Resumo:
Gliclazide, a second-generation sulfonylurea, emerges as a prominent therapeutic agent for patients with type 2 diabetes mellitus. However, this drug's efficacy is hindered by its low water solubility and high cellular permeability, leading to limited oral bioavailability. To circumvent this limitation, the association with cyclodextrins, which can form host-guest supramolecular systems, represents a viable strategy. This study aimed to obtain and characterize inclusion compounds formed between the drug gliclazide, β-cyclodextrin, and hydroxypropyl-β-cyclodextrin, employing analytical and spectroscopic methods. Solubility studies were conducted for both systems to elucidate the thermodynamic parameters involved in the formation process. The systems were prepared using the freeze-drying method and characterized using Fourier-transform infrared spectroscopy (FTIR-ATR) and nuclear magnetic resonance spectroscopy (NMR). Additionally, stability studies were performed to comprehend the effect of cyclodextrins on drug stability. In the solubility studies, the GLI:β-CD system exhibited a BS-type phase solubility diagram, whereas the GLI:HP-β-CD system showed an AL-type diagram. The former system demonstrated higher Ka values compared to the latter. In the temperature range of 37, 47, and 57 °C, both system formation processes were observed to be spontaneous and exothermic. Regarding system characterization, spectral shifts in drug bands were evident in all inclusion compound spectra. Furthermore, band disappearances were identified in the spectra of the GLI:β-CD 1:1 and 1:2 compounds, as well as the GLI:HP-β-CD 1:1 compound. In the 2D-ROESY correlation maps of the 1:1 system, short-distance correlations were initially observed between the internal hydrogens of β-CD and the hydrogens of GLI, indicating the formation of the GLI:β-CD inclusion compound. However, for the GLI:HP-β-CD system, no correlations were discerned between the drug and the cyclodextrin, potentially suggesting the formation of another type of supramolecular system between GLI and HP-β-CD. In stability studies, the presence of β-CD accelerated drug degradation in acidic media, while HP-β-CD exhibited a subtle retarding effect. Notably, in neutral and alkaline media, cyclodextrins had no discernible influence on drug stability in solution.
