坎地沙坦固体分散体的制备和溶出度、稳定性研究.PDFVIP

坎地沙坦固体分散体的制备及溶出度、稳定性研究 * 王美荣，王利珍，林建英 (太原理工大学化学化工学院制药工程系，太原 030024) 摘要：目的 利用固体分散技术提高坎地沙坦的溶解性。方法 以体外溶出度为指标，通过单因素试验，考察处方和工 艺因素对坎地沙坦固体分散体中药物溶出的影响，运用正交试验选定坎地沙坦固体分散体的最优处方；采用 FTIR 、DSC 、 XRD 分析技术对药物与载体间的相互作用及药物在固体分散体中的存在状态进行鉴定，探讨固体分散体的增溶机制，考 察固体分散体的稳定性。结果 以聚乙烯吡咯烷酮(PVPK30)为载体，二氯甲烷 甲醇 乙醇=2 2 1 为混合溶剂制备的 ︰ ︰ ︰ ︰ 固体分散体溶出度 1 h 可达 99% ；红外分析表明坎地沙坦与 PVPK30 间有氢键形成；DSC 及 XRD 表征表明坎地沙坦以 微晶或无定形态分散于 PVPK30 中；稳定性加速试验显示固体分散体经过 30 d 后 XRD 显示药物无明显的团聚，仍以微 晶或无定形态存在。结论 固体分散技术能有效提高坎地沙坦的溶出度。制得的坎地沙坦固体分散体为一稳定体系，具 有实际应用价值。 关键字：坎地沙坦；固体分散体；正交实验；溶出度；稳定性 中图分类号：R944.2; R927.13 文献标志码：A 文章编号：1007-7693(2011)07-0654-05 Studies on Preparation of Candesartan Solid Dispersion and Its Dissolution and Stability * WANG Meirong, WANG Lizhen, LIN Jianying (Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Taiyuan University of Technology, Taiyuan 030024, China) ABSTRACT: OBJECTIVE To improve the solubility of candesartan by using solid dispersion(SD) technology. METHODS Single factor method and orthogonal experimental method were adopted to obtain the optimal formula by using the in vitro dissolution as an index. FTIR, DSC, XRD were used to study the existing status of candesartan in SD and bond between candesartan and carriers, so as to study solubilizing mechanism and the stability. RESULTS The ideal candesartan SD was prepared under the condition as follows, carrier was PVPK30 and the solvent volume ratio was methylene chloride : methanol : ethanol=2 ︰2 ︰1. The dissolution of the candesartan SD is up to 99% in one hour. XRD and DSC results showed that drug exists in crystalli