Preferential Solvation of Cyclosporin in Aqueous Mixtures of Some Polymeric Cosolvents

This article examines how cyclosporin behaves in aqueous mixtures containing polymeric cosolvents such as DEGME, PEG 200, and PEG 400. Using thermodynamic analysis and the inverse Kirkwood-Buff integrals method, the study shows that cyclosporin is generally preferentially solvated by the polymeric cosolvents rather than by water. The findings help explain how solvent composition affects the drug’s solubility and molecular interactions, which is especially relevant for pharmaceutical formulation design. The study is useful for researchers working on solubility enhancement, liquid dosage forms, and physicochemical characterization of poorly water-soluble drugs.

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.