ISSN 1070-4272, Russian Journal of Applied Chemistry, 2007, Vol. 80, No. 4, pp. 634 ! 637. + Pleiades Publishing, Ltd., 2007.
Original Russian Text + D.N. Valeeva, F.Yu. Akhmadullina, V.F. Kurenkov, D.G. Pobedimskii, 2007, published in Zhurnal Prikladnoi Khimii, 2007,
Vol. 80, No. 4, pp. 648 ! 651.
AND POLYMERIC MATERIALS
Intermolecular Association of Tilan
with Vinylpyrrolidone Copolymers
D. N. Valeeva, F. Yu. Akhmadullina, V. F. Kurenkov, and D. G. Pobedimskii
Kazan State Technological University, Kazan, Tatarstan, Russia
Moscow State Academy of Fine Chemical Technology, Moscow, Russia
Received June 6, 2006; in final form, March 2007
Abstract-The results of physicochemical studies of promising prolonging agents for Tilan antibiotic:
polyvinylpyrrolidone and vinylpyrrolidone copolymers, are reported. The optimal component ratios of
the drug formulation were determined by viscometry and conductometric titration. As determined by IR
spectroscopy, the components are associated mainly via intermolecular hydrogen bonds.
As a continuation of our previous studies of pro-
longing agents for water-soluble antibiotics for veter-
inary purposes [13 4], we examined in this study poly-
vinylpyrrolidone (PVP) and various copolymers of
vinylpyrrolidone (VP) with salts of 2-acrylamido-2-
methylpropanesulfonic acid. Tilan, a broad-spectrum
macrolide antibiotic , was used as the pharmaceu-
The simplest way to prolong the action of phar-
maceuticals is covalent and noncovalent binding of
a pharmaceutical with hydrophilic polymers. For
this purpose, a complex of a pharmaceutical with
an auxiliary compound is mainly prepared by mech-
anical dispersion or mechanical activation of a solu-
tion of pharmaceuticals with macromolecular com-
pounds (MMCs). Under these conditions, inter- and
intramolecular bonds in polymer macromolecules are
ruptured and their reactivity increases. Then, the ac-
tivated macromolecules react with the pharmaceutical
to form inclusion complexes or grafted complexes,
depending on the polymer structure .
The association in the antibiotic-MMC systems was
studied by viscometry, conductometric titration, and
IR spectroscopy. These studies allowed more correct
estimation of the binding strength in these systems
and gave an insight into the mechanism and condi-
tions of formation of polycomplexes of Tilan with
PVP and vinylpyrrolidone copolymer.
The choice of vinylpyrrolidone copolymers as
promising auxiliary compounds is caused by the fact
that, among water-soluble synthetic polymers, PVP
and its copolymers are the most widely used in phar-
macy. The reason is that PVP is slowly taken in from
the injection place, thus decelerating the intake of
the pharmaceutical forming a complex with it.This
effect is the most pronounced in the case of intra-
muscular injection of a pharmaceutical [7, 8].
We studied PVP and vinylpyrrolidone copolymers
with calcium and sodium salts of 2-acrylamido-2-
propanesulfonic acid, prepared by copolymerization
of calcium 2-acrylamido-2-propanesulfonate and so-
dium 2-acrylamido-2-propanesulfonate (Ca-APS and
Na-APS) with vinylpyrrolidone in concentrated al-
kaline aqueous solutions of the monomers at 50oC.
The weight ratio of VP and Na-APS was 2 : 98,
6.2 : 93.8, and 12 : 88, and that of VP and Ca-APS,
85.2 : 14.8 .
Since the auxiliary compounds should be nontoxic,
we performed a preliminary toxicological study of
the vinylpyrrolidone copolymers.
The complexation of Tilan with MMC was studied
by viscometry and conductometric titration of iso-
molar series. The viscosity of by 0.2 mg ml