芬苯达唑-甲基-β-环糊精包合物的制备及物相鉴定

doi:10.16431/j.cnki.1671-7236.2024.04.040

摘要/Abstract

摘要： 【目的】提高难溶性兽药芬苯达唑(fenbendazole,FBZ)的水溶性和溶出度,提高药物在临床应用中的治疗效果。【方法】采用恒温磁力搅拌法,配合冷冻干燥技术,制备芬苯达唑-甲基-β-环糊精包合物(FBZ-Me-β-CD)。通过设计单因素正交试验,以包合物的包合率和产率为指标,研究包合物的最佳制备工艺;通过相溶解度试验,根据5种不同环糊精对药物的增溶效果,确定最佳包合材料;使用高效液相色谱法(HPLC)对包合物的溶解度、包合率及体外溶出度进行检测;最后,使用差示扫描量热法(DSC)和扫描电镜(SEM)对包合物的物相结构进行表征。【结果】包合物的最佳制备工艺为:搅拌时间3 h、转速600 r/min、主客摩尔比1∶3,温度50℃,最佳包合材料为甲基-β-环糊精。包合物在水中的溶解度为12.02 mg/mL,是芬苯达唑原药(0.3 μg/mL)的4万倍。包合物的体外溶出度是芬苯达唑原药的7倍。包合物的平均产率、包合率分别为89.50%和29.20%,经扫描电镜和差示扫描量热法分析鉴定,芬苯达唑和环糊精处于非晶体结构的包合状态。【结论】本研究通过制备芬苯达唑环糊精包合物,提高了难溶性药物芬苯达唑的溶解度和体外溶出度,且制备方法简单易行,有利于芬苯达唑的进一步研究。

关键词: 芬苯达唑; 包合物; 环糊精; 水溶性

Abstract: 【Objective】 This study was aimed to improve the water solubility and dissolution rate of the insoluble veterinary drug fenbendazole (FBZ) and improve the therapeutic effect of the drug in clinical application.【Method】 Fbendazole-methyl-β-cyclodextrin inclusion complex (FBZ-Me-β-CD) was prepared by constant temperature magnetic stirring method and freeze-drying technique.Through the design of single factor orthogonal test,the optimum preparation technology of inclusion complex was studied with the inclusion rate and recovery rate as the index.According to the solubilization effect of 5 different cyclodextrins on drugs,the best inclusion material was determined by phase solubility test.High performance liquid chromatography (HPLC) was used to detect the solubility,inclusion rate and in vitro dissolution rate of the inclusion complex.Finally,the phase structure of the inclusion complex was characterized by differential scanning calorimetry (DSC) and scanning electron microscopy (SEM).【Result】 The optimum preparation process of inclusion complex was as follows:Stirring time was 3 h,rotational speed was 600 r/min,molar ratio of subject to guest was 1∶3,temperature was 50 ℃.The best inclusion material was methyl-β-cyclodextrin.The solubility of the inclusion complex in water was 12.02 mg/mL,which was 40 000 times that of fenbendazole (0.3 μg/mL).The dissolution rate of the inclusion complex in vitro was 7 times that of fenbendazole.The average recovery and inclusion rate of the inclusion compounds were 89.50% and 29.20%,respectively.By scanning electron microscopy and differential scanning calorimetry,fenbendazole and cyclodextrin were identified as amorphous inclusion states.【Conclusion】 In this study,the solubility and dissolution rate of the insoluble drug fenbendazole were improved by preparing the cyclodextrin inclusion complex of fenbendazole,and the preparation method was simple and easy,which was conducive to the further study of fenbendazole.

Key words: fenbendazole; inclusion complex; cyclodextrin; water solubility

中图分类号:

S859.1

张志远, 徐淑凤, 聂结华, 马艳芝, 廖洁丹. 芬苯达唑-甲基-β-环糊精包合物的制备及物相鉴定[J]. 中国畜牧兽医, 2024, 51(4): 1729-1736.

ZHANG Zhiyuan, XU Shufeng, NIE Jiehua, MA Yanzhi, LIAO Jiedan. Preparation and Image Identification of Fenbendazole-methyl-β-cyclodextrin[J]. China Animal Husbandry and Veterinary Medicine, 2024, 51(4): 1729-1736.

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