Imaging Technique Improves Quality Control of Pharmaceuticals

A focal plane array designed for the Missile Defense Agency’s (MDA) Exoatmospheric Kill Vehicle has helped a scientist see farther into the infrared spectrum.

National Institutes of Health (NIH) researcher E. Neil Lewis picked up a mercury-cadmium telluride (MCT) array from Ted Heilweil, a colleague at the National Institute of Standards and Technology, and placed it on the step-scanner of his infrared microscope.

A near-infrared image of heartburn medication shows the architecture and spatial distribution of chemicals in a tablet, which would allow a manufacturer to evaluate its quality.

Lewis, an expert in infrared imaging and recipient of numerous technology awards, used the array to extend the range of a microscope he had been refining for a number of years. The MCT substrate had been meant for installation on a subsystem of the Exoatmospheric Kill Vehicle, but a few dead pixels disqualified it from use. For Dr. Lewis, it provided a better window into the infrared (to approximately 11,000 nanometers) through which his spectroscopic microscope could see.

Lewis used the technology as a biodiagnostic tool for disease detection. The microscope could present this information in two ways: by location in an image plane, and by wavelength in a spectrum, all contained in a 3D space called a “hypercube.” This allows pinpointing the location of a molecule of interest as well as the type of molecule present. Dr. Lewis and his group developed computer algorithms to decipher the large quantity of data in the hypercube, allowing the operator to locate a single pixel and view its spectral signature. In 1999, Dr. Lewis founded Spectral Dimensions (Olney, MD), which was subsequently acquired by Malvern Instruments in Westborough, MA.

Spectral Imaging Benefits

Tablets in a blister pack would all look the same to the naked eye, but this near-infrared image shows that one tablet (the white tablet) has a different chemical composition than the others.

Because today’s tablets often have a timed-release component that is entirely dependent on how and where the active ingredient is distributed inside the tablet, it is critical for a pharmaceutical manufacturer to test its properties before packaging. Manufacturers perform dissolution testing, which requires destruction of the tablet in a series of experimental steps. In addition, this analysis depends on sampling, with findings for a limited amount of product being extrapolated to other products in the same lot.

With spectral imaging, a drug manufacturer can accurately visualize the heterogeneity profile of multiple tablets without the limitations and expense of destructive testing.

The Food and Drug Administration rolled out an effort called the Process Analytical Technology (PAT) initiative, encouraging the pharmaceutical industry to use objective techniques wherever possible in quality assurance. Spectral Dimension’s rugged spectrometer, the SapphireTM Near-Infrared Chemical Imaging System, provides the high-fidelity, high-throughput spectral imaging applicable for that sort of testing.

The system operates on a cooled indium-antimonide-based focal plane array, with a wavelength range of 1,200 to 2,450 nanometers and a scan time of about two minutes. Sapphire features an open, accessible sample area and a variable field of view, from square millimeters to square inches. The unit operates with ISys® hyperspectral data manipulation and visualization software, and is designed for characterizing pills. When a larger field of view and greater depth of penetration is desired, Spectral Dimensions offers the MatrixNIRTM system, based on an indium-gallium-arsenide array. Whereas Sapphire is used primarily in pharmaceutical applications, the Matrix is often preferred for food and agricultural analyses, such as crop-seed viability.

In major laboratories such as Johnson & Johnson, Merck, Pfizer, Astra-Zeneca, and Bristol-Myers Squibb, the Sapphire provides information about quality and performance parameters. Some industrial users of the technology advocate that it may ultimately replace the traditional dissolution analysis.