Triboluminescence Used to Test for Drug Efficacy

An instrument has been developed that uses triboluminescence (TL) to enable selective detection of trace crystallinity within amorphous solid dispersions, used in the preparation of pharmaceutical formulations to make the drug more efficacious. The instrument can accurately detect in the early stages of drug development whether a pharmaceutical formulation has trace crystalline content that could negatively impact the drug’s stability and bioavailability.

The TL instrument, developed by a Purdue University research team, measures the light that is emitted when a pharmaceutical powder is crushed. The light that is measured is in direct proportion to the quantity of crystallinity in the pharmaceutical formulation. The instrument can detect crystallinity at levels as low as 140 ppm.

To detect crystallinity, pharmaceutical powder is placed on a microscope slide and an electric charge is applied to the powder using a solenoid. A photomultiplier tube positioned beneath the slide measures the optical radiation resulting from the triboluminescence of the powder. The slide is mechanically moved down the line so that new areas of the powder can be probed.

Front side of the triboluminescence instrument developed by Purdue University researchers to crush pharmaceutical formulations to test for trace crystallinity. The red plastic holds a solenoid that strikes the formulation. A motor moves the microscope slide (black box) down the line. A photomultiplier tube beneath the slide measures the optical radiation resulting from the triboluminescence of the compound. Courtesy of Purdue University.

“This technique would be more like a prescreen off an assembly line in a factory where they’re making these drugs," said researcher Scott Griffin. "They can send a small amount of the material into this instrument for triboluminescence measurements. If they get a positive outcome from the sample, then they can send it off for more rigorous testing.”

Other ways to determine crystallinity include a second harmonic generation process that uses a femtosecond pulsed laser, also developed at Purdue. The TL instrument is simpler, say the researchers.

Back side of the instrument for testing trace crystallinity in pharmaceutical formulations. The main circuit board consists of a high-power voltage regulator to power the striking solenoid. Courtesy of Purdue University.

“It boils down to the earliest time point which crystallinity can be detected," said professor Garth Simpson. "We wanted to have something that would be a simple yes or no assessment that could be done on-site. If something fails, it can be taken to a more advanced instrument to get a better sense of quantitative characterization.”

Simpson said a TL instrument also could be used to determine whether changes in the way a drug is produced could cause crystallinity.

Researchers are working on a flow cell that will enable similar crystallinity testing in slurries, and they are also exploring what fraction of drug molecules and compounds could be responsive to TL analysis.

“New drugs that are coming out are increasingly larger and more hydrophobic, or do not dissolve easily in water. If crystallinity is detected, there’s a good chance that it won’t dissolve in a time frame required to be bioavailable and efficacious,” Simpson said.

The researchers have obtained a provisional patent on the device. The TL instrument is available for licensing from the Office of Technology and Commercialization at Purdue University.

The research was published in Analytical Chemistry (doi:10.1021/acs.analchem.8b01112).

Instrument developed to detect trace crystallinity in pharmaceutical formulations using triboluminescence. Courtesy of Purdue University.