Hepatoprotective cocrystal of ethionamide: A new attempt to refurbish old drug through crystal engineering

Abstract

Refurbishing old drugs through emerging crystal engineering technology may provide a green and efficient path for drug development. In this paper, intending to overcome the severe hepatotoxicity of the second-line anti-tuberculosis drug ethionamide (ETA), we cocrystallized the ETA with the hepatoprotective nutraceutical chrysin (CHR). The structure of the ETA-CHR cocrystal was characterized by single crystal X-ray diffraction, powder X-ray diffraction, and differential scanning calorimetry. Furthermore, the in vitro and in vivo properties of the cocrystal, such as oversaturation phenomenon, intrinsic dissolution rate, pharmacokinetics, and toxicity, were adequately studied. The results demonstrated that the CHR in the cocrystal formation played an ideal hepatoprotective effect, thereby almost eliminating the liver toxicity of the ETA. The investigation may improve the clinical applicability of ETA, which was meaningful for alleviating the epidemic of tuberculosis.