Researchers behind a novel, non-injectable version of infliximab say 3D printing could help biopharmaceutical manufacturers overcome the formulation challenges associated with large molecule drugs.

In 3D printing—which is also known as additive manufacturing—layers of material are built up gradually under computer control to create a three-dimensional structure. A range of materials can be used, including active pharmaceutical ingredients and excipients.

The potential advantages for formulation development are significant, with increased manufacturing speed, flexibility, and safety usually cited as the main benefits.

And the approach has regulatory support. In 2015, the FDA approved its first 3D printed small molecule drug—Aprecia Pharmaceuticals’ seizure pill Spritam (levetiracetam)—citing its enhanced dissolution profile as a benefit of the production method.

For large molecule pharmaceuticals there are even more potential benefits, according to researchers who, as described in a journal article, used 3D printing to develop a formulation of the inflammatory bowel disease (IBD) treatment, infliximab.

Formulation challenges

Infliximab is a monoclonal antibody that binds pro-inflammatory chemicals in the bloodstream, thereby reducing the severity of IBD attacks. Like any protein drug, infliximab’s function is determined by its 3D structure which allows it to interact with specific cytokines in a manner analogous to a lock and key. Unfortunately, proteins are difficult to formulate, according to the researchers, who say current options are limited.

“While its [infliximab’s] macromolecular structure renders it highly potent and specific, it also impedes its permeation through biological barriers and makes it more prone to degradation in the GI tract,” said the authors of the journal paper. “Due to that, infliximab is typically administered intravenously or subcutaneously, however, this has been associated with high incidence of systemic adverse events.”

To address this, the team from University College London, Universidade de Santiago de Compostela, and the biotech firm FabRx used a type of 3D printing called semi-solid extrusion to form suppositories infused with the drug.

Specifically, they relied on a combination of an infliximab-oil mixture and a semi-solid, waxy amphiphilic excipient called Gelucire. And the initial results are promising, both from a formulation manufacturing and a patient-compliance perspective.

According to the authors: “This study demonstrates that SSE 3D printing can serve as a viable method for directly fabricating rectal dosage forms containing biologics.

“This work shows that the rectal route has the potential to be used as an alternative way for delivering monoclonal antibodies, wherein patients could self-administer their own medications without the need for trained healthcare professionals.

“Additionally, it demonstrates the potential of 3D printing to be used as a novel manufacturing platform for biologics, setting the scene for new opportunities in the future.”

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