Preferential Solvation of Cyclosporin in Aqueous Mixtures of Some Polymeric Cosolvents

Abstract
Background: Cyclosporin is a cyclic peptide-drug used as immunosuppressant for the prophylaxis
of transplant rejection whose physicochemical properties in mixed aqueous solvent systems is
still not well understood. The preferential solvation parameters of cyclosporin in aqueous binary
mixtures of diethylene glycol monoethyl ether (DEGME), polyethylene glycol 200 (PEG 200) and
polyethylene glycol 400 (PEG 400) were computed.
Methods: Reported mole fraction solubilities of cyclosporin in DEGME-aqueous mixtures,
PEG 200-aqueous mixtures, and PEG 400-aqueous mixtures were processed by following the
inverse Kirkwood-Buff integrals (IKBI) method as suggested by Marcus and Ben-Naim using some
thermodynamic parameters reported in the literature for these aqueous-polymeric mixtures at
298.15 K.
Results: It is observed that cyclosporin is sensitive to preferential solvation effects in these
aqueous-polymeric binary solvent systems. The preferential solvation parameter by DEGME (δx1,3)
is negative in water-rich mixtures but positive in mixtures of 0.12<x1<1.00. It is conjecturable
that hydrophobic hydration around the non-polar methyl and methylene groups of this drug that
could be present in water-rich mixtures can significantly impact the drug solvation. Otherwise,
in mixtures of 0.12<x1<1.00 in DEGME-aqueous mixtures, as well as in almost all the mixtures
with PEGs, the preferential solvation by polymeric cosolvents could be due to the acidic behavior
of cyclosporin in front of ether and hydroxyl oxygen atoms of these polymeric cosolvents.
Conclusion: Cyclosporin is preferentially solvated by the polymeric solvents in almost all the
studied mixtures of these aqueous-polymeric binary solvent systems.