Printed meds accelerate clinical testing sans toxic solvents
Potentially promising molecules often die in the pipeline due to low solubility and poor dissolution rates. To overcome these challenges, researchers at the University of Michigan have adapted a technology from electronics manufacturing called organic vapor-jet printing.
The study was led by Max Shtein, professor of materials science and engineering, and Olga Shalev, a recent graduate. The paper, which was recently published in the journal Nature Communications, was co-authored by former American Association of Pharmaceutical Scientists (AAPS) President Prof. Gregory Amidon.
Sans solvents
Currently, various solvents are used to pre-dissolve a drug before it is dosed into a petri dish or animal model.
“The current approach has problems, because these solvents aren’t allowed for human trials, so the preliminary results don’t necessarily translate without substantial additional modifications to the drug,” Shtein told Outsourcing-Pharma.com.
However, the new approach – solvent-free organic vapor jet printing – enables researchers to create fine particles (without clumping) from a small molecular compound.
“This allows the material to dissolve much faster, a bit like dissolving granulated sugar versus a big lump of sugar in tea – to an extreme,” explained Shtein.
“This can speed up clinical testing because no toxic solvent is ever needed, whether testing in petri dishes, animal models, or humans, so the early-stage results should have more relevance,” he added.
How does it work?
The active pharmaceutical ingredient (API) is heated and evaporated into a stream of inert carrier gas, which is then jetted onto a surface, before condensing and creating a film.
“Temperature, pressure and flow of the gas, working distance, etc. – are parameters that control the process, and ultimately affect the film morphology,” explained Shtein.
“The technology also offers a much easier way to combine multiple ingredients ... which opens the possibility for sophisticated, precisely tuned, combination therapies and theranostics,” he added.
Commercialization
Dr. Olga Shalev, first author of the published article, told us the researchers are looking to establish collaborations with the pharmaceutical industry in order to accelerate the commercialization of solvent-free organic vapor printing.
“We do believe that this technology can be quite useful and should ultimately improve clinical outcomes, so we are motivated to bring it to market,” added Shtein, eager to put the technology to work.
Next steps include developing specific formulations for specific indications and follow-on efficacy studies.
In the future, the researchers think patients should be able to receive a simple patch or dissolvable tab that contains many medicines with a smart release profile, which could improve treatment compliance.
Shtein also said the approach could eventually enable and enhance outpatient diagnostics.
Source: Nature Communications
doi:10.1038/s41467-017-00763-6
Printing of small molecular medicines from the vapor phase
Authors: 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
