Selective Imaging of Active Pharmaceutical Ingredients in Powdered Blends with Common Excipients Utilizing Two-Photon Excited Ultraviolet-Fluorescence and Ultraviolet-Second Order Nonlinear Optical Imaging of Chiral Crystals

Toth, Scott J.; Madden, Jeremy T.; Taylor, Lynne S.; Marsac, Patrick J.; Simpson, Garth J.

doi:10.1021/ac300917t

Cited by 35 publications

(38 citation statements)

References 53 publications

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“…The second-order optical activity of chiral crystals has been used, for instance, to monitor protein crystal nucleation (104) and to visualize protein microcrystallites in pharmaceutical products with SHG microscopy (105). Cholesterol crystals, which are thought to play a prominent role in atherosclerotic disease progression, are noncentrosymmetric and can be probed by SHG (41) and SFG microscopy.…”

Section: Second-order Vibrational Microscopymentioning

confidence: 99%

Biomolecular Imaging with Coherent Nonlinear Vibrational Microscopy

Chung

Potma

2013

Annu. Rev. Phys. Chem.

104

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Optical imaging with spectroscopic vibrational contrast is a label-free solution for visualizing, identifying, and quantifying a wide range of biomolecular compounds in biological materials. Both linear and nonlinear vibrational microscopy techniques derive their imaging contrast from infrared active or Raman allowed molecular transitions, which provide a rich palette for interrogating chemical and structural details of the sample. Yet nonlinear optical methods, which include both second-order sum-frequency generation (SFG) and third-order coherent Raman scattering (CRS) techniques, offer several improved imaging capabilities over their linear precursors. Nonlinear vibrational microscopy features unprecedented vibrational imaging speeds, provides strategies for higher spatial resolution, and gives access to additional molecular parameters. These advances have turned vibrational microscopy into a premier tool for chemically dissecting live cells and tissues. This review discusses the molecular contrast of SFG and CRS microscopy and highlights several of the advanced imaging capabilities that have impacted biological and biomedical research.

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Section: Second-order Vibrational Microscopymentioning

confidence: 99%

Biomolecular Imaging with Coherent Nonlinear Vibrational Microscopy

Chung

Potma

2013

Annu. Rev. Phys. Chem.

104

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“…Toth et al used the optical properties of chiral crystals to spatially map only the crystalline APIs embedded in powdered excipients very rapidly with combined SHG and TPE images. 20 Windbergs et al used narrow band CARS imaging to map solid dosage form surfaces and to measure dissolution dynamics. 21,22 Additionally, Slipchenko et al used SRS to image pharmaceutical tablets with high spatial resolution of three separately imaged spectral bands with short acquisition times.…”

mentioning

confidence: 99%

Multicomponent Chemical Imaging of Pharmaceutical Solid Dosage Forms with Broadband CARS Microscopy

et al. 2013

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We compare a coherent Raman imaging modality, broadband coherent anti-Stokes Raman scattering (BCARS) microscopy, with spontaneous Raman microscopy for quantitative and qualitative assessment of multicomponent pharmaceuticals. Indomethacin was used as a model active pharmaceutical ingredient (API) and was analyzed in a tabulated solid dosage form, embedded within commonly used excipients. In comparison with wide-field spontaneous Raman chemical imaging, BCARS acquired images 10× faster, at higher spatiochemical resolution and with spectra of much higher SNR, eliminating the need for multivariate methods to identify chemical components. The significant increase in spatiochemical resolution allowed identification of an unanticipated API phase that was missed by the spontaneous wide-field method and bulk Raman spectroscopy. We confirmed the presence of the unanticipated API phase using confocal spontaneous Raman, which provided spatiochemical resolution similar to BCARS but at 100× slower acquisition times.

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“…9–11 An 80 MHz signal from the laser’s internal photodiode (SpectraPhysics MaiTai HP) drove a phase locked loop timing module (Quantum Composer 9530). This timing module provided an approximately 8 kHz TTL signal to drive the fast scan resonant mirror (Electro-Optic Products SC-30) and step a galvanometer mirror (Cambridge Technology 6210H) in the microscope.…”

Section: Methodsmentioning

confidence: 99%

Real-time dynamic range and signal to noise enhancement in beam-scanning microscopy by integration of sensor characteristics, data acquisition hardware, and statistical methods

Kissick

Muir

Sullivan

et al. 2013

Computational Imaging XI

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Despite the ubiquitous use of multi-photon and confocal microscopy measurements in biology, the core techniques typically suffer from fundamental compromises between signal to noise (S/N) and linear dynamic range (LDR). In this study, direct synchronous digitization of voltage transients coupled with statistical analysis is shown to allow S/N approaching the theoretical maximum throughout an LDR spanning more than 8 decades, limited only by the dark counts of the detector on the low end and by the intrinsic nonlinearities of the photomultiplier tube (PMT) detector on the high end. Synchronous digitization of each voltage transient represents a fundamental departure from established methods in confocal/multi-photon imaging, which are currently based on either photon counting or signal averaging. High information-density data acquisition (up to 3.2 GB/s of raw data) enables the smooth transition between the two modalities on a pixel-by-pixel basis and the ultimate writing of much smaller files (few kB/s). Modeling of the PMT response allows extraction of key sensor parameters from the histogram of voltage peak-heights. Applications in second harmonic generation (SHG) microscopy are described demonstrating S/N approaching the shot-noise limit of the detector over large dynamic ranges.

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Selective Imaging of Active Pharmaceutical Ingredients in Powdered Blends with Common Excipients Utilizing Two-Photon Excited Ultraviolet-Fluorescence and Ultraviolet-Second Order Nonlinear Optical Imaging of Chiral Crystals

Cited by 35 publications

References 53 publications

Biomolecular Imaging with Coherent Nonlinear Vibrational Microscopy

Biomolecular Imaging with Coherent Nonlinear Vibrational Microscopy

Multicomponent Chemical Imaging of Pharmaceutical Solid Dosage Forms with Broadband CARS Microscopy

Real-time dynamic range and signal to noise enhancement in beam-scanning microscopy by integration of sensor characteristics, data acquisition hardware, and statistical methods

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