摘要
目的:考察不同pH条件下2-羟丙基-β-环糊精(HPCD)对羟基喜树碱(HCPT)的增溶作用以及HCPT内酯环开闭环平衡的影响。方法:运用相溶解度法进行增溶试验,采用高效液相色谱法分别测定HCPT内酯环形式与开环羧酸盐形式药物浓度,考察不同量的HPCD对HCPT内酯环开闭环转化pH平衡点。结果:随着HPCD浓度增加,HCPT的溶解度增加;包合物表观稳定常数随pH上升而下降;HPCD浓度在0%、10%、25%时,HCPT开闭环pH平衡点分别为6.5、7.0、7.3。结论:HPCD可以提高HCPT的溶解度,对HCPT内酯环有稳定作用。
OBJECTIVE： To study the influence of both pH and complexation by hydroxypropyl - β - cyclodextrin （HPCD） on the overall ,solubility of hydroxycamptothecin （HCPT） with particular focus on the equilibrium between its lactone- and carboxylate- form. METHODS： Phase solubility studies at pH values and physiologically acceptable HPCD concentrations were performed, and the amounts of solubilized HCPT quantified by HPLC. The lactone - carboxylate - ratios from the equilibrium were studied. RESULTS： The solubility of HCPT increased with both increasing pH and HPCD concentration. The apparent complexation constant decreased with increasing pH. The lactone- carboxylate equivalence point shifted from a pH value of 6,5, 7.0 and 7.3 with 0%, 10% and 25% HPCD, respectively. Separate complexation constants for the carboxylate - HCPT and lactone- HCPT could thus be derived. CONCLUSION ： The solubilizing and stabilizing effects of HPCD on HCPT in aqueous solution were good.
出处
《中国药房》
CAS
CSCD
北大核心
2008年第4期269-272,共4页
China Pharmacy
