磺丁基醚-β-环糊精及羟丙基-β-环糊精对伏立康唑的增溶作用比较

Solubilization Comparison between Sulfonated Butyl Ether-β-cyclodextrin and Hydroxypropyl-β-cyclodextrin for Voriconazole by Phase Solubility

目的:考察磺丁基醚-β-环糊精(SBE-β-CD)及羟丙基-β-环糊精(HP-β-CD)对伏立康唑(VCZ)的增溶作用,为其包合物的研制奠定基础。方法:用相溶解度法考察不同浓度的SBE-β-CD及HP-β-CD在不同温度下对VCZ的增溶作用,计算包合常数K及包合动力学参数ΔG、ΔH及ΔS。结果:两种包合材料均能明显提高VCZ的水溶性,而在相同用量及相同温度时,SBE-β-CD的增溶作用较HP-β-CD明显;SBE-β-CD对VCZ的平衡相溶解图为A_N型,而HP-β-CD对VCZ的平衡相溶解图为AL型;温度升高,两种包合材料对VCZ的K值逐渐降低;包合动力学参数ΔG、ΔH及ΔS均为负值。结论:相较于HP-β-CD,SBE-β-CD对VCZ的增溶效果更好,包合为自发形成的放热过程,作用力主要为分子间范德华力。

Objective： To study the solubilization of sulfonated butyl ether-β-cyclodextrin （SBE-β-CD） and hydroxypropyl-β-cyclo- dextrin （HP-β-CD） for voriconazole （VCZ） to lay basis for the preparation of inclusion compounds of VCZ. Methods： The phase-solu- bility method was used, and the solubilization of SBE-β-CD and HP-β-CD at different concentrations for VCZ was studied at various temperatures and the inclusion constant （K） and such inclusion parameters as AG, AH and AS were calculated. Results： Both SBE-β-CD and HP-β-CD could improve the solubility of VCZ in water, while the solubilization of SBE-β-CD was more significant than that of HP-β- CD at the same concentration under the same temperature. The equilibrium phase-solubility diagram of SBE-β-CD vs VCZ was AN type, and that of HP-β-CD vs VCZ was AL type. With the increase of temperature, K of both β-CD decreased. AG, AH and AS were all nega- tive for the inclusion process. Conclusion： Compared with that of HP-β-CD, the solubilization of SBE-β-CD for VCZ is better. The inclusion is spontaneously formed with exothermic process, and the main acting force is Van der Waals＇force.