Enhanced Bioavailability of Digitalis Glycoside by Cyclodextrin Complexation

Abstract

Inclusion complex formations of some digitalis glycosides (digoxin, digitoxin, methyl digoxin) with three cyclodextrins (α-, β, γ-CyDs) in aqueous solution and in solid phase were studied by solubility method, spectroscopies (UV, CD, IR, NMR) and X-ray diffractometry, and their mode of interactions were assessed. Acid hydrolysis of digoxin was found to be retarded by CyDs (in the order of s-> γ-> α-CyD), depending upon the fitness of the drug to CyD cavity. The solid complexes of digitalis glycosides with y-CyD in a molar ratio of 1:4 were obtained, and their dissolution behavior, chemical stability, and oral bioavailability were examined. The rapid dissolving form of digoxin—γ-CyD complex, for example, increased the plasma levels of digoxin (about 5.4 fold) after oral administration to dogs. The enhanced bioavailability of the drug by inclusion complexation suggests the possibility of smaller doses and fewer side effects in oral digitalis glycoside therapy.