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7976317 
Journal Article 
Micronization and coating of bioflavonoids extracted from Citrus sinensis L. peels to preparation of sustained release pellets using supercritical technique 
Salehi, H; Karimi, M; Raofie, F; , 
2021 
Yes 
Journal of the Iranian Chemical Society
ISSN: 1735-207X
EISSN: 1735-2428 
SPRINGER 
NEW YORK 
WOS:000659400200003 
Bioflavonoids such as hesperidin and hesperetin as anticancer and antioxidant agents are widely used in the formulation of many herbal drugs. Recently, promising evidence for the prevention and treatment of COVID 19 using these compounds has been reported. Unfortunately, these compounds are often insoluble in aqueous media and have low stability in gastric acid environment. These factors reduced the bioavailability of related oral dosage forms in digestive system. Reduction of particle size and controlled release delivery system can decline the mentioned problems. In the presented research, extraction of bioflavonoids from Citrus sinensis L. (sweet orange) peels was performed using supercritical carbon dioxide. Experimental central composite design was employed for determination of optimal conditions. Qualification analysis was performed using LC-MS, and hesperidin and hesperetin were identified in herbal extract. Micronization and coating of the flavonoids nanoparticles on sugar spheres have been performed using an inhouse developed supercritical technique. Characterization of coated nanoparticles was done using FESEM and ImageJ software. The in vitro antioxidant activity of coated samples was investigated by ferrous ion chelating activity. According to the extraction results, concentration of ethanol as organic co-solvent has the greatest effect on the extraction yield. Analysis of FESEM images illustrated that nanoparticles of extract components with particle size distribution of 5-100 nm were coated successfully. The solubility and antioxidant activity of nanoparticles in aqueous media have increased significantly compared to original form. This process led to increasing dissolution rate and improving the oral bioavailability of flavonoids.