EFFECTS OF ETHANOL ON FORMATION OF INCLUSION COMPLEXES OF HYDROXYPROPYLCYCLODEXTRINS WITH TESTOSTERONE OR WITH METHYL-ORANGE

Gradual additions of ethanol decreased and eventually abolished the formation of inclusion complexes of testosterone with hydroxypropylcyclodextrins in aqueous solutions. With hydroxypropyl-beta-cyclodextrin this occurred through two mechanisms. At low concentrations of ethanol (< 30%), the solvent primarily acted as a competing guest compound; at higher concentrations the dissociation primarily occurred through non-specific solvent effects. With hydroxypropyl-gamma-cyclodextrin only the dissociation through nonspecific solvent effects was observed. Surprisingly, when ethanolic solutions containing fully dissociated complexes were evaporated, the solid residues had properties characteristic of complexed species, i.e., they showed the rapid and complete dissolution characteristic of complexes prepared by freeze drying of aqueous solutions. That inclusion complexes were formed during the final stages of evaporation of ethanolic solution of components was confirmed by measurements of circular dichroic spectra of a methyl orange: hydroxypropyl-beta-cyclodextrin combination. In this combination the spectra of included species were highly characteristic and were recorded both in aqueous solutions and in solid state after the evaporation of ethanolic solutions but not in concentrated ethanolic solutions.