The Study On The Properties Of Complexation Between Different Cyclodextrin Derivatives And Cilostazol By Rp-hplc

Cilostazol is platelet aggregation inhibitor,which play the role of inhibiting platelet aggregation and motivating vasodilatation by inhibiting phosphodiesterase and increasing the concentration of cAMP in vascular smooth muscle. The clinical use of cilostazol is important,which is used for Takayasu arteritis, thromboangitis obliterans, chronic ulcer, intermittent claudication and so on.But cilostazol taste bitter, slightly soluble in water and the bioavailability is low.Cyclodextrins and cyclodextrin derivatives had a special ring hollow cylinder,which can form a inclusion complex with cilostazol. To improve the physicochemical features of drug, such as covering the bad smell, enhancing the stability and biological availability,we study the reaction of cilostazol with different cyclodextrins by RP-HPLC.The experimental studies and the results are as follows:(1)The study for the reaction of different cyclodextrins with cilostazol was carried out by RP-HPLC on the column temperature of 25℃,37℃and 45℃. To obtain the information on the mechanism of cilostazol affinity different cyclodextrins, the thermodynamic parameters of the complexation(ΔG,ΔH, andΔS) were studied. The results indicated that cilostazol formed a 1:1 molar ratio inclusion complex with four different cyclodextrins(βCD,DM-βCD,HP-βCD,SBE1-βCD) at 25℃,37℃and 45℃. The inclusion mechanism between different cyclodextrins with cilostazol was determined by the formation constant(K) and it is showed as follows: KSBE1-β-CD﹥KDM-β-CD﹥KHP-β-CD﹥Kβ-CD. Moreover,the values of K decreased as the system temperature increased. To obtain the information on the mechanism of cilostazol affinity different cyclodextrins, the thermodynamic parameters of the complexation(ΔG,ΔH, andΔS) were studied. The change in the thermodynamic parameters indicated that the complexation could proceed spontaneously (ΔG<0)along with the releasing of heat(ΔH<0) and the decrease of entropy(ΔS<0).(2)The study for the reaction of different DS cyclodextrins with cilostazol was carried out by RP-HPLC on the column temperature of 25℃,37℃and 45℃. To obtain the information on the mechanism of cilostazol affinity different DS cyclodextrins, the thermodynamic parameters of the complexation(ΔG,ΔH, andΔS) were studied. The results indicated that cilostazol formed a 1:1 molar ratio inclusion complex with three different SBE-β-CD (SBE1-β-CD,SBE4-β-CD,SBE7-β-CD) at 25 ℃,37℃and 45℃. The inclusion mechanism between different DS cyclodextrins with cilostazol was determined by the formation constant(K) and it is showed as follows: KSBE7-β-CD﹥KSBE4-β-CD﹥KSBE1-β-CD. Moreover,the values of K increased as the system temperature decreased. To obtain the information on the mechanism of cilostazol affinity different DS cyclodextrins, the thermodynamic parameters of the complexation(ΔG,ΔH, andΔS) were studied. The change in the thermodynamic parameters indicated that the complexation could proceed spontaneously (ΔG<0)along with the releasing of heat(ΔH<0) and the decrease of entropy(ΔS<0).(3)To establish an RP-HPLC method for the quantitative determination of cilostazol in its supramolecular inclusion complex with different cyclodextrins. An Agilent Extend C18 column(4.6mm×150mm,5μm) was used with the mobile phase of acetonitrile-water (40:60), at the detection wavelength of 254nm. The flow rate was 1.1mL/min. The calibration curves of cilostazol was linear in the concentration range of 5.2～208μg/mL(r=0.9999).The average recoveries were 99.41%,100.07%,99.63%,99.96%,99.40%,99.71%;RSD were 0.41%,0.65%,0.66%,0.86%,0.27%,0.83%. This method is sensitive, accurate and satisfactory in the separable effect,and can be used for the quantitative assay of different cyclodextrins inclusion complex of cilostazol.(4)The inclusion complex of cilostazol with different cyclodextrins was prepared under ultrasonic radiation. The structure was chatacterized by IR and XRD. The entrapment rate and content have been evaluated by RP-HPLC. The results indicated that cilostazol formed a 1:1 molar ratio inclusion complex with different cyclodextrins. All the results were as follows, the content: Cilostazol-β-CD>Cilostazol-DM-β-CD>Cilostazol-SBE1-β-CD>Cilostazol-HP-β-CD>Cilostazol-SBE4-β-CD>Cilostazol-SB E7-β-CD ; the entrapment rate: Cilostazol-SBE7-β-CD > Cilostazol-SBE4-β-CD >Cilostazol-SBE1-β-CD > Cilostazol-HP-β-CD > Cilostazol-DM-β-CD > Cilostazol-β- CD.