Sound Waves Applied to Levitate Liquids, Improving Pharmaceuticals

Scientists employing sonic levitation to enhance the drug development process, which should ultimately yield more effective pharmaceuticals with fewer side effects.

Scientists from the US Department of Energy’s (DOE) Argonne National Laboratory (Argonne, IL, USA) have found a way to use sound waves to levitate individual drops of solutions containing different pharmaceuticals. While the correlation between levitation and drug development may not be clear, an extraordinary relationship emerges at the molecular level.

At the molecular level, pharmaceutical structures fit into one of two categories: amorphous or crystalline. Amorphous agents typically are more efficiently taken up by the body than their crystalline relatives; this is because amorphous drugs are both more highly soluble and have a higher bioavailability, suggesting that a lower dose can generate 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,” said Argonne X-ray physicist Dr. 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,” added Dr. Yash Vaishnav, Argonne senior manager for intellectual property development and commercialization.

Getting pharmaceuticals from solution into an amorphous state, however, is no easy undertaking. 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,” Dr. Benmore said.

To avoid this problem, Dr. Benmore looked for a way to evaporate a solution without it touching anything. Because liquids conform to the shape of their containers, this was almost impossible requirement--so tricky, in fact, that Dr. Benmore had to turn to an acoustic levitator, a device originally developed for US National Aeronautics and Space Administration (NASA) to simulate microgravity conditions.

Levitation or “containerless processing” can form unspoiled 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,” said 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--about 22 kHz. When the top and bottom speakers are exactly aligned, they create two sets of sound waves that perfectly interfere with each other, setting up a phenomenon known as a standing wave.

At specific 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” utilizing this technique, it remains a powerful analytic approach for determining the conditions that make for the best amorphous preparation, Dr. Vaishnav explained.

Argonne researchers have already investigated more than 12 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 modifying the technology for drug research, the Argonne scientists partnered with Prof. Stephen Byrn and Prof. Lynne Taylor at the department of industrial and physical pharmacy at Purdue University (West Lafayette, IN, USA), and Jeffery Yarger of the department of chemistry and biochemistry at Arizona State University (Phoenix, USA).

The investigators are now working on identifying which drugs the levitation instrumentation will impact most strongly.

Related Links:
Argonne National Laboratory