Characterization of Tenofovir Disoproxil Fumarate and Its Behavior under Heating

Abstract

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 13 C 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 13 C 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.

QbD based approach for optimization of Tenofovir disoproxil fumarate loaded liquid crystal precursor with improved permeability

“…DSC thermograms of TDF alone, GMO, PF127, lactose monohydrate, and TDF loaded LCP are shown in Fig. 4 B. TDF alone showed characteristic endothermic peak in the range of 111–115 °C, indicating its melting point, whereas GMO showed melting endotherm at about 39 °C [35] . Additionally, PF127 showed melting endotherm at 56 °C, whereas endotherm at 143 °C for lactose monohydrate suggested loss of water of crystallization by lactose.…”

Co-crystals, Salts or Mixtures of Both? The Case of Tenofovir Alafenamide Fumarates

“…Interestingly, although there are several literature reports on the solid-state properties of TDF [94][95][96][97][98][99], to the best of our knowledge, TAF solid-state chemistry has not yet been described in the scientific literature. The patent literature discloses tenofovir alafenamide monofumarate form I (TA MF1) [100], as well as tenofovir alafenamide hemifumarate (TA HF) [101], which is considered to be the more thermodynamically stable form.…”

Study on influence of polymer and surfactant on in vitro performance of biodegradable aqueous-core nanocapsules of tenofovirdisoproxil fumarate by response surface methodology

“…IR spectra of pure Tenofovir DF and the physical mixtures of drug and polymers were showed in Figure 1. The bands for characteristic groups of the pure Tenofovir DF were observed at 1622.93 cm -1 due to N-H bending; 1675.44 cm -1 due to stretching of imine (R2-C=NR1) group; 1263.23 cm -1 because of theprimary aromatic amine stretching; 1755.23 cm -1 due to carbonyl (C=O) stretching; 1184.24 cm -1 due to P=O stretching and at 3223.48 cm -1 accounting for O-H stretching (Gomes et al, 2015;Silverstein, Webster, Kiemle, 2005). These bands accounting for the characteristic groups of TDF were also observed at the similar positions in the spectra of individual physical mixtures of TDF with the polymers viz.…”