Encapsulation of (E)-N’-(1-(7-(diethylamino)-2-oxo-2H-chromen-3 yl)ethylidene)benzohydrazide (7-diEAHC) in β-cyclodextrins: Optimized synthesis of 7-diEACH and in silico ADME profiling, physical stability, antioxidant properties of encapsulated 7-diEAHC and bioavailability in rats

Abstract

The β-cyclodextrins (β-CD) as supramolecular have extremely attractive pharmaceutical applications. This study focused on the effects of macrocyclic systems complexation on stability, antioxidant activities, and bioavailability of the optimized synthesis coumarin incorporating hydrazone moiety. Optimal synthesis of (E)-N’-(1-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)ethylidene)benzohydrazide (7-diEAHC) was performed by using response surface methodology (RSM) with a temperature of 100 °C, a reaction time of 10 min in the presence of acetic acid (0.85 M). Physicochemical properties and in silico ADME profiling of 7-diEAHC were also determined. The encapsulation efficiencies of the 7-diEAHC were above 81 % for the micro-encapsulates. After sunlight exposure, the 7-diEAHC-β-CD inclusion complex showed a photostability 19.4 % higher than free 7-diEAHC. Additionally, the encapsulated 7-diEAHC exhibited better stability than free 7-diEAHC for the pH varied between 1 and 9. From the results, storage stability showed that the encapsulation method using β-CD conferred a greater ability of 7-diEAHC against temperature. The NMR and FT-IR techniques were employed to evaluate the chemical stability of 7-diEAHC after encapsulation. In addition, in vivo study showed that the micro-encapsulation approach increased the oral bioavailability of 7-diEAHC in treated rats.

Keywords

• Hydrazone coumarin
• β-Cyclodextrins
• Optimization
• ADME parameters
• Micro-encapsulation
• Bio-assay