β-环糊精包合物的制备及对苯佐卡因水解速度的影响

Preparation of β-cyclodextrin inclusion complexes and its effect on the benzocaine hydrolysis

通过优化β-环糊精-苯佐卡因包合物(β-CD-benzocaine,β-CD-ben)的制备条件,研究其对苯佐卡因水解速度的影响。具体以β-环糊精、苯佐卡因为原料,水溶液搅拌法为制备方法,在不同投料比(苯佐卡因:β-CD分别为1∶0. 5、1∶1、1∶2和1∶3)、搅拌时间(3 h、5 h和8 h)、包合温度(40℃、55℃和80℃)、干燥后产物洗涤剂(甲醇、乙醇和异丙醇)的条件下,优化包合物的最佳制备条件,即投料比,苯佐卡因∶β-CD=1∶1,搅拌时间5 h,包合温度55℃,干燥后产物洗涤剂选择异丙醇。通过形态表观、电镜分析及X-射线衍射分析对包合物进行表征,并考察5×10﹣6g/mL的苯佐卡因溶液和β-CD-ben包合物溶液在碱性条件下的水解速度。结果表明:优化条件下制备的β-CD-ben包合物在一定程度上降低了苯佐卡因的水解程度。该研究结果对β-CD-ben包合物制备中的影响因素进行了补充,为增加不稳定药物稳定性提供了一定借鉴。

To study the effect on the hydrolysis of benzocaine,the preparation conditions ofβ-cyclodextrin-benzocaine inclusion complexes(β-CD-benzocaine,β-CD-ben)were optimized,includingβ-cyclodextrin and benzene,through water solution mixing method to prepareβ-CD-ben with the different weight ratio(benzocaine∶β-CD=1∶0.5,1∶1,1∶2 and 1∶3),stirring time(3 h,5 h and 8 h),inclusion temperature(40℃,55℃and 80℃),dried product detergent(methanol,ethanol,isopropanol)conditions.Its purpose was to get the best preparation method of inclusion complexes.The optimal conditions for the preparation ofβ-cyclodextrin-benzocaine inclusion complexes were as follows:the ratio of benzocaine to benzocaine for 1∶1,the stirring time for 5 h and the inclusion temperature for 55℃,together with isopropanol as for the dried product detergent.Appetence characteristics,scan electron microscopy(SEM)and X-ray diffraction(XRD)analysis were used for characterization.The hydrolysis rate of 5×10^-6 g/mL benzocaine solution and inclusion complexes were compared under alkaline conditions.Hydrolysis rate results showed thatβ-CD-ben was reduced in a certain extent.The effects of the study on the preparation ofβ-CD-ben were complemented,which could provide some references for the stability of unstable drug.