Complexes of Ergot Alkaloids and Derivatives II: Interaction of Dihydroergotoxine with Certain Xanthines

Abstract

Intermolecular complexation between a mixture of the comparatively water-insoluble alkaloids comprising 9,10-dihydroergotoxine and several xanthines was investigated. Substantial elevations of aqueous solubility of dihydroergotoxine in 0.1 N HCl and in pH 6.65 phosphate buffer was observed in most of the cases examined. This incongruity in the normally expected solubility data may be attributed to a mutual influence between the ergot derivative and the xanthine under consideration. Dissolution studies indicated a generally enhanced first-order rate of solution in the presence of xanthine which seems to evidence some “driving force” pulling the drug into solution. Partitioning rates (aqueous to chloroform) are usually increased when xanthine is added to the 9,10-dihydroergotoxine at pH 6.65 and the reverse is true in 0.1 N HCl. Biological data in cats and humans are in good agreement with physicochemical work.