Quaternary ammonium compounds incompatibilities

The other three classes of preservatives have been widely used in ophthalmic, nasal, and parenteral products, but not frequently in oral liquid preparations. The neutral preservatives are volatile alcohols their volatility introduces problems of odor and loss of preservative on aging in multidose preparations. The mercurials and quaternary ammonium compounds are excellent preservatives but are subject to incompatibilities.Mercurials are readily reduced to free mercury, and the quaternary compounds are inactivated by anionic substances. 

Antimicrobial activity benzyl alcohol is bacteriostatic and is used as an antimicrobial preservative against Gram-positive bacteria, molds, fungi, and yeasts, although it possesses only modest bactericidal properties. Optimum activity occurs at pH below 5 little activity is shown above pH 8. Antimicrobial activity is reduced in the presence of nonionic surfactants, such as polysorbate 80. However, the reduction in activity is less than is the case with either hydroxybenzo-ate esters or quaternary ammonium compounds. The activity of benzyl alcohol may also be reduced by incompatibilities with some packaging materials, particularly polyethylene see Section 12. 

Incompatible with aluminum and other metals, strong oxidizing agents, strong acids and bases, sodium chloride solutions, lecithin, phenylmercuric compounds, quaternary ammonium compounds, thioglycolate, and proteins. The presence of sodium metabisulfite, edetic acid, and edetates in solutions can reduce the preservative efficacy of thimerosal. ... 

Incompatibilities of anionic emulsifying wax are essentially those of sodium alkyl sulfates and include cationic compounds (quaternary ammonium compounds, acriflavine, ephedrine hydrochloride, antihistamines, and other nitrogenous compounds), salts of polyvalent metals (aluminum, zinc, tin, and lead), and thioglycollates. Anionic emulsifying wax is compatible with most acids above pH 2.5. It is also compatible with alkalis and hard water. 

Nonionic emulsifying wax is incompatible with tannin, phenol and phenolic materials, resorcinol, and benzocaine. It may reduce the antibacterial efficacy of quaternary ammonium compounds. 

CHG is a cationic moiecuie that is generaiiy compatible with other cationic molecules, such as the quaternary ammonium compounds [2], Some nonionic substances such as detergents, aithough not directiy incompatible with CHG, may inactivate the antimicrobiai properties of CHG, depending upon the compound and concentration leveis. CHG is incompatibie with inorganic anions, except in very dilute concentrations, and may aiso be incompatible with organic anions present in soaps containing sodium lauryl suifate, and with a number of pharma-ceuticai dyes [3,4]. 

In small-scale preparation the quaternary ammonium compounds containing an alkyl chain are the most important. Cetrimide (Cetrimonium bromide, see Fig. 23.8) is used in a concentration of 0.5-2 % as emulsifier in creams. Quaternary ammonium compounds of this type are used from a concentration of 0.004 %. They also exhibit antiseptic and preservative properties. Notably benzalkonium chloride, as well as being a surfactant of the oil-in-water emulsifying type, is also important as a preservative in for example eye and nose drops. Catioiuc-active compounds are often incompatible with anionic substances such as sulfobituminose ammonium due to the risk of the formation of insoluble ion pairs. Since it is often difficult to estimate this risk, it is better to avoid these combinations. 

Quaternary ammonium compotmds are incompatible with many anionic substances. Because quaternary ammonium compounds are also surfactants, they also are used as emulsifier (see Sect. 23.6.2). 

Cationic surfactants are widely used as fabric softeners and antimicrobial agents. The most popular cationic siufactants include alkyl quaternary ammonium, alkylbenzyl ammonium, alkyl pyridiniiun, and alkyl imidazohimi compounds. When separating cationic siufactants on reversed-phase columns, it is often difficult to obtain sharp, symmetrical peaks because of the imdesired interactions between the free silanol groups at the stationary-phase surface and the quaternary ammonium analytes. To improve the peak shape of cationic surfactants, a high concentration of salt such as perchlorate is added to the mobile phase, which causes the analytical method to be incompatible with MS... 

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