New Method 3D Prints Pills that Regulate Drug Release

Scientists at the University of East Anglia (UEA)’s School of Pharmacy in England identified a new additive manufacturing (AM) method to 3D print porous medicine tablets that can regulate the rate of drug release in the body when taken orally. The team relied on a thermoplastic droplet deposition 3D printing method from German machine manufacturer Arburg to produce customized porous pharmaceutical solid tablets on-demand. By leveraging Arburg’s 3D printing technology, the researchers hope to build the foundations for the technology needed to create personalized medicine at the point of care in the future.

Led by pharmaceutical engineer at UEA Sheng Qi, the study was published in the International Journal of Pharmaceutics. The project’s findings revealed that by changing the size of the pores, scientists could regulate the speed of a drug escaping from the tablet into the body. However, more research will be needed to tailor the dose and dosing frequency of the medicine to each patient’s needs, such as printing multiple drugs into a single daily poly-pill for patients on a complex medication regimen.

According to Qi, medicines are currently manufactured in a “one-size-fits-all” fashion. Instead, personalized pills built with new manufacturing technology can have accurate dose and drug combinations tailored to individual patients. Qi said it would allow patients to get maximal drug benefits with minimal side effects. It could also be particularly beneficial to the elderly, who often have to take many different types of medicines per day, or patients with “complicated conditions,” such as cancer, mental illness, and inflammatory bowel disease.

University of East Anglia research scientist Sheng Qi. Image courtesy of School of Pharmacy, University of East Anglia.

Pharmaceutical 3D printing research has been rapidly developing in the last five years. However, the researchers noticed that the most commonly used 3D printing methods require the drug being “processed into spaghetti-like filaments before 3D printing.” That’s because fused deposition modeling (FDM) is one of the most common methods used to manufacture personalized pharmaceutical solid dosage forms. Alternatively, Arburg’s open system processes plastic granules instead of filaments, offering a high level of material freedom.

The granules can be produced using the traditional pharmaceutical granulation process. On this basis, the Freeformer additively manufactures various tablet variants and release patterns. The Arburg Plastic Freeforming (APF) process can manufacture entirely new personalized healthcare products thanks to its hot melt droplet deposition printing, which replicates some of the strengths of inkjet technology. The patented process allowed the researchers to tap into a whole new range of options to produce functional parts using qualified standard granulates.

Illustration of two types of AM deposition mechanism: FDM (left) and Arburg’s droplet-based 3D printing (right). Image courtesy of University of East Anglia/International Journal of Pharmaceutics.

The team, including professors Andy Gleadall and Richard Bibb from Loughborough University, revealed that APF can be used to reproduce 3D print porous tablets using pharmaceutical polymers and can produce tablets with a wide range of infills. The study results indicate that porosity may control drug release rates in swellable and erodible systems.

Due to an increase in life expectancy worldwide, the demand for pharmaceuticals is also growing. A 2019 report by California Alta Bates Summit Medical Center revealed that around 44% of men and 57% of women over 65 take five or more drugs each week, with twelve percent of this age group taking at least ten. The majority of these pharmaceuticals are made with generic dosages of active ingredients and release patterns that do not address the individual patient’s needs, leading to overmedication and unwanted side effects.

Preferably, Qi proposes more personalized medicines for patients in the future: “By working alongside colleagues in hospitals and pharmacies, I have seen first hand that customized tablets could be a solution for pediatric, geriatric, and patients with complex chronic conditions.”

Arburg APF printed tablets with 20%, 50% and 80% infills. Image courtesy of University of East Anglia/International Journal of Pharmaceutics.

In 2015, Qi began investigating 3D printing with FDM technology. However, she quickly realized that the materials she could use were limited and not flexible enough, while open platforms offered poor reproducibility for pharmaceuticals. She described that during the FDM process, the pharmaceutical materials are thermally loaded twice. This is because before the material can be discharged through a hot nozzle in the additive manufacturing process, it must first be processed into filaments through extrusion. But this is far from ideal for her research since many drugs have “poor thermal stability.”

At UEA, Qi and her team benchmarked several 3D printers and were “dissatisfied with all of the results.” Alternatively, Arburg’s robust solution offered them high precision and accuracy and the capability to process new and unique production materials. The team could directly use standard granulate from common pharmaceutical polymers and active ingredients. Moreover, with no additional plasticizers, the plastic melt could be discharged in the form of tiny droplets and used to additively manufacture tailored drugs.

Arburg Freeformer 3D printer. Image courtesy of Arburg.

“Using the freeformer, a wide range of filling level variants were able to be tested and created at UEA,” said Qi. “The porosity of the tablet allowed the active ingredient’s release rate to be regulated. The freeformer offered our team the flexibility to optimize various densities and adjust them precisely. The reproducibility of results was steady and robust.”

3D printed drugs could revolutionize personalized pharmaceuticals, provide an excellent solution for patients, reduce healthcare costs, and even improve sustainability. The capability of AM to produce tailored dosages of pills means smaller batches and less waste. For 3D printer manufacturers, it will also be a great opportunity to develop systems suited for hospitals and pharmacies for on-demand production.