Preparation And Characterization Of The Inclusion Complexes Of Butylphthalide With Cyclodextrins

Butylphthalide(NBP)is originally extracted from seeds of Apium,which is used for the treatment of ischemic stroke in clinical.NBP is an oily compound,which has little water-solubility,thus results in low bioavailability in vivo.In order to increase the bioavailability of drug in vivo,how to enhance the water-solubility of NBP has become the reasearching focus.Nowadays,the pharmaceutical excipients cyclodextrins(CDs)and its derivatives has attracted more attention.In general,B-CD that has poor water-solubility is the most useful.Many derivatives of ?-CD has been synthesized to modify water-solubility.The derivatives,namely hydroxypropyl-?-cyclodextrin(HP-?-CD)and sulfobutyl ether-B-cyclodextrin(SBE-B-CD)has been extensively used.The inclusion complexes of NBP/CDs could develop the water-solubility of drug,and then improve the bioavailability of drug in vivo.The aim of this paper is to investigate the enhancement of the water-solubility after complexing NBP with HP-B-CD,SBE-?-CD and ?-CD.1)The preparation of inclusion complexesThe complexes were prepared by solution-stirring method,ultraphonic method and grinding method.The single factor study and orthogonal design method were used to optimize the conditions.The results showed that the solution-stirring method has the highest entrapment efficiency.2)The characterization of inclusion complexesThe formation of complexes were investigated by fourier transform infrared spectroscopy(FT-IR),differential scanning calorometry-thermogravimetric analysis(DSC-TGA)and nuclear magnetic resonance(1H-NMR).The results showed that the type of phase equilibrium curve of inclusion complexes was AL and all of the inclusion ratios were found to be 1:1.It was concluded that the water-solubility and stability of NBP were obviously increased in the inclusion complexes with three CDs and the HP-?-CD is preferred.Thus,this paper utilized solution-stirring method to prepare inclusion complexe of NBP with HP-?-CD.3)Dissolution rate and pharmacokinetic studyThe dissolution rate and pharmacokinetic study of NBP/HP-?-CD inclusion complexe was carried out.The dissolution rate showed that the inclusion complexe has higer dissolution rate then that of pure drug.The drug analysis method in vivo is established and the drug concentration of blood is determined.The results showed that the inclusion complexe of NBP/HP-?-CD improved the bioavailability of drug.