Aqueous compatibility of 15 pharmaceutical antimicrobial preservatives with the macrocycles cucurbit[7]uril and para-sulfonatocalix[4]arene

The compatibility of 15 antimicrobial preservatives used in liquid/semi-solid pharmaceutical dosage formulations with the macrocycles cucurbit[7]uril (CB[7]) and para-sulfonatocalix[4]arene (sCX[4]) was examined by 1H NMR. A preservative was deemed to be compatible with one, or both, of the macrocycles if there was no evidence of host-guest complex formation. Eight preservatives (benzoic acid, ethanol, glycerine, methyl paraben, potassium sorbate, propylene glycol, sodium ethylenediaminetetraacetic acid, and sodium metabisulfite) were determined to be compatible with both CB[7] and sCX[4]. Three preservatives (benzalkonium chloride, cetrimide, and chlorhexidine) were determined to be not compatible with either macrocycle, whereas chlorobutanol and chlorocresol were found to be compatible with sCX[4] but not with CB[7]. Phenoxyethanol was incompatible with sCX[4] but possibly incompatible with CB[7] depending on the concentration of the preservative used with the cucurbituril. Finally, sodium propanoate was compatible with sCX[4] but only possibly compatible with CB[7].