Mapping Active Ingredients In Drug Tablets

A laser-based scanning microscopy method can map the three-dimensional distribution of active pharmaceutical ingredients (APIs) in drug tablets and powdered samples faster and with greater sensitivity than standard methods used for drug analyses, according to work reported in Analytical Chemistry (DOI: 10.1021/ac300917t). The study may lead to rapid tests for quality control and drug stability as well as for detecting counterfeits.

Drug manufacturers evaluate the spatial distribution, crystallinity, and other properties that influence drug stability, bioavailability, and efficacy to ensure their uniformity in solid drug formulations. X-ray powder diffraction and Raman spectroscopy are commonly used techniques, but they suffer from various shortcomings. The X-ray method, for example, is fairly insensitive; its detection limit is often on the order of 1% for an API in a background of inactive drug formulation compounds (excipients). Imaging by Raman spectroscopy often requires long data acquisition times—several hours per frame—and is subject to spectral interference from excipients.

Scott J. Toth, Garth J. Simpson, and Lynne S. Taylor of Purdue University and coworkers have devised a technique that overcomes limitations of the X-ray and Raman methods. It combines ultraviolet nonlinear optical imaging and UV fluorescence methods and generates data from the two methods simultaneously. The team evaluated the method by using it to analyze the antifungal compound griseofulvin, which is a model API, and tadalafil, which is the API in Cialis, a drug to treat erectile dysfunction.

The new method yields analyte signals that can be 10,000 times the size of signals derived from excipients if the API is chiral, which is true for some 80% of relatively new drugs. That level of signal intensity leads to a 1,000-fold increase in detection sensitivity over X-ray powder diffraction. In addition, data acquisition time drops from hours per image, which is required for Raman imaging, to just minutes per image.

“The reported detection sensitivities for pharmaceutical compounds are nothing short of impressive,” says Eric O. Potma, a chemistry professor and laser imaging specialist at the University of California, Irvine. Potma adds that the method’s sensitivity and nondestructive nature set the stage for a much larger role for nonlinear optics in detecting and identifying chemical compounds in common products, including drugs, cosmetics, and food items.

Shawn Yin, a principal scientist at Bristol-Myers Squibb, comments that the new method will provide drug formulators with an alternative technique to determine API particle size and distribution in tablets and capsules. Ensuring drug uniformity is a key parameter in controlling a product’s efficacy and safety, he adds.