Quaternary ammonium compounds benzalkonium chloride

Gall H (1979) Toxic contact dermatitis due to the quaternary ammonium compound benzalkonium chloride. Dermatosen Beruf Umwelt 27 139-140... 

The most widely used preservative remains benzalkonium chloride, which often is supplemented with disodium edetate. The benzalkonium chloride defined in the USP monograph is the quaternary ammonium compound alkylbenzyldimethylammonium chloride, in which the alkyl portion is composed of a mixture of chain lengths ranging from C8 to C16. This compound s popularity is based, despite its compatibility limitations, on its being the most effective and rapid-acting preservative with excellent chemical stability. It is stable over a wide pH range and does not... 

Disinfectants. Several disinfecting agents can be used in hatcheries and two are of particular interest. Because they are not considered dmg or food additive uses by FDA, povidone—iodine compounds can be used to disinfect the surface of eggs (9). Benzalkonium chloride [68424-85-1] and benzethonium chloride (quaternary ammonium compounds), are allowed at 2 mg/L by FDA to disinfect water containing fish. These compounds are also known to have therapeutic properties, especially against external bacteria (9). 

Fig. 10.8 Quaternary ammonium compounds (QACs) A, general structure ofQACs B, benzalkonium chloride (n - S - 18) C, cetrimide (n - 12 - 14 or 16) D, cetylpyridinium chloride.

Substances that have been used as preservatives for disperse systems include chlorocresol, chlorobutanol, benzoates, phenylmercuric nitrate, parabens, and others [76,77]. The use of cationic antimicrobial agents such as quaternary ammonium compounds (e.g., benzalkonium chloride) is contraindicated in many cases because they may be inactivated by other formulation components and/or they may alter the charge of the dispersed phase. Clay suspensions and gels should be adequately preserved with nonionic antimicrobial preservatives. The use of preservatives is generally limited to products that are not intended for parenteral use. Intravenous injectable... 

Quaternary compounds are used for sanitation of noncritical surfaces (floors, bench tops, etc). Their low toxicity has led to their use as sanitizers in food production facilities. The CDC recommends that quaternary ammonium compounds such as benzalkonium chloride not be used as antiseptics because several outbreaks of infections have occurred that were due to growth of pseudomonas and other gram-negative bacteria in quaternary ammonium antiseptic solutions. 

Quaternary ammonium compounds are surface-active agents. Some of them precipitate or denature proteins and destroy microorganisms. The most important disinfectants in this group are cationic surface-active agents, such as benzalkonium chloride, benzethonium chloride and methylbenzethonium chloride, and cetylpyridinium chloride the problems that they cause are similar. 

Benzalkonium chloride is a quaternary ammonium compound used in pharmaceutical formulations as an antimicrobial preservative in applications similar to other cationic surfactants, such as cetrimide. 

A. Anionic and nonionic detergents are only mildly irritating, but cationic detergents are more hazardous because quaternary ammonium compounds may be caustic (benzalkonium chloride solutions of 10% have been reported to cause corrosive bums). 

Quaternary ammonium compounds are widely used antiseptics and disinfectants with a low sensitizing potential. Benzalkonium chloride is used as a skin disinfectant, for disinfection of instruments, and in treatment of burns, ulcers, etc. Cosmetics, deodorants, mouthwashes, and ophthalmic preparations, including contact lens solutions, may contain benzalkonium chloride. 

Benzalkonium chloride is the most widely used preservative in ophthalmology. It is a quaternary ammonium compound that acts as an antimicrobial agent by denaturing proteins and disrupting cytoplasmic membranes. 

Neither anionic nor non-ionic surfactants impair Bronopol s antimicrobial efficacy. For that reason the product is a most suitable preservative for detergent solutions, bath foams, shampoos and hair rinses. Bronopol is also compatible with quaternary ammonium compounds (Section 16.1) and cationic active ingredients such as benzalkonium chloride. 

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 compounds [11, 18.1.]. As these compounds show poor compatibility with anionic and non-ionic surfactants, they are rarely used as cosmetic preservatives. They are more effective in alkaline than in acidic environments, display poor efficacy against pseudomonads, but are highly effective against other Gramnegative bacteria. Gram-positive bacteria and moulds. Cetyltrimethylammonium bromide and benzalkonium chloride are listed as preservatives in EU guidelines. 

The first observations to suggest that some quaternary ammonium compounds, such as benzalkonium chloride, stearalkonium chloride, and cetylpyridine chloride, have antimicrobial activity were made in as early as 1916, but their full potential was first realized in the 1930s [1, 2 J. Since then their uses have steadily increased and include many industrial purposes, water treatment, and antifungal treatment in horticulture, as well as inclusion in pharmaceutical and everyday consumer products. For example, benzalkonium chloride, the most commonly used, is found in products such as eye drops, artificial tears, decongestion nose drops, facial moistures, facial cleansers, acne treatments, sun protection creams and lotions, body lotions, moisturizers, pain relievers, and hand sanitizers [3 ]. Very often good reasons for their use are lacking and claims are limited to assertions that they are bug-killers . 

When phenol derivatives such as polyhydroxybenzyl derivatives are used as preservatives, they may form complexes with any PEG present, resulting in slight inhibition [95]. A very similar effect is observed in the presence of nonionic emulsifiers, though of course it is much more pronounced. Apart from combination products with a fairly wide range of effectiveness and pH values, quaternary ammonium compounds such as benzalkonium chloride have proved very suitable and effective, provided that there are no anionic emulsifiers present in the formulation [96]. 

These are the most important class of disinfecting surfactants, used not only for antisepsis but also as active ingredients in formulas claiming to clean and disinfect in domestic use. (a) Quaternary Ammonium Compounds ( Quats ). Alkylammonium chlorides (e.g., benzalkonium chloride) or bromides (e.g., cetrimonium bromide) are widely used as active ingredients in all-purpose cleaners (APCs). The cation can be viewed as an ammonium ion where the four hydrogen atoms have been replaced by organic groups. 

This method can also be applied to benzalkonium chloride and certain other quaternary ammonium compounds. 

Fig. 10.8 A where the R substituents are alkyl or heterocyclic radicals to give compounds such as cetyltrimethylammonium bromide (cetrimide), cetylpyridinium chloride and benzalkonium chloride. Inspection of the stmctures of these compounds (Fig. 10.8B) indicates the requirement for good antimicrobial activily of having a chain length in the range Cg to Cig in at least one of the R substituents. In the pyridinium compounds (Fig. 10.8C) three of the four covalent links may be satisfied by the nitrogen in a pyridine ring. Polymeric quaternary ammonium salts such as polyquatemium 1 are finding increasing use as preservatives.

Quaternary ammonium salts are organically substituted nitrogen compounds in which the nitrogen atom is pentavalent. Four of the substituents are alkyl, aryl or heterocyclic radicals and the fifth is an anion (a cationic charge). This anion is mostly chloride. Therefore we call them benzalkonium chlorides. 

This preservative is comparatively new to ophthalmic preparations and is a polymeric quaternary ammonium germicide. Its advantage over other quaternary ammonium seems to be its inability to penetrate ocular tissues, especially the cornea. It has been used at concentrations of 0.001-0.01% in contact lens solutions as well as dry eye products. At clinically effective levels of preservative, POLYQUAD is approximately 10 times less toxic than benzalkonium chloride [87,137], Various in vitro tests and in vivo evaluations substantiate the safety of this compound [137,141,142], This preservative has been extremely useful for soft contact lens solutions because it has the least propensity to adsorb onto or absorb into these lenses, and it has a practically nonexistent potential for sensitization. Its ad-sorption/absorption with high water and high ionic lenses can be resolved by carefully balancing formulation components [143],... 

Some quaternary ammonium salts are important because they have disinfectant properties. For example, benzalkonium chloride (Zephiran ) is a well-known antiseptic compound that kills many pathogenic (disease-causing) bacteria and fungi on contact ... 

QUATERNARY AMMONIUM AND PHOSPHONIUM COMPOUNDS 18.1.2. N-Alkyl(C8-Ci8)-N,N-dimethyl-N-benzylammo-niiun chloride = Benzalkonium chloride... 

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