卡前列甲酯-羟丙基-β-环糊精包合物的制备和评价  

Preparation and evaluation of carboprost methylate hydroxypropyl-β-cyclodextrin inclusion complex

作　　者：何瑶 徐晓玉[2] 陈红[3] 薛强[4] HE Yao1, XU Xiao-yu2, CHEN Hong3, XUE Qiang4(1 The Fourth People＇s Hospital of Chongqing, Chongqing 400014, China ; 2 College of Pharmaceutical Sciences ＆ College of Chinese Medicine, Southwest University, Chongqing 400716, China ;3 Department of Pharmacy, Southwest Hospital, Chongqing 400038, China ; 4 College of Pharmacy ＆ College of Traditional Chinese Medicine, Chongqing Medical and Pharmaceutical College, Chongqing 401331, Chin)

机构地区：[1]重庆市第四人民医院药剂科,重庆400014 [2]西南大学药学院,重庆400716 [3]第三军医大学附属西南医院药剂科,重庆400038 [4]重庆医药高等专科学校药学院&中药学院,重庆401331

出　　处：《中国新药杂志》2018年第6期637-643,共7页Chinese Journal of New Drugs

基　　金：国家重大新药创制科技重大专项资助项目(2014ZX09304-306-04);重庆市卫生计生委医学科研项目(20142078);重庆市卫生计生委中医药科技项目(ZY201702130);重庆医药高等专科学校人才引进计划项目(ygz2016304);重庆医药高等专科学校自然科学项目(ygz2017104)

摘　　要：目的:制备和评价卡前列甲酯-羟丙基-β-环糊精(CM-HP-β-CD)包合物,以提高卡前列甲酯(carboprost methylate,CM)溶解度和稳定性,开发CM的临床新制剂。方法:采用搅拌-冷冻干燥法制备CMHP-β-CD包合物,以包合率和包合物收率为指标,采用正交设计优化制备工艺。采用相溶解度法、紫外光谱法(UV)、红外分光光度法(IR)、差示扫描量热法(DSC)对包合物结构进行验证,并考察包合物对CM溶解度和溶出度、稳定性的改善作用。结果:优化的制备工艺条件为:卡前列甲酯与羟丙基-β-环糊精(HP-β-CD)物质的量比为1∶1、包合时间4 h、包合温度为50℃。制得的包合物包合率为(92.70±0.87)%,包合物收率为(96.13±0.49)%。25℃下包合物中2种物质的物质的量比为1∶1,相溶解度图呈AL型。紫外光谱、差示扫描量热法、红外分光光度法结果证明包合物形成。包合物溶解度为(67.59±0.17)mg·mL^(-1),10 min时CM几乎全部溶出,显著优于原料药。室温(25~30℃)放置50 d,CM含量稳定。结论:CM-HP-β-CD包合技术能显著提高CM的溶解度和稳定性,为研制CM的口服和注射新剂型提供了可靠的实验基础和技术支持。Objective： To prepare and evaluate carboprost methylate hydroxypropyl-β-cyclodextrin （CM-HP-β-CD） inclusion complex for improving the solubility and stability of CM. Methods： The inclusion complex was prepared by stirring-freeze-dry method. The preparation technology was optimized by orthogonal test with inclusion rate and yield of inclusion complex as indexes. The inclusion complex was identified and verified by phase solubility method, ultraviolet （UV） spectrometry, infrared spectrophotometry（ IR）, and DSC method, the apparent solubility and dissolution were determined, and the stability was studied. Results ：The optimum preparation procedure was as follows： the molar ratio of CM to HP-β-CD 1 ： 1, inclusion time 4 h, and inclusion temperature 50 ℃. The average inclusion rate of the complex was （92.70 ± 0.87 ） % , and the yield was （96.13 ± 0.49 ） %.The 1：1 molar ratio inclusion complex of CM with HP-β-CD could be formed at 25 ℃. The phase diagram was AL type. The results of UV, DSC and IR showed that the inclusion complex was formed. The apparent solubility was （67.59 ±0. 17） mg·mL^-1 CM was almost completely released at 10 rain, significantly superior to the original drug. After being placed at room temperature （25 - 30 ℃ ） for 50 d, the content of CM in the inclusion complex was stable. The dissolution rate and stability of the inclusion complex were significantly improved. Conclusion：The preparation process of CM-HP-β-CD inclusion complex under the optimum conditions can significantly improve the solubility and stability of CM,and provide a reliable experimental basis and technical support for preparation of new oral and injection dosage forms of CM.

关 键 词：卡前列甲酯 羟丙基-Β-环糊精 包合物 正交实验 

分 类 号：R943[医药卫生—药剂学]