Isomorphous Salts of Anti-HIV Saquinavir Mesylate: Exploring the Effect of Anion-Exchange on Its Solid-State and Dissolution Properties

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.