Pharmaceutical development of solid-state formulations requires testing for uniformity and stability of active pharmaceutical ingredients and excipients. Solid-state properties such as component distribution and grain size are crucial factors of dissolution profile, which greatly affect drug efficacy and toxicity, and can only be analyzed spatially by chemical imaging (CI) techniques. Current CI techniques such as near infrared and confocal Raman spectroscopy do not offer high chemical and spatial resolution at speeds feasible for integration into the pharmaceutical quality control and quality assurance processes. We demonstrate fast chemical imaging by epi-detected sparse spectral sampling stimulated Raman scattering to quantify API and excipient degradation and distribution.
Stimulated Raman scattering (SRS) microscopy enables label-free and quantitative imaging of active pharmaceutical ingredients within the skin, with superior chemical specificity and spatial and temporal resolution. Here, we present a method to study topical formulations on ex vivo human skin using two modalities, SRS and near-infrared light (NIR) transmission. NIR transmission is used to compensate for the SRS signal variance caused by differences in skin thickness and formulation properties. Optical co-registration of the two modalities enables recording the variance in each pixel. The developed method helps to evaluate the cutaneous pharmacokinetics of tretinoin from tretinoin-containing solution and cream formulations.
Pharmaceutical development of solid-state formulations requires testing for uniformity and stability of active pharmaceutical ingredients and excipients. Solid-state properties such as component distribution and grain size are crucial factors of dissolution profile, which greatly affect drug efficacy and toxicity, and can only be analyzed spatially by chemical imaging (CI) techniques. Current CI techniques such as near infrared and confocal Raman spectroscopy do not offer high chemical and spatial resolution at speeds feasible for integration into the pharmaceutical quality control and quality assurance processes. We demonstrate fast chemical imaging by epi-detected sparse spectral sampling stimulated Raman scattering to quantify API and excipient degradation and distribution.
We introduce two multimodal extensions of our optical coherence tomography (OCT) based tethered capsule endomicroscopy (TCE) platform, tailored towards an enhanced clinical applicability for upper gastrointestinal tract imaging. The first extension presented – white light (RGB)-OCT-based TCE – provides both, true-color visualization of the tissue surface and depth-resolved sub-surface OCT imaging, co-registered in time and space. The second extension presented – fluorescence (FL)-OCT-based TCE – enables the addition of tissue specific molecular contrast. We present compact, modular, easily portable, plug-and-play system designs for both extensions, as well as imaging results in swine esophagus, in vivo.
Imaging the entire human cornea with a conventional OCT system configuration requires trade-offs between resolution and depth-of-focus because the cornea is curved over a depth of approximately 4 mm. These system trade-offs result in image quality variations in the corneal image such as a bright apex surrounded by decreasing intensity as the cornea curves away from the apex. These intensity changes cause non-biological ambiguities in interpreting the image, make it difficult to see anatomy in the dim areas, and make automated surface detection difficult in the periphery. To address this problem, we developed a continuously focusing corneal OCT system coupled with a constant linear velocity (CLV) spiral scan pattern that is able to better maintain focus from the apex to the deeper cornea during a scan. The continuous focusing was implemented by introducing a focusing telescope on a motorized stage into the sample arm and matching the translation of the telescope with the CLV scan as it spiraled from the corneal apex outwards. Orthogonal B-scans prior to volume acquisition were used as a reference to estimate and correct motion that occurred during the subsequent CLV scan. A consented subject was imaged, and the resultant image showed increased intensity in the peripheral and deeper cornea and anterior chamber. Continuous focusing with CLV spiral scanning is a promising design change to OCT systems allowing adequate focus over relatively large depths such as for scanning the human cornea.
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