Sunday, 22 Sep 2019

Printed medicines - using organic vapour-jet printing - could reinvent pharmacies and drug research

A technology that can print pure, ultra-precise doses of drugs onto a wide variety of surfaces could one day enable on-site printing of custom-dosed medications at pharmacies, hospitals and other locations

Michigan Engineering - Siddharth Suresh Borsadia prints fluorescein crystals onto a cooled glass plate using organic vapor jet printing

29 Sep 2017 | Editor

A new research study led by Max Shtein, professor of materials science and engineering, and Olga Shalev, a recent graduate who worked on the project while a doctoral student in the same department, showed that the pure printed medication can destroy cultured cancer cells in the lab as effectively as medication delivered by traditional means, which rely on chemical solvents to enable the cells to absorb the medication. Their study is published in the journal Nature Communications.

The technique was developed through a collaboration between the Michigan Engineering departments of chemical engineering and biomedical engineering, as well as the College of Pharmacy and the Department of Physics in the College of Literature, Science, and the Arts.

The researchers adapted a technology from electronics manufacturing called organic vapour-jet printing.

One key advantage of the technique is that it can print a very fine crystalline structure over a large surface area. This helps printed medications dissolve more easily, opening the door to a variety of potential new drugs that today are shelved because they don't dissolve well when administered with conventional approaches, including pills and capsules.

The process begins by heating the active pharmaceutical ingredient—usually a powder—and evaporating it to combine it with a stream of heated, inert gas like nitrogen. The evaporated medication travels, along with the gas, through a nozzle pointed at a cooled surface. The medication then condenses, sticking to the cooled surface in a thin crystalline film. The formation of the film can be tightly controlled by fine-tuning the printing process. The process requires no solvents, no additives and no post-processing.

University of Michigan - Printed medicine shows promise

University of Michigan - Crystal structure of ibuprofen, printed onto a silicon film using organic vapour jet printing

Figure: University of Michigan - Crystal structure of ibuprofen, printed onto a silicon film using organic vapour jet printing

The tight control over solubility may also be useful later in the drug testing process, when potential new drugs are applied to cultured cells in a lab. According to the researchers most compounds must be dissolved in a chemical solvent before they're applied to cells. The new technique could enable printed medications to dissolve easily in the water-based medium used to culture cells, without the need for a solvent.

While printing mass-market drugs is likely years away, the researchers believe that the drug characterisation and testing applications may come to fruition more quickly—internally in pharmaceutical companies.

The team is exploring additional applications for the technology and plans to collaborate with experts in pharmaceutical compound design and manufacturing, as well as those working on treatments. Eventually, they envision vapour jet printing being scaled to mass production, including roll-to-roll continuous manufacturing.

The research was supported by the Air Force Office of Scientific Research, the National Science Foundation, and the U.S. Department of Energy Office of Science User Facility.

"A doctor or pharmacist can choose any number of medications, which the machine would combine into a single dose."

"The machine could be sitting in the back of the pharmacy or even in a clinic."

"Pharma companies have libraries of millions of compounds to evaluate, and one of the first tests is solubility"

"About half of new compounds fail this test and are ruled out. Organic vapor jet printing could make some of them more soluble, putting them back into the pipeline."

Max Shtein, Professor of materials science and engineering

"Organic vapor jet printing may be useful for a variety of drug delivery applications for the safe and effective delivery of therapeutic agents to target tissues and organs."

Geeta Mehta, The Dow Corning Assistant Professor of Materials Science and Engineering and Biomedical Engineering and a co-author on the paper

"When researchers use solvents to dissolve drugs during the testing process, they're applying those drugs in a way that's different from how they would be used in people, and that makes the results less useful."

"Organic vapor jet printing could make those tests much more predictive, not to mention simpler."

Anna Schwendeman, Assistant professor of pharmaceutical sciences at U-M and an author on the paper

"One of the major challenges facing pharmaceutical companies is speed to clinical testing in humans."

"This technology offers up a new approach to accelerate the evaluation of new medicines."

Gregory Amidon, Research professor in the U-M College of Pharmacy and an author on the paper

Printing of small molecular medicines from the vapor phase

Olga Shalev | Shreya Raghavan | J. Maxwell Mazzara | Nancy Senabulya | Patrick D. Sinko | Elyse Fleck | Christopher Rockwell | Nicholas Simopoulos | Christina M. Jones | Anna Schwendeman | Geeta Mehta | Roy Clarke | Gregory E. Amidon | Max Shtein

Nature Communications 8 | Article number: 711 (2017) | doi:10.1038/s41467-017-00763-6

Received: 28 October 2016 | Accepted: 22 July 2017 | Published online: 27 September 2017


There is growing need to develop efficient methods for early-stage drug discovery, continuous manufacturing of drug delivery vehicles, and ultra-precise dosing of high potency drugs. Here we demonstrate the use of solvent-free organic vapor jet printing to deposit nanostructured films of small molecular pharmaceutical ingredients, including caffeine, paracetamol, ibuprofen, tamoxifen, BAY 11-7082 and fluorescein, with accuracy on the scale of micrograms per square centimeter, onto glass, Tegaderm, Listerine tabs, and stainless steel microneedles. The printed films exhibit similar crystallographic order and chemistry as the original powders; controlled, order-of-magnitude enhancements of dissolution rate are observed relative to powder-form particles. In vitro treatment of breast and ovarian cancer cell cultures in aqueous media by tamoxifen and BAY 11-7082 films shows similar behavior to drugs pre-dissolved in dimethyl sulfoxide. The demonstrated precise printing of medicines as films, without the use of solvents, can accelerate drug screening and enable continuous manufacturing, while enhancing dosage accuracy.


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