9-硝基喜树碱羟丙基-β-环糊精包合物的研制及初步评价

Preparation and Preliminary Evaluation of 9-Nitrocamptothecin Hydroxypropyl-β-cyclodextrin Inclusion Complexes

为提高9-硝基喜树碱(1)的溶解度,采用饱和水溶液法制备1的羟丙基-β-环糊精(HP-β-CD)包合物,并以正交设计优化了包合工艺。所得优化工艺为:1与HP-β-CD的投料比为1∶120(摩尔比),60℃包合2 h,HP-β-CD的浓度为507 mmol/L。差示扫描量热法(DSC)和X-射线衍射法分析结果证实1被HP-β-CD包合。包合后1的溶解度由0.01 mg/ml提高到3.85 mg/ml。并且,新鲜制备的包合物中内酯型1的比例为99%;与游离药物相比,包合物中内酯型1更稳定。

To improve the solubility of 9-nitrocamptothecin （1）, the inclusion complexes of 1 with hydroxy- propyl-13-cyclodextrin （HP-β-CD） were prepared by saturated aqueous solution method. The inclusion process was optimized by orthogonal design. The optimal process was as follows： the molar ratio of 1 to HP-β-CD was 1 ：120, the inclusion was carried out at 60℃ for 2 h, the concentration of HP-β-CD was 507 mmol/L. Moreover, the formation of inclusion complexes was verified by differential scanning calorimetry （DSC） and X-ray diffraction method. After inclusion, the solubility of 1 was increased from 0.01 mg/ml to 3.85 mg/ml. Furthermore, the proportion of the lactone form of 1 in the fresh prepared inclusion complexes was 99 %. Compared with the free drug, the lactone form was more stable in the inclusion complexes.