Physicochemical Properties and Anti-Opisthorchosis Effect of Mechanochemically Synthesized Solid Compositions of Praziquantel with Glycyrrhizic Acid Disodium Salt

Abstract

The mechanochemical preparation of solid compositions of praziquantel with plant saponin (glycyrrhizic acid disodium salt) is described. The study of a number of physicochemical parameters showed that dissolving solid compositions in water is accompanied by the inclusion of praziquantel molecules into micelles, which are formed in the solution of the glycyrrhizic acid disodium salt. Using the opisthorchiasis model caused by Opisthorchis felineus, we found a 4- to 11-fold increase in the anthelmintic activity of praziquantel in the composition as compared to the official praziquantel. According to the pharmacokinetic data, the use of the composition increased the bioavailability of praziquantel 3 times.

Anthelmintic Efficacy of Supramolecular Complex of Praziquantel Obtained by Mechanochemical Technology

“…In this regard, the drug is used in an increased dose and in several ways to achieve maximum efficacy. Polyvinylpyrrolidone ( 27 ), polysaccharides ( 11 , 15 ), GA, Na 2 GA ( 6 ), are also used as a means for targeted delivery of anthelmintics. GA is able to form self-associates - micelles in aqueous solution because of the amphiphilic structure ( 7 ).…”

“…Solid phase was conducted in one step of mechanochemical treatment of PZQ with Na 2 GA in a Ball Drum Mill LE-101 (Hungary) in a weight ratio of 1:5, 1:10 and 1:20 ( 11 , 12 ).The drum was set on rolls and the mixture was processed for 4 h at a speed of 156 revolutions per minute; acceleration of grinding media - 1g with steel balls with diameter of 22 mm. Other samples were obtained by mechanochemical technology without an auxiliary substance - Na 2 GA by processing in planetary mill AGO-2 (Novosibirsk, Russia).…”

“…Other samples were obtained by mechanochemical technology without an auxiliary substance - Na 2 GA by processing in planetary mill AGO-2 (Novosibirsk, Russia). Processing mode: acceleration of grinding media – 20 g and 40 g, weight of the material – 2.5 g, drum capacity – 50 mL, grinding media-steel balls (diameter 6 mm, 75.0 g load), processing time – 5 min ( 11 , 12 ).…”

“…Samples (1 mL) were collected from the acceptor plate at appropriate time points (0.25h, 0.5 h, 0.75h, 1.0 h, 1.25h, 1.5 h, 1.75h, 2 h, 2.25h, 2.5h) and were analyzed by HPLC, and the same volume of distilled water was replenished. All these methods have been described previously ( 11 , 12 , 15 – 17 ).…”

Supramolecular Carotenoid Complexes of Enhanced Solubility and Stability—The Way of Bioavailability Improvement

“…Only 15 years ago a novel unusual property of the GA has been discovered, namely its ability to form stable self-associates [38,39,40] which are able to form water-soluble inclusion complexes with other lipophilic molecules. In particular, it was found that glycyrrhizin is able to form water-soluble supramolecular complexes with a variety of lipophilic drugs [35,41,42,43,44,45,46,47,48,49,50,51,52,53] These complexes show significant advantages over other known drug delivery systems, possessing increased solubility, stability and bioavailability. In addition, the membrane modifying ability of GA has been described [21,54,55,56,57].…”