Chemistry Reference
In-Depth Information
2.50E-05
2.00E-05
1
1.50E-05
1.00E-05
5.00E-06
3
2
0.00E+00
0
0.2
0.4
0.6
0.8
1
x
et
FIGURE 10.2
Comparison between experimental (o) (From A. Jouyban, S. Romero, H. K.
Chan, B. J. Clark, and P. Bustamante, 2002, A Cosolvency Model to Predict Solubility of Drugs
at Several Temperatures from a Limited Number of Solubility Measurements,
Chemical and
Pharmaceutical Bulletin,
50, 594) and predicted (solid lines) solubilities of oxolinic acid (
S
is
the mole fraction of oxolinic acid) in the mixed solvent water/ethanol (
x
et
is the mole fraction
of ethanol) at room temperature. 1-solubility calculated using Equations 10.30 and 10.31,
2-solubility calculated using Equation 10.30 and Equation 10.13, and 3-solubility calculated
using log-linear model. (From S. H. Yalkowsky and T. J. Roseman, 1981, Solubilization of
Drugs by Cosolvents, In
Techniques of Solubilization of Drugs
, edited by S. H. Yalkowsky,
New York: Marcel Dekker.) (Reprinted from E. Ruckenstein and I. L. Shulgin, 2003b,
Solubility of Drugs in Aqueous Solutions. Part 1: Ideal Mixed Solvent Approximation,
International Journal of Pharmaceutics
, 258, 193, With permission from Elsevier.)
10.5 SOLUBILITY OF SOLUTES IN MULTICOMPONENT
MIXED SOLVENTS
Binary aqueous mixed solvents usually increase the solubility of a poorly soluble
drug compared to that in pure water; however, they can also increase the risk of tox-
icity. The right selection of a ternary or a multicomponent aqueous mixed solvent can
improve the solubility of the drug with minimal toxic effects. Pharmaceutical prac-
tice has shown that many marketed liquid formulations involve multiple solvents.
However, the experimental determinations of the solubilities in multicomponent
solutions are time consuming because of the large number of compositions needed
to cover the concentration ranges of interest and can be very expensive because of
the high prices of some modern drugs. For this reason, it is important to provide a
reliable method for predicting the solubility of drugs in multicomponent mixed sol-
vents from available experimental solubilities in subsystems such as pure solvents,
binary mixed solvents, and so forth.
The KB theory can be successfully used to predict the solubility of poorly soluble
solute in multicomponent mixed solvents from available experimental solubilities
in subsystems such as pure solvents, binary mixed solvents, and so forth. Such a
method can be used for preselecting a multicomponent mixed solvent with the use of
