Nanoscale mid-infrared imaging of phase separation in a drug-polymer blend

The applicability of nanoscale mid-infrared (mid-IR) spectroscopy for the study of the micro- and nanostructure of pharmaceutical drug–polymer systems was explored. Felodipine–poly(acrylic acid) (PAA) blends were used as model systems. Standard atomic force microscopy evaluation as a function of drug–polymer composition suggested limited miscibility, in line with previous findings. Localized spectra on a 50:50 (w/w) felodipine–PAA dispersion revealed that the discrete submicrometer domains formed corresponded to an amorphous felodipine-rich phase while the continuous phase tended to be rich in PAA. Further, spectroscopic imaging at selected wavenumbers, enabling discrimination between both constituents, confirmed this finding and made it possible to chemically image differences in composition between each phase with submicrometer resolution. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:2066–2073, 2012