2-羟丙基-β-环糊精对吲哚美辛的增溶及稳定作用

 目的 研究吲哚美辛在不同pH的不同摩尔浓度2-羟丙基-β-环糊精水溶液中的溶解度,以及pH为8.0时吲哚美辛在不同温度、不同摩尔浓度2-羟丙基-β-环糊精溶液中的热稳定性。方法 采用相溶解度法和经典恒温加速法,含量测定采用UV和HPLC。结果 不同pH下吲哚美辛溶解度曲线呈A_L型。2-羟丙基-β-环糊精用量越大,对吲哚美辛的增溶量越高。pH升高,增溶效果越好,但包合物的稳定常数减小。2-羟丙基-β-环糊精对吲哚美辛水溶液的稳定作用随2-羟丙基-β-环糊精浓度增大而提高,并且温度越低,2-羟丙基-β-环糊精的稳定作用越明显。结论 2-羟丙基-β-环糊精可以增大吲哚美辛的溶解度,提高吲哚美辛水溶液的稳定性。

Evaluation of 2-hydroxypropy1-β-cyclodextrin as solubilizing/stabilizing agent for indomethacin

OBJECTIVE To study the inclusion complex formation of indomethacin (IDM) with 2-hydroxypropy1-β-cyclodextrin (HPCD) in aqueous solution and the effect of HPCD on the degradation rate of IDM in alkaline solution at pH 8.0.METHODS The complexing behavior of HPCD with IDM in aqueous solution at various pH was investigated by phase-solubility method. The stability of IDM in HPCD aqueous solution of different concentrations was studied at 60,70,80 and 90℃. The concentration of IDM was determined by UV and HPLC methods. RESULTS An A_L -type phase solubility curve was obtained. The apparent solubility of IDM increased with increasing HPCD concentration. The effect of HPCD as solubilizing agent was better at higher pH, but the apparent stability constant of the complex decreased at the same time. With the concentration of HPCD increasing, the stability of the IDM aqueous solution was increased. Furthermore, the stabilizing effect of HPCD on IDM was more significant at lower temperatures. CONCLUSION The solubilizing and stabilizing effects of HPCD on IDM in aqueous solution were good.