西罗莫司-羟丙基-β-环糊精包合物的制备

Preparation of Sirolimus-hydroxypropyl-β-cyclodextrin Inclusion

目的:制备西罗莫司-羟丙基-β-环糊精(HP-β-CD)包合物,并考察HP-β-CD提高西罗莫司溶解度的效果。方法:以西罗莫司与HP-β-CD之比(mol:mol)、包合温度和包合时间为因素,包合率、收得率为指标,采用正交试验筛选西罗莫司-HP-β-CD包合物的制备工艺,并进行溶解度影响、X-射线衍射法结构验证。结果:最佳工艺为:西罗莫司与HP-β-CD之比为1:6(mol:mol)、包合温度为25℃、时间为6h;以此工艺制备3批包合物,平均包合率为25.4%(RSD=1.16%),平均收得率为86.5%(RSD=0.83%);随着HP-β-CD浓度增加,西罗莫司溶解度从1.18μg·mL-1增加到49.97μg·mL-1;包合物的晶体衍射峰形几乎与HP-β-CD完全一致。结论:HP-β-CD包合西罗莫司的工艺简单、易操作,能提高西罗莫司的溶解度。

OBJECTIVE：To prepare Sirolimus-hydroxypropyl-β-cyclodextrin（HP-β-CD）inclusion,and to investigate the improvement effect of HP-β-CD inclusion on the dissolution of sirolimus.METHODS：The preparation technology of Sirolimus-HPβ-CD inclusion was optimized by orthogonal test with ratio of sirolimus to HP-β-CD（mol：mol）,inclusion temperature and inclusion time as factors using inclusion rate and yield rate as index.The validation test was conducted among dissolution and X-ray diffraction method structure.RESULTS：The optimal preparation technology was as follows：ratio of sirolimus to HP-β-CD of 1：6（mol：mol）,inclusion temperature of 25 ℃,inclusion time of 6 h.Average inclusion rate of 3 batches of inclusion was 25.4%（RSD=1.16%）and average yield was 86.5%（RSD=0.83%）.With the increase of HP-β-CD concentration,the dissolution of sirolimus increased from 1.18μg·mL-1 to 49.97μg·mL-1.The crystal diffraction profiles of inclusion were in line with those of HP-β-CD.CONCLUSION：The inclusion process of sirolimus with HP-β-CD is simple and easy to operate,and can improve the dissolution of sirolimus.