Saquinavir (SQV) is an important protease inhibitor used for AIDS/HIV antiretroviral therapy. As a free base it is almost insoluble in water, and it is commercialized as its mesylate salt (SQVM), classified as belonging to class IV (low permeability and solubility). Anion exchange has been used in this work to explore the effect of halides replacing the mesylate anion on the solid state and solubility properties of saquinavir at ambient temperature. All solid forms obtained were characterized via X-ray single crystal and powder diffraction, and their thermal behavior was analyzed via differential scanning calorimetry, thermogravimetric analysis, hot-stage microscopy and variable temperature X-ray powder diffraction. Saquinavir chloride (SQVCl), saquinavir bromide (SQVBr), and saquinavir iodide (SQVI) are all hydrates, the difference in the anion size being responsible for the different number of water molecules (3, 2, and 1, respectively). Dissolution properties have also been investigated, and it has been found that the behavior in water of SQVM and SQVCl are very similar, with 43 and 38% dissolved in 90 min, respectively, whereas for SQVBr and SQVI this percentage was 31 and 18%, respectively. Solid SQVCl could therefore be used as a valid alternative to current pharmaceutical formulations.
Fandaruff, C., Chelazzi, L., Braga, D., Cuffini, S.L., Silva, M.A.S., Resende, J.A.L.C., et al. (2015). Isomorphous Salts of Anti-HIV Saquinavir Mesylate: Exploring the Effect of Anion-Exchange on Its Solid-State and Dissolution Properties. CRYSTAL GROWTH & DESIGN, 15(11), 5233-5239 [10.1021/acs.cgd.5b00696].
Isomorphous Salts of Anti-HIV Saquinavir Mesylate: Exploring the Effect of Anion-Exchange on Its Solid-State and Dissolution Properties
BRAGA, DARIO;GREPIONI, FABRIZIA
2015
Abstract
Saquinavir (SQV) is an important protease inhibitor used for AIDS/HIV antiretroviral therapy. As a free base it is almost insoluble in water, and it is commercialized as its mesylate salt (SQVM), classified as belonging to class IV (low permeability and solubility). Anion exchange has been used in this work to explore the effect of halides replacing the mesylate anion on the solid state and solubility properties of saquinavir at ambient temperature. All solid forms obtained were characterized via X-ray single crystal and powder diffraction, and their thermal behavior was analyzed via differential scanning calorimetry, thermogravimetric analysis, hot-stage microscopy and variable temperature X-ray powder diffraction. Saquinavir chloride (SQVCl), saquinavir bromide (SQVBr), and saquinavir iodide (SQVI) are all hydrates, the difference in the anion size being responsible for the different number of water molecules (3, 2, and 1, respectively). Dissolution properties have also been investigated, and it has been found that the behavior in water of SQVM and SQVCl are very similar, with 43 and 38% dissolved in 90 min, respectively, whereas for SQVBr and SQVI this percentage was 31 and 18%, respectively. Solid SQVCl could therefore be used as a valid alternative to current pharmaceutical formulations.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
