The Glycyrrhizic Acid Derivative Monoammonium Glycyrrhizate Compared to Piperine on Fat-and Water-Soluble Nutrients Bioavailability: Efficacy and Safety Assessment

D. G. Alekseev¹A. V. Kulikov^2,3A. A. Marchenko²V. V. Boltovskaya¹M. Yu. Vlasov¹I. V. Kachalkina¹M. N. Kachalkin¹T. K. Ryazanova^1*V. A. Kurkin¹

• ¹Samarskij gosudarstvennyj medicinskij universitet Ministerstva zdravoohranenia Rossijskoj Federacii, Samara, Russia
• ²AO Farmasintez, Irkutsk, Russia
• ³Rossijskij universitet druzby narodov Medicinskij institut, Moscow, Russia

Background: Bioenhancers are agents that, when co-administered, increase the bioavailability or effectiveness of medicinal products and nutrients. The safety concerns with available bioenhancers highlight the need for alternative bioenhancers with different mechanisms. Literature review and our previous studies indicate that the monoammonium salt of glycyrrhizic acid (MSGA) may be a promising safer candidate. Methods: MSGA was prepared from commercial liquorice extracts using a proprietary method (GlycyrHans®). A comparative evaluation of the pharmacokinetic profiles of nutrients (ascorbic acid, vitamin D3, and omega-3 fatty acids) in combination with BioPerine® and GlycyrHans® was performed in rats. We also assessed in vivo toxicity following a single administration of GlycyrHans® and its combinations with nutrients. Results: Administration of GlycyrHans® in the proposed weight ratios with the selected bioactive compounds resulted in a 1.3–2.8-fold increase in key pharmacokinetic parameters (p < 0.05; Mann-Whitney U test), indicating a substantial enhancement in bioavailability. Notably, BioPerine® at the tested dose did not significantly affect the pharmacokinetics of cholecalciferol or omega-3 PUFAs. However, both BioPerine® and GlycyrHans® demonstrated comparable efficacy in enhancing the bioavailability of vitamin C. Acute toxicity studies of GlycyrHans®, produced using the newly developed technology, demonstrated no toxic effects or behavioral abnormalities following oral administration at doses of 300 mg/kg and 2000 mg/kg body weight. Conclusions: In this study, a novel method for the preparation of GlycyrHans® – a compound exhibiting bioenhancer activity – was developed, along with pharmaceutical compositions demonstrating enhanced bioavailability and corresponding methods for the production thereof. Future investigations of GlycyrHans® are warranted, particularly with respect to other classes of biologically active compounds. Such research could further expand the application of GlycyrHans® in pharmaceutical and nutraceutical development.