伊潘立酮-羟丙基-β-环糊精包合物的制备及验证

摘要

目的:制备伊潘立酮-羟丙基-β-环糊精(HP-β-CD)包合物,并对其进行验证.方法:以溶液-搅拌法制备包合物；采用正交设计,以包合温度、磷酸加入量、伊潘立酮-HP-β-CD投药比(摩尔比)和溶液pH值为因素,以包合率为指标筛选最佳工艺；以红外分光光度法、差示扫描量热法、溶解度法、相溶解度法对包合物进行验证；以紫外分光光度法(275 nm)测定药品含量及包合率.结果:最佳包合工艺为伊潘立酮:HP-β-CD(摩尔比1∶6),包合介质为0.2％磷酸溶液,包合温度为50℃,搅拌时间为30 mn,调节溶液pH为5.5.验证结果表明,伊潘立酮-HP-β-CD包合物形成,包合后伊潘立酮溶解度为原来的1 950倍；增高温度有利于包合.在275 nm波长处,伊潘立酮检测浓度线性范围为2.5～25 μg·mL-1(r=0.999 9),平均回收率为99.88％(RSD=1.14％)；包合物中药品平均含量为4.97％,包合率为98.75％.结论:伊潘立酮-HP-β-CD包合物工艺可行,增加了药物的溶解度,可为进一步开发新的剂型提供参考.%OBJECTIVE: To prepare and verify Iloperidone-hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion compound. METHODS: The inclusion compound was prepared by solution-mixing legal system; the inclusion technology was optimized by orthogonal design with inclusion temperature, amount of phosphoric acid, mole ratio of Iloperidone-HP-β-CD and pH value of solution as factors using inclusion rate as index; IR spectrophotometry, differential scanning calorimetry (DSC), solubility, phase solubility method were adopted to verify inclusion compound; drug content and inclusion rate were determined by UV spectrophotometry (275 nm). RESULTS: The optimum inclusion process was as follows: iloperidone: HP-β-CD (mole ratio=l:6), the inclusion medium was 0.2% phosphoric acid solution, the inclusion temperature was 50 ℃, stirring time was 30 min, and pH value of solution was adjusted to 5.5. The validation showed that the solubility of iloperidone was as 1 950 fold as that of raw material after inclusion complex had been formulated; temperature elevation was conducive to inclusion. The linear range of iloperidone was 2.5— 25 μg·mL-1 (r=0.999 9)with an average recovery of 99.88% (RSD=1.14%). The average content of iloperidone in 3 batches of samples was 4.97% with inclusion rate of 98.75%. CONCLUSION: The process of Iloperidone-HP-β-CD inclusion compound is feasible and can increase drug solubility, which provides reference for the development of new formulations.