Enhancement of the Bioavailability and Anti-Inflammatory Activity of Glycyrrhetinic Acid via Novel Soluplus®—A Glycyrrhetinic Acid Solid Dispersion

Glycyrrhetinic acid (GA) is an anti-inflammatory drug with potential for development. However, the poor solubility of GA in water leads to extremely low bioavailability, which limits its clinical applications. Solid dispersions have become some of the most effective strategies for improving the solubility of poorly soluble drugs. Soluplus^®, a non-cytotoxic amphiphilic solubilizer, significantly improves the solubility of BCS II drugs and improves the bioavailability of insoluble drugs. l-arginine (L-Arg) can be used as a small molecular weight excipient to assist in improving the solubility of insoluble drugs. In this study, we developed a new formulation for oral administration by reacting GA and L-Arg to form salts by co-solvent evaporation and then adding the polymer-solvent Soluplus^® with an amphiphilic chemical structure to prepare a solid dispersion GA-SD. The chemical and physical properties of GA-SD were characterized by DLS, TEM, XRD, FT-IR and TG. The anti-inflammatory activity of GA-SD was verified by LPS stimulation of RAW 267.5 cells simulating a cellular inflammation model, TPA-induced ear edema model in mice, and ethanol-induced gastric ulcer model. The results showed that the amide bond and salt formation of GA-SD greatly improved GA solubility. GA-SD effectively improved the anti-inflammatory effect of free GA in vivo and in vitro, and GA-SD had no significant effect on liver and kidney function, no significant tissue toxicity, and good biosafety. In conclusion, GA-SD with L-Arg and Soluplus^® is an effective method to improve the solubility and bioavailability of GA. As a safe and effective solid dispersion, it is a promising anti-inflammatory oral formulation and provides some references for other oral drug candidates with low bioavailability.

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Material

GA was purchased from Beijing Mairuida Technology Co., Ltd., Soluplus® was purchased from BASF (Ludwigshafen, Germany), and L-Arg was purchased from Beijing Aibifan Biotechnology Co. 12-O-tetradecanoylphorbol-13-acetate (TPA) (p1585, Sigma-Aldrich, Munich, Germany). All other related chemicals and reagents were analytically pure.

Wang, H.; Li, R.; Rao, Y.; Liu, S.; Hu, C.; Zhang, Y.; Meng, L.; Wu, Q.; Ouyang, Q.; Liang, H.; Qin, M. Enhancement of the Bioavailability and Anti-Inflammatory Activity of Glycyrrhetinic Acid via Novel Soluplus^®—A Glycyrrhetinic Acid Solid Dispersion. Pharmaceutics 2022, 14, 1797. https://doi.org/10.3390/pharmaceutics14091797