1070-4272/05/7805-0711+2005 Pleiades Publishing, Inc.
Russian Journal of Applied Chemistry, Vol. 78, No. 5, 2005, pp. 711!714. Translated from Zhurnal Prikladnoi Khimii, Vol. 78, No. 5,
2005, pp. 725!728.
Original Russian Text Copyright + 2005 by O. Sytnik, Krasnoperova, Lebedinets, K. Sytnik.
OF SYSTEMS AND PROCESSES
Polythermal Study of Solubility
of N-[4-(Difluoromethylthio)phenyl]-2-Aminobenzoic Acid
in the System Water!1,2-Propanediol
O. Yu. Sytnik, A. P. Krasnoperova, V. A. Lebedinets, and K. M. Sytnik
Chemical Research Institute, Karazin National University, Kharkov, Ukraine
Ukrainian National Pharmaceutical University, Kharkov, Ukraine
Received August 18, 2003; in final form, January 2005
Abstract-The solubility of N-[4-(difluoromethylthio)phenyl]-2-aminobenzoic acid in the system water3
1,2-propanediol was studied over the entire range of the concentrations of the mixed solvent at 288.153
Anthranilic acid derivatives are commonly used in
modern pharmacology. N-[4-(Difluoromethylthio)-
pheny]l-2-aminobenzoic acid (Difluorant, hereinafter
DF), a nonsteroid antiphlogistic with antipsoriasis
activity, is among them.
Difluorant is a hydrophobic organic compound,
sparingly soluble in water, which makes it difficult to
create on its basis water-containing medicines in the
form of ointments, foams, and emulsions. Therefore, a
study of the DF solubility in nonaqueous solvents,
which can homogenize hydrophobic and hydrophilic
compounds and their mixtures with water, is one of
the main stages of development of highly effective and
inexpensive drugs. The most commonly used solvent
in soft medicines is 1,2-propanediol (1,2-PD) .
This study is concerned with the DF solubility in
the water31,2-PD system over the entire range of
the concentrations of the mixed solvent at 288.153
The water31,2-PD system was prepared gravimet-
rically. 1,2-Propanediol was preliminarily treated by
double vacuum distillation . The quality of 1,2-PD
was checked by the density (r
= 1032.8 kg m
and dielectric permittivity (e = 29.0 at 25oC). As sec-
ond component was used double-distilled water. Prior
to use, DF was dried for 2 h at 353 K under a pressure
of 2.7 kPa. The quality of the preparation was checked
by the melting point (T
= 397 K).
The DF solubility was studied by the isothermal
method, and the concentration of the saturated solu-
tion was determined by the electronic spectroscopy.
To do this, excess amount of the substance under
study was placed in flasks with ground-glass stoppers,
the solvent of the required composition was added,
and the mixture was kept at a constant temperature
controlled to within +0.1 K with continuous agitation
until the thermodynamic equilibrium was attained.
The attainment of the equilibrium was monitored by
taking the solution samples and measuring their opti-
cal density. The equilibrium was assumed to be at-
tained when the optical density A of a series of succes-
sively taken solution samples became constant. Then,
the solutions were allowed to settle for 334hatthe
given temperature, after which they were sampled for
the analysis. The saturation time was from 10 to
100 h, depending on the concentration of the non-
The optical density A was measured on a Specord
M-40 spectrophotometer at l = 310 nm. To do this,
2 ml of the transparent saturated solution was diluted
with ethanol so that A of the solutions obtained was
within 0.330.7. Each value of the solubility is the
average of 334 measurements. The maximum average
error in determining the solubility was 233% at a con-
fidence probability of 0.95. The results obtained are
presented in the table.
Our results show that the DF solubility varies with-
in a wide range depending on the solvent composition
and temperature and is not a linear dependence of
the solvent composition.
Amino acids in strongly polar solvents are in the
form of zwitterions [3, 4]. Since the zwitterions have