Parabens nonionic surfactants

These esters of p-hydroxybenzoic acid have been used primarily to prevent growth of molds but in higher concentrations possess some weak antibacterial activity. Their effective use is limited by low aqueous solubility and by reports of stinging and burning sensations related to their use in the eye. They bind to a number of nonionic surfactants and polymers, thereby reducing their bioactivity. They are used in combination, with the methyl ester at 0.03-0.1% and the propyl ester at 0.01-0.02%. Parabens have also been shown to promote corneal absorption [140]. 

Oral liquid and semisolid formulations containing water as part of the vehicle may be prone to microbial spoilage in the absence of a preservative. In the case of pharmaceutical creams, these are usually oil-in-water emulsions stabilized using a surfactant. Phenolic preservatives, e.g., parabens esters, are inactivated in the presence of nonionic surfactants, and this detrimental interaction can have serious consequences for preservation of the product (20). 

For this reason, a drug product that is to be used multiple times (multidose) must contain a preservative to prevent bacterial growth. A list of preservatives that have been used in pharmaceutical formulations is shown in Table 2. However, most of these are not usually compatible with protein formulations. Some, such as the parabens, are not active in the presence of nonionic surfactants—excipients that are typically required in protein formulations.Others may not be acceptable for a particular route of administration. Benzalkonium chloride, a commonly used preservative in topical formulations, causes ototoxicity when applied to the ear. As with buffering species, the list of preservatives available to the formulation scientist quickly narrows to just a few compounds including benzyl alcohol, phenol, w-cresol, and benzethonium chloride. A benzyl alcohol-containing formulation of epoetin alfa has been shown to be stable, even when dispensed in plastic syringes. ... 

The antimicrobial activity of butylparaben is considerably reduced in the presence of nonionic surfactants as a result of micellization. Absorption of butylparaben by plastics has not been reported but appears probable given the behavior of other parabens. Some pigments, e.g., ultramarine blue and yellow iron oxide, absorb butylparaben and thus reduce its preservative properties. ... 

The antimicrobial activity of methylparaben and other para-bens is considerably reduced in the presence of nonionic surfactants, such as polysorbate 80, as a result of micelliza-tion. ° However, propylene glycol (10%) has been shown to potentiate the antimicrobial activity of the parabens in the presence of nonionic surfactants and prevents the interaction between methylparaben and polysorbate 80. ... 

Among the more commonly used preservatives that do not release formaldehyde are parabens—Dowicil 200 and Kathon CG. Kathon is effective at extremely low concentrations, about 15 ppm. A commonly used mixture of parabens consists of 0.1% methyl paraben and 0.7% propyl paraben. This mixture of parabens is moderately effective alone but is more effective in combination with other preservatives. The European Economic Community (EEC) prohibits the use of parabens above 0.8%. Parabens like most phenolic preservatives are deactivated by nonionic surfactants therefore, parabens should not be used in nonionic formulations like baby shampoos. 

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