Solution chemistry, solubility and solubilization
Solubility
Dissolution limited bioavailability is a very common
problem in pharmaceutical development. The well-
known adage “like dissolves like” is, I am sorry to
say, not true. Well, it is true, but only for liquids. If
the solute is a solid, then the solid properties of the
solute play an often dominant role. Many drugs are
hydrophobic, which makes them poorly soluble in
water. But when we have a nightmarish solubility
problem, one where the hydrophobic solute does
not dissolve in water, but it does not dissolve in
hydrophobic liquids either, then it is best to look at
the solid instead of at the solvent.
The phenanthrene-anthracene example
is very informative because it makes it
very easy to show an important point.
The figure to the left shows the
“magnitude” of the problem. It is a log
scale, so that the solubility in benzene is
about a million times higher than in
water for each of the two compounds.
This means that by solvent manipulation
we can increase the solubility of these
compounds a millionfold. If instead of
phenanthrene and anthracene we had,
say, drug A and drug B, could we
solubilize drug B to the same level of
drug A? The answer is no.
Anthracene will be 25 times less soluble
than phenanthrene in every solvent we
care to try. The black portions of the
bars are a property of the solid and are
completely unaffected by the choice of
solvent. The white part of the bars in the
figure is labeled “Lyophobicity,” that is to
say, how much the solute “dislikes” the
solvent. If the solvent is water, then
lyophobicity=hydrophobicity, but if the solvent is benzene, for example, we see that the dislike of
anthracene and phenanthrene for this solvent is, as expected, not there. Anthracene and
phenanthrene both like benzene equally and very much - this is what is meant by “like dissolves
like.”
