Abstract
The partition of p-hydroxybenzoic acid esters (parabens) between polyoxyethylene alkyl ether (PAE) micelles and an aqueous phase was studied by a solubility method and ultrafiltration. Paraben solubility in aqueous PAE solution and the extent of interaction between parabens at a low concentration and the micelles varied with the structure of PAEs. The binding capability for methyl, ethyl, propyl and butyl paraben per unit hydrocarbon of PAE molecules increased with oxyethylene chain length but decreased with an increase in hydrocarbon chain length. The interactions between parabens and PAEs thus appear to be influenced by the rigid or bulky character of the micelles, which is dependent on the structures of the surfactant micelles.The extent of the interaction is related to the hydrophile-lipophile balance of the surfactants reported by Davies, and to the carbon number in the alkyl group of parabens. We proposed an empirical formula to estimate the magnitude of the interaction, which was successfully applied not only to PAEs but also to ester-type non-ionic surfactants generally used in eye drops and syrups. In the case of aqueous based pharmaceuticals with various non-ionic surfactants, it is highly probable that the paraben concentration required for antibacterial effectiveness could be determined by the empirical formula.
