The issue is we are trying to evaluate the intrinsic permeability of a molecule wich is poorly soluble (Class 2). However, many well-known solubilizers would also affect the permeability. I am trying to get unbiased results if possible. Thus, it would be great to have a cosolvent (available and common) suitable to perform in vitro permeability assay (available and common) that allows us to increase the solubility but without affecting permeability.
I assume that we are talking about oral delivery. Since I do not know which functional groups are present in your molecule, I would try hydrophilic cyclodextrins as a starting point. There is a very good article by Thorsteinn Loftsson, et al, Journal of Pharmaceutical Sciences, 96 (2007) 2532-2546 entitled "Effect of cyclodextrins on drug delivery through biological membranes". This approach should work for BCS Class II drugs.
I agree with Kenneth Sloan, it's hard to suggest without additional information about molecular structure. As a good co-solvent, you should try to use polyvinylpyrrolidone (K-17 or K-25).I heard some information about co-crystallisation with povidones (this method was used to enhanced solubility of Nitrofural, if I not wrong). Also, you can implement extrusion technique with polyethylene glycol (4000 or 6000). The knowledge of polymorphism of your substance may be very useful in the question of solubility.
Once I used carboxymethyl cellulose (CMC) in a compound with poor solubilty.
You can reduce the particle size of your compound by milling or micronization, this will increase the solubility and will not affect permeability. In addition, if your compound is crystalline you may try to get amorphous form which dissolves better.
Preparing a spray dried dispersion of drug with copovidone (Kollidon VA-64) will help to increase the solubility of the drug.
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