Studying tautomerism in an important pharmaceutical glibenclamide confined in the thin nanometric layers

The uniform thin films with variable thicknesses (d = 49, 120, 220 nm) of active pharmaceutical ingredient (API) glibenclamide (GCM) was spin-coated and investigated using broadband dielectric, grazing incident FTIR spectroscopies, atomic force microscopy, and ellipsometry. Data analysis revealed that nanoconfined systems consist of a mixture of amide and imidic acid forms of this pharmaceutical, wherein the ratios of both tautomeric forms in the thin films were different with respect to the molten supercooled bulk system. Moreover, changes in the populations of glibenclamide tautomers, i.e. higher amide to imides ratio in the spatially restricted API with respect to the bulk sample, had a strong impact on the character of the proton transfer reaction. In this context, the kinetic curves constructed on the base of infrared data for the bulk system follow the sigmoidal shape, characteristic for the autocatalytic reaction, while results obtained for the confined samples provide exponential character and indicate first-order transformation. This allows hypothesizing that the autocatalytic nature of the tautomerism in the bulk sample is most likely related to the formation of the amide tautomers which further catalyze the progress of imide-amide transformation. Our results are the first studies showing that the change in the thickness of the film may affect the properties and isomerization kinetics in a pharmaceutical systems. Finally, our data open a new perspective for developing new drug delivery systems.