In situ dissolution analysis of pharmaceutical dosage forms using coherent anti-Stokes Raman scattering (CARS) microscopy

A. L. Fussell, E. T. Garbacik, K. Löbmann, H. L. Offerhaus, P. Kleinebudde, Clare J. Strachan

Research output: Chapter in Book/Report/Conference proceedingConference contributionAcademicpeer-review


A custom-built intrinsic flow-through dissolution setup was developed and incorporated into a home-built CARS microscope consisting of a synchronously pumped optical parametric oscillator (OPO) and an inverted microscope with a 20X/0.5NA objective. CARS dissolution images (512×512 pixels) were collected every 1.12s for the duration of the dissolution experiment. Hyperspectral CARS images were obtained pre- and postdissolution by rapidly imaging while sweeping the wavelength of the OPO in discrete steps so that each frame in the data stack corresponds to a vibrational frequency. An image-processing routine projects this hyperspectral data into a single image wherein each compound appears with a unique color. Dissolution was conducted using theophylline and cimetidine-naproxen co-amorphous mixture. After 15 minutes of theophylline dissolution, hyperspectral imaging showed a conversion of theophylline anhydrate to the monohydrate, confirmed by a peak shift in the CARS spectra. CARS dissolution images showed that monohydrate crystal growth began immediately and reached a maximum with complete surface coverage at about 300s. This result correlated with the UV dissolution data where surface crystal growth on theophylline compacts resulted in a rapidly reducing dissolution rate during the first 300s. Co-amorphous cimetidinenaproxen didn't appear to crystallize during dissolution. We observed solid-state conversions on the compacts surface in situ during dissolution. Hyperspectral CARS imaging allowed visual discrimination between the solid-state forms on the compacts surface. In the case of theophylline we were able to correlate the solid-state change with a change in dissolution rate.

Original languageEnglish
Title of host publicationMultiphoton Microscopy in the Biomedical Sciences XIV
ISBN (Print)9780819498618
Publication statusPublished - 28 Feb 2014
EventSPIE International Biomedical Optics and Biophotonics Conference, BIOS 2014 - San Francisco, United States
Duration: 2 Feb 20144 Feb 2014


ConferenceSPIE International Biomedical Optics and Biophotonics Conference, BIOS 2014
Abbreviated titleBIOS
Country/TerritoryUnited States
CitySan Francisco
OtherPart of SPIE Photonics West 2014


  • carbamazepine
  • cimetidine
  • Coherent anti-Stokes Raman scattering
  • dissolution
  • hyperspectral imaging
  • microscopy
  • naproxen
  • pharmaceutics
  • theophylline

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