Calorimetric, FTIR and 1H NMR measurements in combination with DFT calculations for monitoring solid‐state changes of dynamics of sibutramine hydrochloride

Two forms of sibutramine hydrochloride, monohydrate and anhydrous, have been investigated by calorimetric methods, Fourier transform infrared (FTIR) absorption and 1H nuclear magnetic resonance (NMR) measurements as well as by density functional theory (DFT) of vibrational frequencies and infrared intensities, calculations of steric hindrances and Monte Carlo simulations. The results of FTIR spectra combined with DFT calculations permitted identification of the bands corresponding to the dynamics and vibrations of water molecules. NMR study and Monte Carlo simulations revealed the occurrence of reorientation jumps of the methyl groups in sibutramine cation and also revealed that the reorientation of isopropyl group is possible only in sibutramine monohydrate hydrochloride. The hydration of sibutramine hydrochloride causes a change in the conformation of sibutramine cation.