摘要
目的采用固体分散体技术改善红毛新碱的溶解度,增加其胃肠道吸收。方法以聚乙烯吡咯烷酮为载体,正交实验设计优化红毛新碱固体分散体制备工艺;大鼠在体单向肠灌流法考察肠道吸收情况。结果红毛新碱固体分散体的制备工艺为:红毛新碱和载体质量比为1∶12;溶剂用量比为4∶3;溶剂蒸发温度为65℃;冷冻时间为4h;制备工艺优化的固体分散体平衡溶解度为690.2±9.8μg·mL-1,比红毛新碱提高了33倍,1h累积溶出百分率达94%,比红毛新碱提高近5倍;且固体分散体显著提高了相同质量浓度红毛新碱的在体肠吸收速率常数和表观吸收系数(P<0.05)。结论固体分散体技术提高了红毛新碱的溶解度和溶出速率,增加了其肠道吸收。
Objective To improve the solubility and intestinal absorption of caulophine by solid dispertion technique.Method Caulophine solid dispersion was prepared with PVP K30 as carriers.Orthogonal design was applied to optimize the solid dispersion preparation procedure.Intestinal absorption of caulophine and its solid dispersion were evaluated by an in situ single-pass intestinal perfusion in rats.Result The optimized preparation procedure of caulophine solid dispersion was confirmed,that is,the mass ratio of caulophine and PVP K30 1∶12,the ratio of solvent volume and sample 4∶3,the evaporating temperature 65℃,and the cooling time 4h.The equilibrium solubility of solid dispersion prepared by optimized technology was 690.2±9.8μg·mL^-1,33 times higher than that of caulophine.The percentage of accumulative dissolution of caulophine solid dispersion was 94%in 1h,5times higher than that of caulophine.The absorption rate constant and apparent absorption coefficients of the solid dispersion were much higher than those of caulophine with the same concentration in single-pass intestinal perfusion（P〈0.05）.Conclusion The technique of solid dispersion significantly improved the solubility and dissolution rate of caulophine,and its intestinal absorption in rats.
出处
《西北药学杂志》
CAS
2016年第6期605-608,共4页
Northwest Pharmaceutical Journal
基金
"十二五"国家"重大新药创制"专项(编号:2012ZX09103201-054)
关键词
红毛新碱
固体分散体
溶出度
在体单向肠灌流法
caulophine
solid dispersion
dissolution
single pass intestinal perfusion
