Research and Development of a New Safe Form of Drugs - Aerosols: Measurement, Dosimetry, and Health Effects - page 267

During the mechanochemical synthesis of solid dispersions of GA, its mass excess of 10:1 is
used, which corresponds to mole ratio with pharmacons (2.5:1-4:1). During the solution of the
obtained dispersions, a signiicant increase in pharmacon water solubility is observed, which proves
the high effectiveness of GA as a solubilizer and the effectiveness of the mechanochemical method
in the obtaining of water-soluble solid dispersions.

11.2.1.3 Complexes of Nonsteroid Anti-Inlammatory Drugs with Glycyrrhizic Acid
Complexes of GA with acetylsalicylic acid (ASA), ortophenum (OF), butadionum (BD), and indo-
metacin (IM) with the composition (GA:nonsteroid anti-inlammatory drugs [NSAID]) 1:1 and
2:1 were synthesized by both the solution (Tolstikov et al., 1991a) and solid-phase (Dushkin et al.,
2001) methods. Complex of GA with ibuprofen (IP) with the composition 4:1 was synthesized by
solid-phase method. Complexation was conirmed by spectral analysis. In the IR-spectra of the
complexes the spectral lines of hydroxylic and carbonylic groups of glycoside are shifted to the
short waves.
All the earlier-stated complexes demonstrate anti-inlammatory (AI) activity at the doses lower
than the source pharmacon. The dose range of the complexes (LD 50 /ED 50 ) is 3-11 times higher than
that of the initial NSAID (Tolstikov et al., 1991a) (Table 11.2).
Complexes with ASA and OF (GA: ASA, GA: OF) produce an expressed AI effect in six models
of acute inlammation induced by carragenin, formalin, histamine, serotonin, agar (Difko), tripsin,
as well as at chronic inlammation (“cotton pellet” and “pocket” granulomas) of intact and adrenal-
ectomized animals (Bondarev et al., 1991). A complex of GA with IM 1:1 has a more pronounced
AI effect as compared with initial drug if administered in equal doses (10 mg/kg).
At complexation of NSAID with GA, the potentiation of other kinds of biological activity (anal-
gesic, antipyretic) was observed (Baltina et al., 1988a,b,c; Bondarev et al., 1991). At electrical and
thermal irritation, the analgesic effect of GA complex with OF was more pronounced than that of
OF (57.5 ± 2.0 and 43.2 ± 2.6), and at thermal pain irritation, it exceeded the effect of amidopyrine
(23.4 ± 1.1 and 18.5 ± 1.4). The analgesic effect of GA complex with analgin (AN) was 11.4 stronger
than that of AN (Baltina et al., 1992). The analgesic effect of complex GA:ASA exceeds the effect
of aspirin at thermal pain irritation. At acetylcholine convulsions the analgesic dose range of GA
complexes with ASA and OF is 3 and 2.3 times broader than that of NSAID, respectively. In the
acetum convulsion model the therapeutic ratio of complex GA:ASA was four times higher than that
of aspirin. Complexes GA:ASA and GA:OF have pronounced antipyretic action. Their antipyretic
dose range was two times broader than that of initial pharmacons (Baltina et al., 1991b, 1992;
Bondarev et al., 1991).
Thus, water-soluble complexes GA:ASA and GA:OF have pronounced AI and analgesic effects
with the pharmacological spectrum and therapeutic dose range exceeding those of initial NSAIDs.
The complexes have pronounced membrane stabilizing action that is expressed in a decreased accu-
mulation of primary and secondary lipid peroxidation products in animals with chronic inlammation.

TABLE 11.2
Anti-Inlammatory Dose Range of Glycyrrhizic Acid Complexes
and NSAID

Compounds Dose Range of the Complex a Dose Range of Initial NSAID

GA:ASA (1:1) 4500/82 = 54.8 1900/98 = 19.4

GA:OF (1:1) 1750/12.5 = 140 310/8 = 33.7

GA:BD (1:1) 3150/62 = 50.8 880/56 =15.7

GA:AN (1:1) 8000/68 = 117.6 570/55 = 10.3

a LD 50 /ED 50 ; ED 50 , effective dose.