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Preliminary Assesments of Solid Crystal Suspensions Using Nonlinearmicroscopy
* 1 , 2 , 2 , 1
1  Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Duesseldorf, Germany
2  Optical Sciences, MESA+ Institute for Nanotechnology, University of Twente, Enschede, The Netherlands

Abstract: A few years ago Solid Crystal Suspensions (SCS), made via hot-melt-extrusion, were proposed as sufficient technique to increase the bioavailability of poorly soluble drugs of BCS Class II. The drug particle size and the dispersity of these systems are crucial properties because they determine the drug release. The nonlinear imaging techniques, Coherent Anti Stokes Raman Scattering (CARS) and Second Harmonic generation (SHG) microscopy, were used to characterize SCS in order to understand the dissolution behaviour of different formulations. CARS microscopy is based on the detection of molecular vibrations similar to Raman spectroscopy. The advantage in comparison to conventional Raman spectroscopy is the detection of a single vibrational resonance allowing for much faster imaging with CARS. The setup consists of a laser and an optical parametric oscillator. The beams were scanned over the sample by galvano-mirrors and focused by an objective lens into the sample. The generated CARS signal is shifted to a higher frequency in comparison to the incident beam. The SHG signal is created when the sample contains non-centrosymmetric structures. The generated signal is created simultaneous with the CARS signal in the sample and detected on a different detector. The SCS consisted of drug (Griseofulvin) and matrix (Mannitol). The matrix is detected with CARS microscopy and the drug with SHG microscopy offering high contrast between the compounds. The nonlinear microscopy images of the SCS showed a homogeneous distribution of the drug particles. There were no agglomerates and the drug distribution in the centre was almost the same as at the surface of the objects. The drug particle size was also investigated and similar results like in laser diffraction were found. The combination of the two nonlinear microscopy techniques, CARS and SHG where identified as promising tools to characterize drug distribution and drug particle size in this Solid Crystal Suspension.
Keywords: Solid Crystal Suspension, Hot melt extrusion, Nonlinearmicroscopy, Coherent Anti Stokes Raman, Second Harmonic Generation