Enhancement of oral bioavailability of spironolactone by .BETA.- and .GAMMA.-cyclodextrin complexations.

Abstract

Inclusion complex formations of spironolactone (SP) [an aldosterone antagonist used as an antihypertensive] with 3 cyclodextrins (.alpha.-, .beta.-, .gamma.-CyD) [pharmaceutical adjuncts] in aqueous solution and in the solid state were studied by the solubility method, by spectroscopic methods (UV, CD [circular dichroism], IR) and by X-ray diffractometry, and their modes of interaction were assessed. The solid complexes of SP with .beta.- and .gamma.-CyD were obtained in molar ratios of 1:2 and 2:3, respectively, and their dissolution, membrane permeation and oral absorption properties in dogs were examined. The rates of dissolution and permeation through a cellophane membrane in water were significantly increased by inclusion complexation (.gamma.-CyD complex > .beta.-CyD complex > SP alone), depending upon the solubility of the test samples. The serum levels of SP following oral administration of CyD complexes were greater than those after administration of SP alone. The .gamma.-CyD complex rather than .beta.-CyD complex may have great utility as a faster dissolving form of SP able to produce higher serum levels.