Chemical-selective imaging of adhesive mixtures for inhalation using coherent anti-Stokes Raman scattering (CARS) microscopy

Floris Grasmeijer, Andrew L. Fussell, Henderik W. Frijlink, Anne H. de Boer, Herman L. Offerhaus

The spatial distribution and degree of agglomeration of drug particles throughout adhesive mixtures for inhalation are thought to be relevant to the dispersion behaviour of such formulations. The physical state of these properties is difficult to assess with conventional high resolution imaging techniques, because the small drug particles often cannot be sufficiently distinguished from other fine mixture components. Chemical-selective imaging techniques may be very helpful in this regard. Although several such techniques have been described, chemical-selective imaging is not yet routinely used in the study of adhesive mixtures. Reasons may be found in insufficient contrast formation for the specific chemicals used in adhesive mixtures for inhalation, or insufficient accessibility of the techniques. Additional techniques are therefore desirable. Here we present a first study on the suitability of coherent anti-Stokes Raman scattering (CARS) microscopy for the chemical-selective imaging of adhesive mixtures. Its combination with high resolution scanning electron microscopy (SEM) is presented. The results show that CARS microscopy is a promising technique for the characterisation of adhesive mixtures. It provides a way for their rapid chemical-selective imaging, even when the drug (e.g. budesonide) does not differ from lactose with respect to the chemical elements of which it is composed. However, the attainable field of view with the CARS setup from this study is limited and not all drug particles appear to be detected with the settings used. Therefore, a further optimisation and validation of the techniques is required.

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