nozzles or cartridges. All the required materials are easy to find, because they are regularly used in FDM printers.
"The 3D-printing part of this technology does not require us to feed our own formulated materials into the 3D printer," Siow Ling said. "Our molding method completely circumvented any problem relating to feeding and extruding materials into and out of the 3D printer."
Their proposed 3D-printed mold for the pill casing can control dosage by adjusting height and therefore capacity, but it can also offer personalized medication release time, which hasn't been achieved before. The latter is done through Siow Ling's novel geometric shape concept.
First, a custom mold is created from common 3D-printing material, ABS or PLA filaments. The mold serves as a template for the casing, and gives the product a designated geometric shape. The shape comes into play once the pill enters the body.
After the mold is formed, it's filled with a soluble and biodegradable pill casing called PDMS, which has already been approved by the U.S. Food and Drug Administration. It's placed in the mold in a liquefied state before being left alone to solidify.
When completed, the custom PDMS casing will have a cavity shape that is complementary to the geometric shape in the original printed template.
Because each casing has a unique geometric cut-out exclusively on one side of the casing, only the area beneath it that contains the drug would be exposed to the body after the pill is ingested. Dissolution happens in 2D and the shape limits the way the drug is released.
Any geometric shape can be chosen, depending on a patient's needs.
The researchers say a controlled release is necessary because most extended-release medication dissolves at a quickening rate in the body, but sometimes one might need the opposite effect. And in other cases, it could be important for the pulse of the release profile to match the body's rhythm, for example in hormone therapy.
"Another important biological difference is the activity and strength of hormones in individuals that would require a customized medication," said Siow Ling.
Each pill can also combine a few drugs within its casing, giving the new technology the potential to make it significantly easier to manage scheduling for those individuals who need several medications each day.
The paper, "Customizable drug tablets with constant release profiles via 3D printing technology," published in the April edition of the International Journal of Pharmaceutics, was authored by Yan Jie Neriah Tan, Wai Pong Yong, Han Rou Low, Teng Shuen Ernest Lim, Yajuan Sun, Jonathan Zhi En Wong and Siowling Soh, National University of Singapore; and Jaspreet Singh Kochharb and Jayant Khanolkar, Procter & Gamble International.