Solid, multicomponent samples such as blends for tablets or capsules, compressed tablets or cast films typically exhibit nonhomogeneous distribution of components. Our powerful analytical techniques provide a wealth of chemical and physical information on specific microscopic regions of solid samples. Our complete suite of techniques includes:
- Fourier transform infrared spectroscopy
- Raman spectroscopy
- Near infrared spectroscopy
- X-ray powder diffraction
- Energy dispersive X-ray spectroscopy
- Optical microscopy
While traditional application of these techniques involves examination of a single location in the sample and subsequent collection of the chemical or physical information from only that area, new imaging techniques involve automated data collection from multiple locations over a large area of the sample. This allows for visualization of qualitative distribution, identification of majority or trace components and more accurate quantitative analysis.
Imaging is a general term for collection (usually automated) and analysis of data from a large number of locations on a sample. We employ two common methods of collecting data: use of an array detector, where data for the entire image are collected simultaneously, and automated mapping, in which analysis is carried out on multiple discrete points. Our scientists can observe small particles or domains that would not be resolved with a single analysis of the entire area. Investigation of interfacial interactions is possible by observing differences between adjacent pixels. We can process the array repeatedly, observing different chemical or physical signatures.
Imaging over a large area provides a more representative analysis of the sample for quantitative applications. Each pixel of the image provides a full spectrum that our scientists can compare to spectral databases of known compounds for specific identification. Trace particles can thus provide a pure spectrum of a contaminant. Individual spectra from each pixel allow quantitative distribution within the area analyzed.
Fourier Transform Infrared Spectroscopy Mapping
Fourier transform infrared spectroscopy (FTIR) is a methodology for chemical and structural analysis of organic products, providing a unique “fingerprint” spectrum of each molecule. The resulting spectrum can identify subtle changes in the chemical or physical properties of the sample. Each FTIR spectrum represents an area of the sample as small as 10 µm, and distribution of a single component is easily visualized. With proper selection of conditions, FTIR can overcome limitations of Raman and NIR.
As with FTIR, Raman spectra are unique, allowing for unambiguous chemical identification. Raman is sensitive to the local molecular environment including changes in crystal structure or subtle chemical modifications, and as such, can be used to understand both chemical and physical changes in the drug product.
Near Infrared Imaging
Near infrared (NIR) spectroscopy offers many of the advantages of FTIR and Raman but overcomes some of the limitations. NIR offers the same advantage over FTIR as Raman in that neither glass nor water interferes with the analysis and may also allow for in situ sampling in various packaging configurations. NIR spectra result from absorption of overtones and combination bands from the mid infrared region; therefore, chemical or physical differences detected by FTIR also affect NIR data.
X-Ray Powder Diffraction Mapping
X-ray powder diffraction (XRPD) addresses an entirely different aspect of solid analysis and provides highly reliable analysis of the solid state form of a material. An XRPD mapping study can, for example, provide information about the solid form composition at different regions in a tablet or identify the presence of a trace amount of a particular solid form.
Energy Dispersive Spectrometry Imaging
Energy dispersive spectrometry (EDS) combines the advantages of scanning electron microscopy (SEM) and elemental analysis. Samples examined by SEM can be analyzed for elemental content by EDS under similar conditions of magnification and sampling environment. Each point represents an area as small as 1 Å.
Characterization by an expert in optical microscopy (OM) can be critical to identifying physical changes that occur in the drug product. We have used OM as both a qualitative and quantitative tool for understanding crystallization kinetics in drug products such as tablets, soft gels and topical patches. Our in-house experts have more than 20 years of industrial experience analyzing materials by OM and solving pharmaceutical problems.