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目的制备甲氧苄啶-磺丁基醚-β-环糊精包合物,并对其进行条件优化、表征和分子模拟。方法采用超声微波-冷冻干燥法制备包合物,使用Box-Behnken响应面法进行条件优化;采用红外光谱法(FT-IR)、差示扫描量热法(DSC)、粉末X衍射法(XRPD)及核磁共振法(~1H-NMR)对包合物进行表征;采用分子对接技术,模拟包合物的三维构象及结合能;进行溶出度和稳定性实验。结果甲氧苄啶-磺丁基醚-β-环糊精包合物的最佳制备工艺为包合温度为52℃,包合时间为45 min,投料摩尔比为1.7∶1;红外光谱、差示扫描量热图谱、粉末X衍射图谱和核磁共振图谱均表明TMP/SBE7-β-CD包合物形成;分子模拟的包合物最优构象与表征分析相符,包合物结合能为-9.015 kcal·mol~(-1);包合物的TMP溶出速率明显增加,但包合物易吸湿。结论甲氧苄啶-磺丁基醚-β-环糊精包合物制备工艺合理可行,表征方法系统可靠,包合物相对稳定。
OBJECTIVE To prepare trimethoprim-sulfobutylether-β-cyclodextrin inclusion complex, and optimize its conditions, characterization and molecular simulation. Methods The inclusion complex was prepared by ultrasonic microwave-freeze drying method and the conditions were optimized by Box-Behnken response surface methodology (FT-IR), differential scanning calorimetry (DSC) and X-ray powder diffraction ) And 1H NMR were used to characterize the inclusion complex. The molecular docking technique was used to simulate the three-dimensional conformation and the binding energy of the inclusion complex. The dissolution and stability experiments were carried out. Results The best preparation process of trimethoprim-sulfobutyl ether-β-cyclodextrin inclusion complex was as follows: the inclusion temperature was 52 ℃, the inclusion time was 45 min, the molar ratio was 1.7:1; the IR, Differential scanning calorimetry, powder X-ray diffraction and nuclear magnetic resonance spectroscopy showed that the TMP / SBE7-β-CD inclusion complex was formed. The optimal conformation of the molecular simulation inclusion complex was in good agreement with the characterization and the inclusion complex energy was - 9.015 kcal · mol ~ (-1). The TMP dissolution rate of the inclusion complex increased obviously, but the inclusion complex was hygroscopic. Conclusion The preparation of trimethoprim-sulfobutylether-β-cyclodextrin inclusion complex is reasonable and feasible. The characterization method is reliable and the inclusion compound is relatively stable.