28 February 2014 In situ dissolution analysis of pharmaceutical dosage forms using coherent anti-Stokes Raman scattering (CARS) microscopy
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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 compact’s surface in situ during dissolution. Hyperspectral CARS imaging allowed visual discrimination between the solid-state forms on the compact’s surface. In the case of theophylline we were able to correlate the solid-state change with a change in dissolution rate.
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A. L. Fussell, A. L. Fussell, E. T. Garbacik, E. T. Garbacik, K. Löbmann, K. Löbmann, H. L. Offerhaus, H. L. Offerhaus, P. Kleinebudde, P. Kleinebudde, C. J. Strachan, C. J. Strachan, "In situ dissolution analysis of pharmaceutical dosage forms using coherent anti-Stokes Raman scattering (CARS) microscopy", Proc. SPIE 8948, Multiphoton Microscopy in the Biomedical Sciences XIV, 89482J (28 February 2014); doi: 10.1117/12.2038933; https://doi.org/10.1117/12.2038933

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