In situ high-throughput study of drug polymorphism under controlled temperature and humidity using FT-IR spectroscopic imaging

Abstract

Fourier transform infrared (FT-IR) spectroscopic imaging in combination with a controlled humidity cell was applied to simultaneously monitor crystallisation of several binary mixtures of two drugs under identical environment. The effect of relative humidity was studied on samples of binary mixtures of nifedipine and nitrendipine with different molar ratios as well as on amorphous nitrendipine. All samples were arranged in array format on the surface of BaF 2 window for simultaneous imaging using an infrared focal plane array detector. The effect of sample thickness on the analysis of imaging results was addressed using novel approach to create images. The thickness-independent images have been obtained by plotting the distribution of the wavenumber corresponding to the peak maximum of the ν(N H) vibrational mode which is sensitive to the formation of the various crystalline polymorphs. The FT-IR spectroscopic imaging approach described in this work can be utilised in further high-throughput studies of many samples under controlled environment.