Characterization of tenofovir disoproxil fumarate and its behavior under heating

Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor used worldwide to treat AIDS. The aim of this study was to investigate the structural and dynamic properties of the polymorphic form I of the drug by thermal analysis, Fourier transform infrared spectroscopy, solid-state NMR, and powder X-ray diffraction. A full assignment of 13C NMR resonances was achieved for the first time. Variable-temperature studies were conducted, and the results were related to changes in the TDF structure and dynamics of specific molecular fragments, especially of the fumarate portion of the molecule. It was found that, under heating, the 13C NMR signals related to the carbon atoms of the disoproxil fumarate moiety split into two resonances. The region of the phosphonate vicinity also changes. This can reflect the lack of symmetry of the two molecules in the asymmetric unit after heating. This solid-solid transformation was related to DSC and XRD observations.