The Preparation of Curcumin Sustained-Release Solid Dispersion by Hot-Melt Extrusion—Ⅱ. Optimization of Preparation Process and Evaluation In Vitro and In Vivo

Abstract

The purpose of this study was to optimize hot-melt extrusion (HME) preparation process and evaluate in vitro and in vivo for developing curcumin (CUR) sustained-release solid dispersion, to explore the possibility of HME for one-step preparation of insoluble drug sustained-release solid dispersion. The effect of 3 process parameters—barrel temperature, screw speed, and cooling rate—was systematically studied. Physical state of CUR sustained-release solid dispersion was characterized by differential scanning calorimetry, X-ray powder diffraction, and Fourier transform infrared spectroscopy. It was found that CUR–Eudragit RS/RL system exhibited a good miscibility. Curcumin in the solid dispersion existed in an amorphous state and had molecular interactions with carriers. Stability studies showed no apparent difference of physical state of solid dispersion after 6 months. The mechanism of the CUR release in sustained-release solid dispersion was a diffusion and dissolution coexisting action. Pharmacokinetics study showed the relative bioavailability of the CUR in sustained-release solid dispersion to CUR was 223.44%. The CUR sustained-release solid dispersion have been successfully prepared by HME, significantly extending the half-life, ensuring a stable and effective blood concentration, and improving the bioavailability of CUR. In conclusion, HME can be used to prepared sustained-release solid dispersion of a poorly water-soluble drug as a promising method.