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Proceedings Paper

In situ dissolution analysis of pharmaceutical dosage forms using coherent anti-Stokes Raman scattering (CARS) microscopy
Author(s): A. L. Fussell; E. T. Garbacik; K. Löbmann; H. L. Offerhaus; P. Kleinebudde; C. J. Strachan
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Paper Abstract

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.

Paper Details

Date Published: 28 February 2014
PDF: 9 pages
Proc. SPIE 8948, Multiphoton Microscopy in the Biomedical Sciences XIV, 89482J (28 February 2014); doi: 10.1117/12.2038933
Show Author Affiliations
A. L. Fussell, Univ. Twente (Netherlands)
E. T. Garbacik, Univ. Twente (Netherlands)
K. Löbmann, Univ. of Copenhagen (Denmark)
H. L. Offerhaus, Univ. Twente (Netherlands)
P. Kleinebudde, Heinrich-Heine-Univ. Düsseldorf (Germany)
C. J. Strachan, Univ. of Helsinki (Finland)

Published in SPIE Proceedings Vol. 8948:
Multiphoton Microscopy in the Biomedical Sciences XIV
Ammasi Periasamy; Peter T. C. So; Karsten König, Editor(s)

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