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    Highly Sensitive Detection of the Antibiotic Ciprofloxacin by Means of Fiber Enhanced Raman Spectroscopy
    (Basel : MDPI, 2019) Wolf, Sebastian; Frosch, Timea; Popp, Juergen; Pletz, Mathias W.; Frosch, Torsten
    Sepsis and septic shock exhibit a rapid course and a high fatality rate. Antibiotic treatment is time-critical and precise knowledge of the antibiotic concentration during the patients’ treatment would allow individual dose adaption. Over- and underdosing will increase the antimicrobial efficacy and reduce toxicity. We demonstrated that fiber enhanced Raman spectroscopy (FERS) can be used to detect very low concentrations of ciprofloxacin in clinically relevant doses, down to 1.5 µM. Fiber enhancement was achieved in bandgap shifted photonic crystal fibers. The high linearity between the Raman signals and the drug concentrations allows a robust calibration for drug quantification. The needed sample volume was very low (0.58 µL) and an acquisition time of 30 s allowed the rapid monitoring of ciprofloxacin levels in a less invasive way than conventional techniques. These results demonstrate that FERS has a high potential for clinical in-situ monitoring of ciprofloxacin levels.
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    Fiber-array-based Raman hyperspectral imaging for simultaneous chemical selective monitoring of particle size and shape of active ingredients in analgesic tablets
    (Basel : MDPI, 2019) Frosch, Timea; Wyrwich, Elisabeth; Yan, Di; Popp, Jürgen; Frosch, Torsten
    The particle shape, size and distribution of active pharmaceutical ingredients (API) are relevant quality indicators of pharmaceutical tablets due to their high impact on the manufacturing process. Furthermore, the bioavailability of the APIs from the dosage form depends largely on these characteristics. Routinely, particle size and shape are only analyzed in the powder form, without regard to the effect of the formulation procedure on the particle characteristics. The monitoring of these parameters improves the understanding of the process; therefore, higher quality and better control over the biopharmaceutical profile can be ensured. A new fiber-array-based Raman hyperspectral imaging technique is presented for direct simultaneous in-situ monitoring of three different active pharmaceutical ingredients- acetylsalicylic acid, acetaminophen and caffeine- in analgesic tablets. This novel method enables a chemically selective, noninvasive assessment of the distribution of the active ingredients down to 1 µm spatial resolution. The occurrence of spherical and needle-like particles, as well as agglomerations and the respective particle size ranges, were rapidly determined for two commercially available analgesic tablet types. Subtle differences were observed in comparison between these two tablets. Higher amounts of acetaminophen were visible, more needle-shaped and bigger acetylsalicylic acid particles, and a higher incidence of bigger agglomerations were found in one of the analgesic tablets.