These drops of solution remain suspended for a long period of time, thanks to the vibrational force of sound waves that keep them stationary in an air column. Image: Dan Harris |
It’s
not a magic trick and it’s not sleight of hand—scientists really are using
levitation to improve the drug development process, eventually yielding more
effective pharmaceuticals with fewer side effects.
Scientists
at the U.S. Department of Energy’s (DOE) Argonne National Laboratory have
discovered a way to use sound waves to levitate individual droplets of
solutions containing different pharmaceuticals. While the connection between
levitation and drug development may not be immediately apparent, a special
relationship emerges at the molecular level.
At
the molecular level, pharmaceutical structures fall into one of two categories:
amorphous or crystalline. Amorphous drugs typically are more efficiently taken
up by the body than their crystalline cousins; this is because amorphous drugs
are both more highly soluble and have a higher bioavailability, suggesting that
a lower dose can produce the desired effect.
“One
of the biggest challenges when it comes to drug development is in reducing the
amount of the drug needed to attain the therapeutic benefit, whatever it is,”
says Argonne X-ray physicist Chris Benmore, who led the study.
“Most
drugs on the market are crystalline—they don’t get fully absorbed by the body
and thus we aren’t getting the most efficient use out of them,” adds Yash
Vaishnav, Argonne Senior Manager for Intellectual Property Development and
Commercialization.
Getting
pharmaceuticals from solution into an amorphous state, however, is no easy
task. If the solution evaporates while it is in contact with part of a vessel,
it is far more likely to solidify in its crystalline form. “It’s almost as if
these substances want to find a way to become crystalline,” Benmore says.
In
order to avoid this problem, Benmore needed to find a way to evaporate a
solution without it touching anything. Because liquids conform to the shape of
their containers, this was a nearly impossible requirement—so difficult, in
fact, that Benmore had to turn to an acoustic levitator, a piece of equipment
originally developed for NASA to simulate microgravity conditions.
Levitation
or “containerless processing” can form pristine samples that can be probed in situ
with the high-energy X-ray beam at Argonne’s Advanced Photon Source. “This
allows amorphization of the drug to be studied while it is being processed,”
says Rick Weber, who works on the project team at the synchrotron.
The
acoustic levitator uses two small speakers to generate sound waves at
frequencies slightly above the audible range—roughly 22 kHz. When the top and
bottom speakers are precisely aligned, they create two sets of sound waves that
perfectly interfere with each other, setting up a phenomenon known as a
standing wave.
At
certain points along a standing wave, known as nodes, there is no net transfer
of energy at all. Because the acoustic pressure from the sound waves is
sufficient to cancel the effect of gravity, light objects are able to levitate
when placed at the nodes.
Although
only small quantities of a drug can currently be “amorphized” using this
technique, it remains a powerful analytical tool for understanding the
conditions that make for the best amorphous preparation, Vaishnav explains.
Argonne
researchers have already investigated more than a dozen different
pharmaceuticals, and the laboratory’s Technology Development &
Commercialization Division is currently pursuing a patent for the method.
Technology Development & Commercialization is also interested in partnering
with the pharmaceutical industry to develop the technology further as well as
to license it for commercial development.
After
adapting the technology for drug research, the Argonne scientists teamed up
with Professors Stephen Byrn and Lynne Taylor at the Department of Industrial
and Physical Pharmacy at Purdue University and Jeffery Yarger of the Department
of Chemistry and Biochemistry at Arizona State University. The group is now
working on identifying which drugs the levitation instrumentation will impact
most strongly.
Source: Argonne National Laboratory
Filed Under: Drug Discovery
