Hyperspectral coherent anti-Stokes Raman scattering microscopy for in situ analysis of solid-state crystal polymorphs

Garbacik, E.T.; Fussell, A.L.; Güres, Sinan; Korterik, Jeroen P.; Otto, Cornelis; Herek, Jennifer Lynn; Offerhaus, Herman L.

doi:10.1117/12.2004522

Cited by 3 publications

(3 citation statements)

References 17 publications

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“…These techniques have spread over many fields to image cells, tissues, plants, cosmetics, nanoparticle drugs, and pharmaceutical compounds . However, only one study has been reported on polymorph imaging and identification using CARS . In this paper, we use SRS to image and discriminate various polymorphs and excipients in pharmaceutical tablets over millimetre‐size areas.…”

Section: Introductionmentioning

confidence: 99%

Discriminating polymorph distributions in pharmaceutical tablets using stimulated Raman scattering microscopy

Sarri

Simó

Audier

et al. 2019

J Raman Spectroscopy

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Stimulated Raman scattering (SRS) imaging is used to probe active pharmaceutical ingredient exhibiting polymorphism within compact tablets. We show that few SRS images performed at selected wavenumbers allow to access both active pharmaceutical ingredients polymorphs and excipients from which molecular mapping is retrieved over millimetre-size areas. We exemplified the approach using SRS images acquired at five wavenumbers to map clopidogrel and amibegron polymorphs embedded into excipients (polyethylene glycol, corn starch, and mannitol tablets). Our study demonstrates that SRS imaging can be used as a novel fast molecular mapping technique for pharmaceutical tablets characterization. KEYWORDSactive pharmaceutical ingredients (API), label-free imaging, molecular imaging, pharmaceutical tablets, polymorphism, stimulated Raman scattering (SRS)

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Section: Introductionmentioning

confidence: 99%

Discriminating polymorph distributions in pharmaceutical tablets using stimulated Raman scattering microscopy

Sarri

Simó

Audier

et al. 2019

J Raman Spectroscopy

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“…4. We note that diprophylline and mannitol are known to exhibit variations in their vibrational spectra as functions of crystal orientation [31,32], and we have selected a region of the sample to image that contains few of these variations.…”

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confidence: 99%

Epi-detection of vibrational phase contrast coherent anti-Stokes Raman scattering

et al. 2014

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We demonstrate a system for the phase-resolved epi-detection of coherent anti-Stokes Raman scattering (CARS) signals in highly scattering and/or thick samples. With this setup, we measure the complex vibrational responses of multiple components in a thick, highly-scattering pharmaceutical tablet in real time and verify that the epi-and forward-detected information are in very good agreement. Coherent anti-Stokes Raman scattering (CARS) has matured in recent years into an imaging and spectroscopy technique that is finding applications in a range of disciplines including biology [1][2][3][4], remote sensing [5,6], and pharmaceutics [7,8]. The high spatial and spectral resolutions of CARS, combined with its capabilities for imaging in both transmission and reflection [9,10] at speeds up to video rate [11], have led to work specifically aimed at bringing down costs and complexity [12] to enable its use by non-specialists. However, this technique is not without problems. In particular, a strong, frequencyindependent non-resonant background interferes with the resonant signal of interest, reducing contrast and creating imaging and spectral artifacts that can be difficult to interpret. In order to remove, suppress, or extract this non-resonant background, a number of specialized methods have been developed that exploit polarization [9,13,14], spectral [15], time [16][17][18], and/or phase [19][20][21] dependencies of the CARS process. This last feature is of particular interest because it can be used to determine the full complex vibrational response of an arbitrary sample [22]. We previously introduced a method known as vibrational phase contrast CARS (VPC-CARS) to measure the pure vibrational phase of a sample [23], and used it to measure the full vibrational responses of multiple materials in both heterogeneous and homogeneous mixtures [24]. Heterodyne CARS measurements, in which an external local oscillator is interfered with the CARS emission, contain information about both the vibrational phase of the molecular oscillators and the relative local phases of the optical excitation fields. The local excitation phase is subject to disturbances from the variations in the relative phases of the pump, Stokes, and local oscillator beams, which can come from refractive index differences in the sample, interferometric instabilities, and field-of-view curvature resulting from dispersion in the focusing objective lens. To remove these effects a separate measurement is made in which only the local excitation phase is detected. The difference of the heterodyne and local excitation phases is the pure vibrational phase of the molecular oscillators. In previous experiments, heterodyne and local excitation phase measurements were performed in series on a pixel-by-pixel basis, with the local oscillator at nanowatt levels for the heterodyne process and at multi-millwatt powers for the local excitation phase detection. The exact power of the heterodyne local oscillator was a critical parameter for obtaining shot-noise-limited measurem...

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“…We built a system that is capable of acquiring hyperspectral CARS data stacks in tens of seconds, then quickly processing the complicated three-dimensional data to yield a set of intuitive, two-dimensional images with high visual contrast [18]. This system has become the workhorse of the Optical Sciences CARS lab-it is routinely used as a first-stage diagnostic tool for new samples-and has found use in a number of applications, including the in situ analysis of the constituent components of pharmaceutical oral dosage forms [19]. The introduction of a modulation technique further enables the suppression of certain electronic background contributions, which allowed us to image the in planta distributions of the active compounds in Cannabis sativa L. [20] CHAPTER III covers vibrational phase contrast (VPC)-CARS.…”

Section: Overviewmentioning

confidence: 99%

Contrast in coherent Raman scattering microscopy

Garbacik

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Hyperspectral coherent anti-Stokes Raman scattering microscopy for in situ analysis of solid-state crystal polymorphs

Cited by 3 publications

References 17 publications

Discriminating polymorph distributions in pharmaceutical tablets using stimulated Raman scattering microscopy

Discriminating polymorph distributions in pharmaceutical tablets using stimulated Raman scattering microscopy

Epi-detection of vibrational phase contrast coherent anti-Stokes Raman scattering

Contrast in coherent Raman scattering microscopy

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