EFFECT OF ALKYL CHAIN-LENGTH AND DEGREE OF SUBSTITUTION ON THE COMPLEXATION OF SULFOALKYL ETHER BETA-CYCLODEXTRINS WITH STEROIDS

This study was designed to test how the sulfoalkyl ether (SAE) modific ation of beta-cyclodextrin (beta-CD) affects the binding capacity of t estosterone and progesterone, thereby enhancing their solubility. The SAE-beta-CD derivatives contain either sulfopropyl ether (SPE) or sulf obutyl ether (SBE) groups on the 2-, 3-, and 6-hydroxyl positions of t he dextrose moieties. SAE-beta-CDs are a mixture of positional and reg ional isomers containing from one to as many as 12 SAE groups per CD. The effect of chain length and the degree of substitution on complexat ion behavior was investigated by the phase-solubility method. The resu lts were compared with those obtained with beta-CD, where possible, an d with hydroxypropyl-beta-CD (HP-beta-CD). To determine the effect of degree of substitution (DS) on the binding, mixtures of SAE-beta-CDs w ith multiple substitution levels and varying average degrees of substi tution were studied as well as mixtures of SAE-beta-CDs that contained the same degree of substitution. Mixtures that contained SAE-beta-CDs of the same degree of substitution were isolated from the multiple su bstitution level mixtures by ion-exchange chromatography and purified for investigation. Unlike the parent beta-CD, linear increases in the apparent solubilities of testosterone and progesterone were observed, and the binding potentials were comparable to those of beta-CD or bett er. The results demonstrate that the binding potentials of the SAE-bet a-CD derivatives were dependent on the guest molecule, the degree of s ubstitution, and the alkyl ether chain length. Our previous study show ed the inhibition of complexation by direct sulfonation of the beta-CD . However, in the present work, interferences with the charged sulfona te groups were avoided by repositioning them away from the cavity. Inc reasing the degree of substitution assisted in complex formation; howe ver, its effects were limited. Reduction of the alkyl chain length, as in the case of SPE-beta-CD compared with SBE-beta-CD, decreased the c omplexation potential. This decrease in complexation potential was fur ther suppressed with an increase in the number of substituents placed on the CD torus. Generally, the binding potential of SAE-beta-CD deriv atives increased with increasing alkyl chain length. However, placemen t of more than an optimum number of SAE groups on the CD torus resulte d in inhibition of complexation.