How do I predict the solubility of a compound in a mixture of water and an organic co-solvent?
I think this is very much an open problem. As you may see from the Drexel pages, even solubility prediction in one solvent is still fairly hard, partly because of the lack of experimental data.

The only software that I know capable of making predictions about solubility in mixed solvents is COSMOtherm, based on the COSMO solvation model.

I have never used it, but the capability is mentioned on the website.