Preparation of DNC Solid Dispersion by a Mechanochemical Method with Glycyrrhizic Acid and Polyvinylpyrrolidone to Enhance Bioavailability and Activity

Abstract

To exploit aqueous-soluble formulation and improve the anticoccidial activity of 4,4′-dinitrocarbanilide (DNC, active component of nicarbazin), this paper prepared DNC/GA/PVP K30 solid dispersion (SD) with glycyrrhizic acid (GA) and polyvinylpyrrolidone (PVP) K30 by a mechanical ball milling method without using any organic solvent. Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy were used for the solid state characterization. High performance liquid chromatography, critical micelle concentration, particle characterization, and transmission electron microscopy were used to evaluate the behavior in aqueous solution. In addition, the oral bioavailability, tissue distribution, and anticoccidial activity of DNC/GA/PVP K30 SD were investigated as well. Compared with free drug, the novel formulation not only improved the solubility and dissolution rate of DNC, but also inhibited the fecal output of oocysts and enhanced the therapeutic effect of coccidiosis. According to the experiment results, the DNC/GA/PVP K30 SD increased 4.64-fold in oral bioavailability and dramatically enhanced the concentration in liver which provided a basis for further research in schistosomiasis. In summary, our findings suggested that DNC/GA/PVP K30 SD may have promising applications in the treatment of coccidiosis.

Enhancing the Solubility, Stability, and Bioavailability of Retinol Acetate through Mechanochemistry

“…This study has employed methods like FT-IR, DSC, XRD, and SEM to investigate the molecule configurations and the intermolecular interactions in the RA-SSOS after ball-milling, as they were previously reported to increase the solubility, stability, and bioavailability of difficult-to-solve drugs. − RA-SSOS was first subjected to FT-IR spectroscopy. The spectral analysis showed that hydrogen bonds were generated between RA and the SSOS after ball-milling, facilitating the dispersion and stabilization of RA in solid states.…”

Preparation and Physicochemical Properties of Supramolecular Complexes of Ecdysterone

“…Glycyrrhizic acid and its disodium salt (disodium 30-hydroxy-11,30-dioxoolean-12-en-3β-yl 2-O-β-D-glucopyranuronosyl-β-D-glucopyranosiduronate; Na2GA, fig. 1) are also effective natural low molecular weight complexing agents with increased biodegradability and bioavailability [21][22][23]. Glycyrrhizic acid (GA) is a triterpene glycoside extracted from liquorice root and demonstrates antiviral, anti-inflammatory, and antitumor properties [23].…”