Researchers from the University College London (UCL) have discovered an unexpected chemical reaction whilst 3D printing pharmaceuticals.
Simon Gaisford, Professor of Pharmaceutics, UCL School of Pharmacy, and his research group utilized Stereolithography (SLA) to stack four drugs designed to treat high blood pressure in one pill. Within this formulation, Amlodipine was found undetectable upon experimentation, despite the pill being successfully 3D printed.
In a research paper published in the journal Additive Manufacturing, it is stated that this reaction “demonstrates the importance of careful selection of photocurable resins for the manufacture of drug-loaded oral dosage forms via SLA 3D printing technology.
“[It also] highlights the potential safety-associated challenges for the successful adoption of SLA towards the development of drug delivery platforms in the pharmaceutical arena.”
3D printed pills
Through FabRx, a spin-off biotechnology company from the UCL School of Pharmacy, Professor Gaisford and his research group explore the capabilities of 3D printing pills for patient-specific care. In a previous interview with 3D Printing Industry, Dr. Alvaro Goyanes, one of the four founding partners of FabRx, explained:
“Our idea is to get printers into hospitals or pharmacies. We will supply filaments or raw materials and then the medical doctor, or the pharmacist will select the right dose for the patient, maybe combine different drugs, and just click the button, print and then this medication is given to the patient.”
The company has experimented with FFF technology to developed personalized 3D printed tablets for children with rare metabolic disorder, maple syrup urine disease (MSUD). Most recently, SLA has been implemented for accurate drug formulation due to “its success in the fabrication of single oral dosage forms incorporating up to six drugs,” the research states.
3D printing for drug delivery
Using a Form 1 3D printer, the team successfully produced 3D printed pills known as polyprintlets which contained blood pressure-related medication, i.e., amlodipine, atenolol, irbesartan, and hydrochlorothiazide. It was found that interactions between photocrosslinkable monomers (PEGDA) and amlodipine were present.
This was recognized as a Michael addition reaction. This involves a carbon-carbon bond-forming reaction involving the addition of a carbon nucleophile to an unsaturated carbonyl compound. Professor Gaisford told Chemistry World, “This was a very specific reaction that happened between this specific drug and the monomer we used.
“However, the reaction we reported here was a common type that may happen with other functional groups and possibly with other drugs. It is very important for researchers to keep this in mind when they are making SLA 3D printed drug-loaded medicines.’
The study concludes, “To the best of our knowledge, the findings from our case study was the first to describe the unexpected drug-polymer interactions in 3D printing. As such, this highlights the need to screen for photoreactive monomers to ensure the safety and compatibility of drug-loaded oral dosage forms manufactured by SLA.”
“Stereolithography (SLA) 3D printing of an antihypertensive polyprintlet: Case study of an unexpected photopolymer-drug reaction” is co-authored by Xiaoyan Xu, Pamela Robles-Martinez, Christine M. Madla, Alvaro Goyanes, Fanny Joubert, Abdul W. Basit, and Simon Gaisford.
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Featured image shows an SEM image of the cross-section of the 3D printed pill (from top to bottom) amlodipine, atenolol, irbesartan, and hydrochlorothiazide. Image via UCL.