摘要
为了改善难溶性药物布瑞哌唑水溶性,制备出布瑞哌唑-β-环糊精包合物。采用饱和溶液法制备布瑞哌唑-β-环糊精包合物,通过单因素考察实验,以包合率和回收率为指标,对主客分子摩尔比、包合温度、包合时间、冷藏时间进行优化,确定最佳制备工艺。采用高效液相色谱法对包合率、回收率和平衡溶解度进行检测,采用X-射线衍射法对包合物的结构进行鉴定。结果表明,布瑞哌唑与β-CD摩尔比为1:1时,在50℃的包合温度下反应4 h,溶液冷却至室温后冰箱冷藏92 h待包合物充分析出,抽滤并干燥即得到包合物。平衡溶解度结果表明,包合物的溶解度较原料药提升了约6 400倍。X-射线衍射结果表明,包合物呈现β-CD特征峰,与物理混合物峰形具有较大区别,表明布瑞哌唑包合物制备成功。本实验采用饱和溶液法成功制备布瑞哌唑-β-环糊精包合物,该包合物溶解度显著提升,且制备工艺简单,适用于工业化生产。
In order to improve the aqueous solubility of the insoluble drug brexpiprazole,brexpiprazole-β-cyclodextrin inclusion complexes were prepared.The saturated solution method was used to prepare brexpiprazole-β-cyclodextrin inclusion complexes,and the best preparation process was determined through one-way examination experiments to optimize the hostvip molecule mole ratio,inclusion temperature,inclusion time and refrigeration time using the inclusion rate and recovery as indicators.High performance liquid chromatography(HPLC)was used to detect the inclusion rate,recovery and equilibrium solubility,and X-ray diffraction was used to characterize the structure of the inclusion complexes.The results showed that when the molar ratio of brexpiprazole toβ-CD was 1:1,the reaction was carried out at 50℃for 4 h.The solution was cooled down to room temperature and then refrigerated for 92 h.After the inclusion compound was fully precipitated,the inclusion compound was obtained by filtration and drying.The equilibrium solubility results showed that the solubility of the inclusion compound was increased by about 6400 times compared with that of the API,and the X-ray diffraction results showed that the inclusion compound presented the characteristic peak ofβ-CD,which was quite different from that of the physical mixture,indicating that the preparation of brexpiprazole inclusion compound was successful.In the present experiment,brinpiprazole-β-cyclodextrin inclusion complex was successfully prepared by saturated solution method,which showed a significant increase in solubility,and the preparation process was simple and suitable for industrialized production.
作者
鲁科明
李励
刘灿
郜秋果
LU Keming;LI Li;LIU Can;GAO Qiuguo(Yi Chang HEC ChangJiang Pharmaceutical Co.,Ltd.,Hubei Yichang 443000,China)
出处
《广州化工》
2026年第2期50-52,59,共4页
GuangZhou Chemical Industry
关键词
布瑞哌唑
Β-环糊精
饱和溶液法
包合物
溶解度
brexpiprazole
β-cyclodextrin
saturated solution method
inclusion compounds
solubility
