While analyzing stability data of a particularly potent drug stored inside an HDPE bottle, Metrics Inc. scientist Deanna Williamson discovered an unexpected trend of a previously unidentified molecule.
It wasn’t just any molecule. It was a molecule of a benzophenone, a compound that is often used in the varnish coating of a bottle’s label. And the molecule had traveled on its own – through the label and the bottle – before coming to rest on a tablet inside.
Williamson, quality control group leader at Metrics, presented details of this discovery during a poster session Nov. 15 at the American Association of Pharmaceutical Scientists annual conference.
The pharmaceutical industry has long been aware of the ability of some molecules to migrate – after all, Williamson pointed out, hardly any material in the world is considered truly impermeable. And this particular molecule was not toxic at the levels seen in her stability data; benzophenone has been detected in European food products, including cereals. Still, the discovery gave Williamson pause.
“In this situation, the active ingredient was an agent that needed to be measured using an especially sensitive analytical method,” she said. “Someone making a typical over-the-counter (OTC) drug product may not employ the same sensitive level of testing. So it’s probable that the levels of benzophenone present in those products would go undetected during the course of routine stability monitoring.”
This research has implications for the pharmaceutical industry. If benzophenone is readily migrating onto drugs but going undetected because routine monitoring doesn’t catch it, what does that mean for patients?
“These compounds may have been present all along but, unless you’re looking past a milligram level, you won’t see them,” she said. “At a minimum, this research could impact one’s choice of label varnish, especially in potent products.”
Metrics, Inc. (metricsinc.com) is one of the most respected contract pharmaceutical development and manufacturing companies in the United States today. Started as an analytical laboratory in 1994, Metrics has evolved into a full-service provider of quality pharmaceutical formulation development; first-time-in-man (FTIM) formulations; clinical material manufacturing (CTM) for Phase I, II and III trials; commercial manufacturing; and analytical method development and validation services.
Metrics has particular expertise in FTIM and Phase I, II, and III CTM manufacturing, having conducted more than 120 FTIM projects for different chemical entities in the last five years alone – while developing more than 700 batches of CTM in the same period.