Evaluation of 2-Hydroxypropyl-?-Cyclodextrin as Solubilizing/Stabilizing Agent for Hydroxycamptothecin / 中国药房

ABSTRACT

OBJECTIVE:To study the influence of both pH and complexation by hydroxypropyl-?-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.