New Dimensions in Tablet Imaging - Pharmaceutical Technology

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New Dimensions in Tablet Imaging
Chemical imaging of solid dosage forms has become a powerful analytical tool for the development of solid dosage forms.

Pharmaceutical Technology
Volume 3, Issue 32

Chemical imaging using NIR spectroscopy can obtain data from rounded surfaces, powders, granules, beads, and intact capsules. "With NIR spectroscopy, we can look at beads in a capsule without having to take a capsule apart, it would be very difficult to do that with the mid-IR or Raman," explains Linda Kidder.

"NIR, mid-IR, and Raman can tell formulators whether an API is co-localizing with a particular excipient," adds Kidder. "[Formulators can determine] whether the API has a tendency to associate or aggregate with a particular excipient, which may be affecting the tablet's dissolution properties. You can't get that [information] with HPLC and you can't get it with single-point spectroscopy. That is absolutely unique to imaging."

Figure 2: An RGB (red/green/blue) composite generated from a Raman Chemical Image of a controlled release system. The image was taken on a "Falcon II Raman chemical imaging system (ChemImage). The green and red areas of the image indicate chemically different layers (or coatings) on a bead (indicated by in blue). The goal of the project was to study the uniformity of thickness of multiple controlled-release coatings. This image clearly indicates that the coatings are not uniform in thickness across the bead's surface.
Another common application of NIR, mid-IR, and Raman imaging is mapping thicknesses of coatings and (for Raman) of pigments (see Figure 2). This analysis can be performed two ways. First, imaging can be a primary technique; that is, no correlation with other data is necessary. The tablet is cut in half and the cross section is imaged. The coating is seen as a series of pixels and pixel size variation relates to coating thickness. "We can generate an image through the use of color and show where the thin spots on the tablet are. Because it's imaging, you can actually tell that the coating is 100 μm. And by looking at hundreds of locations, you can obtain a statistical representation of the coating distribution—the mean value—and a standard deviation in that value," explains Kidder.

It is also possible to collect data from the surface of a tablet without first taking a cross section. A tablet is placed on its bottom or its top, and the analyst looks down on the surface. The variation in intensity of the vibrational band associated with the coating across the surface of the tablet provides a statistical variation of the coating thickness. This is a secondary analytical technique, and therefore obtaining absolute (rather than relative) values of the coating thickness requires a correlation with real distance measurements.


For NIR techniques, there has been some confusion between the terms "chemical imaging" and "mapping" because both provide an image and generate the same data. The difference is in how an image is produced and data are collected. "Chemical imaging uses a two-dimensional detector, so you are taking pictures, whereas mapping or 'fast mapping' uses either linear arrays or collects a line of spectra at one time to build up an image while the sample is moving on a stage," explains Kidder. In chemical imaging, the sample does not move—a picture is taken over a series of wavelengths—whereas mapping uses an interferometer, which is based on a moving mirror. This differentiation is also found in both Raman and mid-IR, where both mapping and imaging are used.

Figure 3: NIR chemical image reveals granule distribution in tablet (wavelength = 2060 nm) IMAGE COURTESY OF MALVERN INSTRUMENTS INC.
Because NIR mapping is based on an interferometer, sample surfaces must be very flat to collect good data. In contrast, "the depth of focus for NIR chemical imaging is very forgiving," says Kidder. "We can look at rounded sample and get reasonably good data from the whole sample" (see Figure 3). In addition, Malvern has developed an NIR-based imaging system that has no moving parts. As a stable system, it can move from an R&D setting into QA/QC setting or manufacturing setting and collect data. Mapping systems based on an interferometer have moving sample stages and the instrument stability and therefore spectral quality may be compromised by the vibrations found in a manufacturing or QA/QC environment.


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