Solid Dispersion of Hesperetin Co-crystals Synergistically Attenuates Hepatic Toxicity of Carbon Tetrachloride Oxidative Stress in Rats

Title:Solid Dispersion of Hesperetin Co-crystals Synergistically Attenuates Hepatic Toxicity of Carbon Tetrachloride Oxidative Stress in Rats

Volume: 15 Issue: 10

Author(s): Jaleh Varshosaz*, Mahyasadat Jalali and Ali Hosseini-Sharifabad

Affiliation:

• Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan,Iran

Keywords: Hesperetin (HSP), Isonicotinamide (INM), Co-crystal, solid dispersion, toxicity, liver function.

Abstract: Background: Hesperetin (HSP) is a low water-soluble flavanone aglycone with low bioavailability.

Objectives: This study aimed at enhancing the hepatoprotective effects of HSP by a combinatory technique based on solid dispersions of co-crystals of HSP.

Methods: Co-crystals were prepared using citric acid, tartaric acid, caffeine and isonicotinamide (INM) using two methods of solvent evaporation and co-grinding. The solid dispersion of co-crystals with different ratio of INM, PVP K30 and drug was prepared by the solvent evaporation method. The resulting material was characterized by DSC, XRD, FTIR and SEM, their saturated solubility and dissolution rate were compared to the pure drug. Finally, liver toxicity was induced in rats by carbon tetrachloride (CCl4) and mice were treated with different formulations of HSP. The liver function was tested by measurement of glutamate pyruvate transaminase (SGPT), glutamate oxaloacetate transaminase (SGOT), serum alkaline phosphatase (ALP) and bilirubin as well as histopathological tests.

Results: Although saturation solubility of HSP was enhanced about 5 times by co-crystals of HSP/INM (1:2), solid dispersions of the co-crystals of HSP obtained from PVP K30 and INM enhanced it up to 200 folds. Functional parameters of liver in rats pretreated with a solid dispersion of co-crystals of HSP were significantly lower than those with pure HSP and co-crystals of INM/HSP with 2:1 ratio. Furthermore, this formulations reduced liver damage effectively compared with the CCL4 group.

Conclusion: Solid dispersion of HSP co-crystals synergistically attenuates hepatic toxicity of carbon tetrachloride oxidative stress in rats more effectively than its solid dispersions or co-crystals alone.

Cite this article as:

Varshosaz Jaleh*, Jalali Mahyasadat and Hosseini-Sharifabad Ali , Solid Dispersion of Hesperetin Co-crystals Synergistically Attenuates Hepatic Toxicity of Carbon Tetrachloride Oxidative Stress in Rats, Current Drug Delivery 2018; 15 (10) . https://dx.doi.org/10.2174/1567201815666180730141556