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The Research of Supramolecular Complexes of Edaravone and Cyclodextrins

Author: ZengJian
Tutor: RenYong
School: Nanjing Normal University
Course: Microbial and Biochemical Pharmacy
Keywords: Edaravone Cyclodextrin Configuration Bioavailability Preparation
CLC: R943
Type: Master's thesis
Year: 2011
Downloads: 6
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Abstract


[Objective]:To improve the physicochemical property of edaravone by cyclodextrins supramolecular technology and to provide the technical guidance for the new preparation research of edaravone.[Methods]:The inclusion constant of edaravone and cyclodextrin was investigated by molecular modeling and calculation, ultraviolet spectrophotometry and phase solubility method. The inclusion complexes were prepared by levigation and solution method, characterized by the thermal analysis (DTA、TGA and DSC) methods, X-ray diffractometry (XRD) techniques and nuclear magnetic resonance (NMR) method. The solubility and stability of edaravone were also measured. HPLC method was used to detect the oral bioavailability of edaravone before and after included by cyclodextrin. The closure tablet and freeze-dried injection of edaravone were researched and the hemolysis rates of homemade and commercial preparations were investigated.[Results]:Edaravone formed an optimal inclusion complex with cyclodextrin with the equilibrium constant of 146 M-1~4285 M-1 and the energy of the system was significantly reduced. The two closure modes, the benzene ring included and heterocycle ring included, were demonstrated by the NMR (1H-1H RORESY). Two configurations of edaravone in water were discovered and the inclusion technology was obviously improved the content of keto configuration of edaravone. The inclusion complex also increased the solubility and improved the stability of Edaravone. The oral bioavailability results showed that the maximum blood drug concentration (Cmax)、AUC and half-time (T1/2) after forming the inclusion complex with cyclodextrin were improved 6.0-8.0、9.8-11.3 and 1.7-2.2 times, respectively. And the hemolysis test results showed that the hemolysis rate of the homemade preparation was obviously decreased and was only 1/8-1/3 of that of the commercial preparations. [Conclusion]:The solubility, stability and oral bioavailability of edaravone were significantly improved with cyclodextrin and this technique may have medical values for the development of edaravone preparation.

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