Inositol hexanicotinate self-micelle solid dispersion is an efficient drug delivery system in the mouse model of non-alcoholic fatty liver disease

Abstract

Inositol hexanicotinate (IHN) self-micelle solid dispersion (SD) with glycyrrhizic acid (GA) and arabic gum (AG) was prepared by mechanical ball milling process to improve the solubility, stability of amorphous state, and bioavailability of IHN, which enhanced the treatment of IHN on hyperlipidemia and nonalcoholic fatty liver disease (NAFLD). The physicochemical properties of IHN/GA/AG SDs in solid state were characterized by differential scanning calorimetry, X-ray diffraction studies, and scanning electron microscopy. The characteristics of the sample solutions were analyzed by reverse-phase HPLC, particle characterization, critical micelle concentration, and transmission electron microscopy. Further pharmacokinetic study of this SD formulation in rats showed a significant 3.3-fold increase in bioavailability compared to pure IHN. Moreover, biomarkers in serum and liver of NAFLD mice were significantly ameliorated after oral administration of IHN/GA/AG SDs for 15 days. Altogether, these results establish the mechanochemically prepared IHN/GA/AG SDs as an efficacious formulation for the treatment of hyperlipidemia and NAFLD.