Applied Physics B

, Volume 90, Issue 2, pp 345-354

First online:

VCSEL-based oxygen spectroscopy for structural analysis of pharmaceutical solids

  • T. SvenssonAffiliated withDepartment of Physics, Lund University Email author 
  • , M. AnderssonAffiliated withDepartment of Physics, Lund University
  • , L. RippeAffiliated withDepartment of Physics, Lund University
  • , S. SvanbergAffiliated withDepartment of Physics, Lund University
  • , S. Andersson-EngelsAffiliated withDepartment of Physics, Lund University
  • , J. JohanssonAffiliated withAstra Zeneca R&D
  • , S. FolestadAffiliated withAstra Zeneca R&D

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We present a minimalistic and flexible single-beam instrumentation based on sensitive tunable diode laser absorption spectroscopy (TDLAS) and its use in structural analysis of highly scattering pharmaceutical solids. By utilising a vertical cavity surface emitting laser (VCSEL) for sensing of molecular oxygen dispersed in tablets, we address structural properties such as porosity. Experiments involve working with unknown path lengths, severe backscattering and diffuse light. These unusual experimental conditions has led to the use of the term gas in scattering media absorption spectroscopy (GASMAS). By employing fully digital wavelength modulation spectroscopy and coherent sampling, system sensitivity in ambient air experiments reaches the 10-7 range. Oxygen absorption exhibited by our tablets, being influenced by both sample porosity and scattering, was in the range 8×10-5 to 2×10-3, and corresponds to 2–50 mm of path length through ambient air (Leq). The day-to-day reproducibility was on average 1.8% (0.3 mm Leq), being limited by mechanical positioning. This is the first time sub-millimetre sensitivity is reached in GASMAS. We also demonstrate measurements on gas transport on a 1-s time scale. By employing pulsed illumination and time-correlated single-photon counting, we reveal that GASMAS exhibits excellent correlation with time-domain photon migration. In addition, we introduce an optical measure of porosity by relating oxygen absorption to average photon time-of-flight. Finally, the simplicity, robustness and low cost of this novel TDLAS instrumentation provide industrial potential.