Exploring 3D Printing for Solid Dosage Drugs

3d printer with injector nozzle | Image Credit: ©phonlamaiphoto- stock.adobe.com

Advances in equipment and control systems for three-dimensional printing (3DP) are creating new opportunities to use this alternative manufacturing method for solid dosage drugs. Printers—which are available in good manufacturing practice (GMP) versions—use various additive manufacturing methods to build layer upon layer, which allows precise placement of multiple ingredients within a dose. This customization offers advantages for modified and controlled release, personalized medicine, and point-of-care manufacturing, such as in hospital pharmacies.

“3DP’s material placement turns geometry into a dosing parameter,” explains Sharon Flank, CEO of technology company InfraTrac. “It can use layer thickness, shape, and differential material properties to create complex versions of controlled-release particles.” For example, 3DP can create “upstairs and downstairs layers for a polypill of two or more APIs, or an outer layer and multiple inner layers for precision control of release. Shape manipulation can control release in a way no tablet will ever do,” Flank says. Although 3DP is not as fast as conventional tableting, it can be used to meet the needs of a smaller target patient population that was previously underserved. Custom modifications can be quickly performed via software that controls material placement, compared to conventional tableting that would require tooling changes, Flank explains.

Using 3DP, dosage shapes can go beyond tablets, Flank adds. InfraTrac is working with Stephen Hoag’s Applied Pharmaceutics Lab at the University of Maryland School of Pharmacy on extrusion-based 3DP techniques to create orodispersible films, such as a pediatric rifapentine dose to treat tuberculosis. Outside of oral dosage, the researchers are designing long-acting implants with internal compartments for subdoses.

One example of using 3DP to meet a patient need is Aprecia’s levetiracetam, a high-drug load, rapidly disintegrating design for patients with difficulty swallowing that was approved by FDA in 2015. Made using the company’s 3D-printed ZipDose technology, it was the first drug to be approved using 3DP. It is made with an open-bed, binder-jetting method. More recently, Aprecia has developed its Z-Form 3DP platform integrated with process analytical technology (PAT) that prints doses directly in their primary packaging. The company worked with Battelle to develop the new technology platform for the development and production of dosage forms with a range of functionalities, including the ability to 3D print customized tablets or those with multiple APIs (1).

Microstructure drug delivery

Triastek is using its Melt Extrusion Deposition (MED) 3DP process for microstructured drug delivery platforms that it has designed for modified release, colon targeting, gastric retention, solubility enhancement, and for improving oral bioavailability of peptides. The company has five drug products in clinical development (in the United States, China, or both) that use these platforms, including its most recent, a 3D-printed drug product designed for extended release and absorption of drugs in the upper gastrointestinal tract that received investigational new drug (IND) clearance from FDA in early 2024 (2).

In July 2024, Triastek announced a collaboration with BioNTech to develop oral delivery forms of RNA therapeutics using 3DP. The researchers aim to use multilayer and multi-compartment tablet designs to minimize degradation in the gastrointestinal tract and deliver the dose to where it can be absorbed optimally (3).

Formulation development

In addition to serving smaller patient populations, the flexible, small volumes enabled by 3D printing are useful in formulation development and clinical manufacturing.

“In clinical and preclinical trial supply, a nimble, small-scale production system could save a lot of time and therefore money,” says Flank. “Whether the final doses are produced via 3DP or conventionally, it is clearly helpful to be able to test several different formulations in a single day or even hour.”

Triastek is working with Boehringer Ingelheim to quickly create multiple prototypes of a new chemical entity and examine dose designs and drug release behavior using its 3DP technology (4). The company says its formulation-by-design approach can accelerate early drug development.

Personalized point-of-care

Small 3D printers can be useful for point-of-care manufacturing in a hospital pharmacy or potentially for remote locations, such as battlefields or space travel. A GMP-ready printer from FABRX, the M3DIMAKER, is now available with either one or three printheads and with printhead attachments for different extrusion printing methods—fused deposition modeling, semi-solid extrusion, and direct powder extrusion (DPE).

“We are working with hospitals and healthcare providers to implement our 3D-printing solutions directly into clinical settings, allowing for on-site production of personalized medications,” says Alvaro Goyanes, director and co-founder of FABRX. The United Kingdom-based company also launched a US-based company, FABRX US, in 2024, and is working with InfraTrac and Hoag’s lab on PAT for quality control.

The researchers, funded by the National Institute of Standards and Technology (NIST) through a Small Business Innovation Research program, are working on a predictive model that uses a near infrared (NIR) spectrometer incorporated into the drug printer, in this case the FABRX M3DIMAKER2, says Flank. The lab initially used a Viavi MicroNIR spectrometer and is also testing a Sentronic instrument. “Preliminary results show how NIR can validate and even quantitate API, detect out-of-specification moisture, and reject certain mis-printed doses,” reports Flank. “A robust model should facilitate point-of-care customization by creating pass/fail quality parameters that allow the pharmacist to manage doses and flavorings while delivering GMP product.”

“Integrating PAT and advanced testing capabilities into our machines addresses a critical need for real-time quality control and assurance in 3D-printed pharmaceuticals,” adds Goyanes. “This integration ensures that every product meets stringent quality standards, enhancing the reliability and safety of the medications produced.”

Goyanes points out that the development of effective cleaning protocols for printheads is essential to maintain equipment performance and prevent cross-contamination. FABRX introduced a new DPE printhead cleaner in July 2024 to improve the cleaning process. The company continues to work on technologies to meet other user needs it has identified, including development of modular and scalable 3D printing systems that can be easily adapted to different production volumes and requirements, Goyanes says.

Another technology designed for 3D-printing of personalized medicine in compounding pharmacies is the Pharma Kit from CurifyLabs. The platform includes GMP-manufactured excipient bases (called Pharma Inks); a desktop-sized automated Pharma Printer; software containing a library of validated formulae of Pharma Inks with APIs that guides the user; and integrated, automated quality control tools.

“Our goal was to modernize and bring automation to compounding and hospital pharmacies to make safer products and save time,” says Niklas Sandler, founder and CTO at CurifyLabs.

The developers automated as much of the workflow as possible, including weighing, mixing, dispensing, and packaging, explains Sandler. The built-in quality control tools include NIR to test blend homogeneity and a weigh scale to measure every tablet. The library of premanufactured excipient bases that have been optimized for the printing process and the formulations that have been validated are crucial to the system, says Sandler.

“We did all the validation work up front so that it would be easy and quick for pharmacists to follow the validated process. The technology can be used to produce a wide range of dosage forms, such as tablets and suppositories, and to dispense liquids accurately. The Pharma Kit is used in several markets in Europe,” Sandler adds.

Growing adoption

“Both Europe and North America are witnessing a growing adoption of 3D printing in the pharmaceutical industry,” Goyanes suggests. In 2023, Goyanes and others launched the Pharmaceutical 3D Printing Initiative, an international consortium to facilitate collaboration between academic institutions, healthcare providers, regulatory agencies, and industry players. Other partnerships with universities and hospitals aim to train the next generation of scientists and engineers in 3D printing technologies. “These collaborations are crucial for advancing the field and ensuring that our solutions are continually evolving to meet the dynamic needs of the healthcare industry,” Goyanes concludes.

References

1. Aprecia. Aprecia and Battelle Are Impacting the Pharmaceutical Industry Through 3D Printing Innovation. Press Release, Nov. 15, 2023.
2. Triastek. Triastek’s 3D Printed Gastric Retention Product T22 Receives FDA Clearance of IND Application. Press Release, Jan. 31, 2024.
3. Triastek. Triastek Announces Research Collaboration and Platform Technology License Agreement with BioNTech to Advance 3D Printed Oral RNA Therapeutics. Press Release, July 23, 2024.
4. Triastek. Triastek Announces Collaboration with Boehringer Ingelheim to Advance and Accelerate Research and Development of Innovative Pharmaceutical Products with MED 3D Printing Technology. Press Release, March 17, 2023.

About the author

Jennifer Markarian is a contributing editor to Pharmaceutical Technology®.

Article details

Pharmaceutical Technology®
Vol. 48, No. 10
October 2024
Pages: 22–23

Citation

When referring to this article, please cite it as Markarian, J. Exploring 3D Printing for Solid Dosage Drugs. Pharmaceutical Technology 2024 48 (10).