利用冷冻干燥法制备四烯雌酮固体分散体  

Preparation of Altrenogest Solid Dispersions by Freeze-drying

作　　者：朱珍珍 刘大虎 杨升 ZHU Zhenzhen;LIU Dahu;YANG Sheng(Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry,College of Animal Science and Veterinary Medicine,Tianjin Agricultural University,Tianjin 300392,China)

机构地区：[1]天津农学院动物科学与动物医学学院,天津市农业动物繁育与健康养殖重点实验室,天津300392

出　　处：《畜牧兽医学报》2024年第9期4131-4140,共10页ACTA VETERINARIA ET ZOOTECHNICA SINICA

基　　金：西藏自治区区域科技协同创新专项(QYXTZX-NQ2021-01)。

摘　　要：本研究旨在制备四烯雌酮(altrenogest,ALT)固体分散体,提高四烯雌酮的溶解度及其生物利用度,为其在实际生产中的应用提供参考依据。以聚乙烯吡洛烷酮K30(polyvinyl pyrrolidone k30,PVPK30)为药物载体,叔丁醇为冻干溶剂,冷冻干燥法制备四烯雌酮固体分散体。以固体分散体体外溶出度为评价指标对所得ALT固体分散体的质量进行评估,采用X射线衍射法(X-ray diffraction,XRD)、同步热分析法(simultaneous thermal analysis,TG-DSC)、傅里叶红外光谱法(Fourier transform infrared spectroscopy,FT-IR)、扫描电镜法(scanning electron microscopy,SEM)等方法来描绘其特性,并研究其在体外的溶出规律。结果显示,四烯雌酮固体分散体最优制备工艺为药载比1∶8,叔丁醇浓度为50%,超声时间80 min。固体分散体在pH为7.4的PBS缓冲液中的平衡溶解度为原料药的5.91倍,1∶8混合物的3.65倍,固体分散体6 h体外累积溶出率为89.09%,ALT原料药和物理混合物的累积溶出率为32.94%、28.93%。综上所述,此方法制备的固体分散体能够有效提高四烯雌酮原料药的溶解度。The aim of this study was to prepare altrenogest(ALT)solid dispersion,improve the solubility and bioavailability of altrenogest,and provide a reference for its application in actual production.ALT solid dispersion was prepared by freeze-drying method with polyvinyl pyrrolidone k30(PVPK30)as the drug carrier and tert-butanol as the lyophilized solvent.X-ray diffraction(XRD),simultaneous thermal analysis(TG-DSC),Fourier transform infrared spectroscopy(FT-IR),scanning electron microscopy(SEM)and other methods were used to characterize the properties.The results showed that the optimal preparation process of tetraene estrone solid dispersion was as follows:drug loading ratio of 1∶8,tert-butanol concentration of 50%,and ultrasonic time of 60 min.The equilibrium solubility of the solid dispersion in pH 5.0 buffer was 5.91 times that of the active pharmaceutical ingredient(API),3.65 times that of the 1∶8 mixture,the cumulative dissolution rate of the solid dispersion in vitro for 6 h was 89.09%,and the cumulative dissolution rates of the ALT active ingredient and the physical mixture were 32.94%and 28.93%.In summary,the solid dispersion prepared by this method can effectively improve the solubility of altrenogest API.

关 键 词：四烯雌酮 冷冻干燥法 固体分散体 溶解度 

分 类 号：S859.79[农业科学—临床兽医学]