3D and Topographic Raman Imaging of Drug Delivery Systems

September 1, 2012

Knowledge about the morphology and chemical composition of heterogeneous materials on a submicrometer scale is crucial for the development of new material properties for highly specified drug delivery systems. WITec's ultrasensitive and modular alpha300 and alpha500 microscope series allow for the analysis of the chemical characteristics of a sample three-dimensionally, underneath and at the surface. Confocal Raman microscopy for 3D chemical imaging and TrueSurface Microscopy employed for topographic Raman imaging deliver the highest spectral quality and unmatched spatial resolution.

Knowledge about the morphology and chemical composition of heterogeneous materials on a submicrometer scale is crucial for the development of new material properties for highly specified drug delivery systems. WITec's ultrasensitive and modular alpha300 and alpha500 microscope series allow for the analysis of the chemical characteristics of a sample three-dimensionally, underneath and at the surface. Confocal Raman microscopy for 3D chemical imaging and TrueSurface Microscopy employed for topographic Raman imaging deliver the highest spectral quality and unmatched spatial resolution.

3D Raman Imaging & Depth Profiling — Drug Delivery Coating

In Raman imaging, a complete spectrum is acquired in as little as 760 ms at each image pixel resulting in images consisting of tens of thousands of Raman spectra being collected in less than a minute. Differences in chemical composition will be apparent in the Raman image and can be analyzed with a spatial resolution down to 200 nm. With the various algorithms coming with the integrated software package it is possible to visualize additional material properties such as stress fields or crystallinity. For objective and chemometric data evaluation the optional cluster analysis allows the computerized unveiling of hidden structures automatically. Using the sensitive setup of the alpha300 and alpha500 can also be an advantage when performing measurements on delicate and precious samples requiring the lowest possible levels of excitation power. Figure 1a shows an electron micrograph of a polymer coated drug eluting stent. To characterize such coatings, nondestructively confocal Raman imaging provides the ability to analyze the chemical composition and spatial distribution of the material within the coating. Due to the confocal principle even the thickness of these coatings can be measured. In Figure 1b the Raman spectral image of a coating on a stent is shown. In this case the confocal Raman microscope was used to perform a depth scan along the x–z axis through the coating.

Figure 1a: a: Electron micrograph of a polymer coated stent.

Figure 1b: Confocal Raman depth profile through the coating layer of the stent.

Topographic Raman Imaging — Tablet

WITec's exclusive TrueSurface® microscopy option makes it possible to perform confocal imaging measurements parallel with and guided by large area topographic scans (>1×1 mm2). To achieve this unique capability, the WITec alpha500 microscope series can be equipped with a highly precise sensor for optical profilometry. The large area topographic co-ordinates from the profilometer measurement are used to perfectly trace the samples surface in confocal Raman imaging mode. Sample preparation is reduced to a minimum without having to compromise the confocality of the system. Figure 2a shows a height profile of a pharmaceutical tablet and Figure 2b the same profile with the confocal Raman measurement overlaid. The APIs are labeled red and blue respectively, while the excipient is shown in green.

Figure 2a: Topography of an aspirin tablet.

Figure 2b: Topographic Raman image. APIs: Red and blue, green: excipient.

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