新型抗凝药达比加群酯的处方前研究  

Preformulation study on anticoagulant drug dabigatran etexilate

作　　者：孟园园 谭方云 冯育苗 孔晓龙[1] MENG Yuan-yuan;TAN Fang-yun;FENG Yu-miao;KONG Xiao-long(School of Pharmacy,Guangxi Medical University,Nanning 530000,China;Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China;Pharmaceutical College,Henan University,Kaifeng,Henan 475000,China)

机构地区：[1]广西医科大学药学院,南宁530000 [2]军事科学院军事医学研究院毒物药物研究所,北京100850 [3]河南大学药学院,河南开封475000

出　　处：《军事医学》2022年第1期54-58,共5页Military Medical Sciences

摘　　要：目的 对新型抗凝药达比加群酯进行处方前研究,为其新剂型开发设计提供参考。方法 对达比加群酯的外观形态、晶体结构、熔点以及溶解性进行考察,建立达比加群酯体外含量测定的HPLC方法,并测定其在不同pH缓冲液中的溶解度。结果 达比加群酯为不含有结晶水的白色絮状晶体,无臭味,具有细长棒状结构。难溶于水,且溶解度具有pH依赖性,随溶液pH值的增加而降低,当溶液pH>3时溶解度很低。结论 达比加群酯为难溶性药物,改善其口服制剂的溶解度,将有利于提高其体内生物利用度。Objective To perform a preformulation study for the development of a novel anticoagulant drug dabigatran etexilate. Methods The appearance,crystal structure,melting point and solubility of the drug were investigated. An HPLC method was established for the determination of dabigatran etexilate,and the drug solubility in solutions at different pH values was also studied. Results Dabigatran etexilate was white,odorless and flocculent crystals without crystal water,and had a slender rod-like structure. It was hardly soluble in water,and the solubility was pH-dependent,which decreased with the increase of the pH value of the solution. When the pH of the solution exceeded 3,the solubility was very low. Conclusion Dabigatran etexilate is a poorly water-soluble drug with pH-dependent solubility,suggesting that the improvement of solubility and dissolution will benefit in vivo absorption of the drug.

关 键 词：达比加群酯 处方前研究 溶解度 表征 难溶性 

分 类 号：R943[医药卫生—药剂学]