Antifungal drug solubilizing activity and self-aggregation ability of cationic aminocalix[4]arene in comparison to SBEβCD: effect of addition of water-soluble polymer

Ionized calixarene derivatives often possess properties of typical surfactants, aggregating in aqueous solutions. Their solubilizing properties, in this case, are often greater than conventional excipients, cyclodextrins. This in addition to their reported low toxicity makes these compounds promising pharmaceutical excipients. In this study we investigate the solubilizing ability of a cationic aminocalix[4]arene (CALIX), towards antifungal drugs, alone and with addition of HPMC. Next, the compound's self-aggregation properties in the presence of drug alone or in conjunction with polymer were studied using DLS, and compared to that for SBEβCD. Twenty percent (w/v) CALIX solution solubilizes antifungal drugs more efficiently than SBEβCD, improving for example the solubility of clotrimazole more than 21,000 times compared to its intrinsic solubility, and addition of 0.25 % HPMC into complexation media increases this effect further. Introduction of drug alone or in combination with the polymer into the complexation media significantly changes the microenvironment of excipient's aqueous solution, resulting either in smaller or larger aggregates depending on the drug chosen, presence of the polymer or the excipient used. Growth of the aggregates is observed to a greater extent upon introduction of clotrimazole into the media than with econazole nitrate and in some cases the particles were large enough to be observed by conventional light microscopy.