Improving the aqueous stability of prostaglandin E2 and prostaglandin a2 by inclusion complexation with methylated-β-cyclodextrins

Abstract

The effects of two methylated-β-cyclodextrins, heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CyD) and heptakis(2,3,6-tri-O-raethyl)-β-cyclodextrin (TM-β-CyD), on the dehydration rate of prostaglandin E2 (PGE2) and the isomerization rate of prostaglandin A2 (PGA2) in aqueous alkaline solution were investigated in comparison with natural β-cyclodextrin (β-CyD).In contrast to the acceleration effect of 8-CyD, both DM-β-CyD and TM-8-CyD significantly retarded the reaction rates.The stabilizing effect of DM-β-CyD was larger than that of TM-β-CyD.Stability constants and rate constants of the complexes were kineticall determined on the basis of 1:1 inclusion complex formation.The data suggest that DM-β-CyD is useful in the stabilization of PGEs and PGAs inaqueous solution. © 1984, The Pharmaceutical Society of Japan. All rights reserved.