Handbook of Solvents - George Wypych - ChemTech - Ventech!

1002 An Li
Figure 14.21.2.1. Effects of ethanol on the solubilities of selected organic compounds. (a): � benzene, � naphthalene,
� biphenyl, � anthracene, � benzo(a)pyrene, � perylene, � chrysene; (b) � hydantoic acid, � hydantoin,
� methyl hydantoic acic, � 5-ethyl hydantoin, � 5-isobutyl hydantoin; (c) � triglycine, � diglycine, � glycine
[Adapted, by permission, from Li and Yalkovsky, J. Pharm. Sci., 83, 1735 (1994).]
and the cosolvent are considered as “nonpolar”, those which have a polarity between those
of water and the cosolvent as “semipolar”, and those which are more polar than both water
and cosolvent as “polar”. Figure 14.21.2.1-a illustrates the behavior of relatively hydrophobic
compounds, which tend to have monatonically increasing solubilization curves. The
solubility enhancement is greater for the more hydrophobic solutes. Curves with opposite
trends were mostly observed for polar solutes. The monatonical desolubilization is greater
for more hydrophilic solutes, as evidenced by the curves in Figure 14.21.2.1-c. In-between
are semipolar solutes with slightly parabolic curves shown in 14.21.2.1-b. The impact of
adding cosolvents is much less profound for the semipolars than for the other two groups.
On a linear solubility scale, the parabola tends to be more obvious than on the log scale. The
same general trends were seen for the cosolvents glycerine 61 and propylene glycol 61,62 and
presumably many other water-miscible cosolvents.
It is more difficult to evaluate the effects of cosolvents which have limited miscibility
with water. In the literature, such organic solvents have been termed as both cosolvents and
cosolutes, and there is no clear criteria for the distinction. Cosolvent is usually miscible with
water, or to be used in an attempt to increase the aqueous solubility of the solute. Cosolute,
on the other hand, may be organic chemicals which have a similar chemical structure or behave
similarly with the solute when they exist in water alone. The effects of cosolutes have
been examined in a limited number of published papers. 63-73
Partially water-miscible organic solvents (PMOSs) may act as either cosolvents or
cosolutes, and the research in the past has shown the complexity of their effects. 23,27-30,73-75 It
was demonstrated that in order to exert effects on solubility or sorption of HOCs, PMOSs
must exist as a component of the solvent mixture in an appreciable amount: Munz and
Roberts 23 suggested a mole fraction of greater than 0.005 and Rao and coworkers 27,28 proposed
a volume percent of 1% or a concentration above 10 4 mg/L. Cosolvents with relatively
high water solubility are likely to demonstrate observable effects on the solubilities of
solutes, up to their solubility limits, in a similar manner to cosolvents of complete miscibility
with water. A few experimental examples of the effects of PMOSs include 1-butanol and